Characterization of the novel protein P9TLDR (temporal lobe down-regulated) with a brain-site-specific gene expression modality in Alzheimer’s disease brain

AbstractAlzheimer’s disease (AD) is an aging-related neurodegenerative disorder characterized by irreversible loss of higher cognitive functions. The disease is characterized by the presence of amyloid plaques and neurofibrillary tangles (NFT). In the current study we isolated from an intra-cerebral brain-site-specific (AD temporal lobe vs. AD occipital lobe) polymerase chain reaction (PCR)-select cDNA suppression subtractive hybridization (PCR-cDNA-SSH) expression analysis the novel gene P9TLDR, potentially a microtubule-associated protein involved in neuronal migration, with an altered expression pattern: down-regulated in the temporal lobe cortex of early stage AD brains. In an in vitro AD-related cell model, amyloid-β peptide (Aβ)-treated neurons, reduced P9TLDR expression correlated with increased tau protein phosphorylation. In conclusion, interference with the P9TLDR signalling pathways might be a therapeutic strategy for the treatment of AD

Tunneling and rattling in clathrate crystal

We present tunneling and rattling motions of an off-center guest atom in cage referring to a clathrate crystal La_3Pd_{20}Ge_6. The elastic constant C_{44} of La_3Pd_{20}Ge_6 shows a Debye-type dispersion around 20 K obeying a relaxation time tau = tau_0exp(E/k_{B}T) with an attempt time tau_0 = 2.0*10^{-12} sec and an activation energy E = 197 K. At low temperatures below 3 K down to 20 mK, the C_{44} shows a softening of C_{44} = C_{44}^0(T-T_C^0)/(T-Theta) with T_C^0 = -337.970 mK and Theta = -338.044 mK. These facts are attributed to two different types of the off-center motions with Gamma_5 symmetry in 4a-site cage of La_3Pd_{20}Ge_6, a thermally activated rattling motion over the potential hill and a tunneling motion through the potential hill at low temperatures.Comment: 5 pages, 4 figures, to be published Phys. Rev.

Quadrupolar effect and rattling motion in heavy fermion superconductor PrOs_4Sb_{12}

The elastic properties of a filled skutterudite PrOs_4Sb_{12} with a heavy Fermion superconductivity at T_C=1.85 K have been investigated. The elastic softening of (C_{11}-C_{12})/2 and C_{44} with lowering temperature down to T_C indicates that the quadrupolar fluctuation due to the CEF state plays a role for the Cooper paring in superconducting phase of PrOs_4Sb_{12}. A Debye-type dispersion in the elastic constants around 30 K revealed a thermally activated Gamma_{23} rattling due to the off-center Pr-atom motion obeying tau=tau_{0}exp(E/k_{B}T) with an attempt time tau_0=8.8*10^{-11} sec and an activation energy E=168 K. It is remarkable that the charge fluctuation of the off-center motion with Gamma_{23} symmetry may mix with the quadrupolar fluctuation and enhance the elastic softening of (C_{11}-C_{12})/2 just above T_C.Comment: 5 pages, 4 figures, to be published to Phys. Rev.

Ferroquadrupole ordering and Gamma_5 rattling motion in clathrate compound Ce_3Pd_20Ge_6

Lattice effects in a cerium based clathrate compound Ce_3Pd_20Ge_6 with a cubic Cr_23C_6-type structure have been investigated by ultrasonic and thermal expansion measurements. Elastic softenings of (C_11-C_12)/2 and C_44 proportional to the reciprocal temperature 1/T above T_Q1 = 1.25 K are well described in terms of the quadrupole susceptibility for the ground state Gamma_8 quartet. A huge softening of 50 % in (C_11-C_12)/2 and a spontaneous expansion DL/L = 1.9x10^-4 along the [001] direction in particular indicate the ferroquadrupole ordering of O_2^0 below T_Q1. The elastic anomalies associated with the antiferromagnetic ordering at T_N2 = 0.75 K and the incommensurate antiferromagnetic ordering are also found. Notable frequency dependence of C_44 around 10 K is accounted for by the Debye-type dispersion indicating a Gamma_5 rattling motion of an off-center Ce ion along the [111] direction with eight fractionally occupied positions around the 4a site in a cage. The thermally activated Gamma_5 rattling motion obeying a relaxation time t = t_0exp(E/k_BT) with an attempt time t_0 = 3.1x10^-11 sec and an activation energy E = 70 K dies out with decreasing temperature, and then the off-center tunneling state of Ce ion in the 4a-site cage will appear at low temperatures.Comment: 11 pages, 15 figures, to be published on Phys. Rev.

SORL1 Is Genetically Associated with Late-Onset Alzheimer’s Disease in Japanese, Koreans and Caucasians

To discover susceptibility genes of late-onset Alzheimer’s disease (LOAD), we conducted a 3-stage genome-wide association study (GWAS) using three populations: Japanese from the Japanese Genetic Consortium for Alzheimer Disease (JGSCAD), Koreans, and Caucasians from the Alzheimer Disease Genetic Consortium (ADGC). In Stage 1, we evaluated data for 5,877,918 genotyped and imputed SNPs in Japanese cases (n = 1,008) and controls (n = 1,016). Genome-wide significance was observed with 12 SNPs in the APOE region. Seven SNPs from other distinct regions with p-values ,261025 were genotyped in a second Japanese sample (885 cases, 985 controls), and evidence of association was confirmed for one SORL1 SNP (rs3781834, P=7.3361027 in the combined sample). Subsequent analysis combining results for several SORL1 SNPs in the Japanese, Korean (339 cases, 1,129 controls) and Caucasians (11,840 AD cases, 10,931 controls) revealed genome wide significance with rs11218343 (P=1.7761029) and rs3781834 (P=1.0461028). SNPs in previously established AD loci in Caucasians showed strong evidence of association in Japanese including rs3851179 near PICALM (P=1.7161025) and rs744373 near BIN1 (P = 1.3961024). The associated allele for each of these SNPs was the same as in Caucasians. These data demonstrate for the first time genome-wide significance of LOAD with SORL1 and confirm the role of other known loci for LOAD in Japanese. Our study highlights the importance of examining associations in multiple ethnic populations