Biology subjects

Iwasaki, Y.

Publications and source records attributed to Iwasaki, Y..

At least 19 recordsLinked to original sources

bioRxiv2026

The vagus nerve drives cognitive function through the default mode network

The afferent vagus nerve transmits interoceptive signals to the brain but a systematic understanding of how vagal signals affect brain-wide neuronal dynamics remains elusive. Here, comprehensive spatiotemporal analyses across the entire mouse brain revealed that vagus nerve stimulation activated neuronal ensembles within the default mode network (DMN). In contrast, vagal-independent mechanisms predominantly affected the salience network. The vagal-DMN association was mediated by locus coeruleus neuronal subpopulations. Selective activation or silencing of vagal-responsive DMN neuronal ensembles replicated or abolished VNS-induced enhancement of cognitive behaviors and progressive problem-solving behaviors. These findings establish a unifying framework for how the vagus nerve drives cognitive functions by engaging the DMN.

neuroscience↗

bioRxiv2026

Unsupervised explainable AI reveals similar oligonucleotide-usage zones matching the highest-resolution human chromosome bands

Unsupervised and explainable AI can uncover genomic features that extend beyond human expectations. Oligonucleotides such as penta- and hexanucleotides often function as core binding motifs for regulatory proteins, and their usage provides a powerful tool in functional genomics. We applied an unsupervised, explainable AI approach to odds ratio (observed/expected) profiles of all 1-Mb euchromatic fragments in the human genome. This odds-ratio analysis identified oligonucleotide features independent of mononucleotide composition, thereby highlighting functional roles of oligonucleotide motifs. AI-based clustering of all 1-Mb euchromatic fragments, using either penta- or hexanucleotide odds ratios (1,024 or 4,096 variables), unexpectedly revealed nearly 2,000 distinct zones, despite the large differences in dimensionality. If these [~]2,000 zones represent biologically meaningful segmentations, comparable structures would be expected to emerge when other oligonucleotide types are analyzed. Consistent with this expectation, CG-containing penta- and hexanucleotides (244 and 1,185 variables) produced comparable [~]2,000 zones, indicating that the underlying segmental structures reflect fundamental functional divisions within the genome. Human chromosomes exhibit well-established Giemsa-banding patterns comprising 850 bands at prometaphase and 2,000 bands at prophase. Since single-nucleotide coordinates are available for the 850 bands, we identified a diagnostic oligonucleotide set that distinguishes Giemsa-negative and -positive regions. Computational pseudo-band reconstruction based on this set generated genome segmentations that more closely paralleled the AI-derived [~]2,000 clusters than the 850 bands. These unexpected findings indicate that AI captures the characteristic features of chromosomal bands and can predict high-resolution banding from genome sequences alone, thereby bridging classical cytogenetics and modern AI-based genomics.

genomics↗

bioRxiv2026

Suppressing Bone Resorption and Promoting Mineralization with Tetracycline Derivatives

Osteoporosis is a progressive skeletal disorder characterized by decreased bone mass and an increased risk of fracture. Current treatments are limited by adverse effects and poor long-term compliance, necessitating alternative therapeutic approaches. Tetracycline (TC) derivatives, which are traditionally used as antibiotics, have shown promise in modulating bone remodeling. In this study, the effects of TC and three TC derivatives--oxytetracycline (OC), doxycycline (DC), and minocycline (MC)--on osteoclast and osteoblast activities were investigated using in vitro human cell models and in vivo zebrafish assays. All TC derivatives inhibited osteoclast differentiation and bone resorption, as shown by reductions in the number of TRAP-positive cells, resorption pit volume, and matrix metalloproteinase (MMP)-2/MMP-9 secretion. DC demonstrated the most potent inhibitory effects across all concentrations. Low to moderate concentrations of OC, DC, and MC promoted osteoblast proliferation and mineralization, whereas high doses inhibited these processes. Confocal imaging confirmed the accumulation of TC derivatives in mineralized bone nodules. Zebrafish studies revealed dose-dependent suppression of craniofacial bone development at higher concentrations. These findings highlight the dose dependent, dual effects of TC derivatives on bone cells (osteoblasts and osteoclasts) and underscore the potential of these agents as dual-function therapies for osteoporosis.

