Biology subjects

Yamasaki, M.

Publications and source records attributed to Yamasaki, M..

12 recordsLinked to original sources

bioRxiv2026

Sequential maturation of supramammillary glutamatergic/GABAergic co-transmission onto adult-born dentate granule cells

Hypothalamic supramammillary nucleus (SuM) neurons project to the dentate gyrus and co-release glutamate and GABA, thereby regulating hippocampal information processing. However, how synapses mediating glutamate/GABA co-transmission are established during development remains unclear. Here, we investigated the functional and structural maturation of SuM inputs onto adult-born granule cells (GCs). We found that most newborn GCs received GABAergic responses without detectable glutamatergic responses, whereas a smaller population exhibited glutamate/GABA co-transmission. Newborn GCs with glutamate/GABA co-transmission showed more mature anatomical and physiological properties than GABA-only neurons, with greater dendritic complexity, longer dendritic length, lower input resistance, and stronger medial perforant path inputs. Postsynaptic depolarization failed to induce synapse unsilencing in GABA-only neurons but induced robust long-term potentiation in newborn GCs with glutamatergic transmission, indicating that plasticity at SuM inputs emerges after functional glutamatergic transmission is established. Morphological analysis showed that SuM terminals apposed to newborn GCs contained both VGluT2 and VIAAT, whereas postsynaptic receptor organization remained immature. Moreover, environmental enrichment and chemogenetic activation of SuM neurons increased the proportion of newborn GCs receiving glutamate/GABA co-transmission, suggesting that SuM activity promotes the emergence of glutamatergic transmission. Together, these results suggest that SuM inputs onto newborn GCs undergo sequential maturation from initial GABAergic transmission to glutamate/GABA co-transmission, a process likely supported by SuM activity-dependent postsynaptic maturation.

neuroscience↗

bioRxiv2026

Efficient genomic prediction at reduced training size and moderate marker density in an expanded aus-NAM population of rice

Genomic selection (GS) can accelerate genetic gain in crops, but its effectiveness depends on training population design and marker density. Nested association mapping (NAM) populations provide a structured framework that captures broad allelic diversity within a controlled genetic background. Here, we evaluated genomic prediction (GP) and genome-wide association study (GWAS) performance in an expanded aus-NAM population of rice comprising 1,818 recombinant inbred lines across 14 families and 11 agronomic traits, using genotyping-by-sequencing (GBS) markers and projected whole-genome sequence variants. Prediction accuracy plateaued at moderate marker densities ([~]20k SNPs) and with training populations of [~]500 lines ([~]40-60% of the available pool), with trait heritability emerging as the strongest determinant of predictive performance rather than model choice or marker density. In contrast, GWAS resolution continued to improve with increasing marker density, enabling detection of additional loci, including a chromosome 12 locus associated with heading date, while consistently recovering well-characterized genes such as EARLY HEADING DATE 1 (Ehd1) and SEMIDWARF 1 (SD1). These contrasting patterns indicate that GP reaches near-optimal performance once genome-wide variation is adequately represented, whereas GWAS benefits from higher marker density through improved locus resolution. The present study establishes a benchmark for implementing breeding programs involving japonica/indica crosses using GP in a single environment.

plant biology↗

bioRxiv2025

A cattle-derived human H5N1 isolate suppresses innate immunity despite efficient replication in human respiratory organoids

