Biology subjects

Ando, S.

Publications and source records attributed to Ando, S..

13 recordsLinked to original sources

bioRxiv2025

Candidatus Rickettsia mendelii has the smallest and most ancestral-like genome in the genus Rickettsia

Rickettsia species, which constitute obligate intracellular bacteria adapted to a host-dependent lifestyle, have traditionally been classified into four phylogenetic groups. However, the available genomes are biased toward the Typhus and Spotted Fever groups, with early-diverging Ancestral group (AG) lineages being underrepresented. Here, we isolated six Candidatus Rickettsia mendelii strains from Ixodes turdus ticks in Japan. We obtained their whole-genome sequences, including one closed genome, and found that they form a distinct lineage in the AG and have the smallest genome among the known rickettsial species. Gene tree-aware reconstruction of evolutionary events using amalgamated likelihood estimation revealed that the last common ancestor of Rickettsia had a smaller gene family size than modern species do, and Ca. R. mendelii retains the most similar genomic content to this ancestral state. Various patterns of gene gain and loss among Rickettsia lineages were also suggested, highlighting their divergent evolutionary trajectories. These findings increase our understanding of Rickettsia genome evolution.

microbiology↗

bioRxiv2025

Functional heterogeneity and plasticity in naive CD8 T cells drive superior effector and memory responses

While significant progress has been made in defining subsets among antigen-experienced CD8 T cells, the heterogeneity of naive CD8 T cells remains poorly understood. Here, we identify naive CD8 T cell subsets with superior persistence and an enhanced capacity to generate effector and memory cells, leading to more effective protection. These high-quality naive CD8 T cells are marked by IL-18R, CD73, and CXCR3, and functionally less potent naive CD8 T cells can convert into these superior subsets. Their enhanced response to infections is driven by better survival of the progeny effector cells during the T cell expansion phase. This improved survival is mediated by increased Ly6C2 expression on effector cells derived from these high-quality naive cells. Collectively, our findings reveal functional heterogeneity and plasticity among naive CD8 T cells and uncover a mechanism by which high-quality naive subsets drive robust CD8 T cell responses, providing a previously unrecognized layer of immune regulation. SUMMARYOur study reveals functional heterogeneity and plasticity within naive CD8 T cells, identifying high-quality subsets that can emerge from less potent cells and drive superior immune responses through enhanced survival of effector progeny.

immunology↗

bioRxiv2025

Arabidopsis epigenetic factor AS2 attenuates nucleolar stress by camptothecin and establishes leaf polarity by repressing a CDK inhibitor

The Arabidopsis thaliana leaf, exhibiting a symmetrically extended flat morphology, consists of two distinct cellular domains: adaxial and abaxial layers. The ASYMMETRIC LEAVES2 (AS2) gene is essential for specifying the adaxial domain, and its protein forms nucleolar structures, termed AS2 bodies, at ribosomal-DNA loci. Numerous nucleolus-related genes have been reported to be cooperatively involved in leaf adaxialization together with AS2. However, the molecular relationships between AS2 and these genes remain unclear. To identify chemical modulators of AS2 function, we screened a chemical library containing natural products and identified eight molecules, including camptothecin, that induced filamentous leaves in the as2 mutant. Camptothecin is an inhibitor of topoisomerase I, which is required for transcription of ribosomal-RNA genes, and induces nucleolar stress. Treatment with 10-hydroxy-camptothecin increased KIP-RELATED-PROTEIN5/INHIBITOR-OF-CYCLIN-DEPENDENT-KINASE3 (KRP5/ICK3) transcript levels, encoding a CDK inhibitor, and caused notable changes in the number and morphology of AS2 bodies. Given its role in leaf morphogenesis, our findings suggest that AS2 is a key factor in establishing leaf adaxial-abaxial polarity by regulating cell proliferation and protecting against nucleolar stress through coordinated interactions with nucleolar proteins.

