Biology subjects

Suzuki, C.

Publications and source records attributed to Suzuki, C..

10 recordsLinked to original sources

bioRxiv2026

Metabolic outsourcing from ingested lactic acid bacteria extends Caenorhabditis elegans healthspan via bacterial amino acid and enzyme provision

Lactic acid bacteria promote longevity, yet the host-microbe metabolic mechanisms remain obscure. Using Caenorhabditis elegans, which lacks a urea cycle, we investigated how Lactococcus lactis JCM 5805 (Lc5805) extends lifespan. Live Lc5805 consumption upregulated 74 cuticle-formation genes, primarily collagens, supporting structural integrity for longevity without activating host stress responses. Multi-omics and UPLC-MS analyses revealed a dramatic accumulation of L-citrulline and L-ornithine, driven by high intestinal expression of bacterial arginine deiminase (arcA). The finding that heat-treated Lc5805 failed to induce citrulline accumulation and lifespan extension confirms that this metabolic outsourcing system, the operation of the arginine deiminase pathway, requires active metabolic and enzymatic activity by live bacteria in the gut. By utilizing bacterial metabolites and enzymes to fuel collagen maintenance, the host avoids endogenous energy expenditure. This study unveils a novel symbiotic paradigm of "Metabolic Outsourcing" governing organismal longevity.

physiology↗

bioRxiv2026

Memory transfer unfolds through rapid shifts in memory stability states during sleep in humans

Sleep benefits learning and memory. Fundamental questions remain regarding whether and how sleep transfers memories for adaptive behavior in humans. We demonstrate that declarative to procedural memory transfer occurs through rapid network reorganization and memory stability shifts in human participants. Following local processing in motor circuit during slow wave-spindle coupling in nonrapid eye movement (NREM) sleep, multiregional communication during phasic rapid-eye movement (REM) sleep enables transfer. By leveraging a newly developed time-resolved simultaneous ultrahigh-field magnetic resonance spectroscopy and polysomnography, we further reveal that memory state becomes instantaneously unstable during slow wave-spindle coupling then enters a hyperstable state during phasic-REM sleep. Thus, sleep bridges memory systems, utilizing increased instability in NREM sleep, and transferring memory through hyperstabilization in REM sleep for knowledge integration.

neuroscience↗

bioRxiv2025

A data-driven analysis of spatiotemporal cues and experience accumulation effects for pitch type prediction

Conventional sports anticipation studies have primarily relied on hypothesis-testing paradigms that target predetermined cues. However, such approaches risk overlooking unanticipated sources of predictive information. This study addresses this limitation by introducing data-driven analysis using machine learning (ML) models as a complementary approach to conventional experimental research. Given that predictive cues embedded within movements can enhance the prediction accuracy of ML models, the proposed analysis identified spatiotemporal cues for prediction and quantified the effects of accumulating opponent-specific information across trials. Motion-capture data were collected from eight collegiate baseball pitchers, and joint-angle time series were analyzed using logistic regression models to predict pitch type (fastball vs. breaking ball). Specifically, two analyses were conducted: (1) a sliding time-window analysis to identify when and where predictive cues emerged within target motions and (2) a set-size analysis to evaluate how prediction accuracy varied with dataset size. The main results revealed that (1) predictive cues were distributed across the entire body, but models integrating whole-body information achieved the highest accuracy; (2) informative cues emerged in most body regions around the initiation of the pitchers weight shift; (3) the accumulation of opponent-specific information had a pronounced effect up to approximately 30 pitches; and (4) substantial individual differences existed in when and which cues were effective for pitch-type prediction. Although alignment with human athletes must be carefully examined in future work, these findings highlight the utility of the proposed analysis as a complementary approach to conventional hypothesis-testing experiments.

animal behavior and cognition↗

bioRxiv2025

Chromosome-scale genomes of two wild flowering cherrys (Cerasus itosakura and C. jamasakura) provide insights into structural evolution in Prunus

Flowering cherries (genus Cerasus) are iconic trees in Japan, celebrated for their cultural and ecological significance. Despite their prominence, high-quality genomic resources for wild Cerasus species have been limited. Here, we report chromosome-level genome assemblies of two representative Japanese cherries: Cerasus itosakura, a progenitor of the widely cultivated C. xyedoensis Somei-yoshino, and Cerasus jamasakura, a traditional popular wild species endemic to Japan. Using deep PacBio long-read and Illumina short-read sequencing, combined with reference-guided scaffolding based on near-complete C. speciosa genome, we generated assemblies of 259.1 Mbp (C. itosakura) and 312.6 Mbp (C. jamasakura), with both >98% BUSCO completeness. Consistent with their natural histories, C. itosakura showed low heterozygosity, while C. jamasakura displayed high genomic diversity. Comparative genomic analyses revealed structural variations, including large chromosomal inversions. Notably, the availability of both the previously published C. speciosa genome and our new C. itosakura genome enabled the reconstruction of proxy haplotypes for both parental lineages of Somei-yoshino. Comparison with the phased genome of Somei-yoshino revealed genomic discrepancies, suggesting that the cultivar may have arisen from genetically distinct or admixed individuals, and may also reflect intraspecific diversity. Our results offer genomic foundations for evolutionary and breeding studies in Cerasus and Prunus.