pharmacology and toxicology↗

bioRxiv2026

Gut-derived GLP-1 released by rare sugar D-allulose cooperates with insulin to activate left-sided vagal afferents and enhance insulin sensitivity

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) ameliorate hyperglycemia by directly stimulating insulin secretion from the pancreas. In contrast, the physiological role of short-lived endogenous GLP-1 remains unclear, largely because of its limited access to pancreatic {beta} cells. Here, we show that D-allulose-induced intestinal GLP-1 secretion (AIGS) cooperates with insulin to reduce blood glucose levels by enhancing insulin action, rather than insulin secretion, in male mice. This cooperation and remote signaling require left-sided vagal afferents forming the common hepatic branch, but not right-sided afferents. AIGS-enhanced insulin action required both GLP-1 receptors and insulin receptor substrate 2 in these neurons. Remarkably, AIGS improved insulin resistance and hyperglycemia more rapidly and potently than the GLP-1RA exendin-4. These findings reveal that a subclass of vagal afferent neurons synergistically activated by endogenous intestinal GLP-1 and insulin does not stimulate insulin secretion but augments insulin action to improve glucose tolerance. This novel extra-pancreatic GLP-1 action mediated by vagal afferents provides a promising basis for innovative type 2 diabetes therapies. ARTICLE HIGHLIGHTO_LICompared with GLP-1 receptor agonists, the physiological roles and mechanisms of endogenous, short-lived GLP-1 in glucose metabolism remain poorly understood. C_LIO_LIWe utilized the rare sugar D-allulose, a noncaloric GLP-1 secretagogue, as a tool to elucidate the physiological actions of endogenous GLP-1. C_LIO_LID-allulose-induced intestinal GLP-1 release cooperates with insulin to activate left-sided vagal afferents, enhancing insulin action rather than insulin secretion and thereby regulating glycemic control. C_LIO_LIBecause this acute mechanism improved hyperglycemia in type 2 diabetes more effectively than GLP-1 receptor agonists, targeting GLP-1/insulin-vagal signaling may inform novel therapies and dietary or nutritional interventions for T2DM. C_LI

physiology↗

bioRxiv2026

Exacerbation of sucrose-induced visceral obesity and glucose intolerance by ovariectomy and its GLP-1-dependent amelioration by the rare sugar D-allulose

Estrogen deficiency after menopause promotes visceral fat accumulation and insulin resistance, thereby increasing the risk of type 2 diabetes. Although hormone replacement therapy is partially effective, its use is limited by increased risks of cardiovascular disease and breast cancer, underscoring the need for safer preventive strategies. The rare sugar D-allulose has been reported to stimulate glucagon-like peptide-1 (GLP-1), a gut hormone, secretion and to improve obesity and glucose metabolism, suggesting its potential as a novel intervention for postmenopausal metabolic dysfunction. Here, we examined whether D-allulose improves obesity and glucose intolerance in a GLP-1-dependent manner under sucrose-fed conditions, using ovariectomized (OVX) female C57BL/6J mice as a model of menopause. OVX mice, but not sucrose-fed sham mice, developed exacerbated visceral obesity and glucose intolerance in response to dietary sucrose, despite similar total energy intake. Daily oral administration of D-allulose for two weeks significantly suppressed visceral fat accumulation, improved insulin resistance, and ameliorated glucose intolerance in sucrose-fed OVX mice. These beneficial effects were markedly attenuated in GLP-1 receptor knockout mice. Taken together, we found that sucrose intake after ovariectomy exacerbates visceral obesity and glucose intolerance, and that D-allulose effectively ameliorates these metabolic abnormalities. GLP-1-stimulating dietary components such as D-allulose may represent a safe and promising preventive strategy for metabolic dysfunction associated with menopause.

