Biology subjects

Tanaka, S.

Publications and source records attributed to Tanaka, S..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Deciphering spatial heterogeneity of patient-derived organoids of colorectal tumors for drug discovery

The spatial organization of tumors is critical for drug development, as spatial heterogeneity in cancer cells and the tumor microenvironment can present a significant barrier to effective therapies. Patient-derived tumor organoids (PDOs) offer promising platforms to study tumor biology and for drug development. Previous studies have demonstrated that PDOs can maintain the genomic/clonal heterogeneity of tumors, as well as expression heterogeneity. However, the spatial heterogeneity of PDOs and its correlation with the original tumors remains unclear. We propose an integrated pipeline combining spatial transcriptomics and phenotypic analyses of PDOs to capture and track spatial heterogeneity. This platform integrates multiplexed organoid cultures with imaging-based spatial transcriptomics and analysis at single organoid resolution. We validate the platform by comparing results with non-spatial single-cell transcriptomic data and spatial transcriptomic analysis of donor tumors. The combination of ex vivo PDOs and spatial transcriptomics could open novel avenues for developing drugs.

cancer biology↗

bioRxiv2026

Size-invariant aerobic scope across ontogeny in a giant deep-sea scavenger

Aerobic scope is the aerobic metabolism left after maintenance costs are met, and it sets a simple limit on how much oxygen-dependent activity an animal can support. In many aquatic animals, this margin changes with body size because resting and active metabolic rates do not always scale in the same way. Large deep-sea scavengers are interesting in this respect because they live where food is sparse and unpredictable, but they must still move when carrion or food cues appear. We measured resting metabolic rate (RMR) and post-exercise peak oxygen consumption, here referred to as active metabolic rate (AMR), in the giant isopod Bathynomus doederleini across a body-mass range of 1.7-48.4 g using intermittent-flow respirometry at 10 {degrees}C. RMR and AMR both increased with body mass and had similar scaling exponents. As a result, factorial aerobic scope (FAS = AMR/RMR) did not change with body mass (median FAS = 2.83). A residual analysis also showed that mass-corrected RMR was not significantly related to mass-corrected AMR. Thus, individuals with relatively high maintenance metabolism did not necessarily have higher post-exercise aerobic capacity. These results show that exercise-induced aerobic scope was maintained across ontogeny in this deep-sea scavenger. They also show that body size and individual metabolic phenotype provide different information: body size explained the shared increase in RMR and AMR, whereas residual variation did not show a strong link between the two traits.

physiology↗

bioRxiv2026

Protein folding stress shapes microglial phenotype in progressive supranuclear palsy

Microglia play a pivotal role in neurodegeneration, yet their response to tau pathology remains incompletely understood. Through single-nucleus RNA sequencing of A{beta} plaque-free frontal cortex from 4R tauopathy progressive supranuclear palsy (PSP) brains, we reveal a distinct transcriptional reprogramming of homeostatic microglia. PSP microglia exhibit pronounced protein-folding and ER-stress signatures, elevated homeostatic and MHC class II gene expression, and attenuated cytoskeletal, motility, and interferon-related programs, accompanied by reduced inferred intercellular communication. Neuropathological analysis corroborates a shift toward highly ramified morphologies and increased MHC class II positivity in PSP cortex. In HMC3 cells, pharmacological induction of protein-folding stress recapitulates this phenotype, driving homeostatic gene upregulation and morphological transition to process-bearing forms. We define this protein-folding-stress-associated microglial (PSAM) state as a PSP-linked phenotype mechanistically distinct from disease-associated microglia (DAM), highlighting ER stress as a key driver of microglial remodeling in tauopathies.

neuroscience↗

bioRxiv2026

Atomistic simulation study reveals transduction of mechanical work generated by ATP hydrolysis onto myosin II functional loops

