Biology subjects

Gao, F.

Publications and source records attributed to Gao, F..

At least 109 records · Page 6Linked to original sources

bioRxiv2022

Runx factors launch T-cell and innate lymphoid programs via direct and gene network-based mechanisms

Runx factors are essential for lineage specification of various hematopoietic cells, including T lymphocytes. However, they regulate context-specific genes and occupy distinct genomic regions in different cell types. Here, we show that dynamic Runx binding shifts in early T-cell development are mostly not restricted by local chromatin state but regulated by Runx dosage and functional partners. Runx co-factors compete to recruit a limited pool of Runx factors in early T-progenitors, and a modest increase in Runx protein availability at pre-commitment stages causes premature Runx occupancy at post-commitment binding sites. This results in striking T-lineage developmental acceleration by selectively activating T-identity and innate lymphoid cell programs. These are collectively regulated by Runx together with other, Runx-induced transcription factors that co-occupy Runx target genes and propagate gene network changes.

immunology↗

bioRxiv2022

Individual-specific functional connectivity shows improved performance in detecting and predicting individualized symptoms of Alzheimer's disease in elderly people with/without APOE ε4 allele

To date, no reliable biomarkers are available that link individual-specific functional connectivity and patients individualized symptoms for early detection and prediction of Alzheimers disease (AD) in elderly people with specific genotypes. Meanwhile, functional magnetic resonance imaging (MRI) and machine learning are promising tools that can reveal the relationships between brain and behavior at individual level towards predicting the transition to AD. In this study, individual-specific functional connectivity was constructed in elderly participants with Apolipoprotein E (APOE) {varepsilon}4 allele (N = 120) and without APOE {varepsilon}4 allele (N = 115), respectively. In particular, machine learning based on a recursive feature selection technique was carried out to track multiple clinical symptoms among differing genotypes at individual level from normal aging (NA) and AD. It was found that the captured neuroimaging features in both APOE genotyping groups were able to distinguish the changes of clinical symptoms from NA to AD. Besides, our findings illustrated that the connections between individual-specific functional regions exhibited significantly higher correlation between estimated and observed scores in multiple clinical symptoms than those from atlas-based functional connectivity for both APOE genotyping groups, while no significant performance was detected when the data of two APOE genotyping groups were combined for the estimation models. Further, individual-specific between-network connectivity constitutes a major contributor for accessing cognitive symptoms in both APOE genotyping groups. Therefore, this study demonstrated the essential role of individual variation in cortical functional anatomy and the significance in combining brain and behavior for improving the accuracy in detection and prediction of AD in elderly people with specific genotypes.

neuroscience↗

bioRxiv2022

Compounds derived from N,N-dimethyldithiocarbamate are effective copper-dependent antimicrobials against Streptococcus pneumoniae

N,N-dimethyldithiocarbamate (DMDC) is a potent copper-dependent antimicrobial against several pathogens, including Streptococcus pneumoniae. Despite the availability of several vaccines against multiple disease-causing strains of S. pneumoniae, the rise of antimicrobial resistance and pneumococcal disease caused by strains not covered by the vaccine creates a need for developing novel antimicrobial strategies. We derived novel compounds from DMDC and tested their effectiveness as copper-dependent antimicrobials against S. pneumoniae through in vitro growth and killing curves. Compounds that caused a growth defect and were bactericidal in vitro were tested against other strains of S. pneumoniae and in complex with different transition metals. We found two compounds, sodium N-benzyl-N-methyldithiocarbamate and sodium N-allyl-N-methyldithiocarbamate (herein "Compound 3" and "Compound 4"), were effective against TIGR4, D39, and ATCC(R) 6303 (a type 3 capsular strain) and further increased the internal concentrations of copper to the same previously reported levels as with DMDC and copper treatment. We found that both Compound 3 and Compound 4 were bacteriostatic in combination with zinc. We tested Compound 3 and Compound 4 in vivo against a murine pneumonia model, finding that Compound 3, and not Compound 4, was effective in significantly decreasing the bacterial burden in the blood and lungs of S. pneumoniae-infected mice. We found that the combination of Compound 3 and copper made the pneumococcus more susceptible to activated macrophage mediated killing via an in vitro macrophage killing assay. Collectively, we demonstrate that derivatizing DMDC holds promise as potent bactericidal antibiotics against S. pneumoniae.

