Biology subjects

Liu, W.

Publications and source records attributed to Liu, W..

At least 199 records · Page 11Linked to original sources

bioRxiv2024

An adaptive autoregressive diffusion approach to design active humanized antibody and nanobody

Humanization is a critical process for designing efficiently specific antibodies and nanobodies prior to clinical trials. Developing widely recognized deep learning techniques or frameworks for humanizing conventional antibodies and nanobodies presents a valuable yet challenging task. Inspired by the effectiveness of diffusion models across various applications, we introduce HuDiff, an adaptive diffusion approach for humanizing antibodies and nanobodies from scratch, referred to as HuDiff-Ab and HuDiff-Nb, respectively. This approach begins the humanization process exclusively with complementarity-determining region (CDR) sequences, eliminating the need for humanized templates. On public benchmark datasets, the results of HuDiff-Abs humanized antibodies are more similar to experimentally humanized antibodies than to those of the Sapiens humanization model. Besides, humanized nanobodies produced by HuDiff-Nb exhibit a higher humanness score and greater nativeness than those generated by the Lammanade pipeline for humanization nanobody. We apply HuDiff to humanize a mouse antibody and an alpaca nanobody, both targeting the SARS-CoV-2 RBD, and validate the binding affinity of humanized sequences through Bio-Layer Interferometry (BLI) experiments. The results show the binding affinity of the best humanized antibody is nearly equal to that of the parental mouse antibody (0.15 nM vs. 0.12 nM). Remarkably, the top-performing humanized nanobody exhibits a significantly enhanced binding affinity compared to the parental alpaca nanobody (2.52 nM vs. 5.47 nM), representing a 54% increase. These findings indicate that our approach HuDiff is highly effective in enhancing the humanness of antibodies and nanobodies while maintaining or potentially improving the binding affinity of the designed humanized sequences. The code and checkpoints of HuDiff are available at https://github.com/TencentAI4S/HuDiff.

bioinformatics↗

bioRxiv2024

The Integrated Stress Response Suppresses PINK1-dependent Mitophagy by Preserving Mitochondrial Import Efficiency

Mitophagy is crucial for maintaining mitochondrial health, but how its levels adjust to different stress conditions remains unclear. In this study, we investigated the role of the DELE1-HRI axis of integrated stress response (ISR) in regulating mitophagy, a key mitochondrial stress pathway. Our findings show that the ISR suppresses mitophagy under non-depolarizing mitochondrial stress by positively regulating mitochondrial protein import, independent of ATF4 activation. Mitochondrial protein import is regulated by the rate of protein synthesis under both depolarizing and non-depolarizing stress. Without ISR, increased protein synthesis overwhelms the mitochondrial import machinery, reducing its efficiency. Under depolarizing stress, mitochondrial import is heavily impaired even with active ISR, leading to significant PINK1 accumulation. In contrast, non-depolarizing stress allows more efficient protein import in the presence of ISR, resulting in lower mitophagy. Without ISR, mitochondrial protein import becomes severely compromised, causing PINK1 accumulation to reach the threshold necessary to trigger mitophagy. These findings reveal a novel link between ISR-regulated protein synthesis, mitochondrial import, and mitophagy, offering potential therapeutic targets for diseases associated with mitochondrial dysfunction.

cell biology↗

bioRxiv2024

Direct and indirect selection in a proofreading polymerase

The traits that affect evolvability are subject to indirect selection, as these traits affect the course of evolution over many generations rather than the direct replicative fitness of an individual. However, the evolution of evolvability-determining traits is often difficult to study because putative evolvability alleles often have confounding direct fitness effects of unknown origin and size. Here, we study theoretically and experimentally the evolution of mutation rates in proofreading polymerases with orthogonal control of direct and indirect selection. Mutagenic DNA polymerases enjoy a long-time fitness advantage by enhancing the rate of acquiring beneficial mutations. However, this is offset by a short-time fitness penalty, which we trace to a counterintuitive trade-off between mutation rates and activity in proofreading polymerases. Since these fitness effects act on different timescales, no one number characterizes the fitness of a mutator allele. We find unusual dynamic features in the resulting evolutionary dynamics, such as kinetic exclusion, selection by dynamic environments, and Rock-Paper-Scissors dynamics in the absence of ecology. Our work has implications for the evolution of mutation rates and more broadly, evolution in the context of an anti-correlation between mutation rates and short term fitness.