Myosin II is a paradigm of biological molecular energy transducers that convert the chemical energy of ATP, via hydrolysis, into mechanical work with high efficiency in living cells. The physicochemical mechanisms underlying energy conversion by myosin II have been extensively investigated. However, a remaining challenge concerns the initial stage of the ATP hydrolysis cycle, specifically the conversion of ATP-to-ADP:Pi, because of technical difficulties in directly and seamlessly observing atomic trajectories during this early step and the subsequent processes. Here, we simulate the consequences of the chemical reaction by switching force field parameters between reactant and product systems within classical molecular dynamics simulations. We consider two possible ATP hydrolysis mechanisms in which either singly protonated (Pi{superscript 2}-) or doubly protonated (Pi-) inorganic phosphate is produced. Our results indicate that, in both Pi-generating processes, the kinetic energy supplied by conversion of ATP-to-ADP:Pi increases only transiently, whereas myosin functional loops store several kcal/mol of potential energy. Meanwhile, the amount of potential energy stored in the Pi{superscript 2}--producing reaction is approximately five-fold larger than that in the Pi--producing reaction. Our analysis indicates that this difference emerges when ATP-derived mechanical work is transmitted into the functional loops via rearrangement of intermolecular hydrogen bonds with the hydrolysis products. Notably, these steric interactions remain stably established even when the kinetic energy input associated with ATP-to-ADP:Pi conversion is actively quenched. We therefore propose that transient storage of ATP-derived mechanical work as atomic-scale conformational strain within myosin molecules constitutes a critical step for efficient conversion of ATP chemical energy into mechanical work under conditions of intracellular thermal noise. SignificanceMyosin II converts chemical energy released by ATP hydrolysis into mechanical work with exceptionally high efficiency, even in the presence of substantial thermal fluctuations in living systems. It has long been proposed that release of inorganic phosphate (Pi) from myosin II is a critical step for efficient energy transfer. However, this prevailing view has been challenged by recent state-of-the-art experimental observations, necessitating a reexamination of the chemical steps responsible for ATP-derived energy storage. Here, we employ atomistic molecular dynamics simulations specifically designed to capture key aspects of ATP hydrolysis. We demonstrate that ATP hydrolysis increases the potential energy of myosin II functional loops while Pi remains bound, and that this increase occurs independently of heat release associated with the reaction. Together, these findings identify an alternative mechanism for energy retention and emphasize the intrinsic robustness of myosin II as a highly efficient molecular motor.

biophysics↗

bioRxiv2025

Altered Motor Gamma Activity and Hemispheric Lateralisation Reflect Perinatal Maturity in Preterm Children during Motor Control

Preterm birth, defined as delivery before 37 weeks of gestation, is associated with differences in neurodevelopment and an increased likelihood of motor challenges that may persist throughout childhood. However, the neurophysiological correlates of these motor differences remain insufficiently understood. Oscillatory activity in the primary motor cortex is closely linked to motor execution, yet motor-related oscillations have rarely been examined in children born preterm. In this cross-sectional observational study, we investigated motor-related gamma oscillations in 5- to 7-year-old children using a child-customised magnetoencephalography system. Nineteen children born full-term and 18 children born preterm of comparable age performed a child-friendly dominant-hand finger movement task. Movement-related gamma activity was quantified from bilateral precentral gyrus regions used as anatomical proxies for the primary motor cortices. The preterm group showed longer mean response times and greater intra-individual response-time variability than the full-term group (P = 0.003 and P = 0.030, respectively). Contralateral gamma power was also lower in the preterm group (full-term: 59.89 {+/-} 28.87%; preterm: 37.97 {+/-} 25.82%; t(35) = 2.43, P = 0.020, Cohen's d = 0.80). A significant Group x Hemisphere interaction (F(1, 35) = 13.36, P < 0.001, partial 2 = 0.276) further indicated differences in the hemispheric organisation of gamma activity between groups. The gamma laterality index was also lower in children born preterm (full-term: 0.24 {+/-} 0.21; preterm: -0.11 {+/-} 0.37; t(26.4) = 3.51, P = 0.002, Cohen's d = 1.17), consistent with reduced contralateral dominance. Across the whole sample, greater contralateral gamma lateralisation was associated with higher scores on the Hand Movements subtest of the Kaufman Assessment Battery for Children ({rho} = 0.40, P = 0.014, false discovery rate-adjusted q = 0.042) and earlier independent walking ({rho} = 0.57, P < 0.001, q = 0.002). The association with independent walking was also observed within the preterm group ({rho} = 0.78, P < 0.001, q = 0.002). These findings suggest that reduced contralateral gamma power and reduced hemispheric lateralisation in children born preterm may reflect differences in the developmental organisation of motor cortical networks. This study provides new insight into motor cortical organisation and its relationship with motor development following preterm birth.

