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 $D_s^+\to f_2(1270)\pi^+$ is dominated by the W-annihilation contribution and has the largest branching ratio in $D\to TP$ decays. We argue that the Cabibbo-suppressed mode $D^+\to f_2(1270)\pi^+$ should be suppressed by one order of magnitude relative to $D_s^+\to f_2(1270)\pi^+$. When the finite width effect of the tensor resonances is taken into account, the decay rate of $D\to TP$ is generally enhanced by a factor of $2\sim 3$. Except for $D_s^+\to f_2(1270)\pi^+$, the predicted branching ratios of $D\to TP$ decays are in general too small by one to two orders of magnitude compared to experiment. However, it is very unlikely that the $D\to T$ transition form factors can be enhanced by a factor of $3\sim 5$ 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 calcitonin‐gene related peptide (CGRP) and/or the translocation of NF‐κB. Methodology Mouse trigeminal ganglion (TG) cells were cultured in vitro for 2 days. The effect of P. gingivalis LPS (20 μg/mL) on calcium signalling was assessed (by calcium imaging using Cal‐520 AM) in comparison to the transient receptor potential channel A1 (TRPA1) agonist cinnamaldehyde (CA; 100 μM), the TRP channel V1 (TRPV1) agonist capsaicin (CAP; 1 μM), and high potassium (60 mM KCl). TG cultures were pre‐treated with either 1 μM CLI‐095 to block Toll‐like receptor 4 (TLR4) signalling or with 3 μM HC‐030031 to block TRPA1 signalling. CGRP release was determined using ELISA, and nuclear translocation of NF‐κB was investigated using immunocytochemistry. Data were analysed by one‐way analysis of variance, followed by Bonferroni’s post‐hoc test as appropriate. Results P. gingivalis LPS directly exerted a rapid excitatory response on sensory neurons and non‐neuronal cells (p<0.001 to p<0.05). The effects on neurons appear to be mediated via TLR4‐ and TRPA1‐dependent pathways. The responses were accompanied by an increased release of CGRP (p<0.001) and by NF‐κB nuclear translocation (p<0.01). Conclusions P. gingivalis LPS directly activates trigeminal sensory neurons (via TLR4 and TRPA1 receptors) and non‐neuronal cells, resulting in CGRP release and NF‐κB 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 W W -bosons

We calculate the electroweak and finite width corrections to the decay of an unpolarized top quark into a bottom quark and a $W$-gauge boson where the helicities of the $W$ are specified as longitudinal, transverse-plus and transverse-minus. Together with the $O(\alpha_s)$ 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 b→sℓ+ℓ−b\to s \ell^+ \ell^- 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 $\mu$ and $\tau$ 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 ($t', b')$.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 - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOsem 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