Biology subjects

Yamaguchi, T.

Publications and source records attributed to Yamaguchi, T..

46 records · Page 3Linked to original sources

bioRxiv2021

Deep learning-based chest X-ray age serves as a novel biomarker for cardiovascular aging

Chest X-ray (CXR) is one of the most commonly performed medical imaging tests. Although aging, sex and disease status have been known to cause changes in CXR findings, the extent of these effects has not been fully characterized. Here, we present a deep neural network (DNN) model trained using more than 100,000 CXRs to estimate the patients age and sex solely from CXRs. Our DNN exhibited high performance in terms of estimating age and sex, with Pearsons correlation coefficient between the actual and estimated age of above 0.9 and an area under the ROC curve of 0.98 for sex estimation. The difference between the actual and estimated age is large in CXRs with abnormal findings, suggesting that the estimated age ("CXR age") can be a biomarker for disease status. Furthermore, by applying our DNN to CXRs of consecutive 1,562 hospitalized heart failure patients, we demonstrated that an elevated CXR age is not only associated with aging-related diseases, such as hypertension and atrial fibrillation, but also a worse outcome of heart failure. Given these results, our new concept "CXR age" serves as a novel biomarker for cardiovascular aging and can help clinicians to predict, prevent, and manage cardiovascular diseases.

bioinformatics↗

bioRxiv2020

Structure of the molecular bushing of the bacterial flagellar motor

The bacterial flagellum is a motility organelle, consisting of the basal body acting as a rotary motor, the filament as a helical propeller and the hook connecting these two as a universal joint1,2. The basal body contains three rings: the MS ring as the transmembrane core of the rotor; the C ring essential for torque generation and switching regulation; and the LP ring as a bushing supporting the distal rod for its rapid, stable rotation without much friction. The negatively charged surface of the distal rod suggested electrostatic repulsive force in supporting high-speed rotation of the rod as a drive shaft3, but the LP ring structure was needed to see the actual mechanisms of its bushing function and assembly against the repulsive force. Here we report the LP ring structure by electron cryomicroscopy at 3.5 [A] resolution, showing 26-fold rotational symmetry and intricate intersubunit interactions of each subunit with up to six partners that explains the structural stability. The inner surface is charged both positively and negatively, and positive charges on the P ring presumably play important roles in its initial assembly around the rod in the peptidoglycan layer followed by the L ring assembly in the outer membrane.

molecular biology↗

bioRxiv2020

Genetic characterization of Streptococcus pyogenes emm 89 strains isolated in Japan from 2011 to 2019

Streptococcal toxic shock syndrome (STSS) caused by Streptococcus pyogenes emm89 strains has been increasing in several countries and reported to be linked with a recently emerged clade of emm89 strains, designated clade 3. In Japan, epidemiological and genetic information for emm89 strains remains elusive. In this study, we utilized emm89 strains isolated from both STSS (89 isolates) and non-STSS (72 isolates) infections in Japan from 2011 to 2019, and conducted whole-genome sequencing and comparative analysis, which resulted in classification of a large majority into clade 3 regardless of disease severity. In addition, STSS-associated genes and SNPs were found in clade 3 strains, including mutations of streptokinase (Ska), control of virulence sensor (CovS), serum opacity factor (SOF), sortase (SrtB), and fibronectin-binding protein F1 (PrtF1), and absence of the hylP1 gene encoding hyaluronidase. These findings provide insights into notable genetic features of emm89 strains.

microbiology↗

bioRxiv2019

Isolation of an archaeon at the prokaryote-eukaryote interface

The origin of eukaryotes remains enigmatic. Current data suggests that eukaryotes may have risen from an archaeal lineage known as \"Asgard archaea\". Despite the eukaryote-like genomic features found in these archaea, the evolutionary transition from archaea to eukaryotes remains unclear due to the lack of cultured representatives and corresponding physiological insight. Here we report the decade-long isolation of a Lokiarchaeota-related Asgard archaeon from deep marine sediment. The archaeon, \"Candidatus Prometheoarchaeum syntrophicum strain MK-D1\", is an anaerobic, extremely slow-growing, small cocci ([~]550 nm), that degrades amino acids through syntrophy. Although eukaryote-like intracellular complexities have been proposed for Asgard archaea, the isolate has no visible organella-like structure. Ca. P. syntrophicum instead displays morphological complexity - unique long, and often, branching protrusions. Based on cultivation and genomics, we propose an \"Entangle-Engulf-Enslave (E3) model\" for eukaryogenesis through archaea-alphaproteobacteria symbiosis mediated by the physical complexities and metabolic dependency of the hosting archaeon.