evolutionary biology↗

bioRxiv2024

Biophysical and biochemical evidence for the role of acetate kinases (AckAs) in an acetogenic pathway in pathogenic spirochetes

Unraveling the metabolism of Treponema pallidum is a key component to understanding the pathogenesis of the human disease that it causes, syphilis. For decades, it was assumed that glucose was the sole carbon/energy source for this parasitic spirochete. But the lack of citric-acid-cycle enzymes suggested that alternative sources could be utilized, especially in microaerophilic host environments where glycolysis should not be robust. Recent bioinformatic, biophysical, and biochemical evidence supports the existence of an acetogenic energy-conservation pathway in T. pallidum and related treponemal species. In this hypothetical pathway, exogenous D-lactate can be utilized by the bacterium as an alternative energy source. Herein, we examined the final enzyme in this pathway, acetate kinase (named TP0476), which ostensibly catalyzes the generation of ATP from ADP and acetyl-phosphate. We found that TP0476 was able to carry out this reaction, but the protein was not suitable for biophysical and structural characterization. We thus performed additional studies on the homologous enzyme (75% amino-acid sequence identity) from the oral pathogen Treponema vincentii, TV0924. This protein also exhibited acetate kinase activity, and it was amenable to structural and biophysical studies. We established that the enzyme exists as a dimer in solution, and then determined its crystal structure at a resolution of 1.36 [A], showing that the protein has a similar fold to other known acetate kinases. Mutation of residues in the putative active site drastically altered its enzyme activity. A second crystal structure of TV0924 in the presence of AMP (at 1.3 [A] resolution) provided insight into the binding of one of the enzymes substrates. On balance, this evidence strongly supported the roles of TP0476 and TV0924 as acetate kinases, buttressing the existence of the acetogenic pathway in pathogenic treponemes.

biophysics↗

bioRxiv2024

Latexin facilitates neointimal formation via promoting smooth muscle cell proliferation and macrophage migration

RationaleNeointimal formation is the major cause of cardiovascular diseases such as atherosclerosis and restenosis. Although restenosis rates are significantly reduced by the development of drug-eluting, the stent may not be implanted at all atherosclerotic sites, and long-term dual anti-platelet therapy is needed after stent implantation. Thus, it is essential to elucidate the detailed mechanisms underlying neointimal formation for developing novel therapies. Latexin (LXN), a previously identified pro-inflammatory protein, is highly expressed in vasculature and its expression is regulated by shear stress. Whether it plays a role in vascular remodeling, however, remains unknown. ObjectiveTo determine whether LXN is involved in neointimal formation, and if so, to define the molecular mechanisms involved. Methods and ResultsWe found that the expression of LXN was significantly increased in neointimal hyperplasia, as determined by western blot. Immunofluorescent staining indicated that increased LXN expression was predominantly localized in smooth muscle cells and macrophages. To determine the cell specific roles of LXN in neointimal formation after injury, we generated global, smooth muscle cell (SMC)-specific, endothelial specific-, and myeloid-specific LXN knockout (KO) mice. We found that global, SMC-, and myeloid-specific LXN deficiency markedly prevented neointimal hyperplasia in mice after carotid artery ligation, whereas LXN deficiency in endothelial cells had no effects. Mechanistically, we found that LXN deficiency in SMCs significantly attenuated SMC proliferation and migration, mainly through inhibiting the expression of platelet-derived growth factor (PDGF) receptors. Intriguely, LXN deficiency in macrophages inhibited monocyte chemoattractant protein-1 (MCP-1)-induced macrophage migration through inhibiting ERK phosphorylation. ConclusionsIn summary, we for the first time demonstrated that LXN is essentially involved in SMC proliferation and microphage migration. Specific inhibition of LXN signaling may provide a novel therapeutic strategy for the treatment of cardiovascular diseases, such as restenosis and atherosclerosis. Novelty and SignificanceO_ST_ABSWhat is known?C_ST_ABSO_LILatexin (LXN) is considered to be a novel pro-inflammatory protein and its expression is responsive to laminar shear stress. C_LIO_LIVascular inflammation, SMC proliferation, and macrophage migration are critical events in neointimal hyperplasia. C_LI What new information does this article contribute?O_LILXN is elevated in carotid artery ligation-induced neointimal hyperplasia in mice. C_LIO_LISMC-specific LXN deficiency prevents neointimal hyperplasia through inhibiting SMC proliferation migration via attenuating platelet-derived growth factor receptor expression. C_LIO_LIMyeloid-specific LXN deficiency prevents neointimal hyperplasia through inhibiting monocyte chemoattractant protein-1-induced macrophage migration and extracellular signal-regulated kinase phosphorylation. C_LI Neointimal formation is the major cause of cardiovascular disease such as atherosclerosis and restenosis after stenting or balloon angioplasty. Because of the development of drug-eluting stents, restenosis rates have been significantly reduced; however, it is still essential to explore the detailed mechanisms underlying neointimal hyperplasia. Latexin (LXN) is considered a novel pro-inflammatory protein that is ubiquitously expressed in vascular and immune cells. We found that LXN is elevated in neointimal hyperplasia, and its deficiency in SMCs and macrophages, but not in ECs, markedly prevents neointimal formation after carotid artery ligation in mice. Mechanistically, LXN deficiency in SMCs prevents SMC proliferation and migration via attenuation of platelet-derived growth factor receptor expression. Further, myeloid-specific LXN deficiency inhibits monocyte chemoattractant protein-1-induced macrophage migration via attenuation of extracellular signal-regulated kinase phosphorylation. For the first time, the present study demonstrated that LXN is a crucial mediator implicated in SMC biology and macrophage migration.

