Biology subjects

Ueno, K.

Publications and source records attributed to Ueno, K..

13 recordsLinked to original sources

bioRxiv2026

Novel cell wall-associated genes that enable Cryptococcus neoformans to evade dectin-1-mediated innate immune recognition.

The fungal pathogen Cryptococcus neoformans contains about 200 {micro}g of {beta}-1,3-glucan (1,3BG) per 1 mg of dry cell weight when grown under standard culture conditions (YPD medium at 30 {degrees}C under aerobic conditions). However, 1,3BG exposure is tightly suppressed, even in capsule-deficient strains, allowing the fungus to evade recognition by the immune receptor dectin-1 and anti-1,3BG antibodies. Although other pathogenic fungi mask 1,3BG with -1,3-glucan (1,3AG) to evade dectin-1 recognition, the factors responsible for 1,3BG masking and dectin-1 evasion in C. neoformans remain incompletely understood. To identify capsule-independent 1,3BG masking and dectin-1-evasion factors, we generated a series of cell wall-related gene deletion strains in the capsule-deficient strain cap59{Delta} by using CRISPR-Cas9 and screened for mutants that failed to evade dectin-1 binding. We found eight deletants (cap59{Delta}/mpk1{Delta}, cap59{Delta}/chs3{Delta}, cap59{Delta}/kre5{Delta}, cap59{Delta}/crz1{Delta}, cap59{Delta}/kre6{Delta}/skn1{Delta}, cap59{Delta}/hxl1{Delta}, cap59{Delta}/uge1{Delta}, and cap59{Delta}/ugt1{Delta}) that exhibited increased binding to dectin-1 or anti-1,3BG antibody, or both. As a similar phenotype was not observed in cap59{Delta}/ags1{Delta}, 1,3AG-mediated masking of 1,3BG appears to play a limited role in C. neoformans. These eight deletants induced significantly greater secretion of IL-6 and IL-1{beta} from dendritic cells (DCs) than did cap59{Delta}. This enhanced inflammatory response was markedly attenuated in dectin-1-deficient DCs, indicating that the increased immunogenicity was driven by 1,3BG exposure and subsequent dectin-1 recognition. Collectively, these findings demonstrate that multiple genes involved in maintaining cell wall integrity--including those involved in {beta}-1,6-glucan and chitosan biosynthesis--are essential for regulating 1,3BG exposure and enabling C. neoformans to evade dectin-1-mediated immune recognition. HighlightsO_LIWe identified new capsule-independent {beta}-1,3-glucan-masking genes in C. neoformans C_LIO_LIGene deletants had higher dectin-1 deposition than parental acapsular cap59{Delta} C_LIO_LIDeletion of these genes enhanced IL-6 and IL-1{beta} secretion by dendritic cells C_LIO_LIThe enhanced cytokine response was suppressed in dendritic cells lacking dectin-1. C_LIO_LIDeletant strains may serve as new whole-cell antigens for cryptococcal vaccines C_LI

microbiology↗

bioRxiv2026

Large-scale meta-analysis of over one million individuals reveals the genetic architecture of 127 complex traits in East Asian populations

Genome-wide association studies (GWASs) have disproportionately focused on European (EUR) populations, limiting the characterization of genetic architecture in other ancestries. To address this imbalance, we integrated large-scale biobanks from Japan, Korea, Taiwan, and China to perform the largest phenome-wide meta-analysis to date in East Asian (EAS) populations, encompassing over one million individuals across 127 complex traits. We identified 8,010 previously unreported associations and observed substantial genetic sharing across EAS subpopulations, while also detecting cohort-specific heterogeneity within the broader EAS context. Transethnic analyses revealed moderate genetic correlations between EAS and EUR populations, indicating both shared and ancestry-specific components of disease risk. Pleiotropy analyses highlighted prominent signals within the HLA region, supported by protein-protein interaction connectivity and immune-related pathway enrichment. Decomposition of genome-wide association matrices further uncovered structured cross-trait architectures, revealing a predominantly shared polygenic backbone driven by metabolic, biochemical, and anthropometric traits, together with two discrete latent components enriched for immune-related processes. Together, our findings refine the genetic architecture of complex traits in East Asian populations at unprecedented scale and clarify the balance between shared and population-specific determinants of human diseases.

genetics↗

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

The glomerulus as a selective gate for tumor-derived extracellular vesicles in urine

Urinary small extracellular vesicles (sEVs), which can reflect systemic conditions, hold great promise for non-invasive cancer diagnostics, yet the mechanism by which tumor-derived sEVs reach urine remains unclear. Here, we demonstrate that the glomerulus actively transcytoses circulating tumor-derived sEVs into urine. Using CRISPR gRNA-tagged glioma sEVs and bioluminescent/fluorescent GeNL-tagged lung and pancreatic cancer sEVs, we tracked their journey from tumors to urine in multiple mouse models. In vivo and in vitro analyses revealed endocytic uptake and transcytotic release by glomerular cells, accompanied by changes in sEV size and surface composition. GeNL-tagged sEVs consistently showed higher signals in urine than plasma, indicating selective excretion. These findings redefine the glomerulus as a dynamic regulator of EV processing and establish a mechanistic foundation for urinary liquid biopsy.

