Biology subjects

Suzuki, S.

Publications and source records attributed to Suzuki, S..

At least 55 records · Page 3Linked to original sources

bioRxiv2023

Spontaneous anterior-posterior convergences of oscillation frequencies in the alpha band

Alpha oscillation frequencies vary along the anterior-posterior axis, but they also dynamically converge. We investigated spontaneous anterior-posterior oscillation-frequency convergences while participants rested with their eyes open or closed, by tracking their oscillatory EEG activity in an extended alpha range (5-15 Hz) with appropriate temporal ({bsim}370 ms) and spectral ({bsim}1 Hz) resolutions. Oscillation-frequency convergences were prominent in the alpha band (8-12 Hz) and our analyses revealed three primary characteristics. First, the probability of an additional site joining a frequency convergence increased as more sites frequency-converged, suggesting that synergistic interactions drive anterior-posterior frequency convergences. Second, the oscillatory power at participating sites increased as more sites frequency-converged, suggesting that the synergistic interactions are mediated by regional synchronizations, being boosted by inter-regional frequency matching, facilitating the entrainment of additional regions. Third, frequency convergences generated two opposing phase gradients, posterior-behind and posterior-ahead, potentially mediating directional information flows to and from posterior regions. These gradients became steeper as more sites frequency-converged (while maintaining relatively constant levels of phase consistency), suggesting that frequency convergences increase the directionality of anterior-posterior information flows. Interestingly, when participants closed their eyes, the opposing phase gradients spatially organized, forming posterior-ahead gradients along the midline and posterior-behind gradients within each hemisphere, suggesting that closing eyes streamlines the opposing information flows. Taken together, these results suggest that synergistic interactions drive spontaneous anterior-posterior oscillation-frequency convergences in the alpha band, which may contribute to directional flows of information to and from posterior regions.

neuroscience↗

bioRxiv2023

Virological characteristics of the SARS-CoV-2 XBB.1.5 variant

Circulation of SARS-CoV-2 Omicron XBB has resulted in the emergence of XBB.1.5, a new Variant of Interest. Our phylogenetic analysis suggests that XBB.1.5 evolved from XBB.1 by acquiring the F486P spike (S) mutation, subsequent to the acquisition of a nonsense mutation in ORF8. Neutralization assays showed similar abilities of immune escape between XBB.1.5 and XBB.1. We determined the structural basis for the interaction between human ACE2 and the S protein of XBB.1.5, showing similar overall structures between the S proteins of XBB.1 and XBB.1.5. The intrinsic pathogenicity of XBB.1.5 in hamsters is lower than that of XBB.1. Importantly, we found that the ORF8 nonsense mutation of XBB.1.5 resulted in impairment of MHC expression. In vivo experiments using recombinant viruses revealed that the XBB.1.5 mutations are involved with reduced virulence of XBB.1.5. Together, these data suggest that the mutations in ORF8 and S could enhance spreading of XBB.1.5 in humans.

microbiology↗

bioRxiv2023

Granulomatous inflammatory responses are elicited in the liver of PD-1 knockout mice by de novo genome mutagenesis

Aimsprogrammed death-1 (PD-1) is a negative regulator of immune responses. Upon deletion of PD-1 in mice, symptoms of autoimmunity developed only after they got old. In a model experiment in cancer immunotherapy, PD-1 was shown to prevent cytotoxic T lymphocytes from attacking cancer cells that expressed neoantigens derived from genome mutations. Furthermore, the larger number of genome mutations in cancer cells led to the more robust anti-tumor immune responses after the PD-1 blockade. In order to understand the common molecular mechanisms underlying these findings, we hypothesize that we might have acquired PD-1 during evolution in order to avoid/suppress autoimmune reactions against neoantigens derived from mutations in the genome of aged individuals. Main methods: to test the hypothesis, we introduced random mutations into the genome of young PD-1-/- and PD-1+/+ mice. We employed two different procedures of random mutagenesis: administration of a potent chemical mutagen N-ethyl-N-nitrosourea (ENU) into the peritoneal cavity of mice and deletion of MSH2, which is essential for the mismatch-repair activity in the nucleus and, therefore, for the suppression of accumulation of random mutations in the genome. Key findingswe observed granulomatous inflammatory changes in the liver of the ENU-treated PD-1 knockout (KO) mice, but not in the wild-type (WT) counterparts. Such lesions also developed in the PD-1/MSH2 double KO mice, but not in the MSH2 single KO mice. Significance: the results we obtained support our hypothesis: PD-1 probably functions to avoid/suppress inflammatory responses against neoantigens derived from genome mutations in aged individuals.