neuroscience↗

bioRxiv2025

Sox4 in Treg Cells Suppresses IL-10 Production via c-Maf Degradation and Exacerbates Type 2 Inflammation

The anti-inflammatory cytokine interleukin-10 (IL-10) produced by regulatory T (Treg) cells plays a crucial role in regulating allergic airway inflammation. However, the mechanisms governing IL-10 production in Treg cells remain unclear. In this study, we first identified Sox4 as a gene whose expression is down-regulated in IL-10-producing Treg cells. Comprehensive gene expression profiling of Sox4-deficient Treg cells and Sox4-overexpressing Treg cells revealed specific downregulation of Il10 and Ctla4 by Sox4. Sox4-deficient Treg cells exhibited increased IL-10 production and CTLA-4 expression both in vitro and in vivo and strongly suppressed Th2 cell proliferation compared with Sox4-expressing Treg cells. In a house dust mite (HDM)-induced asthma model, Treg-specific Sox4-deficient (Sox4-cKO) mice exhibited IL-10-dependent reductions in eosinophilic inflammation and Th2 cell infiltration in the airways. A comparison of Sox4-cKO and wild-type Treg cells in the same inflamed environment in mixed bone marrow chimeric mice with HDM-induced asthma revealed that Sox4-mediated suppression of c-Maf is cell-intrinsic. In addition, overexpression of Sox4 in Treg cells repressed the activation of c-Maf-regulated chromatin regions, including those around the Il10 and Ctla4 loci. Moreover, Sox4-induced suppression of IL-10 and CTLA-4 in Treg cells was rescued by forced expression of c-Maf. While Sox4 did not significantly affect Maf mRNA levels, Sox4 degraded c-Maf proteins in Treg cells through its 33 C-terminal residues. Via a domain distinct from its C-terminus, Sox4 physically interacted with c-Maf, subsequently facilitating its degradation through a ubiquitin-proteasome pathway. These findings elucidate a mechanism by which Sox4 influences the asthmatic responses by regulating the c-Maf/IL-10 axis in lung Treg cells.

immunology↗

bioRxiv2025

Induction of meningioma stem signature via hydrogel reprogramming and application of meningioma stem cell marker CXCR4 to pathological diagnosis and treatment.