physiology↗

bioRxiv2025

Lateralized vagal oxytocin signaling separately controls feeding and socioemotional functions via hypothalamic oxytocin signaling

Oxytocin neurons in the paraventricular hypothalamus (PVHOxt) regulate feeding, anxiety, and social behaviors. Activation of Oxt receptor (Oxtr) -expressing vagal sensory neurons engages these PVHOxt neurons and improves hyperphagic obesity; however, their roles in anxiety and sociability remain unclear. Here, we activated vagal Oxtr-expressing neurons in male mice using a single intraperitoneal (IP) Oxt injection or chemogenetics. IP Oxt reduced anxiety-like behavior, enhanced social interaction, and suppressed feeding while activating both vagal sensory neurons and PVHOxt neurons. These effects were abolished by chemogenetic inhibition of PVHOxt neurons or central Oxtr blockade. Subdiaphragmatic vagotomy revealed lateralized functions: right-side vagotomy eliminated anxiolytic and prosocial effects, whereas left-side vagotomy blocked feeding suppression. Consistently, chemogenetic activation of left-sided neurons suppressed feeding, while right-sided activation reduced anxiety and increased sociability. These findings identify Oxtr-expressing vagal sensory neurons as a major peripheral pathway in which left- and right-sided inputs differentially control feeding and socioemotional behaviors.

physiology↗

bioRxiv2025

Early pathogenesis of spinal and bulbar muscular atrophy uncovered by human iPSC-derived motor neurons highlights pathogenic neuropeptides as therapeutic targets

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disorder caused by the expansion of the polyglutamine tract in the androgen receptor (AR). Motor neurons (MNs) derived from patient-specific induced pluripotent stem cells (iPSCs) robustl y recapitulated early SBMA phenotypes driven by endogenous mutant AR in the absence of testosterone (dihydrotestosterone) and detectable mutant AR aggregation. Notably, endoplasmic reticulum stress markedly exacerbated SBMA pathology. Cross-species integrative analyses of patient-derived neurons and spinal cords of transgenic mouse models revealed high expression of multiple disease-associated neuropeptides, including urotensin II (UTS2), in patient spinal MNs that was correlated with disease onset and progression in iPSC-derived MNs. Downstream signaling analyses of these neuropeptides revealed convergent molecular pathways whose pharmacological inhibition rescued cellular phenotypes. Together, these results establish a human disease model harboring endogenous mutant AR that closely reproduces early SBMA pathology and provides molecular leads for elucidating disease mechanisms and biomarkers and developing therapeutic targets.

neuroscience↗

bioRxiv2025

ALKBH1 drives codon-biased, pro-oncogenic translation and tumor microenvironment remodeling in glioma via tRNA wobble oxidation

Gliomas rely on translational plasticity to sustain heterogeneity, stemness, and immune evasion. Here we identify the tRNA dioxygenase ALKBH1 as a central regulator of codon-biased translation and tumor microenvironment remodeling. LC-MS/MS profiling of patient tumors revealed enrichment of ALKBH1-mediated wobble cytidine oxidation modifications in high-grade gliomas. Genetic perturbation demonstrated that ALKBH1 overexpression slows proliferation in vitro but worsens survival in vivo by promoting glioma stem-like and neuronal states and suppressing anti-tumor immunity. Ribosome profiling showed that ALKBH1 establishes an A/T-ending codon-biased translational program, enhancing decoding of rare leucine codons (TTA/TTG) and driving synthesis of pro-stemness transcripts. Single-cell RNA-seq analyses further revealed that ALKBH1 promotes glioma heterogeneity and induces neuronal cell clusters and rewires intercellular communication ECM-related signaling while dampening immune pathways and reducing immune infiltration. These findings establish a mechanistic link between tRNA oxidation, codon bias, and glioma aggressiveness, positioning ALKBH1 as a potential therapeutic target for glioma.

