Altered Kv2.1 functioning promotes increased excitability in hippocampal neurons of an Alzheimer's disease mouse model.

Altered neuronal excitability is emerging as an important feature in Alzheimer's disease (AD). Kv2.1 potassium channels are important modulators of neuronal excitability and synaptic activity. We investigated Kv2.1 currents and its relation to the intrinsic synaptic activity of hippocampal neurons from 3xTg-AD (triple transgenic mouse model of Alzheimer's disease) mice, a widely employed preclinical AD model. Synaptic activity was also investigated by analyzing spontaneous [Ca(2+)]i spikes. Compared with wild-type (Non-Tg (non-transgenic mouse model)) cultures, 3xTg-AD neurons showed enhanced spike frequency and decreased intensity. Compared with Non-Tg cultures, 3xTg-AD hippocampal neurons revealed reduced Kv2.1-dependent Ik current densities as well as normalized conductances. 3xTg-AD cultures also exhibited an overall decrease in the number of functional Kv2.1 channels. Immunofluorescence assay revealed an increase in Kv2.1 channel oligomerization, a condition associated with blockade of channel function. In Non-Tg neurons, pharmacological blockade of Kv2.1 channels reproduced the altered pattern found in the 3xTg-AD cultures. Moreover, compared with untreated sister cultures, pharmacological inhibition of Kv2.1 in 3xTg-AD neurons did not produce any significant modification in Ik current densities. Reactive oxygen species (ROS) promote Kv2.1 oligomerization, thereby acting as negative modulator of the channel activity. Glutamate receptor activation produced higher ROS levels in hippocampal 3xTg-AD cultures compared with Non-Tg neurons. Antioxidant treatment with N-Acetyl-Cysteine was found to rescue Kv2.1-dependent currents and decreased spontaneous hyperexcitability in 3xTg-AD neurons. Analogous results regarding spontaneous synaptic activity were observed in neuronal cultures treated with the antioxidant 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). Our study indicates that AD-related mutations may promote enhanced ROS generation, oxidative-dependent oligomerization, and loss of function of Kv2.1 channels. These processes can be part on the increased neuronal excitability of these neurons. These steps may set a deleterious vicious circle that eventually helps to promote excitotoxic damage found in the AD brain

Solution of the Fokker-Planck equation with a logarithmic potential and mixed eigenvalue spectrum

Motivated by a problem in climate dynamics, we investigate the solution of a Bessel-like process with negative constant drift, described by a Fokker-Planck equation with a potential V(x) = - [b \ln(x) + a\, x], for b>0 and a<0. The problem belongs to a family of Fokker-Planck equations with logarithmic potentials closely related to the Bessel process, that has been extensively studied for its applications in physics, biology and finance. The Bessel-like process we consider can be solved by seeking solutions through an expansion into a complete set of eigenfunctions. The associated imaginary-time Schroedinger equation exhibits a mix of discrete and continuous eigenvalue spectra, corresponding to the quantum Coulomb potential describing the bound states of the hydrogen atom. We present a technique to evaluate the normalization factor of the continuous spectrum of eigenfunctions that relies solely upon their asymptotic behavior. We demonstrate the technique by solving the Brownian motion problem and the Bessel process both with a negative constant drift. We conclude with a comparison with other analytical methods and with numerical solutions.Comment: 21 pages, 8 figure

GRB 970228 Revisited: Evidence for a Supernova in the Light Curve and La te Spectral Energy Distribution of the Afterglow

At the time of its discovery, the optical and X-ray afterglow of GRB 970228 appeared to be a ringing endorsement of the previously untried relativistic fireball model of gamma-ray burst (GRB) afterglows, but now that nearly a dozen optical afterglows to GRBs have been observed, the wavering light curve and reddening spectrum of this afterglow make it perhaps the most difficult of the observed afterglows to reconcile with the fireball model. In this Letter, we argue that this afterglow's unusual temporal and spectral properties can be attributed to a supernova that overtook the light curve nearly two weeks after the GRB. This is the strongest case yet for a GRB/supernova connection. It strengthens the case that a supernova also dominated the late afterglow of GRB 980326, and the case that GRB 980425 is related to SN 1998bw.Comment: Accepted to The Astrophysical Journal (Letters), 14 pages, LaTe