BackgroundsMeningioma accounts for about 40% of brain tumors, but there was no effective treatment for recurrent or inoperable cases. We have previously found that when cancer cells are cultured on certain hydrogels, cancer stem cells are efficiently induced in various cancer types and we named this process as hydrogel activated reprogramming (HARP) phenomenon. In this study, we aimed to identify a key molecule that induced meningioma stem cells via hydrogels. MethodsMeningioma cells cultured on hydrogels were analyzed for expression of regular stem cell markers and their tumor genericity. Microarray analysis was performed to identify meningioma stem cell specific markers and to examine the application of such marker molecules as a therapeutic targets or pathological diagnosis for grading. ResultsRegular stem cell markers such as Nanog, and Oct3/4 were induced by culturing meningioma cells on hydrogels, and comprehensive gene expression analysis identified molecules involved in cancer stem cell activity. Among them, CXCR4 was selected as a therapeutic target molecule. Stimulation of CXCR4 via CXCL12 led to an increase in stem cell markers. In human meningioma pathological specimens and cultured cell lines, there was a correlation between CXCR4 expression levels and NF2 mutations and/or deletions. CXCR4 immunohistochemistry also detected along with the brain invasion. Thus, CXCR4 immunohistochemistry may be useful to suggest typical CNS WHO grade 1 meningioma, that do not require molecular analysis. ConclusionsWe have defined meningioma stem cell signature via HARP phenomenon and identified CXCR4 with biological significance as being diagnostic target. Key PointsO_LIWe induce meningioma stem signature via Hydrogel activated reprogramming (HARP) phenomena. C_LIO_LIWe identified CXCR4 as a candidate molecule as stemness marker and therapeutic target. C_LIO_LITranslational research using pathological specimens reveal CXCR4 immunohistochemistry has been shown to play an auxiliary role in the diagnosis of meningiomas. C_LI Importance of the StudyIn addition to morphology, immunohistochemistry and gene alteration are being adopted as diagnostic criteria for CNS tumors. From CNS5 onwards, epigenetic changes such as methylation analysis are being adopted as diagnostic criteria. We induced epigenetic changes in meningioma cells and induced cancer stemness, and this technique will be of great importance in the research and diagnosis of meningioma. In addition, microarray analysis was used to select CXCR4 from the molecules that increased simultaneously during stem cell induction on the three hydrogels, and further analysis revealed that CXCR4 immunostaining may indicate the distribution of meningioma stem cells, also making it useful for diagnosis. This report will contribute to the advancement of meningioma research and diagnosis by conducting basic research and using histopathological specimens.

bioengineering↗

bioRxiv2025

Intraspecific differences in habitat depth in a deep-sea isopod, Bathynomus doederleini (Crustacea: Isopoda: Cirolanidae), off the west coast of Kyushu, Japan

The giant deep-sea isopod, Bathynomus doederleini, is a benthic scavenger distributed in the northwestern Pacific. Despite its ecological importance, little is known about its habitat use and intraspecific variation in body size in relation to depth. In this study, we examined the habitat depth, size structure, and distributional limits of B. doederleini off the western coast of Kyushu, Japan, using baited traps deployed at depths ranging from 151 to 821 m. A total of 1,152 individuals were collected, with the highest catch per unit effort (CPUE) observed between 300 and 500 m. CPUE declined sharply below 700 m, likely due to thermal constraints and interspecific competition. Body size distribution varied significantly with depth: minimum body size increased with depth, while maximum body size remained constant. Smaller individuals were more abundant in shallower, warmer waters, suggesting ontogenetic habitat segregation possibly driven by metabolic and competitive factors. No brooding individuals were captured, supporting previous findings that reproductive females avoid baited traps. These results suggest that B. doederleini forms a reproductively active population in the East China Sea, with ecological adaptations to thermal conditions and depth-related niche partitioning. This study highlights the importance of trap type and environmental gradients in understanding deep-sea species ecology.

ecology↗

bioRxiv2025

A non-spike nucleocapsid R204P mutation in SARS-CoV-2 Omicron XEC enhances inflammation and pathogenicity

The global circulation of SARS-CoV-2 in human populations has driven the emergence of Omicron subvariants, which have become highly diversified through recombination. In late 2024, SARS-CoV-2 Omicron XEC variant emerged from the recombination of two JN.1 progeny, KS.1.1 and KP.3.3, and became predominant worldwide. Here, we investigated virological features of the XEC variant. Epidemic dynamics modeling suggested that spike substitutions in XEC mainly contribute to its increased viral fitness. Additionally, four licensed antivirals were effective against XEC. Although the fusogenicity of XEC spike is comparable to that of the JN.1 spike, the intrinsic pathogenicity of XEC in hamsters was significantly higher than that of JN.1. Notably, we found that the nucleocapsid R204P mutation of XEC enhanced inflammation through NF-{kappa}B activation. Recent studies suggest that the evolutionary potential of spike protein is reaching its limit. Indeed, our findings highlight the critical role of non-spike mutations in the future evolution of SARS-CoV-2.

