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3 results on '"Yukie Kanno"'

1. Down syndrome cell adhesion molecule like-1 (DSCAML1) links the GABA system and seizure susceptibility

Author

Yoneko Hayase, Shigeru Amano, Koichi Hashizume, Takashi Tominaga, Hiroyuki Miyamoto, Yukie Kanno, Yukiko Ueno-Inoue, Takayoshi Inoue, Mayumi Yamada, Shigehiro Ogata, Shabeesh Balan, Ken Hayashi, Yoshiki Miura, Kentaro Tokudome, Yukihiro Ohno, Takuma Nishijo, Toshihiko Momiyama, Yuchio Yanagawa, Akiko Takizawa, Tomoji Mashimo, Tadao Serikawa, Akihiro Sekine, Eiji Nakagawa, Eri Takeshita, Takeo Yoshikawa, Chikako Waga, Ken Inoue, Yu-ichi Goto, Yoichi Nabeshima, Nobuo Ihara, Kazuhiro Yamakawa, Shinichiro Taya, and Mikio Hoshino

Subjects
DSCAML1, Seizure susceptibility, Ihara epileptic rat, Gabaergic neurons, Patient-type model mouse, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract The Ihara epileptic rat (IER) is a mutant model with limbic-like seizures whose pathology and causative gene remain elusive. In this report, via linkage analysis, we identified Down syndrome cell adhesion molecule-like 1(Dscaml1) as the responsible gene for IER. A single base mutation in Dscaml1 causes abnormal splicing, leading to lack of DSCAML1. IERs have enhanced seizure susceptibility and accelerated kindling establishment. Furthermore, GABAergic neurons are severely reduced in the entorhinal cortex (ECx) of these animals. Voltage-sensitive dye imaging that directly presents the excitation status of brain slices revealed abnormally persistent excitability in IER ECx. This suggests that reduced GABAergic neurons may cause weak sustained entorhinal cortex activations, leading to natural kindling via the perforant path that could cause dentate gyrus hypertrophy and epileptogenesis. Furthermore, we identified a single nucleotide substitution in a human epilepsy that would result in one amino acid change in DSCAML1 (A2105T mutation). The mutant DSCAML1A2105T protein is not presented on the cell surface, losing its homophilic cell adhesion ability. We generated knock-in mice (Dscaml1 A2105T ) carrying the corresponding mutation and observed reduced GABAergic neurons in the ECx as well as spike-and-wave electrocorticogram. We conclude that DSCAML1 is required for GABAergic neuron placement in the ECx and suppression of seizure susceptibility in rodents. Our findings suggest that mutations in DSCAML1 may affect seizure susceptibility in humans.

Published
2020
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2. Potential involvement of DSCAML1 mutations in neurodevelopmental disorders

Author

Mikio Hoshino, Takeo Yoshikawa, Hidehiko Takahashi, Kei Hori, Shinichiro Taya, Shabeesh Balan, Yoneko Hayase, Shigehiro Ogata, Yukie Kanno, and Koichi Hashizume

Subjects
Male, Glycosylation, Autism Spectrum Disorder, In silico, Dendritic Spines, Mutant, Protein degradation, Biology, Hippocampus, 03 medical and health sciences, Mice, Neurodevelopmental disorder, L Cells, Genetics, medicine, Cell Adhesion, Animals, Humans, Rats, Wistar, Gene, 030304 developmental biology, 0303 health sciences, Cell Membrane, Molecular Sequence Annotation, Cell Biology, medicine.disease, DOWN SYNDROME CELL ADHESION MOLECULE-LIKE 1, Neurodevelopmental Disorders, Mutation, Proteolysis, Synapses, Schizophrenia, Autism, Female, Mutant Proteins, Cell Adhesion Molecules, Intracellular
Abstract

The molecular mechanisms underlying neurodevelopmental disorders (NDDs) remain unclear. We previously identified Down syndrome cell adhesion molecule like 1 (Dscaml1) as a responsible gene for Ihara epileptic rat (IER), a rat model for human NDDs with epilepsy. However, the relationship between NDDs and DSCAML1 in humans is still elusive. In this study, we screened databases of autism spectrum disorders (ASD), intellectual disability (ID)/developmental disorders (DD) and schizophrenia for genomic mutations in human DSCAML1. We then performed in silico analyses to estimate the potential damage to the mutated DSCAML1 proteins and chose three representative mutations (DSCAML1C729R , DSCAML1R1685* and DSCAML1K2108Nfs*37 ), which lacked a cysteine residue in the seventh Ig domain, the intracellular region and the C-terminal PDZ-binding motif, respectively. In overexpression experiments in a cell line, DSCAML1C729R lost its mature N-glycosylation, whereas DSCAML1K2108Nfs*37 was abnormally degraded via proteasome-dependent protein degradation. Furthermore, in primary hippocampal neurons, the ability of the wild-type DSCAML1 to regulate the number of synapses was lost with all mutant proteins. These results provide insight into understanding the roles of the domains in the DSCAML1 protein and further suggest that these mutations cause functional changes, albeit through different mechanisms, that likely affect the pathophysiology of NDDs.

Published
2020

3. Parallel Processing of 3-D Rigid-Plastic Finite Element Method Using Diagonal Matrix

Author

Yukie Kanno, Hidenori Yoshimura, Ken-ichiro Mori, and Yuji Otomo

Subjects
Combinatorics, Matrix (mathematics), Band matrix, Tridiagonal matrix, Pentadiagonal matrix, Diagonal matrix, Mathematical analysis, Symmetric matrix, Block matrix, Square matrix, Mathematics
Abstract

To realize large‐scale 3‐D simulation of metal forming processes, the 3‐D rigid‐plastic finite element method using a diagonal matrix is extended to parallel processing. In the present method, uncoupled equilibrium equations expressed by a matrix with three rows and three columns at each nodal point are repeatedly calculated in turn without solving the large global simultaneous equations. The method using a diagonal matrix is suitable for the parallel processing because of the iterative calculation at each nodal point. The convergence of the solution is examined in the simulation of upsetting of rectangular block with an inclined tool. The computing time is improved by the parallel processing.

Published
2004
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