Metal abundances in extremely distant Galactic old open clusters. II. Berkeley 22 and Berkeley 66

We report on high resolution spectroscopy of four giant stars in the Galactic old open clusters Berkeley~22 and Berkeley~66 obtained with HIRES at the Keck telescope. We find that $[Fe/H]=-0.32\pm0.19$ and $[Fe/H]=-0.48\pm0.24$ for Berkeley~22 and Berkeley~66, respectively. Based on these data, we first revise the fundamental parameters of the clusters, and then discuss them in the context of the Galactic disk radial abundance gradient. We found that both clusters nicely obey the most updated estimate of the slope of the gradient from \citet{fri02} and are genuine Galactic disk objects.Comment: 20 pages, 6 eps figures, accepted for publication in the Astronomical Journa

The Nature of the Halo Population of NGC 5128 Resolved with NICMOS on the Hubble Space Telescope

We present the first infrared color-magnitude diagram (CMD) for the halo of a giant elliptical galaxy. The CMD for the stars in the halo of NGC 5128 (Centaurus A) was constructed from HST NICMOS observations of the WFPC2 CHIP-3 field of Soria et al. (1996) to a 50% completeness magnitude limit of [F160W]=23.8. This field is located at a distance of 08'50" (~9 kpc) south of the center of the galaxy. The luminosity function (LF) shows a marked discontinuity at [F160W]=20.0. This is 1-2 mag above the tip of the red giant branch (TRGB) expected for an old population (~12 Gyr) at the distance modulus of NGC 5128. We propose that the majority of stars above the TRGB have intermediate ages (~2 Gyr), in agreement with the WFPC2 observations of Soria et al. (1996). Five stars with magnitudes brighter than the LF discontinuity are most probably due to Galactic contamination. The weighted average of the mean giant branch color above our 50% completeness limit is [F110W]-[F160W]=1.22+-0.08 with a dispersion of 0.19 mag. From our artificial-star experiments we determine that the observed spread in color is real, suggesting a real spread in metallicity. We estimate the lower and upper bounds of the stellar metallicity range by comparisons with observations of Galactic star clusters and theoretical isochrones. Assuming an old population, we find that, in the halo field of NGC 5128 we surveyed, stars have metallicities ranging from roughly 1% of solar at the blue end of the color spread to roughly solar at the red end, with a mean of [Fe/H]=-0.76 and a dispersion of 0.44 dex.Comment: Accepted for publication in AJ, 23 pages of text, 13 figures, uses aastex v5.

Influence of laser-lok surface on immediate functional loading of implants in single-tooth replacement: a 2-year prospective clinical study.

he purpose of this study was to evaluate the influence of a Laser-Lok microtexturing surface on clinical attachment level and crestal bone remodeling around immediately functionally loaded implants in single-tooth replacement. Seventy-seven patients were included in a prospective, randomized study and divided into two groups. Group 1 (control) consisted of non-Laser-Lok type implants (n = 39), while in group 2 (test), Laser-Lok type implants were used (n = 39). Crestal bone loss (CBL) and clinical parameters including clinical attachment level (CAL), Plaque Index (PI), and bleeding on probing were recorded at baseline examinations and at 6, 12, and 24 months after loading with the final restoration. One implant was lost in the control group and one in the test group, giving a total survival rate of 96.1% after 2 years. PI and BOP outcomes were similar for both implant types without statistical differences. A mean CAL loss of 1.10 ± 0.51 mm was observed during the first 2 years in group 1, while the mean CAL loss observed in group 2 was 0.56 ± 0.33 mm. Radiographically, group 1 implants showed a mean crestal bone loss of 1.07 ± 0.30 mm compared with 0.49 ± 0.34 mm for group 2. The type of implant did not influence the survival rate, whereas Laser-Lok implants resulted in greater CAL and in shallower radiographic peri-implant CBL than non-Laser-Lok implants