microbiology↗

bioRxiv2025

Human TIMELESS, a potential circadian clock regulator, plays an essential role in survival and reawakening of metastasis-initiating cells in bone

Bone metastasis is becoming increasingly common globally. In such cases, cancer cells disseminate from the primary site to bone, subsequently entering a dormant state. Following a certain incubation period, the cells reawaken and grow, forming a metastatic mass. These dormant cells are called metastasis-initiating cells (MICs), but their survival and reawakening are poorly understood. Here, we established an in vivo MIC-reawakening mouse model in bone. Microarray analysis demonstrated enrichment for mitochondrial oxidative phosphorylation (OXPHOS) and fatty acid synthesis in isolated MICs. In addition, transcriptional regulator TIMELESS was identified as an independent poor prognostic factor by using clinical transcriptomic datasets, which was validated by immunostaining on 209 breast cancer cases. TIMELESS-deficient breast, prostate, and bladder cancer cell lines exhibited reduced viability and MIC reawakening in bone. Single-cell analysis on the epigenetic landscape of MICs revealed that motif activities of CLOCK and BMAL1/ARNTL were enhanced in a cluster with increased TIMELESS accessibility scores. As TIMELESS regulates stemness through the OXPHOS metabolic state, an inhibitor targeting the metabolic pathway, MP-A08, was identified to suppress MIC reawakening and growth in bone more efficiently than cisplatin. These results suggest that TIMELESS regulates survival and reawakening in MICs and MP-A08 could contribute to adjuvant therapeutic strategies.

cancer biology↗

bioRxiv2025

Floating offshore wind farms cause Japanese horse mackerel to congregate

Floating offshore wind farms (F-OWFs) are becoming key components of renewable energy production, yet their ecological impacts on marine ecosystems remain largely unexplored. Using environmental DNA (eDNA) analysis in the East China Sea, this study investigated the tendency for Japanese horse mackerel (Trachurus japonicus) to congregate beneath F-OWFs. Water samples were collected at stations near an F-OWF and control stations farther away at various depths and seasons. A total of 115 samples were analyzed, and eDNA of T. japonicus was detected in 83% of all samples. eDNA concentrations were significantly higher near an F-OWF (F-OWF stations) than at control stations. The highest recorded eDNA concentration reached 2,280 copies/L at an F-OWF station, whereas the maximum concentration at control stations was 783 copies/L. Seasonal variations were also observed, with lower concentrations in summer and higher concentrations from autumn to spring. Generalized linear model (GLM) analysis further revealed that wind turbines had a significant influence on eDNA concentration, whereas other environmental variables, such as water temperature and depth, were not significant. These findings suggest that F-OWFs may function as artificial reefs, providing habitat for commercially important fish and influencing fish distributions at both spatial and temporal scales. However, potential conflicts with fisheries due to spatial restrictions, displacement of fishery resources, and increased navigation costs necessitate further long-term ecological and socio-economic assessments. Integrating eDNA monitoring with traditional survey methods, such as acoustic surveys and ROV observations, is crucial for coexistence of adaptive offshore wind farm management and sustainable fisheries. Future research should also explore the long-term effects of F-OWFs on fish assemblages and biodiversity to support evidence-based decision-making for offshore energy development.

ecology↗

bioRxiv2025

Distribution of myogenic stem cell activator, hepatocyte growth factor, in skeletal muscle extracellular matrix and effect of short-term disuse and reloading