cancer biology↗

bioRxiv2025

Revisiting flippase specificity: Drs2-Cdc50 transports multiple anionic lipid substrates

P4-ATPase lipid flippases maintain transbilayer lipid asymmetry in eukaryotic membranes, which is essential for many cellular processes. In yeast, the Drs2-Cdc50 flippase complex was previously shown to specifically transport phosphatidylserine (PS) from the exoplasmic to the cytosolic leaflet of the trans-Golgi network (TGN), thereby controlling vesicular trafficking in the secretory and endocytic pathways. Using an improved proteoliposome-based lipid flippase assay, we now show that the Drs2-Cdc50 complex transports multiple anionic glycerophospholipids, including PS, phosphatidylinositol, phosphatidylglycerol, and phosphatidic acid. In vivo cell-based lipid uptake assays further support the transport of these lipids. To understand the basis of this substrate promiscuity, we analyzed cryo-EM structures of the complex with occluded lipids. These structures revealed that the water network surrounding the lipid headgroup plays a critical role in enabling Drs2-Cdc50 to recognize different lipids. These data unveil an unexpected broad specificity of the Drs2-Cdc50 complex for anionic lipids, which may significantly impact their transbilayer distribution in the yeast TGN.

biochemistry↗

bioRxiv2025

A vagal sensory--hypothalamic oxytocin--brown adipose tissue pathway mediates cholecystokinin-induced thermogenesis

Thermoregulation is essential for survival in homeothermic animals. Vagal sensory nerves are well known to detect visceral signals and regulate physiological functions, including feeding, metabolism and immunity. However, their role in thermoregulation remains poorly understood. Cholecystokinin (CCK), a gut hormone released postprandially, activates vagal sensory nerves via CCK-A receptors (CCK-AR). Exogenous CCK has been reported to induce thermogenesis in the intrascapular brown adipose tissue (iBAT), but the involvement of vagal sensory nerves and the central neural mechanisms that mediate this effect are not fully understood. In this study, we assessed the thermogenic effect of intraperitoneally (I.P.) administered CCK-8 and investigated the underlying autonomic reflex pathways. I.P. CCK-8 transiently and dose-dependently increased rectal temperature. This response was significantly attenuated by pharmacological blockade of CCK-AR, subdiaphragmatic vagotomy, or knockdown of CCK-AR primarily targeting in vagal sensory neurons. In addition, CCK-8 activated sympathetic nerve activity via vagal afferents. CCK-8-induced thermogenesis was blunted by iBAT sympathectomy or {beta}3-adrenergic receptor blockade. Furthermore, I.P. CCK-8 activated oxytocin neurons in the paraventricular nucleus of the hypothalamus (PVHOXT). Chemogenetic inhibition of PVHOXT neurons or intracerebroventricular administration of an oxytocin receptor (OXTR) antagonist attenuated the thermogenic response. These findings demonstrate, for the first time, the full neural circuitry underlying CCK-induced thermogenesis by delineating its afferent input (CCK-AR-expressing vagal sensory neurons), central integrative hub (PVHOXT neurons and OXTR signaling), and efferent output (iBAT sympathetic nerves). This study further suggests that CCK-AR -expressing vagal sensory neurons may contribute to thermoregulation under physiological conditions in which CCK is endogenously released. Key points summaryO_LIVagal sensory nerves, which connect the gut and the brain, play a key role in regulating meal-related physiology, however their role in thermoregulation remains incompletely understood. C_LIO_LIThis study reveals for the first time the full autonomic reflex pathways underlying thermogenic effect of the gut hormone cholecystokinin (CCK), comprising afferent input (CCK-A receptor-expressing vagal afferents), a central integrative hub (oxytocin neurons in the hypothalamic paraventricular nucleus; PVHOXT neurons), and efferent output (intrascapular brown adipose tissue via sympathetic nerves). C_LIO_LIBoth CCK-A receptors-expressing vagal afferents and sympathetic nerves innervating brown adipose tissue are required for thermogenesis induced by exogenous CCK-8. C_LIO_LIActivation of PVHOXT neurons by CCK-8 is critically involved in mediating this thermogenic effect. C_LIO_LIThis newly identified gut-brain-fat axis may contribute to part of diet-induced thermogenesis, and its impairment could be involved in the development of metabolic disorders such as obesity. C_LI