developmental biology↗

bioRxiv2024

Predictive visual patterns during table tennis forehand rallies

The purpose of this study was to clarify predictive visual patterns of skilled table tennis players during forehand rallies. Collegiate male table tennis players (n = 7) conducted forehand rallies at a constant tempo (100, 120 and 150 bpm) using a metronome. In each tempo condition, participants performed a total of 30 strokes (three conditions). Gaze fixation time, gaze targets and saccade eye movements were detected by video footage of an eye tracking device. We found that participants gazed at a ball approaching them only 20 % of the total rally time. Participants tended to gaze at the ball when the opponent hit the ball and move their gaze away from the ball after that. Furthermore, saccades were directed toward the opposite side of the court including the opponent after tracking the ball. These findings suggest that focusing on the opponent motion is important for successful forehand table tennis rallies. Taken together, skilled table tennis players are likely to use unique visual patterns for interceptive sports players to estimate spatiotemporal information about the ball.

physiology↗

bioRxiv2023

Importance of head movements in gaze tracking during table tennis forehand stroke

The purpose of this study was to clarify the properties of gaze and head movements during forehand stroke in table tennis. Collegiate table tennis players (n = 12) conducted forehand strokes toward a ball launched by a skilled experimenter. A total of ten trials were conducted for the experimental task. Horizontal and vertical movements of the ball, gaze, head and eye were analyzed from the image recorded by an eye tracking device. The results showed that participants did not always keep their gaze and head position on the ball throughout the entire ball path. Our results indicate that table tennis players tend to gaze at the ball in the initial ball-tracking phase. Furthermore, there was a significant negative correlation between eye and head position especially in the vertical direction. This result suggests that horizontal VOR is relatively suppressed than vertical VOR in ball-tracking during table tennis forehand stroke. Finally, multiple regression analysis showed that the contribution of head position to gaze position was significantly higher than that of eye position. This result indicates that gaze position during forehand stroke could be associated with head position rather than eye position. Taken together, head movements may play an important role in maintaining the ball in a constant egocentric direction in table tennis forehand stroke.

neuroscience↗

bioRxiv2023

Dentate neurogenesis mediates cognitive flexibility via modulation of the hippocampal longitudinal-axis network

Adult neurogenesis endows the hippocampus with unparalleled neural plasticity, essential for intricate cognitive functions. However, the manner in which sparse newborn neurons (NBNs) modulate neural activities and subsequently shape behavior remains enigmatic. Utilizing a newly engineered NBN-Tetanus Toxin mouse model, we non-invasively silenced NBNs and confirmed their crucial role in cognitive flexibility, as demonstrated through reversal learning in the Morris water maze and the Go/Nogo task in operant learning. Pairing task-based functional MRI (tb-fMRI) with operant learning revealed a dorsal hippocampal hyperactivation during Nogo task, implying that hippocampal hyperexcitability might underlie the observed behavioral deficits. Notably, resting-state fMRI (rs-fMRI) revealed enhanced functional connectivity between the dorsal and ventral dentate gyrus following NBN silencing. Further exploration of PV+ interneurons and mossy cells activities highlighted NBNs integral part in preserving the excitation/inhibition balance within the hippocampus. Our findings emphasize how the neural plasticity driven by NBNs extensively modulates the hippocampus, sculpting cognitive flexibility.

neuroscience↗

bioRxiv2022

Analysis of IGHA1 and other salivary proteins post half marathon in female participants

