706 research outputs found

    Raft-derived tau-associated vesicles

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    Aims: Neurofibrillary tangles (NFTs), a cardinal pathological feature of neurodegenerative disorders, such as Alzheimer's disease (AD) are primarily composed of hyper‐phosphorylated tau protein. Recently, several other molecules, including flotillin‐1, phosphatidylinositol‐4,5‐bisphosphate [PtdIns(4,5)P2] and cyclin‐dependent kinase 5 (CDK5), have also been revealed as constituents of NFTs. Flotillin‐1 and PtdIns(4,5)P2 are considered markers of raft microdomains, whereas CDK5 is a tau kinase. Therefore, we hypothesized that NFTs have a relationship with raft domains and the tau phosphorylation that occurs within NFTs. Methods: We investigated six cases of AD, six cases of other neurodegenerative diseases with NFTs and three control cases. We analysed the PtdIns(4,5)P2‐immunopositive material in detail, using super‐resolution microscopy and electron microscopy to elucidate its pattern of expression. We also investigated the spatial relationship between the PtdIns(4,5)P2‐immunopositive material and tau kinases through double immunofluorescence analysis. Results: Pretangles contained either paired helical filaments (PHFs) or PtdIns(4,5)P2‐immunopositive small vesicles (approximately 1 μm in diameter) with nearly identical topology to granulovacuolar degeneration (GVD) bodies. Various combinations of these vesicles and GVD bodies, the latter of which are pathological hallmarks observed within the neurons of AD patients, were found concurrently in neurons. These vesicles and GVD bodies were both immunopositive not only for PtdIns(4,5)P2, but also for several tau kinases such as glycogen synthase kinase‐3β and spleen tyrosine kinase. Conclusions: These observations suggest that clusters of raft‐derived vesicles that resemble GVD bodies are substructures of pretangles other than PHFs. These tau kinase‐bearing vesicles are likely involved in the modification of tau protein and in NFT formation

    Magnetization reversal driven by spin-injection : a mesoscopic spin-transfer effect

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    A mesoscopic description of spin-transfer effect is proposed, based on the spin-injection mechanism occurring at the junction with a ferromagnet. The effect of spin-injection is to modify locally, in the ferromagnetic configuration space, the density of magnetic moments. The corresponding gradient leads to a current-dependent diffusion process of the magnetization. In order to describe this effect, the dynamics of the magnetization of a ferromagnetic single domain is reconsidered in the framework of the thermokinetic theory of mesoscopic systems. Assuming an Onsager cross-coefficient that couples the currents, it is shown that spin-dependent electric transport leads to a correction of the Landau-Lifshitz-Gilbert equation of the ferromagnetic order parameter with supplementary diffusion terms. The consequence of spin-injection in terms of activation process of the ferromagnet is deduced, and the expressions of the effective energy barrier and of the critical current are derived. Magnetic fluctuations are calculated: the correction to the fluctuations is similar to that predicted for the activation. These predictions are consistent with the measurements of spin-transfer obtained in the activation regime and for ferromagnetic resonance under spin-injection.Comment: 20 pages, 2 figure

    Induced sensorimotor brain plasticity controls pain in phantom limb patients

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    The cause of pain in a phantom limb after partial or complete deafferentation is an important problem. A popular but increasingly controversial theory is that it results from maladaptive reorganization of the sensorimotor cortex, suggesting that experimental induction of further reorganization should affect the pain, especially if it results in functional restoration. Here we use a brain-machine interface (BMI) based on real-time magnetoencephalography signals to reconstruct affected hand movements with a robotic hand. BMI training induces significant plasticity in the sensorimotor cortex, manifested as improved discriminability of movement information and enhanced prosthetic control. Contrary to our expectation that functional restoration would reduce pain, the BMI training with the phantom hand intensifies the pain. In contrast, BMI training designed to dissociate the prosthetic and phantom hands actually reduces pain. These results reveal a functional relevance between sensorimotor cortical plasticity and pain, and may provide a novel treatment with BMI neurofeedback.This research was conducted under the ‘Development of BMI Technologies for Clinical Application’ of SRPBS by MEXT and AMED. This research was also supported in part by JST PRESTO; JSPS KAKENHI JP24700419, JP26560467, JP22700435, JP26242088, JP26282165, JP15H05710 and JP15H05920; Brain/MINDS and SICP from AMED; ImPACT; Ministry of Health, Labor, and Welfare (18261201); and the Japan Foundation of Aging and Health

    Observation of Spin-Dependent Charge Symmetry Breaking in ΛN\Lambda N Interaction: Gamma-Ray Spectroscopy of Λ4^4_{\Lambda }He

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    The energy spacing between the ground-state spin doublet of Λ4^4_\Lambda He(1+^+,0+^+) was determined to be 1406±2±21406 \pm 2 \pm 2 keV, by measuring γ\gamma rays for the 1+0+1^+ \to 0^+ transition with a high efficiency germanium detector array in coincidence with the 4^4He(K,π)(K^-,\pi^-) Λ4^4_\Lambda He reaction at J-PARC. In comparison to the corresponding energy spacing in the mirror hypernucleus Λ4^4_\Lambda H, the present result clearly indicates the existence of charge symmetry breaking (CSB) in ΛN\Lambda N interaction. It is also found that the CSB effect is large in the 0+0^+ ground state but is by one order of magnitude smaller in the 1+1^+ excited state, demonstrating that the ΛN\Lambda N CSB interaction has spin dependence
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