physiology↗

bioRxiv2025

Application of environmental DNA-based assessment for upstream-downstream comparison of river macroinvertebrates in a metal-contaminated river

Environmental DNA (eDNA) is a powerful tool for biological monitoring with the potential to overcome weaknesses of conventional macroinvertebrate surveys in running waters. However, the ability of eDNA to detect changes of macroinvertebrate communities immediately downstream of a perturbation, particularly in upstream-downstream comparisons, has not been adequately explored. To address this issue, we investigated the potential of eDNA-based assessment of a perturbation by comparing the results with macroinvertebrate surveys in a river influenced by the inflow of a metal-contaminated tributary. Both methods revealed distinctly lower richness of taxa and zero-radius operational taxonomic units (ZOTUs) at the metal-contaminated tributary site compared to other study sites. Results from collection of macroinvertebrates indicated that most richness and abundance metrics were significantly reduced at three metal-contaminated sites located 150-750 m downstream from the inflow of the tributary. In contrast, the eDNA-based assessment revealed similar ZOTU richness at a reference site and the downstream, contaminated sites. Although statistically not significant because sample sizes were small, eDNA-based non-metric multidimensional scaling revealed some separation between the reference site and two downstream sites. However, no separation was apparent between the reference site and the site immediately downstream. This result suggested that eDNA at a site 150 m downstream from the inflow was likely affected by downstream drift of eDNA from the upstream reference area. That drift complicated assessment of the community a short distance from the perturbation. The site separation detected by eDNA-based assessment was promising, but the ZOTUs that contributed to the separation were mainly from dipteran taxa rather than from metal-sensitive mayflies, which were significantly lower in abundance at the downstream, contaminated sites. Developing reliable local DNA barcoding information, particularly for these mayflies, may help overcome the limitations of making evaluations over relatively small spatial scales, such as upstream-downstream comparisons.

ecology↗

bioRxiv2025

A skeletal muscle-sympathetic nerve-intestine network underlies muscle inflammation and atrophy induced by immobilization

Immobility is a common cause of muscle atrophy, but the underlying mechanisms have remained unclear. Here we show that limb immobilization in mice elicits inflammation and atrophy of skeletal muscle that are preventable by neutralizing antibodies to the chemokine CXCL10. Limb immobilization also induced changes to the gut microbiota and intestinal inflammation, and either sterilization of the intestine with antibiotics or administration of 10-hydroxy-cis-12-octadecenoic acid--a linoleic acid-derived gut microbial metabolite--prevented intestinal and muscle inflammation as well as muscle atrophy induced by immobilization, implicating intestinal inflammation in muscle inflammation and atrophy. Limb immobilization activated sympathetic nerves and increased {beta}2-adrenergic receptor gene (Adrb2) expression in the intestine. Single-cell RNA-sequencing analysis revealed that, among cells expressing Adrb2 in the intestine, immobilization increased only the population of macrophages. Pharmacological inhibition or macrophage-specific ablation of Adrb2 prevented immobilization-induced intestinal and muscle inflammation. Our results thus implicate a previously unrecognized muscle-nerve-intestine network in immobilization-induced muscle atrophy.

molecular biology↗

bioRxiv2024

Translational response to mitochondrial stresses is orchestrated by tRNA modifications.