The H5N1 high pathogenicity avian influenza virus (HPAIV) of clade 2.3.4.4b, which spreads globally via wild birds, has become a major public health concern because it can infect a variety of mammals, including humans. In 2024, infection of dairy cattle with H5N1 HPAIV clade 2.3.4.4b was confirmed in the United States, and subsequent human cases were reported. Although these viruses are highly pathogenic in animal models, human infections have generally been mild, revealing a striking discrepancy. Here, we characterized the cattle-derived human H5N1 isolate A/Texas/37/2024 (TX37-H5N1) using three-dimensional human respiratory organoids derived from induced pluripotent stem (iPS) cells. Despite efficient replication, TX37-H5N1 induced minimal interferon and inflammatory cytokine responses. Bulk and single-cell RNA sequencing revealed reduced STAT1-mediated transcriptional activity in TX37-H5N1-infected organoids compared to the historic H5N1 human isolate A/Vietnam/1203/2004. These findings suggest that TX37-H5N1 fails to trigger the strong innate responses, including robust cytokine production, that are typically associated with severe H5N1 disease and are thought to contribute to cytokine storm-medicated pathogenesis. This attenuated response may help explain the discrepancy between the high pathogenicity of TX37-H5N1 in animal models and its mild clinical presentation in humans. While zoonotic influenza risk is often assessed using cell lines or animal models, our study highlights the value of using human respiratory organoids to evaluate human-specific virus-host interactions. This platform provides a complementary tool for assessing the risk of emerging avian influenza viruses. HighlightsO_LIHuman respiratory organoids were used to model zoonotic B3.13 H5N1 infections. C_LIO_LIA cattle-derived human isolate, TX37-H5N1, replicated more efficiently than historical VN1203-H5N1. C_LIO_LITX37-H5N1 suppressed STAT-IRF-mediated innate immune responses. C_LIO_LITX37-H5N1 was sensitive to baloxavir and oseltamivir but less sensitive to favipiravir. C_LIO_LIHuman respiratory organoids offer a complementary platform for zoonotic influenza risk assessment. C_LI In briefOur study used human iPSC-derived respiratory organoids to investigate the mild clinical presentation of zoonotic B3.13 H5N1 viruses. We found that TX37-H5N1 replicates efficiently but suppresses innate immune responses, providing mechanistic insight into species-specific pathogenesis and highlighting the utility of human organoids for zoonotic risk assessment.

microbiology↗

bioRxiv2024

MitoNEET reduces the mitochondrial oxidative phosphorylation during epithelial-mesenchymal transition

Mitochondrial functions range from catabolic to anabolic, which are tightly coordinated to meet cellular demands for proliferation and motility. MitoNEET is a mitochondrial outer membrane protein with a CDGSH domain and is involved in mitochondrial function. Epithelial-to-mesenchymal transition (EMT) is the process in which cells lose their epithelial characteristics and acquire mesenchymal traits, such as motility, which is a vital step for organism development and wound-healing. Cellular motility is associated with high ATP consumption owing to lamellipodia formation, which is supported by upregulated oxidative phosphorylation (OXPHOS) capacity. However, how mitoNEET is involved in the regulation of OXPHOS capacity and subsequent cellular motility remains unclear. Here we show that loss of mitoNEET regulation during EMT impairs both OXPHOS enhancement and cell motility in non-transformed NMuMG mouse mammary gland epithelial cells. We found that mitoNEET is downregulated during EMT, and that the aberrant expression of mitoNEET abolishes the upregulation of OXPHOS, leading to the inhibition of cell motility. Furthermore, we found that mitoNEET topology may be crucial for the regulation of the mitochondrial electron transfer chain, suggesting an additional regulatory pathway for OXPHOS capacity. Our results demonstrate that mitochondrial OXPHOS capacity during EMT is partly regulated by the dynamics of the outer membrane protein. We believe that our findings are the first step towards understanding the mechanisms by which mitochondrial outer membrane protein topology affects organelle functions.

cell biology↗

bioRxiv2024

Distinct roles of two thalamostriatal systems in learning processes of visual discrimination in common marmosets

The thalamostriatal projections arising from the intralaminar thalamic nuclei (ILN) constitute the principal source of input information to specified subregions of the striatum, a key structure of the cortico-basal ganglia circuitry. However, the roles of primate ILN in cortico-basal ganglia circuit functions remain unclear. Here, we performed immunotoxin-induced selective targeting of two representative structures of the ILN, the parafascicular nucleus (Pf) and centre median nucleus (CM) projecting to the caudate nucleus (Cd) and putamen (Pu), respectively, in common marmosets. Elimination of Pf-Cd neurons resulted in impaired reversal learning of a two-choice visual discrimination task, whereas removal of CM-Pu neurons disturbed the task acquisition. No marked impact of such manipulations was observed on either motor skill learning or spontaneous locomotor activity. Our findings reveal that the two thalamostriatal systems play distinct roles in the learning processes of external cue-dependent decision-making in nonhuman primates.

