868 research outputs found
Amyotrophic lateral sclerosis-associated mutant SOD1 inhibits anterograde axonal transport of mitochondria by reducing Miro1 levels
Defective axonal transport is an early neuropathological feature of amyotrophic lateral sclerosis (ALS). We have previously shown that ALS-associated mutations in Cu/Zn superoxide dismutase 1 (SOD1) impair axonal transport of mitochondria in motor neurons isolated from SOD1 G93A transgenic mice and in ALS mutant SOD1 transfected cortical neurons, but the underlying mechanisms remained unresolved.
The outer mitochondrial membrane protein mitochondrial Rho GTPase 1 (Miro1) is a master regulator of mitochondrial axonal transport in response to cytosolic calcium (Ca2+) levels ([Ca2+]c) and mitochondrial damage. Ca2+ binding to Miro1 halts mitochondrial transport by modifying its interaction with kinesin-1 whereas mitochondrial damage induces Phosphatase and Tensin homolog (PTEN)-induced putative kinase 1 (PINK1) and Parkin-dependent degradation of Miro1 and consequently stops transport.
To identify the mechanism underlying impaired axonal transport of mitochondria in SOD1-related ALS we investigated [Ca2+]c and Miro1 levels in ALS mutant SOD1 expressing neurons. We found that expression of ALS mutant SOD1 reduced the level of endogenous Miro1 but did not affect [Ca2+]c. ALS mutant SOD1 induced reductions in Miro1 levels were Parkin dependent. Moreover, both overexpression of Miro1 and ablation of PINK1 rescued the mitochondrial axonal transport deficit in ALS mutant SOD1-expressing cortical and motor neurons.
Together these results provide evidence that ALS mutant SOD1 inhibits axonal transport of mitochondria by inducing PINK1/Parkin-dependent Miro1 degradation
Gauge Invariant Geometric Variables For Yang-Mills Theory
In a previous publication [1], local gauge invariant geometric variables were
introduced to describe the physical Hilbert space of Yang-Mills theory. In
these variables, the electric energy involves the inverse of an operator which
can generically have zero modes, and thus its calculation is subtle. In the
present work, we resolve these subtleties by considering a small deformation in
the definition of these variables, which in the end is removed. The case of
spherical configurations of the gauge invariant variables is treated in detail,
as well as the inclusion of infinitely heavy point color sources, and the
expression for the associated electric field is found explicitly. These
spherical geometries are seen to correspond to the spatial components of
instanton configurations. The related geometries corresponding to Wu-Yang
monopoles and merons are also identified.Comment: 21 pp. in plain TeX. Uses harvmac.te
Hadronic Charmed Meson Decays Involving Tensor Mesons
Charmed meson decays into a pseudoscalar meson P and a tensor meson T are
studied. The charm to tensor meson transition form factors are evaluated in the
Isgur-Scora-Grinstein-Wise (ISGW) quark model. It is shown that the
Cabibbo-allowed decay is dominated by the
W-annihilation contribution and has the largest branching ratio in
decays. We argue that the Cabibbo-suppressed mode
should be suppressed by one order of magnitude relative to . When the finite width effect of the tensor resonances is taken
into account, the decay rate of is generally enhanced by a factor of
. Except for , the predicted branching ratios
of decays are in general too small by one to two orders of magnitude
compared to experiment. However, it is very unlikely that the
transition form factors can be enhanced by a factor of within the
ISGW quark model to account for the discrepancy between theory and experiment.
As many of the current data are still preliminary and lack sufficient statistic
significance, more accurate measurements are needed to pin down the issue.Comment: 11 page
Porphyromonas gingivalis lipopolysaccharide rapidly activates trigeminal sensory neurons and may contribute to pulpal pain
Aim
To determine whether Porphyromonas gingivalis lipopolysaccharide (LPS) can directly activate trigeminal neurons, to identify which receptors are involved, and to establish whether activation leads to secretion of the neuropeptide calcitoninâgene related peptide (CGRP) and/or the translocation of NFâÎșB.
Methodology
Mouse trigeminal ganglion (TG) cells were cultured in vitro for 2 days. The effect of P. gingivalis LPS (20 ÎŒg/mL) on calcium signalling was assessed (by calcium imaging using Calâ520 AM) in comparison to the transient receptor potential channel A1 (TRPA1) agonist cinnamaldehyde (CA; 100 ÎŒM), the TRP channel V1 (TRPV1) agonist capsaicin (CAP; 1 ÎŒM), and high potassium (60 mM KCl). TG cultures were preâtreated with either 1 ÎŒM CLIâ095 to block Tollâlike receptor 4 (TLR4) signalling or with 3 ÎŒM HCâ030031 to block TRPA1 signalling. CGRP release was determined using ELISA, and nuclear translocation of NFâÎșB was investigated using immunocytochemistry. Data were analysed by oneâway analysis of variance, followed by Bonferroniâs postâhoc test as appropriate.