immunology↗

bioRxiv2023

ULK1-regulated AMP sensing by AMPK and its application for the treatment of chronic kidney disease

AMP-activated protein kinase (AMPK) is a central kinase involved in energy homeostasis. Increased intracellular adenosine monophosphate (AMP) levels result in AMPK activation through the binding of AMP to the {gamma}-subunit of AMPK. Recently, we reported that AMP-induced AMPK activation is impaired in the kidneys in chronic kidney disease (CKD) despite an increase in the AMP/ATP ratio. However, the mechanisms by which AMP sensing is disrupted in CKD are unclear. In this study, we identified mechanisms of energy homeostasis in which Unc-51-like kinase 1 (ULK1)-dependent phosphorylation of AMPK{gamma}1 at Ser260/Thr262 promotes AMP sensitivity of AMPK. AMPK activation by AMP was impaired in Ulk1-/- mice despite an increased AMP/ATP ratio. We also demonstrated that MK8722, an allosteric AMPK activator, activates AMPK in the kidneys of a CKD mouse model via a pathway that is independent of AMP sensing. MK8722 treatment significantly attenuates the deterioration of renal function in CKD and is a potential therapeutic option in CKD therapeutics.

molecular biology↗

bioRxiv2023

A role for Vps13-mediated lipid transfer at the ER-endosome contact site in ESCRT-mediated sorting

Endosomes are specialized organelles that function in the secretory and endocytic protein sorting pathways. Endocytosed cell surface receptors and transporters destined for lysosomal degradation are sorted into intralumenal vesicles (ILVs) at endosomes by Endosomal Sorting Complex Required for Transport (ESCRT) proteins. The endosomes (multivesicular bodies, MVBs) then fuse with the lysosome. During endosomal maturation, the number of ILVs increases, but the size of endosomes does not decrease despite consumption of the limiting membrane during ILV formation. Vesicle-mediated trafficking is thought to provide lipids to support MVB biogenesis. However, we have uncovered an unexpected contribution of a large bridge-like lipid transfer protein, Vps13, in this process. Here, we reveal that Vps13-mediated lipid transfer at ER-endosome contact sites is required for the ESCRT pathway. We propose that Vps13 may play a critical role in supplying lipids to the endosome, ensuring continuous ESCRT-mediated sorting during MVB formation.

cell biology↗

bioRxiv2023

SAM68-regulated ALE selection of Pcdh15 maintains proper synapse development and function

Thousands of mammalian genes encode alternatively spliced isoforms in their 3 untranslated region (3UTR). Alternative 3UTR diversity may contribute to several neurological processes in developing and adult brains. SAM68 is the key splicing regulator for the diversity of neuronal 3UTR isoforms through alternative last exon (ALE) selection. However, the mechanisms underlying the control of splicing at the 3 end and its function in the nervous system remain unclear. Here, we show that neuronal SAM68-dependent ALE splicing is regulated depending on its target transcripts. For example, the selection of the ALE of protocadherin-15 (Pcdh15), a gene implicated in Usher syndrome and several neuropsychiatric disorders, is largely dependent on the expression of SAM68, partially regulated via the CaMK pathway, but independent of the U1 small nuclear ribonucleoprotein. We found that the aberrant ALEs of Pcdh15 caused membrane-to-soluble isoform conversion of the produced protein and disrupted its localization into excitatory and inhibitory synapses. In addition, the neuronal expression of the soluble form of PCDH15 (sPCDH15) preferentially affected the number of inhibitory synapses. sPCDH15 further reduced neuroligin-2-induced inhibitory, but not excitatory, synapses in artificial synapse formation assays. Our findings provide insights into the role of alternative 3UTR isoform selections in synapse development.

neuroscience↗

bioRxiv2023

The detection of brood parasitism and quasi-parasitism in the burying beetle Nicrophorus quadripunctatus under natural conditions

Intraspecific brood parasitism (IBP), where a parasitic female lays eggs in the nest of another female of the same species, occurs in insects and birds. Also, quasi-parasitism (QP), where a parasitic female copulates with a host male at his nest and lays eggs that are fertilized by the male, has been documented in a few monogamous birds, but QP has not been observed in any insects. Burying beetles, genus Nicrophorus, use small vertebrate carcasses for reproducing and providing biparental care for their offspring. IBP has been observed in one burying beetle by laboratory experiments, but has not been well reported under natural conditions. IBP and QP may occur under natural conditions in burying beetles. Here we focused on a burying beetle, Nicrophorus quadripunctatus. Ten broods, consisting of larvae and their parental female and male, were collected from a deciduous forest. To investigate the kin relationship between parents and larvae, eight microsatellite DNA loci were used. We detected three types of parasitic larvae: 1) larva not related to either its parental female or male, 2) larva not related to its parental female, but unknown regarding its parental male, and 3) larva not related to its parental female, but related to its parental male. These results suggested that IBP and QP can occur with certain frequencies in the reproduction of N. quadripunctatus under natural conditions. QP is thought to have a benefit for a parental male to enhance his paternity within one brood in this species.