neuroscience↗

bioRxiv2024

Distinct release properties of glutamate/GABA co-transmission serve as a frequency-dependent filtering of supramammillary inputs

Glutamate and GABA co-transmitting neurons exist in several brain regions; however, the mechanism by which these two neurotransmitters are co-released from the same synaptic terminals remains unclear. Here, we show that the supramammillary nucleus (SuM) to dentate granule cell synapses, which co-release glutamate and GABA, exhibit differences between glutamate and GABA release properties in paired-pulse ratio, Ca2+-sensitivity, presynaptic receptor modulation, and Ca2+ channel-vesicle coupling configuration. Moreover, uniquantal synaptic responses show independent glutamatergic and GABAergic responses. Morphological analysis reveals that most SuM terminals form distinct glutamatergic and GABAergic synapses in proximity, each characterized by GluN1 and GABAA1 labeling, respectively. Notably, glutamate/GABA co-transmission exhibits distinct short-term plasticities, with frequency-dependent depression of glutamate and frequency-independent stable depression of GABA. Our findings suggest that glutamate and GABA are co-released from different synaptic vesicles within the SuM terminals, and reveal that distinct transmission modes of glutamate/GABA co-release serve as frequency-dependent filters of SuM inputs.

neuroscience↗

bioRxiv2022

Degenerate oligonucleotide primer MIG-seq: an effective PCR-based method for high-throughput genotyping

Multiplexed inter-simple sequence repeats genotyping by sequencing (MIG-seq) is an next-generation sequencing library construction method developed for the analysis of DNA in ecology. Although MIG-seq can generate libraries from low-quality DNA, few polymorphisms can be obtained in species with small genomes. In this study, we developed degenerate oligonucleotide primer MIG-seq (dpMIG-seq) as an effective polymorphism discovery method that allows for variation in the number of polymorphisms while retaining the advantages of MIG-seq, including independence from DNA quality. In dpMIG-seq, a proportion of the simple sequence repeats in the primer sequence of the first PCR in MIG-seq was changed to degenerate oligonucleotides to enable annealing to a wider range of sequences. In tests of several crop species other than wheat, the number of loci that could be sequenced using dpMIG-seq with a data volume of 0.3 gigabases (Gb) was increased compared with that sequenced using MIG-seq. In wheat, the number of polymorphisms obtained via dpMIG-seq was higher than that obtained via MIG-seq when a data volume of about [≥]2 Gb was obtained. In dpMIG-seq, different loci could be sequenced by changing the positions of the degenerate oligonucleotides. By applying dpMIG-seq, we constructed a linkage map consisting of 5,142 markers for the rice inter-subspecies F2 population, and we detected quantitative trait loci for heading date in the regions where known heading-related genes were located. Overall, our results show that dpMIG-seq is a useful tool for the genetic analysis of crop species.