microbiology↗

bioRxiv2019

The first functional characterization of ancient interleukin-15-like (IL-15L) reveals shared and distinct functions of the IL-2, -15 and -15L family cytokines

The ancient cytokine interleukin 15-like (IL-15L) was lost in humans and mice but not throughout mammals. This is the first study to describe IL-15L functions, namely in the fish rainbow trout. Fish have only one -chain receptor gene IL-15R, whereas in mammalian evolution this gene duplicated and evolved into IL-15R plus IL-2R. Trout IL-2, IL-15 and IL-15L all could bind IL-15R and were able to induce phosphorylation of transcription factor STAT5. Reminiscent of the mammalian situation, trout IL-15 was more dependent on \"in trans\" presentation by IL-15R than IL-2. However, whereas trout IL-15 could also function as a free cytokine as known for mammalian IL-15, trout IL-15L function showed a total dependency on in trans presentation by IL-15R. Trout lymphocytes from the mucosal tissues gill and intestine were sensitive to IL-15, but refractory to IL-2 and IL-15L, which is reminiscent of sensitivities to IL-15 in mammals. Distinguishing engagement of the IL-2R/IL-15R receptor chain may explain why IL-2 and IL-15 were selected in evolution as major growth factors for regulatory T cells and lymphocytes in mucosal tissues, respectively. Trout IL-15L efficiently induced expression of IL-4 and IL-13 homologues in CD4-CD8-IgM- splenocytes, and we speculate that the responsive cells within that population were type 2 innate lymphoid cells (ILC2). In contrast, trout IL-15 efficiently induced expression of interferon {gamma} and perforin in CD4-CD8-IgM- splenocytes, and we speculate that in this case the responsive cells were natural killer (NK) cells. In fish, in apparent absence of IL-25, IL-33 and TSLP, primitive IL-15L may have an important role early in the type 2 immunity cytokine cascade. Among trout thymocytes, only CD4-CD8- thymocytes were sensitive to IL-15L, and different than in mammals the CD4+CD8+ thymocytes were quite sensitive to IL-2. In addition, the present study provides (i) the first molecular evidence for inter-species cytokine with receptor chain interaction across fish-mammal borders, and (ii) suggestive evidence for a tendency of IL-2/15/15L cytokines to form homodimers as an ancient family trait. This is the first comprehensive study on IL-2/15/15L functions in fish and it provides important insights into the evolution of this cytokine family.

evolutionary biology↗

bioRxiv2019

Generation of human hepatic progenitor cells with regenerative and metabolic capacities from primary hepatocytes

Hepatocytes are regarded as the only effective cell source for cell transplantation to treat liver diseases; however, their availability is limited due to a donor shortage. Thus, a novel cell source must be developed. We recently reported that mature rodent hepatocytes can be reprogrammed into progenitor-like cells with a repopulative capacity using small molecule inhibitors. Here, we demonstrate that hepatic progenitor cells can be obtained from human infant hepatocytes using the same strategy. These cells, named human chemically induced liver progenitors (hCLiPs), had a significant repopulative capacity in injured mouse livers following transplantation. hCLiPs redifferentiated into mature hepatocytes in vitro upon treatment with hepatic maturation-inducing factors. These redifferentiated cells exhibited cytochrome P450 (CYP) enzymatic activities in response to CYP-inducing molecules and these activities were comparable with those in primary human hepatocytes. These findings will facilitate liver cell transplantation therapy and drug discovery studies.

cell biology↗

bioRxiv2019

Isolation of lactic acid bacteria capable of reducing environmental alkyl and fatty acid hydroperoxides, and the effect of their oral administration on oxidative-stressed nematodes and rats

Reinforcement of hydroperoxide-eliminating activity in the intestines and colon should prevent associated diseases. We previously isolated a lactic acid bacterium, Pediococcus pentosaceus Be1, that facilitates a 2-electron reduction of hydrogen peroxide to water. In this study, we successfully isolated an alternative lactic acid bacterium, Lactobacillus plantarum P1-2, that can efficiently reduce environmental alkyl hydroperoxides and fatty acid hydroperoxides to their corresponding hydroxy derivatives through a 2-electron reduction. Each strain exhibited a wide concentration range with regard to the environmental reducing activity for each hydroperoxide. Given this, the two lactic acid bacteria were orally administered to the oxygen-sensitive short-lived nematode mutant, and this resulted in a significant expansion of its lifespan. This observation suggests that P. pentosaceus Be1 and L. plantarum P1-2 inhibit internal oxidative stress. To determine the specific organs involved in this response, we performed a similar experiment in rats, involving induced lipid peroxidation by iron-overloading. We observed that only L. plantarum P1-2 inhibited colonic mucosa lipid peroxidation in rats with induced oxidative stress.