Mitochondrial stress and dysfunction play important roles in many pathologies. However, how cells respond to mitochondrial stress is not fully understood. Here, we examined the translational response to electron transport chain (ETC) inhibition and arsenite induced mitochondrial stresses. Our analysis revealed that during mitochondrial stress, tRNA modifications (namely f5C, hm5C, queuosine and its derivatives, and mcm5U) dynamically change to fine tune codon decoding, usage, and optimality. These changes in codon optimality drive the translation of many pathways and gene sets, such as the ATF4 pathway and selenoproteins, involved in the cellular response to mitochondrial stress. We further examined several of these modifications using targeted approaches. ALKBH1 knockout (KO) abrogated f5C and hm5C levels and led to mitochondrial dysfunction, reduced proliferation, and impacted mRNA translation rates. Our analysis revealed that tRNA queuosine (tRNA-Q) is a master regulator of the mitochondrial stress response. KO of QTRT1 or QTRT2, the enzymes responsible for tRNA-Q synthesis, led to mitochondrial dysfunction, translational dysregulation, and metabolic alterations in mitochondria-related pathways, without altering cellular proliferation. In addition, our analysis revealed that tRNA-Q loss led to a domino effect on various tRNA modifications. Some of these changes could be explained by metabolic profiling. Our analysis also revealed that utilizing serum deprivation or alteration with Queuine supplementation to study tRNA-Q or stress response can introduce various confounding factors by altering many other tRNA modifications. In summary, our data show that tRNA modifications are master regulators of the mitochondrial stress response by driving changes in codon decoding.

molecular biology↗

bioRxiv2023

Novel phosphatidylinositol flippases contribute to phosphoinositide homeostasis in the plasma membrane

Phosphatidylinositol is a precursor of various phosphoinositides, which play crucial roles in intracellular signaling and membrane dynamics and have impact on diverse aspects of cell physiology. Phosphoinositide synthesis and turnover occur in the cytoplasmic leaflet of the organellar and plasma membranes. P4-ATPases (lipid flippases) are responsible for translocating membrane lipids from the exoplasmic (luminal) to the cytoplasmic leaflet, thereby regulating membrane asymmetry. However, the mechanism underlying phosphatidylinositol translocation across cellular membranes remains elusive. Here, we discovered that the phosphatidylcholine flippases ATP8B1, ATP8B2, and ATP10A can also translocate phosphatidylinositol at the plasma membrane. To explore the function of these phosphatidylinositol flippases, we used cells depleted of CDC50A, a protein necessary for P4-ATPase function. Upon activation of the Gq-coupled receptor, depletion of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] was accelerated in CDC50A knockout cells compared with control cells, suggesting a decrease in PtdIns4,5P2 levels within the plasma membrane of the knockout cells. These findings highlight the pivotal role of P4-ATPases in maintaining phosphoinositide homeostasis and suggest a mechanism for enrichment of phosphatidylinositol in the cytoplasmic leaflet of the plasma membrane.

cell biology↗

bioRxiv2023

Atg15 is a vacuolar phospholipase that disintegrates organelle membranes

Atg15 (autophagy-related 15) is a vacuolar phospholipase essential for the degradation of cytoplasm-to-vacuole targeting (Cvt) bodies and autophagic bodies, hereinafter referred to as intravacuolar autophagic compartments (IACs), but it remains unknown if Atg15 directly disrupts IAC membranes. Here we show that the recombinant Chaetomium thermophilum Atg15 lipase domain (CtAtg15(73-475)) possesses phospholipase activity that in acidic environments digests phospholipid to generate lysophospholipid and free fatty acid. The activity of CtAtg15(73-475) was markedly elevated by limited digestion with proteinase K. Proteinase K-treated CtAtg15(73-475) was detected as three fragments, with cleavage between S159 and V160, and between F209 and N210. We inserted the human rhinovirus 3C protease recognition sequence into the two sites and found that cleavage between S159 and V160 was important to activate CtAtg15(73-475). We confirmed that CtAtg15 compensated for the absence of ATG15 in Saccharomyces cerevisiae cells, indicating that CtAtg15 could disintegrate S. cerevisiae IAC in vivo. Further, both mitochondria and IAC were disintegrated by CtAtg15 in S. cerevisiae. This study suggests that Atg15 can degrade any organelle membrane, indicating that Atg15 plays a role in disrupting organelle membranes delivered to vacuoles by autophagy.