physiology↗

bioRxiv2024

Inter-Kingdom Interactions and Environmental Influences on the Oral Microbiome in Severe Early Childhood Caries

Dental caries arise from intricate interactions among oral microorganisms, impacting ecological stability and disease progression. This study delves into the bacterial-fungal dynamics in severe early childhood caries (S-ECC) among 61 children aged 3-4 years with complete deciduous dentition. We evaluated environmental factors such as saliva pH, buffering capacity, and trace elements (iron, fluoride). We examined the performance of 16S rRNA V1-V9 regions gene and internal transcribed spacer (ITS) primers for bacteria and fungi from plaque and saliva to characterize community compositions and diversity. Saliva pH and buffering capacity were also measured. Findings revealed significant shifts in bacterial diversity in S-ECC saliva samples, marked by decreased diversity and elevated abundance of cariogenic species, particularly Streptococcus mutans. Candida albicans was notably more prevalent in the S-ECC group, implicating its potential role in pathogenesis. Iron and fluoride concentrations showed no significant correlation with microbial community structure. Network analyses uncovered complex intra- and inter-kingdom interactions, underscoring cooperative and competitive dynamics. S-ECC children exhibited higher abundances of bacteria (Streptococcus mutans, Granulicatella, Actinomyces) and fungi (Candida albicans), with specific microbial taxa associated with reduced saliva pH. ImportanceThis study illuminates the intricate relationship between bacteria and fungi within the oral microbial community of children, specifically highlighting differences between those with severe early childhood caries (S-ECC) and those without caries. Through an extensive analysis of the microbial composition in both saliva and dental plaque, we identified a significant increase in the abundance of specific bacterial taxa (e.g., S. mutans, Granulicatella, Actinomyces) and fungal species (e.g., C. albicans) in the oral cavities of children with S-ECC. This finding underscores the potential role of these microorganisms in the development of caries. Contrary to previous studies that emphasize the importance of iron and fluoride in oral health, our research found no significant correlation between the concentrations of these elements and the composition of oral microbial communities. This result challenges conventional understanding and opens new avenues for future research. Additionally, we discovered an association between certain microbial species and reduced salivary pH, offering fresh insights into the relationship between the oral microenvironment and caries development. The implications of our findings are substantial for the development of prevention and intervention strategies targeting childhood caries. They also underscore the critical need for a deeper exploration of oral microbial interactions and their environmental influences.