microbiology↗

bioRxiv2018

Residual Structure of Unfolded Ubiquitin as Revealed by Hydrogen/Deuterium-Exchange 2D NMR

The characterization of residual structures persistent in unfolded proteins in concentrated denaturant solution is currently an important issue in studies of protein folding, because the residual structure present, if any, in the unfolded state may form a folding initiation site and guide the subsequent folding reactions. Here, we thus studied the hydrogen/deuterium (H/D)-exchange behavior of unfolded ubiquitin in 6.0 M guanidinium chloride at pH 2.6 and 20{degrees}C. We employed a dimethylsulfoxide (DMSO)-quenched H/D-exchange NMR technique with the use of spin desalting columns, which allowed us to make a quick medium exchange from 6.0 M guanidinium chloride to a quenching DMSO solution. The technique is particularly effective for studies of the H/D-exchange kinetics of unfolded proteins in concentrated denaturant. By the backbone resonance assignment of the hetero-nuclear single quantum coherence spectrum of 15N-labeled ubiquitin in the DMSO solution, we successfully investigated the H/D-exchange kinetics of 27 identified peptide amide groups in the ubiquitin sequence. Although most of these amide groups were not protected, the four amide groups of Ile3, Val5, Ile13 and Leu73 were weakly but significantly protected with a protection factor of 2.5-3.0, indicating that there were residual structures in unfolded ubiquitin and that these amide groups were 60-67% hydrogen-bonded by the residual structures. We show that the first native {beta}-hairpin, composed of residues 2-16 in the native ubiquitin structure, is partially structured even in 6.0 M guanidinium chloride and that the amide group of Leu73 is protected by a nonnative hydrogen-bonding interaction. From comparison with the previous folding studies of ubiquitin, it is concluded that the residual native {beta}-hairpin in unfolded ubiquitin forms a folding initiation site and guides the subsequent folding reactions of the protein.

biophysics↗

bioRxiv2018

A genetically-encoded fluorescent sensor enables rapid and specific detection of dopamine in flies, fish, and mice

Dopamine (DA) is a central monoamine neurotransmitter involved in many physiological and pathological processes. A longstanding yet largely unmet goal is to measure DA changes reliably and specifically with high spatiotemporal precision, particularly in animals executing complex behaviors. Here we report the development of novel genetically-encoded GPCR-Activation-Based-DA (GRABDA) sensors that enable these measurements. In response to extracellular DA rises, GRABDA sensors exhibit large fluorescence increases ({Delta}F/F0[~]90%) with sub-second kinetics, nanomolar to sub-micromolar affinities, and excellent molecular specificity. Importantly, GRABDA sensors can resolve a single-electrical-stimulus evoked DA release in mouse brain slices, and detect endogenous DA release in the intact brains of flies, fish, and mice. In freely-behaving mice, GRABDA sensors readily report optogenetically-elicited nigrostriatal DA release and depict dynamic mesoaccumbens DA changes during Pavlovian conditioning or during sexual behaviors. Thus, GRABDA sensors enable spatiotemporal precise measurements of DA dynamics in a variety of model organisms while exhibiting complex behaviors.

neuroscience↗

bioRxiv2018

Electric field dependent effects of motor cortical TDCS

Transcranial direct current stimulation (TDCS) can modulate motor cortical excitability. However, its after-effects are highly variable between individuals. Individual cranial and brain anatomy may contribute to this variability by producing varying electric fields in each subjects brain. Here we show that these fields are related to excitability changes following anodal TDCS of the primary motor cortex (M1). We found in two experiments (N=28 and N=9) that the after-effects of TDCS were proportional to the individual electric field in M1, calculated using MRI-based models. Individuals with the lowest and highest local electric fields in M1 tended to produce opposite changes in excitability. Furthermore, the effect was field-direction dependent and non-linear with stimulation duration or other experimental parameters. The electric field component pointing into the brain was negatively proportional to the excitability changes following 1 mA 20 min TDCS of right M1 (N=28); the effect was opposite after 1 mA 10 min TDCS of left M1 (N=9). Our results demonstrate that a large part of variability in the after-effects of motor cortical TDCS is due to inter-individual differences in the electric fields. We anticipate that individualized electric field dosimetry could be used to control the neuroplastic effects of TDCS, which is increasingly being explored as a treatment for various neuropsychiatric diseases.

neuroscience↗