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Biology subjects

Higashi, H.

Publications and source records attributed to Higashi, H..

8 recordsLinked to original sources

Low-dimensional latent spaces identify the functional structure of individual behavioral phenotypes

Extracting stable individual traits from behavior observed across diverse contexts is a central challenge in behavioral modeling. We propose a framework for inferring domain-invariant individual latent representations by jointly encoding behaviors across multiple domains. Using large-scale telemetry data from professional Counter-Strike 2 gameplay, we demonstrate that these representations are stable across distinct environments and roles, improving behavior prediction in novel domains. Our analysis reveals that complex idiosyncratic movement policies can be effectively compressed into low-dimensional embeddings, with as few as two dimensions capturing the majority of individual strategic variation. Crucially, the learned latent space forms a structured metric space where Euclidean distances predict the degradation of transfer performance. Furthermore, we show that the latent axes align with interpretable behavioral phenotypes, such as risk-taking and social cohesion. These findings suggest that multi-domain integration is a robust method for uncovering the functional structure of latent individuality in complex decision-making tasks, bridging the gap between high-dimensional telemetry data and meaningful psychological constructs.

animal behavior and cognition↗

Serial dependence in the perception of proportion

The influence of previously encountered stimuli on subsequent perceptual judgments is termed serial dependence. Serial dependence has been robustly demonstrated across a broad spectrum of visual features, ranging from low-level attributes, such as orientation and color, to high-level representations, including facial identity. To further understand this dependency, the present study investigated the presence of serial dependence in judgments of relative proportions within visual stimuli. Participants completed a two-alternative forced-choice (2AFC) task involving stimuli composed of two symbols. These symbols differed only in brightness in Experiment 1 and only in shape in Experiment 2. Participants were required to judge which symbol occupied the larger proportion. The results revealed a systematic bias in the participants responses. Specifically, Experiment 1 yielded a repulsive bias (negative serial dependence), where current judgments shifted away from the proportion observed in the preceding trial. Conversely, Experiment 2 exhibited an attractive bias (positive serial dependence), pulling current judgments toward the preceding proportion. Furthermore, the magnitude and direction of this serial dependence appeared to be modulated by both the participants confidence in their judgments and the feature similarity between successive stimuli. These findings suggest that the perception of proportion has serial dependence and extend the generality of this phenomenon to higher-level visual summary statistics.

animal behavior and cognition↗

A residual memory trace in an accumulator explains serial dependence

Human perception is not a series of isolated snapshots; our recent past continuously shapes what we currently see, a phenomenon known as serial dependence. While convolutional neural networks (CNNs) excel as models of vision, they are typically static and fail to capture such dynamic, history-dependent effects. Here, we introduce SDNet, a model that explains how serial dependence arises from the mechanics of decision-making. SDNet integrates a standard CNN with a recurrent network that functions as a sequential evidence accumulator. We hypothesize that this bias is not a flaw or a feature for optimality, but a natural byproduct of the accumulator retaining a residual memory trace of past decisions. Without being directly fit to behavioral data, SDNet spontaneously reproduces the characteristic patterns of serial dependence from human orientation and numerosity judgment tasks. The model even captures a key feature of human perception: that the bias grows stronger as task difficulty increases. This work provides a concrete, neurally plausible mechanism for serial dependence, challenging theories that frame it as a purely optimal strategy. By showing how a fundamental perceptual bias emerges from an intrinsic property of a dynamic system, SDNet represents a significant advance in building more biologically realistic models of human vision.

animal behavior and cognition↗

Individuality transfer: Predicting human decision-making across tasks

Predicting an individuals behaviour in one task condition based on their behaviour in a different condition is a key challenge in modeling individual decision-making tendencies. We propose a novel framework that addresses this challenge by leveraging neural networks and introducing a concept we term the "individual latent representation." This representation, extracted from behaviour in a "source" task condition via an encoder network, captures an individuals unique decision-making tendencies. A decoder network then utilizes this representation to generate the weights of a task-specific neural network (a "task solver"), which predicts the individuals behaviour in a "target" task condition. We demonstrate the effectiveness of our approach in two distinct decision-making tasks: a value-guided task and a perceptual task. Our framework offers a robust and generalizable approach for parameterizing individual variability, providing a promising pathway toward computational modeling at the individual level--replicating individuals in silico.

