Biology subjects

Higuchi, K.

Publications and source records attributed to Higuchi, K..

5 recordsLinked to original sources

bioRxiv2022

Spatial frequency-based correction of the spherical aberration in living brain imaging

We previously developed a fully automated spherical aberration compensation microscope system, Deep-C, to obtain spherical aberration-free images, but the contrast-based algorithm (Peak-C) may limit applications for low signal-to-noise ratio images. Herein we propose a new spatial frequency-based algorithm called Peak-F and compared its performance to Peak-C. Unlike Peak-C, Peak-F is robust to any noise level since it is independent of the dynamic range of the images, and it does not suffer from image saturation. Finally, Peak-F was implemented in a two-photon microscope to observe living aged and young mouse brains. Consequently, the average refractive index of brain tissue was higher in old mice than in young mice. The Peak-F algorithm determines high-resolution microscopic images stably and robustly.

biophysics↗

bioRxiv2022

High performance, large-scale multi-compartment Hodgkin-Huxley simulation of Drosophila's whole-brain neural circuit model

A major challenge in neurosciences is the elucidation of neural mechanisms in brains that are crucial for the processing of sensory information and the generation of adaptive behavior. In conjunction with the ever-growing body of experimental data, computational simulations have become crucial in integrating information and testing hypotheses, requiring fast large-scale simulators. We constructed a whole-brain neural circuit model of the fly Drosophila with biophysically detailed multi-compartment Hodgkin-Huxley models based on the morphologies of individual neurons published in open databases. Performance tuning of the simulator enabled near real-time simulation of the resting state of the Drosophila whole-brain model in the large-scale computational environment of the supercomputer Fugaku, for which we achieved in excess of 630 TFLOPS using 480k cores. In our whole-brain model, neural circuit dynamics related to a standard insect learning paradigm, the association of taste rewards with odors could be simulated.

neuroscience↗

bioRxiv2021

Macrophages in the reticuloendothelial system inhibit the propagation phase of mouse apolipoprotein A-II amyloidosis

Amyloidosis refers to a group of degenerative diseases that are characterized by the deposition of misfolded protein fibrils in various organs. Deposited amyloid may be removed by a phagocyte-dependent innate immune system; however, the precise mechanisms during disease progression remain unclear. We herein investigated the properties of macrophages that contribute to amyloid degradation and disease progression using transmissible apolipoprotein A-II amyloidosis model mice. Intravenously injected AApoAII amyloid was efficiently engulfed by reticuloendothelial macrophages in the liver and spleen and disappeared by 24 h. While cultured murine macrophages degraded AApoAII via the endosomal-lysosomal pathway, AApoAII fibrils reduced cell viability and phagocytic capacity. Furthermore, the depletion of reticuloendothelial macrophages prior to the induction of AApoAII markedly increased hepatic and splenic AApoAII deposition. These results highlight the physiological role of reticuloendothelial macrophages against inter-individual amyloid propagation and suggest the maintenance of phagocytic integrity as a therapeutic strategy to inhibit disease progression.

molecular biology↗

bioRxiv2021

A candidate for the sex-determination gene in tunas (Thunnus fishes)

Fish species have a variety of sex determination systems. Tunas (genus Thunnus) have an XY genetic sex-determination system. However, the Y chromosome or responsible locus has not yet been identified in males. In a previous study, a female genome of Pacific bluefin tuna (T. orientalis) was sequenced, and candidates for sex-associated DNA polymorphisms were identified by a genome-wide association study using resequencing data. In the present study, we sequenced a male genome of Pacific bluefin tuna by long-read and linked-read sequencing technologies, and explored male-specific loci through a comparison with the female genome. As a result, we found a unique region carrying the male-specific haplotype, where a homolog of estrogen sulfotransferase gene was predicted to be encoded. The genome-wide mapping of previously resequenced data indicated that, among the functionally annotated genes, only this gene, named sult1st6y, was paternally inherited in the males of Pacific bluefin tuna. We reviewed the RNA-seq data of southern bluefin tuna (T. maccoyii) in the public database and found that sult1st6y of southern bluefin tuna was expressed in all male testes, but absent or suppressed in the female ovary. Since estrogen sulfotransferase is responsible for the inactivation of estrogens, it is reasonable to assume that the expression of sult1st6y in gonad cells may inhibit female development, thereby inducing the individuals to become males. Thus, our results raise a promising hypothesis that sult1st6y is the sex-determination gene in Thunnus fishes, or at least functions at a crucial point in the sex-differentiation cascade.

genomics↗

bioRxiv2020

Curcumin promotes progression of AApoAII amyloidosis and peroxisome proliferation in mice by activating the PPARα signaling pathway

Curcumin is a polyphenol compound that exhibits multiple physiological activities. To elucidate the mechanisms by which curcumin affects systemic amyloidosis, we investigated amyloid deposition and molecular changes in a mouse model of amyloid apolipoprotein A-II (AApoAII) amyloidosis, in which mice were fed a curcumin-supplemented diet. Curcumin supplementation for 12 weeks significantly increased AApoAII amyloid deposition relative to controls, especially in the liver and spleen. Liver weights and plasma ApoA-II and high-density lipoprotein concentrations were significantly elevated in curcumin-supplemented groups. RNA-sequence analysis revealed that curcumin intake affected hepatic lipid metabolism via the peroxisome proliferator-activated receptor (PPAR) pathway, especially PPAR activation, resulting in increased Apoa2 mRNA expression. The increase in liver weights was due to activation of PPAR and peroxisome proliferation. Taken together, these results demonstrate that curcumin is a PPAR activator and may affect expression levels of proteins involved in amyloid deposition to influence amyloidosis and metabolism in a complex manner.

molecular biology↗