158 research outputs found
Interactome network analysis identifies multiple caspase-6 interactors involved in the pathogenesis of HD
Caspase-6 (CASP6) has emerged as an important player in Huntington disease (HD), Alzheimer disease (AD) and cerebral ischemia, where it is activated early in the disease process. CASP6 also plays a key role in axonal degeneration, further underscoring the importance of this protease in neurodegenerative pathways. As a protein's function is modulated by its protein-protein interactions we performed a high throughput yeast-2-hybrid (Y2H) screen against ∼17,000 human proteins to gain further insight into the function of CASP6. We identified a high confidence list of 87 potential CASP6 interactors. From this list, 61% are predicted to contain a CASP6 recognition site. Of nine candidate substrates assessed, six are cleaved by CASP6. Proteins that did not contain a predicted CASP6 recognition site were assessed using a LUMIER assay approach and 51% were further validated as interactors by this method. Of note, 54% of the high-confidence interactors identified show alterations in human HD brain at the mRNA level, and there is a significant enrichment for previously validated huntingtin (HTT) interactors. One protein of interest, STK3, a proapoptotic kinase, was validated biochemically to be a CASP6 substrate. Furthermore, our results demonstrate that in striatal cells expressing mutant huntingtin (mHTT) an increase in full length and fragment levels of STK3 are observed. We further show that caspase-3 is not essential for the endogenous cleavage of STK3. Characterization of the interaction network provides important new information regarding key pathways of interactors of CASP6 and highlights potential novel therapeutic targets for HD, AD and cerebral ischemia
Partially Annealed Disorder and Collapse of Like-Charged Macroions
Charged systems with partially annealed charge disorder are investigated
using field-theoretic and replica methods. Charge disorder is assumed to be
confined to macroion surfaces surrounded by a cloud of mobile neutralizing
counterions in an aqueous solvent. A general formalism is developed by assuming
that the disorder is partially annealed (with purely annealed and purely
quenched disorder included as special cases), i.e., we assume in general that
the disorder undergoes a slow dynamics relative to fast-relaxing counterions
making it possible thus to study the stationary-state properties of the system
using methods similar to those available in equilibrium statistical mechanics.
By focusing on the specific case of two planar surfaces of equal mean surface
charge and disorder variance, it is shown that partial annealing of the
quenched disorder leads to renormalization of the mean surface charge density
and thus a reduction of the inter-plate repulsion on the mean-field or
weak-coupling level. In the strong-coupling limit, charge disorder induces a
long-range attraction resulting in a continuous disorder-driven collapse
transition for the two surfaces as the disorder variance exceeds a threshold
value. Disorder annealing further enhances the attraction and, in the limit of
low screening, leads to a global attractive instability in the system.Comment: 21 pages, 2 figure
Shrinking a large dataset to identify variables associated with increased risk of Plasmodium falciparum infection in Western Kenya
Large datasets are often not amenable to analysis using traditional single-step approaches. Here, our general objective was to apply imputation techniques, principal component analysis (PCA), elastic net and generalized linear models to a large dataset in a systematic approach to extract the most meaningful predictors for a health outcome. We extracted predictors for Plasmodium falciparum infection, from a large covariate dataset while facing limited numbers of observations, using data from the People, Animals, and their Zoonoses (PAZ) project to demonstrate these techniques: data collected from 415 homesteads in western Kenya, contained over 1500 variables that describe the health, environment, and social factors of the humans, livestock, and the homesteads in which they reside. The wide, sparse dataset was simplified to 42 predictors of P. falciparum malaria infection and wealth rankings were produced for all homesteads. The 42 predictors make biological sense and are supported by previous studies. This systematic data-mining approach we used would make many large datasets more manageable and informative for decision-making processes and health policy prioritization
Global Search for New Physics with 2.0/fb at CDF
Data collected in Run II of the Fermilab Tevatron are searched for
indications of new electroweak-scale physics. Rather than focusing on
particular new physics scenarios, CDF data are analyzed for discrepancies with
the standard model prediction. A model-independent approach (Vista) considers