animal behavior and cognition↗

Sexual Dimorphism of Plasma and Tissue Proteomes in Human Calcific Aortic Valve Stenosis Pathogenesis

BACKGROUNDCalcific aortic valve stenosis (CAVS) is a global clinical burden, impacting around 2% of the population over 65 years of age. No pharmacotherapeutics exist, with surgical repair and transcatheter valve replacement being the only intervention. Females are underrepresented in studies of CAVS, leading to delay in timely intervention and increased mortality. Histopathology demonstrates female CAVS presents with decreased valvular calcification but increased fibrosis and severity of symptoms. We hypothesize that the underlying molecular mechanisms contributing to disease progression and fibrocalcific burden in AS differs between male and female patients. Our goal for this study is to use previously acquired proteomic datasets of a clinically-defined human AS cohort to examine sex disparities and underlying sex-specific disease signatures. METHODS and RESULTSAge-matched human AS tissue samples (n=4 females, n=14 males) were each segmented into non-diseased, fibrotic, and calcified disease stages and analyzed using LC-MS/MS proteomics and quantitative histopathology. CAVD plasma samples (n=20 females, n=30 males) were analyzed for circulating sex-specific biomarkers via LC-MS/MS. Unbiased principal component analysis shows sex- and stage-specific proteome clustering. AS pathogenesis drove sex-specific disparities in the valvular proteome: 338/1503 total proteins were differentially-enriched by sex across disease stages. Compared to sex-specific non-diseased controls, female fibrotic tissue resulted in 2.75-fold greater number of differentially-enriched proteins than did male fibrotic tissue (female: 42, male: 16; p<0.05 threshold). In contrast, female calcific tissue identified 2.473-fold less differentially-enriched proteins than male calcific tissue (female: 157, male 356; q<0.05 threshold). By Functional Enrichment Analysis revealed specific proteins responsible for the exacerbated valvular fibrosis signature in females, implicated adenosine phosphate metabolism as a potential male-specific driver of AS, and further reinforce the shared contribution of aberrant lipid and cholesterol activity to AS progression in both sexes. CONCLUSIONSWe reveal a sexually-dimorphic AS proteome, including the novel overabundance of ECM remodeling pathways in female calcified aortic valve tissues. This analysis allows for identification of potential sex-specific protein drug targets implicated in AS pathobiology.

pathology↗

Silkworm model for Bacillus anthracis infection and virulence determination

Bacillus anthracis is an obligate pathogen and a causative agent of anthrax. Its major virulence factors are plasmid-coded; however, recent studies have revealed chromosome-encoded virulence factors, indicating that the current understanding of its virulence mechanism is elusive and needs further investigation. In this study, we established a silkworm (Bombyx mori) infection model of B. anthracis Sterne. We showed that silkworms were killed by B. anthracis and cured of the infection when administered with antibiotics. We quantitatively determined the lethal dose of the bacteria that kills 50% larvae and effective doses of antibiotics that cure 50% infected larvae. Furthermore, we demonstrated that B. anthracis mutants with disruption in virulence genes such as pagA, lef, and atxA had attenuated silkworm-killing ability and reduced colonization in silkworm hemolymph. The silkworm infection model established in this study can be utilized in large-scale infection experiments to identify novel virulence determinants and develop novel therapeutic options against B. anthracis infections.

microbiology↗

Conserved and Divergent Modulation of Calcification in Atherosclerosis and Aortic Valve Disease by Tissue Extracellular Vesicles

BackgroundFewer than 50% of patients develop calcification of both atherosclerotic plaques and aortic valves, implying differential pathogenesis. While circulating extracellular vesicles (EVs) act as biomarkers of cardiovascular diseases, tissue-entrapped EVs associate with early mineralization, but their contents, function, and contributions to disease remain unknown. ResultsGlobal proteomics of human carotid artery endarterectomies and calcified aortic valves from a total of 27 donors/patients revealed significant over-representation of proteins with vesicle-associated pathways/ontologies common to both diseases. We exploited enzymatic digestion, serial (ultra)centrifugation and OptiPrep density-gradient separation to isolate EV populations from diseased arteries and valves. Mass spectrometry found 22 EV marker proteins to be highly enriched in the four least-dense OptiPrep fractions while extracellular matrix proteins predominated in denser fractions, as confirmed by CD63 immunogold electron microscopy and nanoparticle tracking analysis. Proteomics and miRNA-sequencing of OptiPrep-enriched tissue EVs quantified 1,104 proteins and 123 miR cargoes linked to 5,182 target genes. Pathway networks of proteins and miR targets common to artery and valve tissue EVs revealed a shared regulation of Rho GTPase and MAPK intracellular signaling cascades. 179 proteins and 5 miRs were significantly altered between artery and valve EVs; multi-omics integration determined that EVs differentially modulated cellular contraction and p53-mediated transcriptional regulation in diseased vascular vs. valvular tissue. ConclusionsOur findings delineate a strategy to isolate, purify, and study protein and RNA cargoes from EVs entrapped in fibrocalcific tissues. Multi-omics and network approaches implicated tissue-resident EVs in human cardiovascular disease.