genomics↗

bioRxiv2025

Non-DNA-damaging DNA-PK activation improving hearing and prolonging life due to NAD+ and SIRT upregulation

Emerging evidence strongly supports a close relationship between age-related hearing loss and frailty, highlighting the importance of early detection and intervention. Recently, we invented a mitochondria-homing drug named mitochonic acid 5 (MA-5), that increases the adenosine triphosphate (ATP) levels, rescue mitochondrial function, and protect tissue damages. Currently, the phase I clinical trial has been finished in Japan (jRCT2031210495) and the phase 2 clinical trial has already been approved by PMDA. Here we show that MA-5 improved various types of hearing loss in mouse models. Structural chemical bioanalysis revealed that MA-5 is a mixture of equal amount of S- and R- enantiomer and both S- and R- enantiomer increase ATP by binding mitochondrial protein, mitofilin. However, S-enantiomer significantly increased the NAD+ levels by binding to the NAD+-producing key enzyme nicotinamide phosphoribosyltransferase (NAMPT). Moreover, the S-enantiomer increased the sirtuin 1 protein by suppressing polyubiquitination induced by tripartite motif containing 28 (TRIM28) phosphorylation which was triggered by DNA-dependent protein kinase (DNA-PK) activation in the absence of DNA damage. Transcriptomic signatures showed that the signature of MA-5 shows an inverse correlation with aging and mortality and is oriented in the same direction as the OSKM-related iPSCs, suggesting the modification of aging pathways. Oral administration of MA-5 to mitochondrial disease model mouse showed increased survival. Our findings suggest that, in addition to enhancing ATP levels, the coordinated regulation of NAD+ metabolism, SIRT protein expression, and DNA-PK activity-constituting a novel therapeutic triad may contribute to the amelioration of hearing impairment and mitochondrial dysfunction, thereby improving life prognosis.

cell biology↗

bioRxiv2024

Human deep sleep facilitates faster cerebrospinal fluid dynamics linked to brain oscillations for sleep homeostasis and memory

How sleep maintains our healthy brain function has remained one of the biggest mysteries in neuroscience, medical settings, and daily lives. While cerebrospinal fluid (CSF) during sleep have been implicated in metabolic waste reduction in animals, how CSF dynamics are driven in the healthy human brain during deep sleep remains elusive. A myriad of research has shown that crucial cognitive processing manifests in slow wave and rapid-eye movement (REM) sleep, suggesting that a key to maintaining brain functions lies in deep sleep. By leveraging a simultaneous sparse-fMRI and polysomnography method, we demonstrate that deep sleep-specific faster CSF dynamics are associated with spontaneous brain oscillations in healthy young human participants. Slow waves and sleep spindles during slow-wave sleep and rapid eye movements and sawtooth waves during rapid eye movement (REM) sleep are tightly linked to low-amplitude faster CSF fluctuations. In contrast, slow waves during light sleep and arousals produced large but slower CSF signal changes. Furthermore, CSF signals are significantly faster in frequency during deep than light sleep. These brain oscillations during light and deep sleep recruited essentially different brain networks, with deep sleep involving memory and homeostatic circuits. Thus, human deep sleep has a unique way of enabling faster CSF dynamics that are distinctive from arousal mechanisms. Significance StatementSleep is indispensable to our life, but its functions remain a significant mystery in the field of neuroscience. One of the most enigmatic issues in sleep is whether and how sleep regulates the CSF. The present study demonstrates deep sleep-specific faster CSF dynamics time locked to sleep brain oscillations in healthy young human participants. Slow waves and sleep spindles during slow-wave sleep and rapid eye movements and sawtooth waves during REM sleep are tightly linked to CSF fluctuations, contributing to faster CSF signals. Our results consistently demonstrate that human deep sleep has a unique way of enabling faster CSF dynamics that are distinctive from arousal mechanisms.

neuroscience↗

bioRxiv2023

Role of Immature Choroid Plexus in the Pathology of Autism Spectrum Disorder

During gestation, the choroid plexus (ChP) produces protein-rich cerebrospinal fluid and matures prior to brain development. It is assumed that ChP dysfunction has a profound effect on developmental neuropsychiatric disorders, such as Autism Spectrum Disorder (ASD). However, the mechanisms linking immature ChP to the onset of ASD remain unclear. In this study, we found that ChP-specific CAMDI-knockout mice developed an immature ChP, alongside decreased multiciliogenesis and expression of differentiation marker genes following disruption of the cerebrospinal fluid barrier. These mice exhibited ASD-like behaviors, including impaired socialization with delayed critical period. Additionally, administration of Metformin, an FDA-approved drug, before the critical period achieved ChP maturation and restored social behaviors. Furthermore, ASD model mice and ASD patient-derived organoids developed immature ChP. These results indicate towards involvement of immature ChP in the pathogenesis of ASD and suggest the targeting of functional maturation of ChP as a therapeutic strategy for ASD.

