Pathophysiological Role of TRPM2 in Age-Related Cognitive Impairment in Mice

Aging causes various functional changes, including cognitive impairment and inflammatory responses in the brain. Transient receptor potential melastatin 2 (TRPM2), a Ca2+-permeable channel expressed abundantly in immune cells, exacerbates inflammatory responses. Previously, we reported that TRPM2 on resident microglia plays a critical role in exacerbating inflammation, white matter injury, and cognitive impairment during chronic cerebral hypoperfusion; however, the physiological or pathophysiological role of TRPM2 during age-associated inflammatory responses remains unclear. Therefore, we examined the effects of TRPM2 deletion in young (2–3 months) and older (12–24 months) mice. Compared with young wild-type (WT) mice, middle-aged (12–16 months) WT mice showed working and cognitive memory dysfunction and aged (20–24 months) WT mice exhibited impaired spatial memory. However, these characteristics were not seen in TRPM2 knockout (TRPM2-KO) mice. Consistent with the finding of cognitive impairment, aged WT mice exhibited white matter injury and hippocampal damage and an increase in the number of Iba1-positive cells and amounts of pro-inflammatory cytokines in the brain; these characteristics were not seen in TRPM2-KO mice. These findings suggest that TRPM2 plays a critical role in exacerbating inflammatory responses and cognitive dysfunction during aging

Reducing nonideal to ideal coupling in random matrix description of chaotic scattering: Application to the time-delay problem

We write explicitly a transformation of the scattering phases reducing the problem of quantum chaotic scattering for systems with M statistically equivalent channels at nonideal coupling to that for ideal coupling. Unfolding the phases by their local density leads to universality of their local fluctuations for large M. A relation between the partial time delays and diagonal matrix elements of the Wigner-Smith matrix is revealed for ideal coupling. This helped us in deriving the joint probability distribution of partial time delays and the distribution of the Wigner time delay.Comment: 4 pages, revtex, no figures; published versio

A Genetic Algorithm for Path Generation and its Applications

Abstract-Path generation is an optimization problem mainly performed on grid maps that combines generation of paths with minimization of their cost. Several methods that belong to the class of exhaustive searches are available; however, these methods are only able to obtain a single path as a solution for each iteration of the search. Conversely, while genetic algorithms involving a type of multipoint search methods have been proposed as suitable candidates for this problem with the goal of simultaneously searching for multiple candidate paths, these methods are limited to particular applications, and there are limitations on the types of paths that can be represented. This paper therefore proposes a path generation method that is applicable to more general-purpose applications compared to previous methods based on a new design of the genotype used in the genetic algorithm

Composite Yb : YAG/Cr4+: YAG ceramics picosecond microchip lasers

Efficient laser-diode pumped picosecond self-Q-switched all-ceramic composite Yb: YAG/ Cr4+: YAG microchip lasers with 0.72 MW peak power has been developed. Lasers with nearly diffraction-limited beam quality (M-2 < 1.09), oscillate at stable single- and multi- longitudinal-modes due to the combined etalon effects in the Yb:YAG and Cr4(+:) YAG parts of its binary structure. (C) 2007 Optical Society of America

AC resistivity of d-wave ceramic superconductors

We model d-wave ceramic superconductors with a three-dimensional lattice of randomly distributed $\pi$ Josephson junctions with finite self-inductance. The linear and nonlinear ac resistivity of the d-wave ceramic superconductors is obtained as function of temperature by solving the corresponding Langevin dynamical equations. We find that the linear ac resistivity remains finite at the temperature $T_p$ where the third harmonics of resistivity has a peak. The current amplitude dependence of the nonlinear resistivity at the peak position is found to be a power law. These results agree qualitatively with experiments. We also show that the peak of the nonlinear resistivity is related to the onset of the paramagnetic Meissner effect which occurs at the crossover temperature $T_p$, which is above the chiral glass transition temperature $T_{cg}$.Comment: 7 eps figures, Phys. Rev. B (in press

Identification of the matricellular protein Fibulin-5 as a target molecule of glucokinase-mediated calcineurin/NFAT signaling in pancreatic islets

Glucokinase-mediated glucose signaling induces insulin secretion, proliferation, and apoptosis in pancreatic β-cells. However, the precise molecular mechanisms underlying these processes are not clearly understood. Here, we demonstrated that glucokinase activation using a glucokinase activator (GKA) significantly upregulated the expression of Fibulin-5 (Fbln5), a matricellular protein involved in matrix-cell signaling, in isolated mouse islets. The islet Fbln5 expression was induced by ambient glucose in a time- and dose-dependent manner and further enhanced by high-fat diet or the deletion of insulin receptor substrate 2 (IRS-2), whereas the GKA-induced increase in Fbln5 expression was diminished in Irs-2-deficient islets. GKA-induced Fbln5 upregulation in the islets was blunted by a glucokinase inhibitor, KATP channel opener, Ca2+ channel blocker and calcineurin inhibitor, while it was augmented by harmine, a dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) 1 A inhibitor. Although deletion of Fbln5 in mice had no significant effects on the glucose tolerance or β-cell functions, adenovirus-mediated Fbln5 overexpression increased glucose-stimulated insulin secretion in INS-1 rat insulinoma cells. Since the islet Fbln5 expression is regulated through a glucokinase/KATP channel/calcineurin/nuclear factor of activated T cells (NFAT) pathway crucial for the maintenance of β-cell functions, further investigation of Fbln5 functions in the islets is warranted

DPP-4 inhibition improves early mortality, β cell function, and adipose tissue inflammation in db/db mice fed a diet containing sucrose and linoleic acid

Additional file 3: Figure S2. Liver and epididymal fat weights in db/+ mice and db/db mice. The experiments were performed in db/+ or db/db mice fed an SL diet, SO diet, SL containing DPP-4 inhibitor (0.4% des-fluoro-sitagliptin) diet, or SO containing DPP-4 inhibitor diet for 8 weeks. (left) Liver weights as a proportion of body weight (n = 5). (right) Epididymal fat weights as a proportion of body weight (n = 5)

Effect of ytterbium concentration on Yb : YAG microchip laser performance at ambient temperature

The microchip laser performance of Yb:YAG crystals doped with different ytterbium concentrations (10, 15, and 20 at.%) has been investigated at ambient temperature. Efficient laser oscillation for 1-mm-thick YAG doped with 10 at.% Yb3+ ions was achieved at 1030 and 1049 nm with slope efficiencies of 85 and 81%, correspondingly