Biology subjects

Kumagai, S.

Publications and source records attributed to Kumagai, S..

5 recordsLinked to original sources

bioRxiv2025

A skeletal muscle-sympathetic nerve-intestine network underlies muscle inflammation and atrophy induced by immobilization

Immobility is a common cause of muscle atrophy, but the underlying mechanisms have remained unclear. Here we show that limb immobilization in mice elicits inflammation and atrophy of skeletal muscle that are preventable by neutralizing antibodies to the chemokine CXCL10. Limb immobilization also induced changes to the gut microbiota and intestinal inflammation, and either sterilization of the intestine with antibiotics or administration of 10-hydroxy-cis-12-octadecenoic acid--a linoleic acid-derived gut microbial metabolite--prevented intestinal and muscle inflammation as well as muscle atrophy induced by immobilization, implicating intestinal inflammation in muscle inflammation and atrophy. Limb immobilization activated sympathetic nerves and increased {beta}2-adrenergic receptor gene (Adrb2) expression in the intestine. Single-cell RNA-sequencing analysis revealed that, among cells expressing Adrb2 in the intestine, immobilization increased only the population of macrophages. Pharmacological inhibition or macrophage-specific ablation of Adrb2 prevented immobilization-induced intestinal and muscle inflammation. Our results thus implicate a previously unrecognized muscle-nerve-intestine network in immobilization-induced muscle atrophy.

molecular biology↗

bioRxiv2019

Allele frequency spectra in structured populations: Novel-allele probabilities under the labelled coalescent

We address the effect of population structure on key properties of the Ewens sampling formula. We use our previously-introduced inductive method for determining exact allele frequency spectrum (AFS) probabilities under the infinite-allele model of mutation and population structure for samples of arbitrary size. Fundamental to the sampling distribution is the novel-allele probability, the probability that given the pattern of variation in the present sample, the next gene sampled belongs to an as-yet-unobserved allelic class. Unlike the case for panmictic populations, the novel-allele probability depends on the AFS of the present sample. We derive a recursion that directly provides the marginal novel-allele probability across AFSs, obviating the need first to determine the probability of each AFS. Our explorations suggest that the marginal novel-allele probability tends to be greater for initial samples comprising fewer alleles and for sampling configurations in which the next-observed gene derives from a deme different from that of the majority of the present sample. Comparison to the efficient importance sampling proposals developed by De Iorio and Griffiths and colleagues indicates that their approximation for the novel-allele probability generally agrees with the true marginal, although it may tend to overestimate the marginal in cases in which the novel-allele probability is high and migration rates are low.

evolutionary biology↗

bioRxiv2019

ATP Binding Cassette Proteins ABCG37 and ABCG33 are required for potassium-independent cesium uptake in Arabidopsis roots

Radiocesium, accumulated in the soil by nuclear accidents is a major environmental concern. The transport process of cesium (Cs+) is tightly linked to the indispensable plant nutrient potassium (K+) as they both belong to the group I alkali metal with similar chemical properties. Most of the transporters that had been characterized to date as Cs+ transporters are directly or indirectly linked to K+. Using a combinatorial approach of physiology, genetics, cell biology and root uptake assay, here we identified two ATP-Binding Cassette (ABC) proteins, ABCG37 and ABCG33 as facilitators of Cs+ influx. The gain-of-function mutant of ABCG37 (abcg37-1) showed hypersensitive response to Cs+-induced root growth inhibition, while the double knock out mutant of ABCG33 and ABCG37 (abcg33-1abcg37-2) showed resistance. Single loss-of-function mutant of ABCG33 and ABCG37 did not show any alteration in Cs+ response. Short term uptake experiment with radioactive Cs+ revealed reduced Cs+ uptake in abcg33-1abgc37-2 compared with wild type in presence or absence of K+. Potassium response and content were unaffected in the double mutant background confirming that Cs+ uptake by ABCG33 and ABCG37 is independent of K+. Collectively, this work identified two ABC proteins as new Cs+ influx carriers, which act redundantly and independent of K+ uptake pathway.

plant biology↗

bioRxiv2018

Inductive determination of allele frequency spectrum probabilities in structured populations

We present a method for inductively determining exact allele frequency spectrum (AFS) probabilities for samples derived from a population comprising two demes under the infinite-allele model of mutation. This method builds on a labeled coalescent argument to extend the Ewens sampling formula (ESF) to structured populations. A key departure from the panmictic case is that the AFS conditioned on the number of alleles in the sample is no longer independent of the scaled mutation rate ({theta}). In particular, biallelic site frequency spectra, widely-used in explorations of genome-wide patterns of variation, depend on the mutation rate in structured populations. Variation in the rate of substitution across loci and through time may contribute to apparent distortions of site frequency spectra exhibited by samples derived from structured populations.

evolutionary biology↗

bioRxiv2018

Automated Adherent Cell Elimination by a High-Speed Laser Mediated by a Light-Responsive Polymer

Conventional cell handling and sorting methods require manual dissociation, which decreases cell quality and quantity and is not well suited for monitoring applications. To purify adherent cultured cells, in situ cell purification technologies that are high throughput and can be utilized in an on-demand manner are expected. Previous demonstrations using direct laser-mediated cell elimination revealed only limited success in terms of their usability and throughput. Here, we developed a Laser-Induced, Light-responsive-polymer-Activated, Cell Killing (LILACK) system that enables high-speed and on-demand adherent cell sectioning and purification. This system employs a visible laser beam, which does not kill cells directly, but induces local heat production through the trans-cis-trans photo-isomerization of azobenzene moieties in only the irradiated area of a light-responsive thin layer. Using this system in each passage for sectioning, human induced pluripotent stem cells (hiPSCs) were maintained their pluripotency and self-renewal during long-term culture. Furthermore, combined with deep machine-learning analysis on fluorescent and phase contrast images, a label-free and automatic cell processing system was developed by eliminating unwanted spontaneously differentiated cells in undifferentiated hiPSC culture conditions.

bioengineering↗