Hepatocyte growth factor (HGF) is a key myogenic stem cells (satellite cells) activator, that resides in the extracellular matrix (ECM). However, HGF distribution in the ECM varies depending on the muscle fiber type. Furthermore, aging impedes the binding of HGF to its receptors due to nitration by peroxynitrite (ONOO-). Though oxidative stress increases rapidly during muscle disuse atrophy, satellite cells are rapidly activated upon reloading. In this study, we investigated the distribution of HGF in the ECM in various muscle fiber types, and examined nitration of HGF in disuse and reloading models. Immunofluorescence staining was performed on the soleus (Sol), plantaris (Pla), and gastrocnemius (Gas) muscles of 10-week-old mice. Three mice were used to assess HGF distribution, while 12 mice, divided into control, disuse, and reloading groups were used for qualitative evaluation of nitrated HGF (nitroHGF). In Sol muscle, type IIa and IIx muscle fibers exhibited higher HGF distribution in the ECM (70.7{+/-}1.9% and 63.9{+/-}2.6%, respectively) than type I fibers (28.0{+/-}1.7%; p<0.001). In Pla and Gas muscle, type IIa (65.4{+/-}2.3% and 70.3{+/-}2.2%, respectively) and type IIx fibers (55.3{+/-}1.8% and 61.4{+/-}3.2%, respectively) had significantly higher HGF distribution in the ECM than type IIb fibers (13.1{+/-}1.8% and 5.9{+/-}1.6%; p<0.001, respectively). The amount of nitroHGF increased in the disuse group compared to that in the control group but decreased in the reloading group compared to that in the disuse group. This preferential HGF distribution around type IIa and IIx muscle fibers indicates a distinct mechanism for satellite cell activation, differing from the satellite cell-rich environment associated with type I fibers and the lower HGF association with type IIb fibers. Disuse-induced HGF nitration may inhibit satellite cell activation. Reloading likely triggers mechanisms that counteract nitration, enabling satellite cell reactivation in young muscle.

biochemistry↗

bioRxiv2025

Evolution of BA.2.86 to JN.1 reveals functional changes in non-structural viral proteins are required for fitness of SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19), is still circulating among humans, leading to the continuous evolution. SARS-CoV-2 Omicron JN.1 evolved from a distinct SARS-CoV-2 lineage, BA.2.86, spread rapidly worldwide. It is unclear why BA.2.86 did not become dominant and was quickly replaced by JN.1, which possesses one amino acid substitution in the spike protein (S:L455S) and two in the non-spike proteins NSP6 and ORF7b (NSP6:R252K and ORF7b:F19L) compared to BA.2.86. Here, we utilized recombinant viruses to elucidate the impact of these mutations on the virological characteristics of JN.1. We found that the mutation in the spike attenuated viral replication, but the non-spike mutations enhanced replication, suggesting the mutations in the non-spike proteins compensate for the one in the spike to improve viral fitness, as the mutations in the spike contribute to further immune evasion. Our findings suggest that functional changes in both the spike and non-spike proteins are necessary in the evolution of SARS-CoV-2 to enable evasion of adaptive immunity within the human population while sustaining replication. IMPORTANCEBecause the spike protein is strongly associated with certain virological properties of SARS-CoV-2, such as immune evasion and infectivity, most previous studies on SARS-CoV-2 variants have focused on spike protein mutations. However, the non-spike proteins also contribute to infectivity, as observed throughout the evolution of Omicron subvariants. In this study, we demonstrate a "trade-off" strategy in SARS-CoV-2 Omicron JN.1 in which the reduced infectivity caused by spike mutation is compensated by non-spike mutations. Our results provide insight into the evolutionary scenario of the emerging virus in the human population.

microbiology↗

bioRxiv2025

Evolutionary and structural basis of SLAM utilization in morbilliviruses - Its implications for host range and cross-species transmission