animal behavior and cognition↗

bioRxiv2022

Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants

In late 2022, the SARS-CoV-2 Omicron subvariants have highly diversified, and XBB is spreading rapidly around the world. Our phylogenetic analyses suggested that XBB emerged by recombination of two co-circulating BA.2 lineages, BJ.1 and BM.1.1.1 (a progeny of BA.2.75), during the summer of 2022 around India. In vitro experiments revealed that XBB is the most profoundly resistant variant to BA.2/5 breakthrough infection sera ever and is more fusogenic than BA.2.75. Notably, the recombination breakpoint is located in the receptor-binding domain of spike, and each region of recombined spike conferred immune evasion and augmented fusogenicity to the XBB spike. Finally, the intrinsic pathogenicity of XBB in hamsters is comparable to or even lower than that of BA.2.75. Our multiscale investigation provided evidence suggesting that XBB is the first documented SARS-CoV-2 variant increasing its fitness through recombination rather than single mutations.

microbiology↗

bioRxiv2022

Dynamics of species-rich predator-prey networks and seasonal alternations of keystone species

In nature, entangled webs of predator-prey interactions constitute the backbones of ecosystems. Uncovering the network architecture of such trophic interactions has been recognized as the essential step for exploring species with great impacts on ecosystem-level phenomena and functions. However, it has remained a major challenge to reveal how species-rich networks of predator-prey interactions are continually reshaped though time in the wild. We here show that dynamics of species-rich predator-prey interactions can be characterized by remarkable network structural changes and alternations of potential keystone species. Based on high-throughput detection of prey DNA from 1,556 spider individuals collected in a grassland ecosystem, we reconstructed dynamics of interaction networks involving, in total, 50 spider species and 974 prey species/strains through eight months. The networks were compartmentalized into modules (groups) of closely interacting predators and prey in some but not all months. As the modules differed in detritus/grazing food chain properties, complex fission-fusion dynamics of below-ground and above-ground energy channels was reconstructed across the seasons. The substantial shifts of network structure entailed alternations of spider species located at the core positions within the entangled webs of interactions. These results indicate that knowledge of dynamically shifting food webs is essential for understanding the temporally-varying roles of keystone species that interlink multiple energy channels.

ecology↗

bioRxiv2022

Complete loss of RelA and SpoT homologs in Arabidopsis reveals the importance of the plastidial stringent response in the interplay between chloroplast metabolism and plant defense response

The highly phosphorylated nucleotide, guanosine tetraphosphate (ppGpp), functions as a secondary messenger in bacteria and chloroplasts. The accumulation of ppGpp alters plastidial gene expression and metabolism, which are required for proper photosynthetic regulation and robust plant growth. However, because four plastid-localized ppGpp synthases/hydrolases function redundantly, the impact of the loss of ppGpp-dependent stringent response on plant physiology remains unclear. We used the CRISPR/Cas9 technology to generate an Arabidopsis thaliana mutant lacking all four ppGpp synthases/hydrolases, and characterized its phenotype. The mutant showed 20-fold less ppGpp levels than the wild type (WT) under normal growth conditions, and exhibited leaf chlorosis and increased expression of defense-related genes as well as salicylic acid and jasmonate levels upon transition to nitrogen-starvation conditions. These results demonstrate that proper levels of ppGpp in plastids are required for controlling not only plastid metabolism but also phytohormone signaling, which is essential for plant defense.

plant biology↗

bioRxiv2022

Subjectivity of time perception alters choice preference for future rewards through fronto-striatal value signal dynamics