microbiology↗

bioRxiv2022

Tumor suppressor p53 deficiency increases tumor immunogenicity through promoting IL33-mediated anti-tumor immune responses

Recent studies have shown that p53 contributes to poor survival during immune checkpoint blockade (ICB) therapy. Lung cancer patients with p53 mutations have significantly improved response rates to PD-1 ICB therapy. While previous studies have shown that tumor-derived IL-33 is required for the anti-tumor immune response and efficacy of ICB therapies, the relationship between p53 and IL-33 during ICB therapy is unknown. In this study, we characterized the role of the p53/IL-33 axis in regulating the tumor microenvironment (TME) in response to ICB therapy. CRISPR-Cas9-mediated deletion of Trp53 in tumor cells combined with PD-1 ICB therapy synergistically inhibited tumor growth in a murine MC38 colon adenocarcinoma model. We observed increased CD4+ and CD8+ T cell infiltration, as well as reduced Treg infiltration. IL-33 was upregulated and its expression increased with time and response to treatment. Simultaneous deletion of Il33 in the MC38 tumor cells reversed the efficacy of PD-1 ICB therapy. ST2-/-(IL-33 receptor) mice with Trp53-deficient MC38 tumors also showed no response to PD-1 ICB. Our findings depict a novel mechanism by which the loss of p53 in tumors treated with ICB therapy induces upregulation of tumoral IL-33 and host ST2 signaling. p53 mutations may be a double-edged sword for cancer, i.e. loss of the tumor suppressor initially facilitates tumorigenesis, but also leads to upregulation of danger signals in the tumor. These danger signals, such as IL-33, mediate the anti-tumor effect of ICB.

immunology↗

bioRxiv2022

Dissecting aneuploidy phenotypes by constructing Sc2.0 chromosome VII and SCRaMbLEing synthetic disomic yeast

Aneuploidy compromises genomic stability, often leading to embryo inviability, and is frequently associated with tumorigenesis and aging. Different aneuploid chromosome stoichiometries lead to distinct transcriptomic and phenotypic changes, making it helpful to study aneuploidy in tightly controlled genetic backgrounds. By deploying the engineered SCRaMbLE system to the newly synthesized Sc2.0 megabase chromosome VII (synVII), we constructed a synthetic disomic yeast and screened hundreds of SCRaMbLEd derivatives with diverse chromosomal rearrangements. Phenotypic characterization and multi-omics analysis revealed that fitness defects associated with aneuploidy could be restored by i) removing most of the chromosome content, or ii) modifying specific regions in the duplicated chromosome. These findings indicate that both chromosome copy number and chromosomal regions contribute to the aneuploidy-related phenotypes, and the synthetic yeast resource opens new paradigms in studying aneuploidy. In briefUse of SCRaMbLE and newly synthesized Mb-scale Sc2.0 chromosome VII enables insights into genotype/phenotype relationships associated with aneuploidy HighlightsO_LIDe novo design and synthesis of a Mb-scale synthetic yeast chromosome VII, carrying 11.8% sequence modifications and representing nearly 10% of the yeast genome. C_LIO_LIA disomic yeast (n + synVII) is constructed for dissecting the aneuploidy phenotype C_LIO_LISCRaMbLE enables systematic exploration of regions causing aneuploidy phenotypes C_LIO_LIChromosomal copy number and content both contribute to aneuploidy phenotypes C_LIO_LIA 20 Kb deletion on the right arm of synVII leads to fitness improvement linked to up-regulation of protein synthesis C_LI

synthetic biology↗

bioRxiv2022

Ori-Finder 2022: A Comprehensive Web Server for Prediction and Analysis of Bacterial Replication Origins