Morbilliviruses, including measles virus (MV), canine distemper virus (CDV), and cetacean morbillivirus, pose a significant threat to humans and animals. While the host range of morbilliviruses is generally well-defined, severe cross-species transmission events also have been reported. Their entry into immune cells, the primary targets of morbilliviruses, relies on the signaling lymphocytic activation molecule (SLAM), a receptor whose species-specific variations influence viral host range. However, the extent to which SLAM diversity is a barrier to cross-species transmission remains poorly understood. In this study, we systematically investigated SLAM-mediated host specificity. We found that most morbilliviruses efficiently utilize SLAM from multiple host species, except for human SLAM. Among the morbilliviruses tested, only MV efficiently utilized human SLAM. Bats are natural reservoirs for many zoonotic viruses. Recent discoveries of novel morbilliviruses in bats provide new insights into morbillivirus evolution. Bats may have played a significant role in morbillivirus evolution because bat (Myotis) SLAM also functioned as an efficient receptor for multiple morbilliviruses. Unlike other morbilliviruses, MV utilized Myotis bat SLAM inefficiently. We conducted an MV adaptation experiment with Myotis bat SLAM to better understand SLAM recognition by morbilliviruses. MV readily adapted to utilize Myotis bat SLAM by acquiring a single N187Y mutation in its hemagglutinin protein, and computational structural modeling and fragment molecular orbital calculations with molecular dynamics simulations revealed key interaction changes that facilitated MVs adaptation to Myotis bat SLAM. These findings highlight the adaptability of morbilliviruses in utilizing diverse animal SLAMs. Notably, hypothetical ancestral SLAMs reconstructed in this study acted as universal receptors for all morbilliviruses. These results reinforced that morbillivirus receptor usage is primarily supported by evolutionarily conserved structural features of SLAM, highlighting a molecular basis that enables morbilliviruses to rapidly adapt to diverse animal SLAMs. Author SummaryOur study explores how viruses in the genus morbillivirus, such as measles virus, canine distemper virus, and rinderpest virus, which are notorious for deadly outbreaks in humans and animals, can jump between species. The host range of morbilliviruses is significantly influenced by a receptor molecule on cell surfaces known as the signaling lymphocytic activating molecule (SLAM). By examining SLAMs from various animals, including humans, dolphins, dogs, seals, and bats, we observed how these viruses can infect or adapt to infect different hosts. We found that in some cases slight differences in SLAM may act as initial barriers to cross-species transmission. However, these viruses rapidly overcome such barriers, showing a remarkable ability to adapt. Our research highlights the importance of monitoring these viruses to predict and prevent potential cross-species infections, which is crucial for protecting public health and animal welfare over time.

microbiology↗

bioRxiv2025

The rice ethylene receptor OsERS1 negatively regulates the shoot growth and salt tolerance in rice seedlings

Ethylene is a gaseous plant hormone that regulates various aspects of growth and development. It promotes shoot growth in etiolated rice seedlings, which is crucial for seedling establishment and has significant agricultural implications. Of the five ethylene receptors in rice, OsERS1 is the most abundantly expressed in seedlings. Therefore, we investigated the localization and role of OsERS1 in shoot growth. When expressed in rice protoplasts, OsERS1 was localized in the endoplasmic reticulum. Knockout mutants of OsERS1 exhibited enhanced shoot growth in etiolated seedlings under normal and ethylene-treated conditions. Additionally, the induction of ethylene-responsive genes was increased in the mutants, indicating an elevated ethylene response due to OsERS1 knockout. The mutants also showed increased salt tolerance. In conclusion, our findings suggest that OsERS1 negatively regulates shoot growth and salt tolerance in etiolated rice seedlings.

plant biology↗

bioRxiv2025

Gamma-aminobutyric acid treatment reduces estradiol-stimulated breast cancer cell growth and estradiol-induced breast tumorigenesis

Gamma-aminobutyric acid (GABA) is a non-protein amino acid and contained in various foods, such as fruits and vegetables. Although various health benefits of GABA have been reported, GABA seems to have unidentified functions. In this study, we first show increase in intracellular GABA level in GABA-treated breast cancer cell lines, MCF-7 and T-47D, in amino acid analyses and immunofluorescence. In our experimental condition, GABA treatment reduced estradiol-stimulated cell growth in these cell lines. In addition, we performed mouse early breast cancer induction model system to investigate GABA function in mammary dysplasia formation. In the results, GABA administration reduced dysplasia formation, suggesting that GABA prevents breast tumorigenesis. This study demonstrates a novel function of GABA to maintain normal breast tissues.