gross features of the data, and is sensitive to new large cross-section
physics. Further sensitivity to new physics is provided by two additional
algorithms: a Bump Hunter searches invariant mass distributions for "bumps"
that could indicate resonant production of new particles; and the Sleuth
procedure scans for data excesses at large summed transverse momentum. This
combined global search for new physics in 2.0/fb of ppbar collisions at
sqrt(s)=1.96 TeV reveals no indication of physics beyond the standard model.Comment: 8 pages, 7 figures. Final version which appeared in Physical Review D
Rapid Communication
Observation of Orbitally Excited B_s Mesons
We report the first observation of two narrow resonances consistent with
states of orbitally excited (L=1) B_s mesons using 1 fb^{-1} of ppbar
collisions at sqrt{s} = 1.96 TeV collected with the CDF II detector at the
Fermilab Tevatron. We use two-body decays into K^- and B^+ mesons reconstructed
as B^+ \to J/\psi K^+, J/\psi \to \mu^+ \mu^- or B^+ \to \bar{D}^0 \pi^+,
\bar{D}^0 \to K^+ \pi^-. We deduce the masses of the two states to be m(B_{s1})
= 5829.4 +- 0.7 MeV/c^2 and m(B_{s2}^*) = 5839.7 +- 0.7 MeV/c^2.Comment: Version accepted and published by Phys. Rev. Let
Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set
We report a measurement of the bottom-strange meson mixing phase \beta_s
using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays
in which the quark-flavor content of the bottom-strange meson is identified at
production. This measurement uses the full data set of proton-antiproton
collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment
at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity.
We report confidence regions in the two-dimensional space of \beta_s and the
B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2,
-1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in
agreement with the standard model expectation. Assuming the standard model
value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +-
0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +-
0.009 (syst) ps, which are consistent and competitive with determinations by
other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012
Measurement of the Bs Lifetime in Fully and Partially Reconstructed Bs -> Ds- (phi pi-)X Decays in pbar-p Collisions at sqrt(s) = 1.96 TeV
We present a measurement of the Bs lifetime in fully and partially
reconstructed Bs -> Ds(phi pi)X decays in 1.3 fb-1 of pbar-p collisions at
sqrt(s) = 1.96 TeV collected by the CDF II detector at the Fermilab Tevatron.
We measure tau(Bs) = 1.518 +/- 0.041 (stat.) +/- 0.027 (syst.) ps. The ratio of
this result and the world average B0 lifetime yields tau(Bs)/tau(B0) = 0.99
+/-0.03, which is in agreement with recent theoretical predictions.Comment: submitted to Phys. Rev. Let
W boson polarization measurement in the ttbar dilepton channel using the CDF II Detector
We present a measurement of boson polarization in top-quark decays in
events with decays to dilepton final states using of integrated luminosity in collisions collected by the
CDF II detector at the Tevatron. A simultaneous measurement of the fractions of
longitudinal () and right-handed () bosons yields the results
and . Combining this measurement
with our previous result based on single lepton final states, we obtain and . The results are consistent with standard
model expectation.Comment: Published in Phys. Lett.
Observation of the structure in the Mass Spectrum in cays
The observation of the structure in decays produced in collisions at \sqrt{s}=1.96~\TeV is
reported with a statistical significance greater than 5 standard deviations. A
fit to the mass spectrum is performed assuming the presence of a
Breit-Wigner resonance. The fit yields a signal of resonance
events, and resonance mass and width of
4143.4^{+2.9}_{-3.0}(\mathrm{stat})\pm0.6(\mathrm{syst})~\MeVcc and
15.3^{+10.4}_{-6.1}(\mathrm{stat})\pm2.5(\mathrm{syst})~\MeVcc respectively.
The parameters of this resonance-like structure are consistent with values
reported from an earlier CDF analysis.Comment: 7 pages, 2 figures, submited to Phys. Rev. Let
Measurement of the ttbar Production Cross Section in ppbar collisions at sqrt s = 1.96 TeV in the All Hadronic Decay Mode
We report a measurement of the ttbar production cross section using the
CDF-II detector at the Fermilab Tevatron. The analysis is performed using 311
pb-1 of ppbar collisions at sqrt(s)=1.96 TeV. The data consist of events
selected with six or more hadronic jets with additional kinematic requirements.
At least one of these jets must be identified as a b-quark jet by the
reconstruction of a secondary vertex. The cross section is measured to be
sigma(tbart)=7.5+-2.1(stat.)+3.3-2.2(syst.)+0.5-0.4(lumi.) pb, which is
consistent with the standard model prediction.Comment: By CDF collaboratio
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