microbiology↗

bioRxiv2024

Single-cell virology: On-chip, quantitative characterization of the dynamics of virus spread from one single cell to another

Virus spread at the single-cell level is largely uncharacterized. We have designed and constructed a microfluidic device in which each nanowell contained a single, infected cell (donor) and a single, uninfected cell (recipient). Using a GFP-expressing poliovirus as our model, we observed both lytic and non-lytic spread. Donor cells supporting lytic spread established infection earlier than those supporting non-lytic spread. However, non-lytic spread established infections in recipient cells substantially faster than lytic spread and yielded higher rates of genome replication. While lytic spread was sensitive to the presence of capsid entry/uncoating inhibitors, non-lytic spread was not. Consistent with emerging models for non-lytic spread of enteroviruses using autophagy, reduction of LC3 levels in cells impaired non-lytic spread and elevated the fraction of virus in donor cells spreading lytically. The ability to distinguish lytic and non-lytic spread unambiguously will enable discovery of viral and host factors and host pathways used for non-lytic spread of enteroviruses and other viruses as well.

cell biology↗

bioRxiv2024

Swarming bacteria exhibit developmental phase transitions to establish scattered colonies in new regions

The bacterial Type 9 Secretion System (T9SS) is essential for the development of periodontal diseases and Bacteroidetes gliding motility. T9SS-driven motile bacteria, abundant within the human oral microbiota, transport non-motile oral microbes and bacteriophages as cargo, shaping the spatial structure of polymicrobial communities. However, the physical rules governing the dispersal of T9SS-driven bacterial swarms are barely understood. Here, we collected time-lapse images, under anaerobic conditions, of developing swarms of a T9SS-driven microbe common to the human oral microbiota. Tracking of swarms revealed that small peripheral flares emerging from a colony develop structures that resemble fireworks displaying a chrysanthemum effect and flower-like patterns that convert to wave-like patterns and which further evolve into scattered microcolonies. Particle-image velocimetry showed density-dependent phase transitions and initial vorticity within these emerging patterns. Numerical simulations demonstrate that these patterns arise due to changes in swarm speed and alignment strength. Our data reveal a strategy used by an anaerobic swarming bacterium to control swarm behavior, resulting in scattered microcolonies distant from the mother colony, thus reducing competition for resources among colony members. This might ensure species survival even if conditions change drastically in one location of the human oral cavity.

microbiology↗

bioRxiv2024

Proteomic responses of oat (Avena sativa L.) to drought stress

Drought is a major abiotic factor limiting the growth and development of the oat industry, and understanding its drought tolerance mechanisms is vital to oat production. In this study, we measured the phenotypic and physiological indices of drought-resistant (Grain King [G]) and water-sensitive (XiYue [X]) oat varieties and performed comparative proteomic analysis under drought stress and normal water supply (soil water content of 75% {+/-} 5% of field water holding capacity) conditions. The results indicated that plant height, aboveground biomass, and underground biomass of variety X were 7.9%, 9.5%, and 14.6% lower than those under normal water supply, respectively, and the difference in plant height was significant (p < 0.05), whereas the decrease in all these indicators of variety G was small. Drought stress significantly increased malondialdehyde (MDA) content, soluble sugar (SS) content, superoxide dismutase (SOD) activity, and peroxidase (POD) activity of variety G by 48.6%, 68.5%, 81.3%, and 101.7%, respectively (p < 0.05). Variety X also showed increases up to various extents, but the increases were smaller than those of variety G. Additionally, 151 and 792 differentially expressed proteins (DEPs) identified in varieties G and X, respectively. Weighted Gene Co-expression Network Analysis(WGCNA), Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genome(KEGG) analyses demonstrated that the DEPs who were highly correlated with POD and SOD activity and SS content in variety G, were majorly involved in energy metabolism, protein translation, RNA processing, amino acid metabolism, and protein folding, whereas those with high correlation with the above three physiological indicators in variety X were primarily involved in RNA processing, protein stabilization, plant photosynthesis, intracellular signal transduction, and protein folding. Overall, the study elucidated the drought resistance mechanisms of different types of oats at the protein level

molecular biology↗

bioRxiv2024

Towards genuine three-dimensional diffusion imaging with physiological motion compensation