Our preference for a reward depends on the time of delay for its delivery. Here we show that changes in the external environment can manipulate the perceived duration of time, which alters the formation of the choice preference through value signals in the cortical and subcortical brain regions. Humans anticipated a real liquid reward delayed by tens of seconds, during which colors of visually presented panels gradually changed. The color-change delay was perceived as shorter than a control color-constant delay. Interestingly, participants with greater perceptual bias of the delay showed stronger preference for rewards with the color-change delay. The ventrolateral prefrontal cortex (vlPFC) and ventral striatum (VS) showed dynamic neural signatures of value components that were modulated by subjectively perceived duration. Crucially, these effects were specifically observed while a future reward was anticipated, and moreover, the vlPFC activity was weaker in participants with greater bias in the duration perception. These results demonstrate that subjective time experience leads to biased choice preference of delayed rewards, which is regulated by dynamic value signals of future rewards and accurate perception of the external world in the vlPFC-VS systems.

neuroscience↗

bioRxiv2022

Multi-ancestry genome-wide analysis identifies common genetic variants for self-reported sleep duration and shared genetic effects

Both short and long sleep duration are associated with increased risk of chronic diseases, but the genetic determinants of sleep duration are largely unknown outside of European populations. Here we report transferability of a polygenic score of 78 European ancestry sleep duration SNPs to an African (n=7,288; p=0.003), a South Asian (n=7,485; p=0.025), and a Japanese (n=13,618; p=6x10-4) cohort, but not to a cohort of Hispanic/Latino (n- XXX; p=0.71) participants. Furthermore, in a pan-ancestry (N = 483,235) meta-analysis of genome-wide association studies (GWAS) for habitual sleep duration, 5 novel and 68 known loci are associated with genome-wide significance. For the novel loci, sleep duration signals colocalize with expression-QTLs for PRR12 and COG5 in brain tissues, and pleiotropic associations are observed with cardiovascular and neuropsychiatric traits. Overall, our results suggest that the genetic basis of sleep duration is at least partially shared across diverse ancestry groups.

genomics↗

bioRxiv2022

Single mutation makes Escherichia coli an insect mutualist

We report an experimental system in which Escherichia coli evolves into an insect mutualist. When the essential gut symbiont of the stinkbug Plautia stali was replaced by E. coli, a few survivor insects exhibited specific localization and vertical transmission of E. coli. Through trans-generational maintenance with P. stali, several hyper-mutating E. coli lines independently evolved hosts high adult emergence and improved body color. Such "mutualistic" E. coli lines exhibited independent mutations disrupting the carbon catabolite repression (CCR) global transcriptional regulator. Each of the mutations reproduced the mutualistic phenotypes when introduced into wild-type E. coli, confirming that the single CCR mutations instantly make E. coli an insect mutualist. Our discovery uncovers that evolution of elaborate mutualism can proceed more easily and rapidly than conventionally envisaged.

evolutionary biology↗

bioRxiv2022

Modeling Pulse Dynamics of Juvenile Fish Enables the Short-term Forecasting of Population Dynamics in Japanese Pufferfish: A Latent Variable Approach

The time lag between data collection and management implementation is a source of uncertainty and bias in the calculation of acceptable biological catch. Here, we developed a method to use small-scale survey data for juvenile Japanese pufferfish (Takifugu rubripes) to shorten this time lag and achieve accurate short-term forecasting. A survey of juvenile fish at a local sandy beach in Ise-Mikawa Bay, Japan provides data for the strength of year classes before fisheries recruitment; however, it is difficult to use the raw data owing to the small sample size and large observation errors. We found that a random-effect model overcame these problems and more accurately predicted pulse patterns of catch rates to derive a standardized recruitment index compared with a fixed-effect model. We then showed that a stock assessment model using the standardized recruitment index from the random-effect model outperformed models without the standardized recruitment index with respect to retrospective forecasting ability. This study highlights the applicability of a latent-variable approach for standardizing small-scale survey data and thereby for unbiased forecasting of short-term fish dynamics.

ecology↗

bioRxiv2021

A phase-shifting anterior-posterior network organizes global phase relations

Prior research has identified a variety of task-dependent networks that form through inter-regional phase-locking of oscillatory activity that are neural correlates of specific behaviors. Despite ample knowledge of task-specific functional networks, general rules governing global phase relations have not been investigated. To discover such general rules, we focused on phase modularity, measured as the degree to which global phase relations in EEG comprised distinct synchronized clusters interacting with one another at large phase lags. Synchronized clusters were detected with a standard community-detection algorithm, and the degree of phase modularity was quantified by the index q. Notably, we found that the mechanism controlling phase modularity is remarkably simple. A network comprising anterior-posterior long-distance connectivity coherently shifted phase relations from low-angles (|{Delta}{theta}| < {pi}/4) in low-modularity states (bottom 5% in q) to high-angles (|{Delta}{theta}| > 3{pi}/4) in high-modularity states (top 5% in q), accounting for fluctuations in phase modularity. This anterior-posterior network may play a fundamental functional role as (1) it controls phase modularity across a broad range of frequencies (3-50 Hz examined) in different behavioral conditions (resting with the eyes closed or watching a silent nature video) and (2) neural interactions (measured as power correlations) in beta-to-gamma bands were consistently elevated in high-modularity states. These results may motivate future investigations into the functional roles of phase modularity as well as the anterior-posterior network that controls it.