cancer 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

Monoterpene glucosides accumulated in Eustoma grandiflorum roots promote hyphal branching in arbuscular mycorrhizal fungi

Host plant-derived strigolactones trigger hyphal branching in arbuscular mycorrhizal (AM) fungi, initiating a symbiotic interaction between land plants and AM fungi. However, our previous studies revealed that gibberellin-treated Eustoma grandiflorum (Gentianaceae) activates rhizospheric hyphal branching in AM fungi using unidentified molecules other than strigolactones. In this study, we analyzed independent transcriptomic data of E. grandiflorum and found that the gentiopicroside (GPS) and swertiamarin (SWM), which are characteristic monoterpene glucosides in Gentianaceae, were highly biosynthesized in gibberellin-treated E. grandiflorum roots. Moreover, these metabolites considerably promoted hyphal branching in the Glomeraceae AM fungi Rhizophagus irregularis and R. clarus. GPS treatment also enhanced R. irregularis colonization of the monocotyledonous crop Allium schoenoprasum. Interestingly, these metabolites did not provoke the germination of the root parasitic plant Orobanche minor. Altogether, our study unveiled the crucial role of GPS and SWM in activating the symbiotic relationship between AM fungi and E. grandiflorum.

plant biology↗

bioRxiv2022

Autophagy promotes organelle clearance and organized cell separation of living root cap cells in Arabidopsis thaliana

The root cap is a multi-layered tissue covering the tip of a plant root that directs root growth through its unique functions such as gravity-sensing and rhizosphere interaction. To prevent damages from the soil environment, cells in the root cap continuously turn over through balanced cell division and cell detachment at the inner and the outer cell layers, respectively. Upon displacement toward the outermost layer, columella cells at the central root cap domain functionally transition from gravity-sensing cells to secretory cells, but the mechanisms underlying this drastic cell fate transition are largely unknown. By using live-cell tracking microscopy, we here show that organelles in the outermost cell layer undergo dramatic rearrangements, and at least a part of this rearrangement depends on spatiotemporally regulated activation of autophagy. Notably, this root cap autophagy does not lead to immediate cell death, but rather is necessary for organized separation of living root cap cells, highlighting a previously undescribed role of developmentally regulated autophagy in plants. Summary statementTime-lapse microscope imaging revealed spatiotemporal dynamics of intracellular reorganization associated with functional transition and cell separation in the Arabidopsis root cap and the roles of autophagy in this process.

plant biology↗

bioRxiv2021

Identification of Lagopus muta japonica plant food resources in the Northern Japan Alps using DNA metabarcoding

DNA metabarcoding was employed to identify plant-derived food resources of the Japanese rock ptarmigan (Lagopus muta japonica), registered as a natural living monument in Japan, in the Northern Japanese Alps in Toyama Prefecture, Japan, in July to October, 2015-2018. By combined use of rbcL and ITS2 local databases of 74 alpine plant species found in the study area, a total of 43 plant taxa were identified and could be assigned to 40 species (93.0%), two genera (4.7%), and one family (2.3%). Rarefaction analysis of each sample collection period showed that this study covered more than 90% of the plant food resources found in the study area. Of the 21 plant families identified using the combined rbcL and ITS2 local databases, the most dominant families were Ericaceae (98.1% of 105 fecal samples), followed by Rosaceae (42.9%), Apiaceae (35.2%), and Poaceae (19.0%). In all fecal samples examined, the most frequently encountered plant species were Vaccinium ovalifolium var. ovalifolium (69.5%), followed by Empetrum nigrum var. japonicum (68.6%), Vaccinium sp. (54.3%), Kalmia procumbens (42.9%), and Tilingia ajanensis (34.3%). Rarefaction analysis of each collection period in the study revealed that this study covered more than 90% (from 91.0% in July to 97.5% in September) of the plant food resources found in the study area, and 98.1% of the plant food taxa were covered throughout the entire study period. Thus, DNA metabarcoding using the rbcL and ITS2 local databases of alpine plants in combination and rarefaction analysis are considered to be well suited for estimating the dominant food plants in the diet of Japanese rock ptarmigans. Further, the local database constructed in this study can be used to survey other areas with similar flora.

ecology↗

bioRxiv2021

An endogenous basis for synchronization manners of the circadian rhythm in proliferating Lemna minor plants