The replication of DNA is a complex biological process that is essential for life. Bacterial DNA replication is initiated at genomic loci referred to as replication origins (oriCs). Integrating the Z-curve method, DnaA box distribution, and comparative genomic analysis, we developed a web server to predict bacterial oriCs in 2008 called Ori-Finder, which contributes to clarify the characteristics of bacterial oriCs. The oriCs of hundreds of sequenced bacterial genomes have been annotated in their genome reports using Ori-Finder and the predicted results have been deposited in DoriC, a manually curated database of oriCs. This has facilitated large-scale data mining of functional elements in oriCs and strand-biased analysis. Here, we describe Ori-Finder 2022 with updated prediction framework, interactive visualization module, new analysis module, and user-friendly interface. More species-specific indicator genes and functional elements of oriCs are integrated into the updated framework, which has also been redesigned to predict oriCs in draft genomes. The interactive visualization module displays more genomic information related to oriCs and their functional elements. The analysis module includes regulatory protein annotation, repeat sequence discovery, homologous oriC search, and strand-biased analyses. The redesigned interface provides additional customization options for oriC prediction. Ori-Finder 2022 is freely available at http://tubic.tju.edu.cn/Ori-Finder2022 and https://tubic.org/Ori-Finder2022.

bioinformatics↗

bioRxiv2022

Multi-Molecular Hyperspectral PRM-SRS Imaging

Lipids play crucial roles in many biological processes under physiological and pathological conditions. Mapping spatial distribution and examining metabolic dynamics of different lipids in cells and tissues in situ are critical for understanding aging and diseases. Commonly used imaging methods, including mass spectrometry-based technologies or labeled imaging techniques, tend to disrupt the native environment of cells/tissues and have limited spatial or spectral resolution, while traditional optical imaging techniques still lack the capacity to distinguish chemical differences between lipid subtypes. To overcome these limitations, we developed a new hyperspectral imaging platform that integrates a Penalized Reference Matching algorithm with Stimulated Raman Scattering (PRM-SRS) microscopy. With this new approach, we directly visualized and identified multiple lipid species in cells and tissues in situ with high chemical specificity and subcellular resolution. High density lipoprotein (HDL) particles containing non-esterified cholesterol was observed in the kidney, indicating that these pools of cholesterol are ectopic deposits, or have yet to be enriched. We detected a higher Cholesterol to phosphatidylethanolamine (PE) ratio inside the granule cells of hippocampal samples in old mice, suggesting altered membrane lipid synthesis and metabolism in aging brains. PRM-SRS imaging also revealed subcellular distributions of sphingosine and cardiolipin in the human brain sample. Compared with other techniques, PRM-SRS demonstrates unique advantages, including faster data processing and direct user-defined visualization with enhanced chemical specificity for distinguishing clinically relevant lipid subtypes in different organs and species. Our method has broad applications in multiplexed cell and tissue imaging.

bioengineering↗

bioRxiv2022

PERK-ATAD3A interaction protects mitochondrial proteins synthesis during ER stress

Widespread repression of protein synthesis rates is a key feature of Endoplasmic Reticulum (ER) stress, mediated by the ER sensor kinase PERK. While select transcripts escape this repression, global translational down-regulation impacts crucial protein levels in all cellular compartments, beyond the ER. How the cell manages this paradox is unclear. PERK has a unique cytoplasmic loop within its kinase domain that binds PERKs target, eIF2. We identified the mitochondrial protein, ATAD3A, as a new interactor of the loop, binding to a highly conserved region within it. During ER stress, increased interaction between ATAD3A and PERK attenuates PERK signalling to eIF2, removing the translational block on several mitochondrial proteins. This occurs at novel context-dependent, mitochondria-ER contact sites. The interaction provides a previously unknown mechanism for fine-tuning translational repression at a local level, mitigating the impact of ER stress on mitochondria. Further, it represents a new target for selective modulation of PERK-eIF2 signalling in diseases from cancer to neurodegeneration. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=153 HEIGHT=200 SRC="FIGDIR/small/501280v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@f74252org.highwire.dtl.DTLVardef@1234633org.highwire.dtl.DTLVardef@d5dc9aorg.highwire.dtl.DTLVardef@8606fe_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2022