neuroscience↗

bioRxiv2021

Anticipatory dynamics in the human brain guide foraging for primary rewards

Deciding whether to wait for a future reward is crucial for acquiring rewards in an uncertain world and involves anticipating future reward attainment. While seeking for a reward in natural environments, behavioral agents constantly face a trade-off between staying in their current environment or leaving it. It remains unclear, however, how humans make continuous decisions in such situations. Here we show that anticipatory brain activity in the anterior prefrontal cortex (aPFC) and hippocampus underpins continuous stay-leave decision making. Human participants awaited for real liquid rewards available after tens of seconds, and continuous decision was tracked by monitoring dynamic patterns of brain activity. Participants stopped waiting more frequently and sooner after they experienced longer delays and received smaller rewards. When dynamic activity reflecting the anticipation of a future reward was enhanced in the aPFC, participants remained in their current environment, but when this activity diminished, they left the environment for a new one. The anticipatory activity in the aPFC and hippocampus was associated with distinct decision strategies; aPFC activity was enhanced in participants adopting a leave strategy, whereas those remaining stationary showed enhanced activity in the hippocampus. Our results suggest that fronto-hippocampal anticipatory dynamics underlie continuous decision making while anticipating a future reward.

neuroscience↗

bioRxiv2021

Recruitment and organization of ESCRT-0 and ubiquitinated cargo via condensation

The general mechanisms by which ESCRTs are specifically recruited to various membranes, and how ESCRT subunits are spatially organized remain central questions in cell biology. At the endosome and lysosomes, ubiquitination of membrane proteins triggers ESCRT-mediated substrate recognition and degradation. Using the yeast lysosome/vacuole, we define the principles by which substrate engagement by ESCRTs occurs at this organelle. We find that multivalent interactions between ESCRT-0 and polyubiquitin is critical for substrate recognition at yeast vacuoles, with a lower-valency requirement for cargo engagement at endosomes. Direct recruitment of ESCRT-0 induces dynamic foci on the vacuole membrane, and forms fluid condensates in vitro with polyubiquitin. We propose that self-assembly of early ESCRTs induces condensation, an initial step in ESCRT-assembly/nucleation at membranes. This property can be tuned specifically at various organelles by modulating the number of binding interactions. One-Sentence SummaryCondensation of multivalent ESCRT-0/polyubiquitin assemblies organizes cargo sorting reactions at lysosomes

cell biology↗

bioRxiv2021

An efficient polymer cocktail-based transportation method for cartilage tissue, yielding chondrocytes with enhanced hyaline cartilage expression during in vitro culturing

Chondrocytes are used in cell-based therapies such as autologous chondrocyte implantation (ACI) and matrix-associated cartilage implantation (MACI). To transport the cartilage tissue to the laboratory for in vitro culturing, phosphate-buffered saline (PBS), Euro-Collins solution (ECS) and Dulbeccos Modified Eagles Medium (DMEM) are commonly employed at 4-8 {degrees}C. In this study, eight samples of human cartilage biopsy tissues from elderly patients with severe osteoarthritis undergoing arthroscopy, which would otherwise have been discarded, were used. The cartilage tissue samples were compared to assess the cell yield between two transportation groups: i) a thermo-reversible gelation polymer (TGP) based method without cool preservation (~25 {degrees}C) and ii) ECS transport at 4 {degrees}C. These samples were subjected to in vitro culture in a two-dimensional (2D) monolayer for two weeks and subsequently in a three-dimensional (3D) TGP scaffold for six weeks. The cell count obtained from the tissues transported in TGP was higher (0.2 million cells) than those transported in ECS (0.08 million cells) both after initial processing and after in vitro culturing for 2 weeks in 2D (18 million cells compared with 10 million cells). In addition, mRNA quantification demonstrated significantly higher expression of Col2a1 and SOX-9 in 3D-TGP cultured cells and lower expression of COL1a1 in RT-PCR, characteristic of the hyaline cartilage phenotype, than in 2D culture. This study confirms that the TGP cocktail is suitable for both the transport of human cartilage tissue and for in vitro culturing to yield better-quality cells for use in regenerative therapies.

cell biology↗