Endogenous circadian rhythms in plants play a role in adaptation to day-night cycles. The circadian clock is a cell-autonomous system that functions through the coordination of time information in the plant body. Synchronization of cellular clocks is based on coordination mechanisms; the synchronization manners in proliferating plants remain unclear. We performed spatiotemporal analysis of the circadian rhythm of fronds (leaf-like plant units) of proliferating Lemna minor plants carrying a circadian bioluminescence reporter, AtCCA1:LUC. Noninvasive observations of the bioluminescence of fast-growing two-dimensional plants allowed us to analyze the circadian rhythms at a cell-level resolution and obtain information regarding frond lineage. We focused on spontaneous circadian organization under constant light conditions for plants with light/dark treatment (LD-grown) or without it (LL-grown). Even fronds developing from an LL-grown parental frond showed coherent circadian rhythms among them. This allowed the maintenance of circadian rhythmicity in proliferating plants. Inside a frond, a centrifugal phase/period pattern was observed in LD-grown plants, whereas various phase patterns with traveling waves were formed in LL-grown plants. These patterns were model-simulated by local coupling of cellular circadian oscillators with different initial synchronous states in fronds. Taken together with similar patterning previously reported for detached leaves of Arabidopsis, it is strongly suggested that local coupling is the primary force for the development of these phase patterns in plants lacking long-distance communication. We propose a basic framework of spontaneous phase patterning with three stages of circadian organization: initial phasing, evolution of patterning, and desynchronization/randomizing of phase, in association with altering cell-cell coupling.

plant biology↗

bioRxiv2020

Calibration of consonant perception to room reverberation

PurposeWe examined how consonant perception is affected by a preceding speech carrier simulated in the same or a different room, for a broad range of consonants. Carrier room, carrier length, and carrier length/target room uncertainty were manipulated. A phonetic feature analysis tested which phonetic categories are most influenced by the acoustic context of the carrier. MethodTwo experiments were performed, each with 9 participants. Targets consisted of vowel-consonant (VC) syllables presented in one of 2 strongly reverberant rooms, preceded by a VC carrier presented either in the same room, a different reverberant room, or an anechoic room. In Experiment 1 the carrier length and the target room randomly varied from trial to trial while in Experiment 2 they were fixed within blocks of trials. ResultsCompared to the no-carrier condition, a consistent carrier provided only a small advantage for consonant perception, whereas inconsistent carriers disrupted performance significantly. For a different-room carrier, carrier length had an effect; performance dropped significantly in the 2-VC compared to the 4-VC carrier length. The only effect of carrier uncertainty was an overall drop in performance. Phonetic analysis showed that an inconsistent carrier significantly degraded identification of the manner of articulation, especially for stop consonants, and, in one of the rooms, also of voicing. ConclusionsCalibration of consonant perception to strong reverberation is exhibited through disruptions in perception when the room is switched. The strength of calibration varies across different consonants and phonetic features, as well as across rooms and durations of exposure to a given room.

neuroscience↗

bioRxiv2018

Low Computational-cost Cell Detection Method for Calcium Imaging Data

The rapid progress of calcium imaging has reached a point where the activity of tens of thousands of cells can be recorded simultaneously. However, the huge amount of data in such records makes it difficult to carry out cell detection manually. Consequently, because the cell detection is the first step of multicellular data analysis, there is a pressing need for automatic cell detection methods for large-scale image data. Automatic cell detection algorithms have been pioneered by a handful of research groups. Such algorithms, however, assume a conventional field of view (FOV) (i.e. 512 x 512 pixels) and need a significantly higher computational power for a wider FOV to work within a practical period of time. To overcome this issue, we propose a method called low computational-cost cell detection (LCCD), which can complete its processing even on the latest ultra-large FOV data within a practical period of time. We compared it with two previously proposed methods, constrained non-negative matrix factorization (CNMF) and Suite2P. We found that LCCD makes it possible to detect cells from a huge-amount of high-density imaging data within a shorter period of time and with an accuracy comparable to or better than those of CNMF and Suite2P.

neuroscience↗

bioRxiv2018

Carbon monoxide, a retrograde messenger generated in post-synaptic mushroom body neurons evokes local dopamine release

Dopaminergic neurons innervate extensive areas of the brain and release dopamine (DA) onto a wide range of target neurons. However, DA release is also precisely regulated, and in Drosophila, DA is released specifically onto mushroom body (MB) neurons, which have been coincidentally activated by cholinergic and glutamatergic inputs. The mechanism for this precise release has been unclear. Here we found that coincidentally activated MB neurons generate carbon monoxide (CO) which functions as a retrograde signal evoking local DA release from presynaptic terminals. CO production depends on activity of heme oxygenase in post-synaptic MB neurons, and CO-evoked DA release requires Ca2+ efflux through ryanodine receptors in DA terminals. CO is only produced in MB areas receiving coincident activation, and removal of CO using scavengers blocks DA release. We propose that DA neurons utilize two distinct modes of transmission to produce global and local DA signaling.\n\nSIGNIFICANCE STATEMENTDopamine (DA) is needed for various higher brain functions including memory formation. However, DA neurons form extensive synaptic connections, while memory formation requires highly specific and localized DA release. Here we identify a mechanism through which DA release from presynaptic terminals is controlled by postsynaptic activity. Postsynaptic neurons activated by cholinergic and glutamatergic inputs generate carbon monoxide, which acts as a retrograde messenger inducing presynaptic DA release. Released DA is required for memory-associated plasticity. Our work identifies a novel mechanism that restricts DA release to the specific postsynaptic sites that require DA during memory formation.

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↗