A novel quantification method for RPE phagocytosis using a VLC-PUFA-based strategy

The vertebrate retinal pigment epithelium (RPE) lies adjacent to the photoreceptors and is responsible for the engulfment and degradation of shed photoreceptor outer segment fragments (POS) through receptor-mediated phagocytosis. Phagocytosis of POS is critical for maintaining photoreceptor function and is a key indicator of RPE functionality. Popular established methods to assess RPE phagocytosis rely mainly on quantifying POS proteins, especially their most abundant protein rhodopsin, or on fluorescent dye conjugation of bulk, unspecified POS components. While these approaches are practical and quantitative, they fail to assess the fate of POS lipids, which make up about 50% of POS by weight and whose processing is essential for life-long functionality of RPE and retina. Here, we have developed a novel VLC-PUFA-based approach for evaluating RPE phagocytic activity by primary bovine and rat RPE and the human ARPE-19 cell line and validated its results using traditional methods. This new approach can be used to detect the dynamic process of phagocytosis at varying POS concentrations and incubation times and offers a robust, unbiased, and reproducible assay that will have utility in studies of POS lipid processing.

biochemistry↗

bioRxiv2022

Genetic Diversity of Candidatus Liberibacter asiaticus Based on Four Hypervariable Genomic Regions in China

Huanglongbing (HLB; greening disease), caused by Candidatus Liberibacter asiaticus (CLas), is the most damaging citrus disease worldwide. The disease has spread throughout the citrus-producing regions of Guangxi, Guangdong, Fujian, and others in China. A total of 1,789 HLB-like symptomatic or asymptomatic samples were collected from the Guangxi and Fujian provinces of China to decipher the genetic diversity of CLas and its correlation with pathogenicity and host range. The disease was the most severe in orange and the least in pomelo. CLas bacteria associated with the specific geographical and citrus variety infected more than 50% of the HLB-like symptomatic samples. We identified a total of 6,286 minor variations by comparing 35 published CLas genomes and observed a highly heterogeneous variation distribution across the genome. Highly diverse regions, including two prophages, were generally more unstable and prone to lose. In the collected CLas strains, four highly diverse non-prophage segments and three prophage segments in the prophage region were chosen for PCR amplification and genotyping. Four hypervariable regions were used to decipher CLas diversity. A total of 100 strains were divided into four groups, of which 90 strains were clustered into two clades with 15 reported reference genomes, while 10 were grouped in two clades separately from the reported genomes. This study provides insight into the molecular characteristics and genetic variations of different CLas strains in China and might help develop HLB prevention and control strategies. ImportanceThe objective of the present study is to characterize the hypervariable genomic region sequence, decipher the genetic diversity of CLas strains from China, understand how various strains differ, and lay the foundation for developing HLB prevention and control strategies.

microbiology↗

bioRxiv2022

Introducing an argonaute-facilitated PCR platform

Argonaute proteins are characterized by highly efficient guide DNA/RNA-directed binding to target nucleic acids with high fidelity. Employing this feature, we designed an argonaute-facilitated PCR platform by making use of an argonaute derived from Mesorhizobium japonicum (MejAgo) which does not carry nuclease activity and exposes the 3 end of guide DNA when binding. Each reaction cycle of the MejAgo-PCR platform consists of a denaturing step and a polymerase-mediated extension step, omitting the annealing step required by the traditional PCR. More importantly, MejAgo-PCR could significantly improve the sensitivity of PCR in template detection due to the argonaute-facilitated pairing between guide DNA/primer and template. Thus, an argonaute-facilitated PCR has the potential to be developed as an advanced PCR platform with higher sensitivity and efficiency.