molecular biology↗

bioRxiv2023

Identical tau filaments in subacute sclerosing panencephalitis and chronic traumatic encephalopathy

Subacute sclerosing panencephalitis (SSPE) occurs in some individuals after measles infection, following a symptom-free period of several years. It resembles chronic traumatic encephalopathy (CTE), which happens after repetitive head impacts or exposure to blast waves, following a symptom-free period. As in CTE, when present, the neurofibrillary changes of SSPE are concentrated in superficial cortical layers. Here we used electron cryo-microscopy of tau filaments from two cases of SSPE to show that the tau folds of SSPE and CTE are identical. Two types of filaments were each made of two identical protofilaments with an extra density in the {beta}-helix region. Like in CTE, the vast majority of tau filaments were Type I, with a minority of Type II filaments. These findings suggest that the CTE tau fold can be caused by different environmental insults, which may be linked by inflammatory changes.

neuroscience↗

bioRxiv2022

Deducing ensemble dynamics and information flow from the whole-brain imaging data

Recent development of large-scale activity imaging of neuronal ensembles provides opportunities for understanding how activity patterns are generated in the brain and how information is transmitted between neurons or neuronal ensembles. However, methodologies for extracting the component properties that generate overall dynamics are still limited. In this study, the results of time-lapse 3D imaging (4D imaging) of head neurons of the nematode C. elegans were analyzed by hitherto unemployed methodologies. By combining time-delay embedding with independent component analysis, the whole-brain activities were decomposed to a small number of component dynamics. Results from multiple samples, where different subsets of neurons were observed, were further combined by matrix factorization, revealing common dynamics from neuronal activities that are apparently divergent across sampled animals. By this analysis, we could identify components that show common relationships across different samples and those that show relationships distinct between individual samples. We also constructed a network model building on time-lagged prediction models of synaptic communications. This was achieved by dimension reduction of 4D imaging data using the general framework gKDR (gradient kernel dimension reduction). The model is able to decompose basal dynamics of the network. We further extended the model by incorporating probabilistic distribution, resulting in models that we call gKDR-GMM and gKDR-GP. The models capture the overall relationships of neural activities and reproduce the stochastic but coordinated dynamics in the neural network simulation. By virtual manipulation of individual neurons and synaptic contacts in this model, information flow could be estimated from whole-brain imaging results.

neuroscience↗

bioRxiv2022

AI-based search for convergently expanding, advantageous mutations in SARS-CoV-2 by focusing on oligonucleotide frequencies

Among mutations that occur in SARS-CoV-2, efficient identification of mutations advantageous for viral replication and transmission is important to characterize and defeat this rampant virus. Mutations rapidly expanding frequency in a viral population are candidates for advantageous mutations, but neutral mutations hitchhiking with advantageous mutations are also likely to be included. To distinguish these, we focus on mutations that appear to occur independently in different lineages and expand in frequency in a convergent evolutionary manner. Batch-learning SOM (BLSOM) can separate SARS-CoV-2 genome sequences according by lineage from only providing the oligonucleotide composition. Focusing on remarkably expanding 20-mers, each of which is only represented by one copy in the viral genome, allows us to correlate the expanding 20-mers to mutations. Using visualization functions in BLSOM, we can efficiently identify mutations that have expanded remarkably both in the Omicron lineage, which is phylogenetically distinct from other lineages, and in other lineages. Most of these mutations involved changes in amino acids, but there were a few that did not, such as an intergenic mutation.

bioinformatics↗