neuroscience↗

bioRxiv2022

Cell-surface protein YwfG of Lactococcus lactis binds to α-1,2-linked mannose

Lactococcus lactis strains are used as starter cultures in the production of fermented dairy and vegetable foods, but the species also occurs in other niches such as plant material. Lactococcus lactis subsp. lactis G50 (G50) is a plant-derived strain and potential candidate probiotics. Western blotting of cell-wall proteins using antibodies generated against whole G50 cells detected a 120-kDa protein. MALDI-TOF MS analysis identified it as YwfG, a Leu-Pro-any-Thr-Gly cell-wall-anchor-domain-containing protein. Based on a predicted domain structure, a recombinant YwfG variant covering the N-terminal half (aa 28-511) of YwfG (YwfG28-511) was crystallized and the crystal structure was determined. The structure consisted of an L-type lectin domain, a mucin-binding protein domain, and a mucus-binding protein repeat. Recombinant YwfG variants containing combinations of these domains (YwfG28-270, YwfG28-311, YwfG28-511, MubR4) were prepared and their interactions with monosaccharides were examined by isothermal titration calorimetry; the only interaction observed was between YwfG28-270, which contained the L-type lectin domain, and D-mannose. Among four mannobioses, -1,2-mannobiose had the highest affinity for YwfG28-270 (dissociation constant = 34 M). YwfG28-270 also interacted with yeast mannoproteins and yeast mannan. Soaking of the crystals of YwfG28-511 with mannose or -1,2-mannobiose revealed that both sugars bound to the L-type lectin domain in a similar manner, although the presence of the mucin-binding protein domain and the mucus-binding protein repeat within the recombinant protein inhibited the interaction between the L-type lectin domain and mannose residues. Three of the YwfG variants (except MubR4) induced aggregation of yeast cells. Strain G50 also induced aggregation of yeast cells, which was abolished by deletion of ywfG from G50, suggesting that surface YwfG contributes to the interaction with yeast cells. These findings provide new structural and functional insights into the interaction between L. lactis and its ecological niche via binding of the cell-surface protein YwfG with mannose.

microbiology↗

bioRxiv2020

Mitochondrial dysfunction underlying sporadic inclusion body myositis is ameliorated by the mitochondrial homing drug MA-5

Sporadic inclusion body myositis (sIBM) is the most common idiopathic inflammatory myopathy, and several reports have suggested that mitochondrial abnormalities are involved in its etiology. We recruited 9 sIBM patients and found significant histological changes and an elevation of growth differential factor 15 (GDF15), a marker of mitochondrial disease, strongly suggesting the involvement of mitochondrial dysfunction. Bioenergetic analysis of sIBM patient myoblasts revealed impaired mitochondrial function. Decreased ATP production, reduced mitochondrial size and reduced mitochondrial dynamics were also observed in sIBM myoblasts. Cell vulnerability to oxidative stress also suggested the existence of mitochondrial dysfunction. Mitochonic acid-5 (MA-5) increased the cellular ATP level, reduced mitochondrial ROS, and provided protection against sIBM myoblast death. MA-5 also improved the survival of sIBM skin fibroblasts as well as mitochondrial morphology and dynamics in these cells. The reduction in the gene expression levels of Opa1 and Drp1 was also reversed by MA-5, suggesting the modification of the fusion/fission process. These data suggest that MA-5 may provide an alternative therapeutic strategy for treating not only mitochondrial diseases but also sIBM.

neuroscience↗

bioRxiv2017

Tracking Individual Differences in Perception by TMS-EEG Intrinsic Effective Connectivity

Non-invasive human electroencephalography (EEG) coupled with transcranial magnetic stimulation (TMS) is currently used to measure coarse stimulus-response relationships in brain physiology during behavior. However, with key modifications, the TMS-EEG technique holds even greater promise for monitoring fine-scale neural signatures of human behavior. Here, we demonstrate that a novel TMS-EEG co-registration technique can dynamically monitor individual human variation in perception based solely on EEG resting-state intrinsic effective connectivity probed by TMS-based phase resetting of ongoing activity. We used a bistable stimulus task, where the percept is perceived as either horizontal or vertical apparent motion, to record gamma band interhemispheric integration of information. Fine-grained inter-individual behavioral differences in horizontal motion bias could be measured by tracking resting-state gamma-band effective connectivity from right hMT+ to left hMT+. Thus, our method of triggering intrinsic resting-state effective connectivity in oscillatory dynamics can monitor individual differences in perception via the long-range integration of information. This technique will be useful for the manipulative dissection of individual-scale human cognition mediated by neural dynamics and may also expand neurofeedback approaches.

neuroscience↗