Results
P. gingivalis LPS directly exerted a rapid excitatory response on sensory neurons and nonâneuronal cells (p<0.001 to p<0.05). The effects on neurons appear to be mediated via TLR4â and TRPA1âdependent pathways. The responses were accompanied by an increased release of CGRP (p<0.001) and by NFâÎșB nuclear translocation (p<0.01).
Conclusions
P. gingivalis LPS directly activates trigeminal sensory neurons (via TLR4 and TRPA1 receptors) and nonâneuronal cells, resulting in CGRP release and NFâÎșB nuclear translocation. This indicates that P. gingivalis can directly influence activity in trigeminal sensory neurons and this may contribute to acute and chronic inflammatory pain
Electroweak and finite width corrections to top quark decays into transverse and longitudinal -bosons
We calculate the electroweak and finite width corrections to the decay of an
unpolarized top quark into a bottom quark and a -gauge boson where the
helicities of the are specified as longitudinal, transverse-plus and
transverse-minus. Together with the corrections these
corrections may become relevant for the determination of the mass of the top
quark through angular decay measurements.Comment: 4 pages, 7 postscript figures adde
Analysis of Various Polarization Asymmetries In The Inclusive Decay In The Fourth-Generation Standard Model
In this study a systematical analysis of various polarization asymmetries in
inclusive b \rar s \ell^+ \ell^- decay in the standard model (SM) with four
generation of quarks is carried out. We found that the various asymmetries are
sensitive to the new mixing and quark masses for both of the and
channels. Sizeable deviations from the SM values are obtained. Hence, b \rar s
\ell^+ \ell^- decay is a valuable tool for searching physics beyond the SM,
especially in the indirect searches for the fourth-generation of quarks (.Comment: 19 Pages, 10 Figures, 3 Table
Forward-backward asymmetry of top quark in unparticle physics
The updated CDF measurement of the forward-backward asymmetry (FBA) in the
top quark production p{bar p} -> t{bar t} at Tevatron (with the CMS energy 1.96
TeV) shows a deviation of 2*sigma from the value predicted by the Standard QCD
Model. We present calculation of this quantity in the scenario where colored
unparticle physics contributes to the s-channel of the process, and obtain the
regions in the plane of the unparticle parameters lambda and dU which give the
values of the FBA and of the total t{bar t} production cross section compatible
with the present measurements.Comment: 15 pages, 5 figures; various typos corrected, fig.3 has higher
resolution, Ref.[16](2nd entry) is new; version to appear in Phys.Lett.
RNA sequencing reveals region-specific molecular mechanisms associated with epileptogenesis in a model of classical hippocampal sclerosis
We report here the first complete transcriptome analysis of the dorsal (dDG) and ventral dentate gyrus (vDG) of a rat epilepsy model presenting a hippocampal lesion with a strict resemblance to classical hippocampal sclerosis (HS). We collected the dDG6CAPES - COORDENAĂĂO DE APERFEIĂOAMENTO DE PESSOAL DE NĂVEL SUPERIORFAPESP - FUNDAĂĂO DE AMPARO Ă PESQUISA DO ESTADO DE SĂO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTĂFICO E TECNOLĂGICOsem informaçãosem informaçãosem informaçã
Exclusive B-> M \nu \bar{\nu} (M= \pi, K, \rho, K^*) Decays and Leptophobic Z^\prime Model
We consider the exclusive flavor changing neutral current processes B -> M
\nu \bar{\nu} (M= \pi, K, \rho, K^*) in the leptophobic Z^\prime model, in
which the charged leptons do not couple to the extra Z^\prime boson. We find
that these exclusive modes are very effective to constrain the leptophobic
Z^\prime model. In the leptophobic Z^\prime model, additional right-handed
neutrinos are introduced and they can contribute to the missing energy signal
in B -> M + E_missing decays. Through the explicit calculations, we obtain
quite stringent bounds on the model parameters, |U_{sb}^{Z^\prime}| \leq 0.29
and |U_{db}^{Z^\prime}| \leq 0.61, from the already existing experimental data.
We also briefly discuss an interesting subject of massive right-handed
neutrinos, which might be connected with the dark matter problem.Comment: 17 pages, 3 figures, minor corrections, version to appear in PL
Test of Factorization Hypothesis from Exclusive Non-leptonic B decays
We investigate the possibility of testing factorization hypothesis in
non-leptonic exclusive decays of B-meson. In particular, we considered the non
factorizable \bar{B^0} -> D^{(*)+} D_s^{(*)-} modes and \bar{B^0} -> D^{(*)+}
(\pi^-, \rho^-) known as well-factorizable modes. By taking the ratios
BR(\bar{B^0}-> D^{(*)+}D_s^{(*)-})/BR(\bar{B^0}-> D^{(*)+}(\pi^-,\rho^-)), we
found that under the present theoretical and experimental uncertainties there's
no evidence for the breakdown of factorization description to heavy-heavy
decays of the B meson.Comment: 11 pages; submitted to PR
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