University of Tokyo

About: University of Tokyo is a education organization based out in Tokyo, Japan. It is known for research contribution in the topics: Population & Gene. The organization has 134564 authors who have published 337567 publications receiving 10178620 citations. The organization is also known as: Todai & Universitas Tociensis.

ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy

Abstract: APOE4 is the strongest genetic risk factor for late-onset Alzheimer disease. ApoE4 increases brain amyloid-β pathology relative to other ApoE isoforms. However, whether APOE independently influences tau pathology, the other major proteinopathy of Alzheimer disease and other tauopathies, or tau-mediated neurodegeneration, is not clear. By generating P301S tau transgenic mice on either a human ApoE knock-in (KI) or ApoE knockout (KO) background, here we show that P301S/E4 mice have significantly higher tau levels in the brain and a greater extent of somatodendritic tau redistribution by three months of age compared with P301S/E2, P301S/E3, and P301S/EKO mice. By nine months of age, P301S mice with different ApoE genotypes display distinct phosphorylated tau protein (p-tau) staining patterns. P301S/E4 mice develop markedly more brain atrophy and neuroinflammation than P301S/E2 and P301S/E3 mice, whereas P301S/EKO mice are largely protected from these changes. In vitro, E4-expressing microglia exhibit higher innate immune reactivity after lipopolysaccharide treatment. Co-culturing P301S tau-expressing neurons with E4-expressing mixed glia results in a significantly higher level of tumour-necrosis factor-α (TNF-α) secretion and markedly reduced neuronal viability compared with neuron/E2 and neuron/E3 co-cultures. Neurons co-cultured with EKO glia showed the greatest viability with the lowest level of secreted TNF-α. Treatment of P301S neurons with recombinant ApoE (E2, E3, E4) also leads to some neuronal damage and death compared with the absence of ApoE, with ApoE4 exacerbating the effect. In individuals with a sporadic primary tauopathy, the presence of an e4 allele is associated with more severe regional neurodegeneration. In individuals who are positive for amyloid-β pathology with symptomatic Alzheimer disease who usually have tau pathology, e4-carriers demonstrate greater rates of disease progression. Our results demonstrate that ApoE affects tau pathogenesis, neuroinflammation, and tau-mediated neurodegeneration independently of amyloid-β pathology. ApoE4 exerts a 'toxic' gain of function whereas the absence of ApoE is protective.

Dynamical evolution of star clusters in tidal fields

Abstract: We report the results of a large set of N-body calculations aimed at studying the evolution of multimass star clusters in external tidal fields. Our clusters start with the same initial mass functions, but varying particle numbers, orbital types and density profiles. Our main focus is to study how the stellar mass function and other cluster parameters change under the combined influence of stellar evolution, two-body relaxation and the external tidal field. We find that the lifetimes of star clusters moving on similar orbits scale as T ∼ T x , where T rh is the relaxation time, and the exponent x depends on the initial concentration of the cluster and is around x ≈ 0.75. The scaling law does not change significantly if one goes from circular orbits to eccentric ones. From the results for the lifetimes, we predict that between 53 and 67 per cent of all Galactic globular clusters will be destroyed within the next Hubble time. Low-mass stars are preferentially lost and the depletion is strong enough to turn initially increasing mass functions into mass functions that decrease towards the low-mass end. The details of this depletion are insensitive to the starting condition of the cluster and can be characterized as a function of a single variable, such as, for example, the fraction of time spent until total cluster dissolution. The preferential depletion of low-mass stars from star clusters leads to a decrease of their mass-to-light ratios except for a short period close to final dissolution, when the mass fraction in the form of compact remnants starts to dominate. The fraction of compact remnants increases throughout the evolution. They are more strongly concentrated towards the cluster cores than main-sequence stars and their mass fraction in the centre can reach 95 per cent or more around and after core collapse. For a sample of Galactic globular clusters with well-observed parameters, we find a correlation between the observed slope of the mass function and the lifetimes predicted by us. It seems possible that Galactic globular clusters started with a mass function similar to what one observes for the average mass function of the Galactic disc and bulge.

Liver tumor promotion by the cyanobacterial cyclic peptide toxin microcystin-LR.

Abstract: Certain waterblooms of toxic cyanobacteria (blue-green algae) are a health threat because of their production of toxic peptides, termed microcystins, which cause liver damage in wild and domesticated animals. The most widely studied microcystin is microcystin-LR, a heptapeptide containing the twol-amino acids, leucine and arginine. The inhibition of protein phosphatase type 1 and type 2A activities by microcystin-LR is similar to that of the known protein phosphatase inhibitor and tumor promoter okadaic acid. We show in this report that microcystin-LR, applied below the acute toxicity level, dose-dependently increases the number and percentage area of positive foci for the placental form of glutathioneS-transferase in rat liver, which was initiated with diethylnitrosamine. The result was obtained independently through two animal experiments. This observation indicates that microcystin-LR is a new liver tumor promoter mediated through inhibition of protein phosphatase type 1 and type 2A activities. This provides further evidence that the okadaic acid pathway is a general mechanism of tumor promotion in various organs, such as mouse skin, rat glandular stomach and rat liver.

Current-induced skyrmion dynamics in constricted geometries

Abstract: Magnetic skyrmions--vortex-like swirling spin structures with a quantized topological number that are observed in chiral magnets--are appealing for potential applications in spintronics because it is possible to control their motion with ultralow current density. To realize skyrmion-based spintronic devices, it is essential to understand skyrmion motions in confined geometries. Here we show by micromagnetic simulations that the current-induced motion of skyrmions in the presence of geometrical boundaries is very different from that in an infinite plane. In a channel of finite width, transverse confinement results in steady-state characteristics of the skyrmion velocity as a function of current that are similar to those of domain walls in ferromagnets, whereas the transient behaviour depends on the initial distance of the skyrmion from the boundary. Furthermore, we show that a single skyrmion can be created by an electric current in a simple constricted geometry comprising a plate-shaped specimen of suitable size and geometry. These findings could guide the design of skyrmion-based devices in which skyrmions are used as information carriers.