bioengineering↗

bioRxiv2024

Deep Learning-Based Inference of Uterine Contractions from Maternal ECG

BackgroundPreterm birth and stillbirth have multifaceted causes, many of which remain unknown. Factors such as maternal age, sexually transmitted infections, and genetic abnormalities are notably implicated. Globally, there has been minimal improvement in preterm birth rates, leading to substantial economic losses and underscoring the need for innovative approaches. ObjectiveThis study aims to analyze and detect uterine contractions by applying deep learning techniques to physiological data derived from maternal electrocardiograms (ECGs). Leveraging ECGs, which are easily obtainable from wearable devices, allows for effective and convenient monitoring of uterine contractions outside clinical settings. Since uterine contractions are a critical indicator for assessing the risk of preterm birth, our algorithm has the potential to facilitate early identification of high-risk individuals, thereby contributing to timely interventions and improved maternal-fetal outcomes. MethodsParticipants meeting all inclusion criteria and none of the exclusion criteria were recruited from patients admitted to or attending outpatient services at Saintpaulia Misao Ladies Hospital in Gifu, Japan, between December 6, 2023, and July 31, 2024. Our deep learning model was developed using maternal ECG data, uterine contraction waveforms obtained from cardiotocograms (CTGs). The collected data were divided into training and evaluation datasets. The AI-generated uterine contraction waveforms from the developed model were compared with ground truth labels obtained from the fetal monitoring devices. This study was reviewed and approved by the Ethics Committee of the Graduate School of Medicine at Gifu University and was conducted as a collaborative research effort with nonat Inc. (the lead research institution) and Saintpaulia Misao Ladies Hospital (joint research institution). ResultsFinally, 73 participants took part in this study, and 57 datasets were used for algorithm development and evaluation. Multiple measurements were taken on the same subjects on different days only with their consent. Our analysis demonstrated a strong correlation between the uterine contraction waveforms estimated by the developed model and the ground truth waveforms from CTGs, achieving an average correlation across all evaluation data (Pearson correlation coefficient = 0.53). ConclusionThis is the worlds first trial to detect uterine contractions from maternal ECGs using deep learning algorithms. In this study, we successfully developed a deep learning algorithm capable of accurately inferring uterine contraction waveforms from maternal ECGs. Given that ECGs can be easily obtained using wearable devices, this approach may provide healthcare professionals with objective and precise information on uterine contractions--a crucial indicator of preterm labor--even in resource-limited settings outside hospital environments.

physiology↗

bioRxiv2024

High-Recovery Desalting Tip Columns for a Wide Variety of Peptides in Mass Spectrometry-based Proteomics

In mass spectrometry-based proteomics, loss-minimized peptide purification techniques play a key role in improving sensitivity and coverage. We have developed a desalting tip column packed with thermoplastic polymer-coated chromatographic particles, named ChocoTip, to achieve high recoveries in peptide purification by pipette-tip-based LC with centrifugation (tipLC). ChocoTip identified more than twice as many peptides from 20 ng of tryptic peptides from Hela cell lysate compared to a typical StageTip packed with chromatographic particles entangled in a Teflon mesh in tipLC. The high recovery of ChocoTip in tipLC was maintained for peptides with a wide variety of physical properties over the entire retention time range of the LC/MS/MS analysis, and was especially noteworthy for peptides with long retention times. These excellent properties are attributable to the unique morphology of ChocoTip, in which the thermoplastic polymer covers the pores, thereby inhibiting irreversible adsorption of peptides into mesopores of the chromatographic particles. ChocoTip is expected to find applications, especially in clinical proteomics and single-cell proteomics, where sample amounts are limited.

biochemistry↗