systems biology↗

Functional Importance of Second Heart Field-derived Cells During Thoracic Aortic Aneurysm Formation

BackgroundThe ascending aorta is a common location for aneurysm and dissection. This aortic region is populated by a mosaic of medial and adventitial cells that are embryonically derived from either the second heart field (SHF) or the cardiac neural crest. SHF-derived cells populate areas that coincide with the spatial specificity of thoracic aortopathies. The purpose of this study was to determine whether and how SHF-derived cells contribute to ascending aortopathies. MethodsAscending aortic pathologies were examined in patients with sporadic thoracic aortopathies and angiotensin II (AngII)-infused mice. Ascending aortas without overt pathology from AngII-infused mice were subjected to mass spectrometry assisted proteomics, and molecular features of SHF-derived cells were determined by single cell transcriptomic analyses. Genetic deletion of either low-density lipoprotein receptor-related protein 1 (Lrp1) or transforming growth factor-{beta} receptor 2 (Tgfbr2) in SHF- derived cells was conducted to examine the impact of SHF-derived cells on vascular integrity. ResultsPathologies in human ascending aortic aneurysmal tissues were predominant in outer medial layers and adventitia. This gradient was mimicked in mouse aortas following AngII infusion that was coincident with the distribution of SHF-derived cells. Proteomics indicated that brief AngII infusion, prior to overt pathology, evoked downregulation of SMC proteins and differential expression of extracellular matrix proteins, including several LRP1 ligands. LRP1 deletion in SHF-derived cells augmented AngII-induced ascending aortic aneurysm and rupture. Single cell transcriptomic analysis revealed that brief AngII infusion decreased Lrp1 and Tgfbr2 mRNA abundance in SHF-derived cells and induced a unique fibroblast population with low abundance of Tgfbr2 mRNA. SHF-specific Tgfbr2 deletion led to embryonic lethality at E12.5 with dilatation of the outflow tract and retroperitoneal hemorrhage. Integration of proteomic and single cell transcriptomics results identified plasminogen activator inhibitor 1 (PAI1) as the most increased protein in SHF-derived SMCs and fibroblasts during AngII infusion. Immunostaining revealed a transmural gradient of PAI1 in both ascending aortas of AngII-infused mice and human ascending aneurysmal aortas that mimicked the gradient of medial and adventitial pathologies. ConclusionSHF-derived cells exert a critical role in maintaining vascular integrity through LRP1 and TGF-{beta} signaling associated with increases of aortic PAI1. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=89 SRC="FIGDIR/small/930917v6_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@185e3d9org.highwire.dtl.DTLVardef@131d702org.highwire.dtl.DTLVardef@11afa42org.highwire.dtl.DTLVardef@242786_HPS_FORMAT_FIGEXP M_FIG C_FIG Clinical PerspectiveO_ST_ABSWhat is new?C_ST_ABS- SHF-derived SMCs and fibroblasts associate with AngII-induced aortic pathologies. - AngII induces a distinct fibroblast sub-cluster that is less abundant for mRNAs related to major extracellular components and TGF{beta} ligands and receptors, but more abundant for proliferative genes. - TGFBR2 deletion in SHF-derived cells are embryonic lethal with significant dilatation of the outflow tract in mice. - SHF-specific deletion of LRP1 leads to aortic pathologies in mice, supporting the importance of SHF-derived cells in maintaining ascending aortic wall integrity. What are the clinical implications?- Heterogeneity of the embryonic origins of SMCs and fibroblasts contributes to complex mechanisms of vasculopathy formation, which should be considered when investigating the pathogenesis of thoracic aortopathies.

pathology↗