27 research outputs found
Planar CuO_2 hole density estimation in multilayered high-T_c cuprates
We report that planar CuO_2 hole densities in high-T_c cuprates are
consistently determined by the Cu-NMR Knight shift. In single- and bi-layered
cuprates, it is demonstrated that the spin part of the Knight shift K_s(300 K)
at room temperature monotonically increases with the hole density from
underdoped to overdoped regions, suggesting that the relationship of K_s(300 K)
vs. p is a reliable measure to determine p. The validity of this K_s(300 K)-p
relationship is confirmed by the investigation of the p-dependencies of
hyperfine magnetic fields and of spin susceptibility for single- and bi-layered
cuprates with tetragonal symmetry. Moreover, the analyses are compared with the
NMR data on three-layered Ba_2Ca_2Cu_3O_6(F,O)_2, HgBa_2Ca_2Cu_3O_{8+delta},
and five-layered HgBa_2Ca_4Cu_5O_{12+delta}, which suggests the general
applicability of the K_s(300 K)-p relationship to multilayered compounds with
more than three CuO_2 planes. We remark that the measurement of K_s(300 K)
enables us to separately estimate p for each CuO_2 plane in multilayered
compounds, where doped hole carriers are inequivalent between outer CuO_2
planes and inner CuO_2 planes.Comment: 7 pages, 5 figures, 2 Tables, to be published in Physical Review
Anti-Aβ Drug Screening Platform Using Human iPS Cell-Derived Neurons for the Treatment of Alzheimer's Disease
Background:Alzheimer's disease (AD) is a neurodegenerative disorder that causes progressive memory and cognitive decline during middle to late adult life. The AD brain is characterized by deposition of amyloid β peptide (Aβ), which is produced from amyloid precursor protein by β- and γ-secretase (presenilin complex)-mediated sequential cleavage. Induced pluripotent stem (iPS) cells potentially provide an opportunity to generate a human cell-based model of AD that would be crucial for drug discovery as well as for investigating mechanisms of the disease. Methodology/Principal Findings:We differentiated human iPS (hiPS) cells into neuronal cells expressing the forebrain marker, Foxg1, and the neocortical markers, Cux1, Satb2, Ctip2, and Tbr1. The iPS cell-derived neuronal cells also expressed amyloid precursor protein, β-secretase, and γ-secretase components, and were capable of secreting Aβ into the conditioned media. Aβ production was inhibited by β-secretase inhibitor, γ-secretase inhibitor (GSI), and an NSAID; however, there were different susceptibilities to all three drugs between early and late differentiation stages. At the early differentiation stage, GSI treatment caused a fast increase at lower dose (Aβ surge) and drastic decline of Aβ production. Conclusions/Significance:These results indicate that the hiPS cell-derived neuronal cells express functional β- and γ-secretases involved in Aβ production; however, anti-Aβ drug screening using these hiPS cell-derived neuronal cells requires sufficient neuronal differentiation
プロスタグランジン E2 ワ EP1 ジュヨウタイ ニ サヨウシ センジョウタイ ニ オイテ ドパミン D1 オヨビ D2 ジュヨウタイ シグナル オ ゾウキョウスル
京都大学0048新制・論文博士博士(医学)乙第12190号論医博第1954号新制||医||968(附属図書館)UT51-2008-C960大阪大学大学院医学系研究科未来医療開発専攻(主査)教授 髙橋 良輔, 教授 渡邉 大, 教授 大森 治紀学位規則第4条第2項該当Doctor of Medical ScienceKyoto UniversityDA
Leucine-Histidine Dipeptide Attenuates Microglial Activation and Emotional Disturbances Induced by Brain Inflammation and Repeated Social Defeat Stress
The number of patients with mental illnesses is rapidly increasing, and daily lifestyle is closely associated with the development of symptoms. It is suggested that inflammatory molecules derived from microglia play crucial roles for the pathophysiology of depression. In the present study, we discovered that leucine-histidine (LH) dipeptide suppressed activation of primary microglia. The effects of LH dipeptide orally administered were measured using tail suspension test (TST) in mice injected with lipopolysaccharide and social interaction test in mice received social defeat stress. LH dipeptide reduced pro-inflammatory cytokines upon stimulation in microglia. Orally administered LH dipeptide was delivered to the brain and suppressed the production of pro-inflammatory cytokines in the brain and concomitant depression-like behavior in the TST. Moreover, oral administration of LH dipeptide suppressed the induction of depression- and anxiety-like behaviors induced by repeated social defeat stress. These results indicate that LH dipeptide suppressed the activation of microglia and ameliorated depression-associated emotional disturbances. Further, we found that LH dipeptide was abundant in various fermented products. Together with previous epidemiological reports that daily intake of these fermented foods is negatively associated with the incidence of psychiatric diseases, our findings suggest that food rich in LH dipeptide may improve mental health
Tryptophan-Tyrosine Dipeptide, the Core Sequence of β-Lactolin, Improves Memory by Modulating the Dopamine System
Tryptophan-tyrosine (WY)-related peptides including the β-lactopeptide of the glycine-threonine-tryptophan-tyrosine peptide, β-lactolin, improve spatial memory. However, whether and how the WY dipeptide as the core sequence in WY-related peptides improves memory functions has not been investigated. This study assessed the pharmacological effects of the WY dipeptide on memory impairment to elucidate the mechanisms. Here, we showed that oral administration of dipeptides of WY, tryptophan-methionine (WM), tryptophan-valine, tryptophan-leucine, and tryptophan-phenylalanine improved spontaneous alternation of the Y-maze test in scopolamine-induced amnesic mice. In contrast, tyrosine-tryptophan, methionine-tryptophan, tryptophan, tyrosine, and methionine had no effect. These results indicated that the conformation of dipeptides with N-terminal tryptophan is required for their memory improving effects. WY dipeptide inhibited the monoamine oxidase B activity in vitro and increased dopamine levels in the hippocampus and frontal cortex, whereas tryptophan did not cause these effects. In addition, the treatment with SCH-23390, a dopamine D1-like receptor antagonist, and the knockdown of the hippocampal dopamine D1 receptor partially attenuated the memory improvement induced by the WY dipeptide. Importantly, WY dipeptide improved the spontaneous alternations of the Y-maze test in aged mice. These results suggest that the WY dipeptide restores memory impairments by augmenting dopaminergic activity. The development of supplements rich in these peptides might help to prevent age-related cognitive decline