PurposeWe aim to implement a 3D DWI sequence and show its usage on patients with new ischemic lesions. Materials and MethodsThe proposed 3D DWI sequence was implemented by integrating second-order gradient moment nulling (M2) and cardiac motion synchronization (Sync). All data were acquired on a 3T MAGNETOM Prisma scanner (Siemens Healthcare, Erlangen, Germany) using a 64 channel head and neck coil. 21 healthy volunteers underwent 3D DWI scans at 0.9 mm isotropic resolution using four motion compensation methods for comparison: no compensation (M0), M2 only, Sync only and the proposed M2+Sync method. 2D phase variation maps with different motion compensation methods were also acquired for one subject to illustrate the mechanism of the proposed method. A ghost-to-signal ratio (GSR) and blurring index was defined and compared among the four methods with repeated measures ANOVA and Tukeys test. 3D DWI was compared with 2D DWI for ADC quantification. Image quality and ischemic lesion conspicuity were evaluated with 12 patients after endovascular treatment. >ResultsWhole brain 3D DWI was achieved at 0.9 mm isotropic resolution within 5 minutes using the proposed sequence. M2+Sync achieved the lowest level of GSR and blurring along the slice direction. ADC quantification showed no statistically significant difference between M2+Sync compared to 2D DWI. 3D DWI showed similar image quality, higher lesion conspicuity and counts compared to 2D DWI. ConclusionDirect 3D DWI can be achieved by the combination of second order gradient moment nulling and cardiac synchronization.

bioengineering↗

bioRxiv2024

Inhibition on neutrophil extracellular traps by oligomeric procyanidins alleviate chemotherapy-induced chronic kidney injury via gut-kidney axis

Cisplatin is one of the most widely used chemotherapeutic agents for various solid tumors in the clinic, but its use is limited by adverse effects in normal tissues. In particular, cisplatin administration often damages the kidneys. However, little is known about how to alleviate cisplatin-induced chronic kidney disease (CKD) specifically. Here, we found that repeated low-dose cisplatin (RLDC) recruited susceptible neutrophils to the proximal tubule, thereby promoting the progression of CKD in the mouse model. Mechanically, cisplatin destroyed the intestinal epithelium, which induced dysregulation of gut flora and intestinal leakage. Under the dual stimulation of intestinal bacteria and cisplatin, neutrophils become extremely susceptible to form Neutrophil extracellular traps (NETs), accumulating in the proximal tubule and promoted chronic inflammation, fibrosis, and chronic hypoxia, leading to poor regeneration that promoted CKD progression. NETs provided a scaffold for tissue factors (TF) adhesion and metalloid-matrix protease 9 (MMP-9) activation, which triggered local ischemia and hypoxia. In addition, NETs promoted inflammasome construction through NOD-like receptor thermal protein domain associated protein 3 (NLRP3) shear and secretion of mature interleukin-18 (IL18), which subsequently released interferon- {gamma} (IFN-{gamma}), contributing to renal interstitial fibrosis. We proposed that oligomeric procyanidins (OPCs) ameliorated RLDC-induced CKD through multi-targeting damage induced by NETs. OPCs ameliorated microcirculatory disorders and inhibited inflammation by protecting the intestinal mucosa barrier and subsequent bacterial endotoxin translocation. Furthermore, we found that OPCs altered the susceptibility of neutrophils to form NETs. In summary, OPC alleviates CKD by inhibiting NETs production via TF/MMP-9 and IL-18-NLRP3 pathways. OPCs protect the kidney through anti-inflammatory and antioxidant activities, and restore the balance of the intestinal flora.

immunology↗

bioRxiv2024

Characterization of tumor heterogeneity through segmentation-free representation learning