BackgroundHigh intensity exercise, such as in marathons and triathlons, suppresses transient local and systemic immunity. Much is known about the systemic immunosuppression response, but little is known about its local response in the oral cavity, lungs, bronchial tubes, and skin. The oral cavity is an entrance for bacteria or viruses to enter the body. Saliva covers the epidermis of the oral cavity and plays an important role in the local stress response by preventing infection. In this study, we examined the properties of saliva secreted during the local stress response induced by a half marathon (HM) using quantitative proteomic analysis. MethodsThe Exercise group (ExG), 19 healthy female university students participated in (HM) race. The non-exercise group (NExG), 16 healthy female university students had not participated in the ExG. In ExG, saliva samples were collected 1h pre and 2h and 4h post HM. NExG were collected in same time interval. Saliva volume, protein concentration and relative IGHA1 expression were analyzed. In addition, 1h pre and 2h post HM saliva were analyzed by iTRAQ. The identified factors of iTRAQ, analyzed for the ExG and NExG by western blotting. ResultsWe identified kallikrein 1 (KLK1), immunoglobulin kappa chain (IgK) and cystatin S (CST4) as suppression factors, as well as immunoglobulin heavy constant alpha 1 (IGHA1), which has been reported as an immunological stress marker. KLK1 (p = 0.011), IGK (p = 0.002), and CST4 (p = 0.003) were suppressed 2 h post-HM compared to pre-HM, and KLK1 (p = 0.004) and CST4 (p = 0.006) were suppressed 4 h post-HM. There was also a positive correlation between IGHA1, IGK, and CST4 2 and 4 h post-HM. In addition, KLK1 and IGK after 2 h post-HM showed a positive correlation. ConclusionOur study demonstrated that the salivary proteome is regulated and antimicrobial proteins are suppressed post-HM. These results suggest that oral immunity was transiently suppressed post-HM. The positive correlation of each protein at 2 and 4 h post-HM suggests that the suppressed state was similarly regulated up to 4 h after a HM. The proteins identified in this study may have applications as stress markers for recreational runners and individuals who perform high- and moderate-intensity exercises in their daily lives.

physiology↗

bioRxiv2022

Discovery of S-217622, a Non-Covalent Oral SARS-CoV-2 3CL Protease Inhibitor Clinical Candidate for Treating COVID-19

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in millions of deaths and threatens public health and safety. Despite the rapid global spread of COVID-19 vaccines, effective oral antiviral drugs are urgently needed. Here, we describe the discovery of S-217622, the first oral non-covalent, non-peptidic SARS-CoV-2 3CL protease inhibitor clinical candidate. S-217622 was discovered via virtual screening followed by biological screening of an in-house compound library, and optimization of the hit compound using a structure-based drug-design strategy. S-217622 exhibited antiviral activity in vitro against current outbreaking SARS-CoV-2 variants and showed favorable pharmacokinetic profiles in vivo for once-daily oral dosing. Furthermore, S-217622 dose-dependently inhibited intrapulmonary replication of SARS-CoV-2 in mice, indicating that this novel non-covalent inhibitor could be a potential oral agent for treating COVID-19.

biochemistry↗

bioRxiv2020

Multidrug treatment with nelfinavir and cepharanthine against COVID-19

Antiviral treatments targeting the emerging coronavirus disease 2019 (COVID-19) are urgently required. We screened a panel of already-approved drugs in a cell culture model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and identified two new antiviral agents: the HIV protease inhibitor Nelfinavir and the anti-inflammatory drug Cepharanthine. In silico modeling shows Nelfinavir binds the SARS-CoV-2 main protease consistent with its inhibition of viral replication, whilst Cepharanthine inhibits viral attachment and entry into cells. Consistent with their different modes of action, in vitro assays highlight a synergistic effect of this combined treatment to limit SARS-CoV-2 proliferation. Mathematical modeling in vitro antiviral activity coupled with the known pharmacokinetics for these drugs predicts that Nelfinavir will facilitate viral clearance. Combining Nelfinavir/Cepharanthine enhanced their predicted efficacy to control viral proliferation, to ameliorate both the progression of disease and risk of transmission. In summary, this study identifies a new multidrug combination treatment for COVID-19.

microbiology↗

bioRxiv2020

Patterns of functional and structural brain information are preserved over generations

There is clear evidence of intergenerational transmission of life values, cognitive traits, psychiatric disorders, and even aspects of daily decision making. To investigate biological substrates of this phenomenon, brain has received increasing attention as a measurable biomarker and potential target for intervention. However, no previous study has quantitatively and comprehensively investigated the effects of intergenerational transmission on functional and structural brain networks from parents to their children. Here, by employing an unusually large cohort dataset, we show that patterns of functional and structural brain networks are preserved over a generation. We also demonstrate that several demographic and behavioural phenotypes have effects on brain similarity. Collectively, our results provide a comprehensive picture of neurobiological substrates of parent-child similarity, and demonstrate the usability of our dataset for investigating the neurobiological substrates of intergenerational transmission.