genetics↗

bioRxiv2021

Activation of extrasynaptic kainate receptors drives hilar mossy cell activity

Mossy cells (MCs) of the dentate gyrus (DG) are key components of an excitatory associative circuit established by reciprocal connections with dentate granule cells (GCs). MCs are implicated in place field encoding, pattern separation and novelty detection, as well as in brain disorders such as temporal lobe epilepsy and depression. Despite their functional relevance, little is known about the determinants that control MC activity. Here, we examined whether MCs express functional kainate receptors (KARs), a subtype of glutamate receptors involved in neuronal development, synaptic transmission and epilepsy. Using mouse hippocampal slices, we found that bath application of submicromolar and micromolar concentrations of the KAR agonist kainic acid induced inward currents and robust MC firing. These effects were abolished in GluK2 KO mice, indicating the presence of functional GluK2-containing KARs in MCs. In contrast to CA3 pyramidal cells, which are structurally and functionally similar to MCs, and express synaptic KARs at mossy fiber (MF) inputs (i.e., GC axons), we found no evidence for KAR-mediated transmission at MF-MC synapses, indicating that most KARs at MCs are extrasynaptic. Immunofluorescence and immunoelectron microscopy analyses confirmed the extrasynaptic localization of GluK2-containing KARs in MCs. Finally, blocking glutamate transporters, a manipulation that increases extracellular levels of endogenous glutamate, was sufficient to induce KAR-mediated inward currents in MCs, suggesting that MC-KARs can be activated by increases in ambient glutamate. Our findings provide the first direct evidence of functional extrasynaptic KARs at a critical excitatory neuron of the hippocampus. Significance StatementHilar mossy cells (MCs) are an understudied population of hippocampal neurons that form an excitatory loop with dentate granule cells. MCs have been implicated in pattern separation, spatial navigation, and epilepsy. Despite their importance in hippocampal function and disease, little is known about how MC activity is recruited. Here, we show for the first time that MCs express extrasynaptic kainate receptors (KARs), a subtype of glutamate receptors critically involved in neuronal function and epilepsy. While we found no evidence for synaptic KARs in MCs, KAR activation induced strong action potential firing of MCs, raising the possibility that extracellular KARs regulate MC excitability in vivo and may also promote dentate gyrus hyperexcitability and epileptogenesis.

neuroscience↗

bioRxiv2021

SIPA1L1/SPAR1 is a non-PSD protein involved in GPCR signaling

SIPA1L1 (also known as SPAR1) has been proposed to regulate synaptic functions that are important in maintaining normal neuronal activities, such as regulating spine growth and synaptic scaling, as a component of the postsynaptic density (PSD)-95/N-methyl-D-aspartate receptor (NMDA-R)-complex. However, contrary to this view, our super-resolution and immunoelectron microscopic analyses demonstrate that SIPA1L1 is mainly localized to general submembranous and cytoplasmic regions in neurons, but scarcely to PSD. Our screening for native interactors of SIPA1L1 identified spinophilin and neurabin-1, regulators of G protein-coupled receptor (GPCR) signaling, but rejected PSD-95/NMDA-R-complex components. Furthermore, Sipa1l1-/- mice showed normal spine size distribution and NMDA-R-dependent synaptic plasticity. Nevertheless, Sipa1l1-/- mice showed aberrant responses to 2-adrenergic receptor (a spinophilin target) or adenosine A1 receptor (a neurabin-1 target) agonist stimulation and striking behavioral anomalies, such as hyperactivity, enhanced anxiety, learning impairments, social interaction deficits, and enhanced epileptic seizure susceptibility. Our findings revealed unexpected properties of SIPA1L1, suggesting a possible association of SIPA1L1 deficiency with neuropsychiatric disorders related to dysregulated GPCR signaling, such as epilepsy, attention deficit hyperactivity disorder (ADHD), autism, or fragile X syndrome.

neuroscience↗

bioRxiv2020

Anti-severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) potency of Mefloquine as an entry inhibitor in vitro

Coronavirus disease 2019 (COVID-19) has caused serious public health, social, and economic damage worldwide and effective drugs that prevent or cure COVID-19 are urgently needed. Approved drugs including Hydroxychloroquine, Remdesivir or Interferon were reported to inhibit the infection or propagation of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), however, their clinical efficacies have not yet been well demonstrated. To identify drugs with higher antiviral potency, we screened approved anti-parasitic/anti-protozoal drugs and identified an anti-malarial drug, Mefloquine, which showed the highest anti-SARS-CoV-2 activity among the tested compounds. Mefloquine showed higher anti-SARS-CoV-2 activity than Hydroxychloroquine in VeroE6/TMPRSS2 and Calu-3 cells, with IC50 = 1.28 M, IC90 = 2.31 M, and IC99 = 4.39 M in VeroE6/TMPRSS2 cells. Mefloquine inhibited viral entry after viral attachment to the target cell. Combined treatment with Mefloquine and Nelfinavir, a replication inhibitor, showed synergistic antiviral activity. Our mathematical modeling based on the drug concentration in the lung predicted that Mefloquine administration at a standard treatment dosage could decline viral dynamics in patients, reduce cumulative viral load to 7% and shorten the time until virus elimination by 6.1 days. These data cumulatively underscore Mefloquine as an anti-SARS-CoV-2 entry inhibitor.