The interaction between tumors and their microenvironment is complex and heterogeneous. Recent developments in high-dimensional multiplexed imaging have revealed the spatial organization of tumor tissues at the molecular level. However, the discovery and thorough characterization of the tumor microenvironment (TME) remains challenging due to the scale and complexity of the images. Here, we propose a self-supervised representation learning framework, CANVAS, that enables discovery of novel types of TMEs. CANVAS is a vision transformer that directly takes high-dimensional multiplexed images and is trained using self-supervised masked image modeling. In contrast to traditional spatial analysis approaches which rely on cell segmentations, CANVAS is segmentation-free, utilizes pixel-level information, and retains local morphology and biomarker distribution information. This approach allows the model to distinguish subtle morphological differences, leading to precise separation and characterization of distinct TME signatures. We applied CANVAS to a lung tumor dataset and identified and validated a monocytic signature that is associated with poor prognosis.

cancer biology↗

bioRxiv2024

Developmental control of E-cadherin junctions by mechanical contractility in Drosophila embryos

Adherens junctions are very plastic structures that change their composition and structure depending on the state of the epithelial tissue, involving mechanical stress and tissue dynamics. In Drosophila embryos, adherens junctions mature only during gastrulation following their formation a few minutes before during cellularization. Although the developmental maturation is obvious during gastrulation, the factors and conditions controlling it have remained unclear. Here, we assay the levels, distribution pattern, and mobility of E-cadherin during Drosophila gastrulation. Indicating a maturation, we find an increase in total levels at junctions and a drop in the mobile fraction of E-cadherin molecules. Both developmental changes depend on Myo-II contractility. Consistent with stereotypic Myo-II regulation, we find that interference with Rho signaling leads to corresponding changes in E-cadherin levels and mobility, at least in part. Besides Rho signaling, Src42A contributes to junction maturation, as tested by both loss-function and gain-of-function situations. Together, we demonstrate developmental maturation of adherens junctions and identify Rho signaling and Src42A as upstream regulatory pathways.

developmental biology↗

bioRxiv2024

Natural genetic and transcriptomic variation in photosynthesis associated pathways contribute to adaptive traits variation in worldwide Arabidopsis thaliana population

Photosynthesis is the most important reaction underlying carbon fixation. Despite its potential in boosting carbon assimilation, nature variations underlying genes in photosynthesis pathway and their role in adaptive traits variation remains elusive. In this study, we investigated the genetic, transcriptomic variation of 1103 genes in photosynthesis associated pathways, including 82 photosynthesis core genes, 24 plastid-encoded RNA polymerase related genes, 2 nucleus-encoded RNA polymerase-related genes, 34 photomorphogenesis-related genes, 40 genes involved in transcription and translation (TAC) and 938 other nuclear-encoded chloroplast-targeted genes. By de novo assembling the chloroplast genomes of 28 representative accessions and leveraging whole-genome, transcriptome sequencing data from the 1001 Genome Project, we revealed extensive natural genetic and transcriptome variations these genes in worldwide Arabidopsis thaliana population. 34.0% of them were identified with regulatory variations in expression quantitative locus mapping (eQTL) mapping, including key components of Rubisco (RBCS1B, RBCS2B), and Rubisco activase (RCA). Genome-wide and transcriptome-wide association analysis (GWAS/TWAS) showed that these genetic and transcriptomic variations made considerable contribution to variation of adaptive traits. Overall, our study provides insight into the natural genetic variation of these genes among worldwide Arabidopsis thaliana accessions and their role in complex traits variation and adaptation.

plant biology↗

bioRxiv2024

Rapid synthesis and screening of natively paired antibodies against influenza hemagglutinin stem via oPool+ display

Antibody discovery is crucial for developing therapeutics and vaccines as well as understanding adaptive immunity. However, the lack of approaches to synthesize antibodies with defined sequences in a high-throughput manner represents a major bottleneck in antibody discovery. Here, we presented oPool+ display, a high-throughput cell-free platform that combined oligo pool synthesis and mRNA display to rapidly construct and characterize many natively paired antibodies in parallel. As a proof-of-concept, we applied oPool+ display to probe the binding specificity of >300 uncommon influenza hemagglutinin (HA) antibodies against 9 HA variants through 16 different screens. Over 5,000 binding tests were performed in 3-5 days with further scaling potential. Follow-up structural analysis of two HA stem antibodies revealed the previously unknown versatility of IGHD3-3 gene segment in recognizing the HA stem. Overall, this study established an experimental platform that not only accelerate antibody characterization, but also enable unbiased discovery of antibody molecular signatures.