neuroscience↗

bioRxiv2020

Targeting STAT3 signalling using stabilised sulforaphane (SFX-01) inhibits endocrine resistant stem-like cells in ER-positive breast cancer

PURPOSEEstrogen receptor (ER) positive breast cancer is frequently sensitive to endocrine therapy. Multiple mechanisms of endocrine therapy resistance have been identified, including cancer stem-like cell (CSC) activity. Sulforaphane (SFN) has previously been shown to target CSCs but its mechanism of action is unclear. Here we investigate SFX-01, a stabilised formulation of SFN, for its effects on breast CSC activity in ER+ preclinical models and to study its mechanism. EXPERIMENTAL DESIGNCSC activity was measured by mammosphere formation efficiency (MFE), aldehyde dehydrogenase (ALDH) activity, and tumor formation using patient samples and patient-derived xenograft (PDX) tumors treated with SFX-01 alone or in combination with tamoxifen or fulvestrant. Gene expression and SFN target proteins in treated samples were assessed. RESULTSSFX-01 reduced MFE of both ER+ primary and metastatic patient samples. Both tamoxifen and fulvestrant increased MFE and ALDH activity of PDX tumors, which was reversed by combination with SFX-01. SFX-01 significantly reduced tumor initiating cell frequency in secondary transplants at limiting dilution and reduced the formation of spontaneous lung micrometastases by PDX tumors in mice. Mechanistically, we establish that both tamoxifen and fulvestrant induce STAT3 phosphorylation. SFX-01 suppressed phospho-STAT3 and SFN directly bound STAT3 in patient and PDX samples. Analysis of ALDH+ cells from endocrine-resistant patient samples revealed activation of STAT3 target genes MUC1 and OSMR, which were inhibited by SFX-01 in patient samples. Increased expression of these genes after 3 months endocrine treatment of ER+ patients (n=68) predicted poor prognosis. CONCLUSIONSOur data establish the importance of STAT3 signaling in CSC-mediated resistance to endocrine therapy and the potential of SFX-01 for improving clinical outcomes in ER+ breast cancer.

cancer biology↗

bioRxiv2019

Functional connectome linking child-parent relationships with psychological problems in adolescence

Paternal- and maternal-child relationships are associated with partly distinct psychobehavioral problems, which often manifest differently between boys and girls. In order to understand neural mechanisms underlying complicated mappings between child-parent relationship and adolescents problems, we used a dataset of early adolescents (N=93) and separately estimated the effects of paternal- and maternal-child relationships on resting-state functional connectivity and problems in boys and girls. General linear models identified the effects of paternal- and maternal-child relationships in different sets of functional connectivity, which we termed functional brain connectomes associated with paternal- and maternal-child relationship (FBCp and FBCm), respectively. Subsequent connectome-based models using these FBCs significantly predicted aggressive behaviors only for boys and internalizing problems selectively only girls. Lastly, a causal discovery method identified causal paths from daughter-mother relationship to FBCm, and then to daughters internalizing problems. These observations highlight sex-dependent mechanisms linking child-parent relationship, brain, and psychobehavioral problems in early adolescence.

neuroscience↗

bioRxiv2018

Development of the Brief Personal Values Inventory for sense of values in the Japanese general population

The Portrait Values Questionnaire (PVQ) is a widely used questionnaire for assessing sense of values; however, it has limitations, especially for children. Therefore, the present study aims to develop a questionnaire for sense of values, called the Brief Personal Values Inventory (BPVI), consisting of simple questions and a smaller number of items compared to the PVQ. We first created 12 items for the BPVI and then tested their validity and reliability in 167 Japanese general population (81 males, mean age (SD) [range]: 23.4 (8.2) [15-57] years). Each of these items was correlated with one or more values in the PVQ-57. The BPVI items covered all higher-order values in Schwartzs theory (Openness to Change, Self-Enhancement, Conservation, and Self-Transcendence). In sum, the BPVI has an acceptable criterion-related validity and corresponds to higher-order values in Schwartzs value theory. The BPVI is suitable for a reliable and direct comparison of sense of values between children and adults, which may be useful for elucidating the developmental pathway of personal sense of values.

scientific communication and education↗