biochemistry↗

bioRxiv2022

Vertical HIV-1 transmission in the setting of maternal broad and potent antibody responses

Despite the worldwide availability of antiretroviral therapy (ART), approximately 150,000 pediatric HIV infections continue to occur annually. ART can dramatically reduce HIV mother-to-child transmission (MTCT), but inconsistent drug access and adherence, as well as primary maternal HIV infection during pregnancy and lactation are major barriers to eliminating vertical HIV transmission. Thus, immunologic strategies to prevent MTCT, such as an HIV vaccine, will be required to attain an HIV-free generation. A primary goal of HIV vaccine research has been to elicit broadly neutralizing antibodies (bnAbs) given the ability of passive bnAb immunization to protect against sensitive strains, yet we previously observed that HIV-transmitting mothers have more plasma neutralization breadth than non-transmitting mothers. Additionally, we have identified infant transmitted/founder (T/F) viruses that escape maternal bnAb responses. In this study, we examine a cohort of postpartum HIV-transmitting women with neutralization breadth to determine if certain maternal bnAb specificities drive the selection of infant T/F viruses. Using HIV pseudoviruses that are resistant to neutralizing antibodies targeting common bnAb epitopes, we mapped the plasma bnAb specificities of this cohort. Significantly more transmitting women with plasma bnAb activity had a mappable plasma bnAb specificity (six of seven, or 85.7%), compared to that of non-transmitting women with plasma bnAb activity (seven of twenty-one, or 33.3%, p=0.029 by 2-sided Fisher exact test). Our study suggests that having multispecific broad activity and/or uncommon epitope-specific bnAbs in plasma may be associated with protection against the vertical HIV transmission in the setting of maternal bnAb responses. ImportanceAs mother to child transmission (MTCT) of HIV plays a major part in the persistence of the HIV/AIDS epidemic and bnAb-based passive and active vaccines are a primary strategy for HIV prevention, research in this field is of great importance. While previous MTCT research has investigated the neutralizing antibody activity of HIV-infected women, this is to our knowledge the largest study identifying differences in bnAb specificity of maternal plasma between transmitting and non-transmitting women. Here, we show that among HIV-infected women with broad and potent neutralization activity, more postpartum-transmitting women had a mappable plasma broadly neutralizing antibody (bnAb) specificity, compared to that of non-transmitting women, suggesting that the non-transmitting women more often have multi-specific bnAb responses or bnAb responses that target uncommon epitopes. Such responses may be required for protection against vertical HIV transmission in the setting of maternal bnAb responses.

immunology↗

bioRxiv2022

Impact of various vaccine boosters on neutralization against Omicron following prime vaccinations with inactivated or adenovirus-vectored vaccine

Since the first report on November 24, 2021, the Omicron SARS-CoV-2 variant is now overwhelmingly spreading across the world. Two SARS-CoV-2 inactivated vaccines (IAVs), one recombinant protein subunit vaccine (PRV), and one adenovirus-vectored vaccine (AdV) have been widely administrated in many countries including China to pursue herd immunity. Here we investigated cross-neutralizing activities in 341 human serum specimens elicited by full-course vaccinations with IAV, PRV and AdV, and by various vaccine boosters following prime IAV and AdV vaccinations. We found that all types of vaccines induced significantly lower neutralizing antibody titers against the Omicron variant than against the prototype strain. For prime vaccinations with IAV and AdV, heterologous boosters with AdV and PRV, respectively, elevated serum Omicron-neutralizing activities to the highest degrees. In a mouse model, we further demonstrated that among a series of variant-derived RBD-encoding mRNA vaccine boosters, it is only the Omicron booster that significantly enhanced Omicron neutralizing antibody titers compared with the prototype booster following a prime immunization with a prototype S-encoding mRNA vaccine candidate. In summary, our systematical investigations of various vaccine boosters inform potential booster administrations in the future to combat the Omicron variant.