immunology↗

bioRxiv2024

Boundaries in the eyes: measure event segmentation during naturalistic video watching using eye tracking

During naturalistic information processing, individuals spontaneously segment their continuous experiences into discrete events, a phenomenon known as event segmentation. Traditional methods for assessing this process, which include subjective reports and neuroimaging techniques, often disrupt real-time segmentation or are costly and time intensive. Our study investigated the potential of measuring event segmentation by recording and analyzing eye movements while participants view naturalistic videos. We collected eye movement data from healthy young adults as they watched commercial films (N=104), or online Science, Technology, Engineering, and Mathematics (STEM) educational courses (N=44). We analyzed changes in pupil size and eye movement speed near event boundaries and employed inter-subject correlation analysis (ISC) and hidden Markov models (HMM) to identify patterns indicative of event segmentation. We observed that both the speed of eye movements and pupil size dynamically responded to event boundaries, exhibiting heightened sensitivity to high-strength boundaries. Our analyses further revealed that event boundaries synchronized eye movements across participants. These boundaries, can be effectively identified by HMM, yielded higher within-event similarity values and aligned with human-annotated boundaries. Importantly, HMM-based event segmentation metrics responded to experimental manipulations and predicted learning outcomes. This study provided a comprehensive computational framework for measuring event segmentation using eye-tracking. With the widespread accessibility of low-cost eye-tracking devices, the ability to measure event segmentation from eye movement data promises to deepen our understanding of this process in diverse real-world settings.

neuroscience↗

bioRxiv2024

Scupa: Single-cell unified polarization assessment of immune cells using the single-cell foundation model

Immune cells undergo cytokine-driven polarization in respond to diverse stimuli. This process significantly modulates their transcriptional profiles and functional states. Although single-cell RNA sequencing (scRNA-seq) has advanced our understanding of immune responses across various diseases or conditions, currently there lacks a method to systematically examine cytokine effects and immune cell polarization. To address this gap, we developed Single-cell unified polarization assessment (Scupa), the first computational method for comprehensive immune cell polarization analysis. Scupa is trained on data from the Immune Dictionary, which characterizes 66 cytokine-driven polarization states across 14 immune cell types. By leveraging the cell embeddings from the Universal Cell Embeddings model, Scupa effectively identifies polarized cells in new datasets generated from different species and experimental conditions. Applications of Scupa in independent datasets demonstrated its accuracy in classifying polarized cells and further revealed distinct polarization profiles in tumor-infiltrating myeloid cells across cancers. Scupa complements conventional single-cell data analysis by providing new insights into immune cell polarization, and it holds promise for assessing molecular effects or identifying therapeutic targets in cytokine-based therapies.

bioinformatics↗

bioRxiv2024

Behavioral and Eye-Tracking Evidence for Disrupted Event Segmentation during Continuous Memory Encoding Due to Short Video Watching

The proliferation of short-video platforms prompts critical investigation of their effects on human cognitive functions. We hypothesized that the frequent, user-driven content shifts inherent to short-video watching impair event segmentation--a cognitive process critical for organizing continuous experience into discrete, episodic memory. To investigate this hypothesis, we combined behavioral memory tasks, eye-tracking, and self-report questionnaires. Study 1 (N=113) revealed that exposure to randomly selected short videos impaired subsequent memory for continuous movies. This impairment was not observed following exposure to personalized short videos, nor was it present in trial-based static image encoding tasks (Study2, N=60), suggesting a selective disruption of continuous memory encoding. Intersubject correlation (ISC) analysis of eye movements revealed decreased synchronization at event boundaries during movie watching after exposure to random short videos. Furthermore, the Hidden Markov Model (HMM) analysis indicated that this exposure led to more fragmented event segmentation during continuous memory encoding. In contrast, while pupil size and gaze moving speed were sensitive to event boundaries, these metrics were not modulated by prior short video watching, indicating the disruption is specific to the segmentation process itself and not to lower-level boundary detection. Collectively, these findings demonstrate a negative impact of certain short video watching habits on event segmentation and subsequent memory, underscoring the powerful role of platform algorithms in shaping human cognition.

neuroscience↗