microbiology↗

bioRxiv2019

Seasonal and annual fluctuations of deer populations estimated by a Bayesian state-space model

Deer overabundance is a contributing factor in the degradation of plant communities and ecosystems worldwide. The management and conservation of the deer-affected ecosystems requires us to urgently grasp deer population trends and to identify the factors that affect them. In this study, we developed a Bayesian state-space model to estimate the population dynamics of sika deer (Cervus nippon) in a cool-temperate forest in Japan, where wolves (Canis lupus hodophilax) are extinct. The model was based on field data collected from block count surveys, road count surveys by vehicles, mortality surveys during the winter, and nuisance control for 12 years (2007-2018). We clarified the seasonal and annual fluctuation of the deer population. We found two peaks of deer abundance (2007 and 2010) over 12 years. In 2011 the estimated deer abundance decreased drastically and has remained at a low level then. The deer population increased from spring to autumn and decreased from autumn to winter in most years. The seasonal fluctuation we detected could reflect the seasonal migration pattern of deer and the population recruitment through fawn births in early summer. In our model, snowfall accumulation, which can be a lethal factor for deer, may have slightly affected their mortality during the winter. Although we could not detect a direct effect of snow on population dynamics, snowfall decrease due to global warming may decelerate the winter migration of deer; subsequently, deer staying on-site may intensively forage evergreen perennial plants during the winter season. The nuisance control affected population dynamics. Even in wildlife protection areas and national parks where hunting is regulated, nuisance control could be effective in buffering the effect of deer browsing on forest ecosystems.

ecology↗

bioRxiv2019

Choosing the optimal population for a genome-wide association study: a simulation using whole-genome sequences from rice

A genome-wide association study (GWAS) needs to have a suitable population. The factors that affect a GWAS, e.g. population structure, sample size, and sequence analysis and field testing costs, need to be considered. Mixture populations containing subpopulations of different genetic backgrounds may be suitable populations. We conducted simulation experiments to see if a population with high genetic diversity, e.g., a diversity panel, should be added to a target population, especially when the target population harbors small genetic diversity. The target population was 112 accessions of Oryza sativa subsp. japonica, mainly developed in Japan. We combined the target population with three populations that had higher genetic diversities. These were 100 indica accessions, 100 japonica accessions, and 100 accessions with various genetic backgrounds. The results showed that the GWAS power with a mixture population was generally higher than with a separate population. Also, the GWAS optimal population varied depending on the fixation index FST of the quantitative trait nucleotide (QTN) and its polymorphism of QTN in each population. When a QTN is polymorphic in a target population, a target population combined with a higher diversity population improves the QTN detection power. Investigating FST and the expected heterozygosity He as factors influencing the detection power, we showed that SNPs with high FST or low He are less likely to be detected by GWAS with mixture populations. Sequenced/genotyped germplasm collections can improve the GWAS detection power by using a subset of them with a target population.\n\nCore ideas (3-5 impact statements, 85 char max for each)\n\n- Genome-wide association studies with mixture populations are expected to improve the detection power of novel genes due to the increase of the sample size although the influence of population structure is a concern.\n- When a quantitative trait nucleotide (QTN) is polymorphic in a target population, a combination of the target population and a population with higher diversity than the target population improves the detection power of the QTN.\n- We found that the fixation index (FST) and the expected heterozygosity (He) were strongly related to the detection power of QTNs.\n- Germplasm collections which have been already sequenced/genotyped are useful for improving the detection power of GWAS without any addition of sequence costs by using a subset of them with a target population.

genomics↗