immunology↗

bioRxiv2022

Decoding the IGF1 Signaling Gene Regulatory Network Behind Alveologenesis from A Mouse Model of Bronchopulmonary Dysplasia

Lung development is precisely controlled by underlying Gene Regulatory Networks (GRN). Disruption of genes in the network can interrupt normal development and cause diseases such as bronchopulmonary dysplasia (BPD)-a chronic lung disease in preterm infants with morbid and sometimes lethal consequences characterized by lung immaturity and reduced alveolarization. Here, we generated a transgenic mouse exhibiting a moderate severity BPD phenotype by blocking IGF1 signaling in secondary crest myofibroblasts (SCMF) at the onset of alveologenesis. Using approaches mirroring the construction of the model GRN in sea urchins development, we constructed the IGF1 signaling network underlying alveologenesis using this mouse model that phenocopies BPD. The constructed GRN, consisting of 43 genes, provides a birds-eye view of how the genes downstream of IGF1 are regulatorily connected. The GRN also reveals a mechanistic interpretation of how the effects of IGF1 signaling are transduced within SCMF from its specification genes to its effector genes and then from SCMF to its neighboring alveolar epithelial cells with WNT5A and FGF10 signaling as the bridge. Consistently, blocking WNT5A signaling in mice phenocopies BPD as inferred by the network. A comparative study on human samples suggests that a GRN of similar components and wiring underlies human BPD. Our network view of alveologenesis is transforming our perspective to understand and treat BPD. This new perspective calls for the construction of the full signaling GRN underlying alveologenesis, upon which targeted therapies for this neonatal chronic lung disease can be viably developed.

developmental biology↗

bioRxiv2022

cpSRP43 is both highly flexible and stable: Structural insights using a combined experimental and computational approach

The novel multidomain protein, cpSRP43, is a unique subunit of the post-translational chloroplast signal recognition particle (cpSRP) targeting pathway in higher plants. The cpSRP pathway is responsible for targeting and insertion of light-harvesting chlorophyll a/b binding proteins (LHCPs) to the thylakoid membrane. Nuclear-encoded LHCPs are synthesized in the cytoplasm then imported into the chloroplast. Upon emergence into the stroma, LHCPs form a soluble transit complex with the cpSRP heterodimer, which is composed of cpSRP43 and cpSRP54, a 54 kDa subunit homologous to the universally conserved GTPase in cytosolic SRP pathways. cpSRP43 is irreplaceable as a chaperone to LHCPs in their translocation to the thylakoid membrane and remarkable in its ability to dissolve aggregates of LHCPs without the need for external energy input. In previous studies, cpSRP43 has demonstrated significant flexibility and interdomain dynamics. However, the high flexibility and structural dynamics of cpSRP43 is yet unexplained by current crystal structures of cpSRP43. This is due, in part, to the fact that free full length cpSRP43 is so flexible that it is unable to crystalize. In this study, we explore the structural stability of cpSRP43 under different conditions using various biophysical techniques and find that this protein is concurrently highly stable and flexible. This conclusion is interesting considering that stable proteins typically possess a non-dynamic structure. Molecular dynamics (MD) simulations which correlated with data from biophysical experimentation were used to explain the basis of the extraordinary stability of cpSRP43. This combination of biophysical data and microsecond-level MD simulations allows us to obtain a detailed perspective of the conformational landscape of these proteins.

biophysics↗

bioRxiv2022

Ccdc38 is required for sperm flagellum biogenesis and male fertility in mouse

Sperm flagellum is essential for male fertility, defects in flagellum biogenesis are associated with male infertility. Deficiency of CCDC42 is associated with malformation of the mouse sperm flagella. Here, we find that the testis-specific expressed protein CCDC38 (coiled-coil domain containing 38) interacts with CCDC42 and localizes on manchette and sperm tail during spermiogenesis. Inactivation of CCDC38 in male mice results in distorted manchette, multiple morphological abnormalities of the flagella (MMAF) of spermatozoa, and eventually male sterility. Furthermore, we find that CCDC38 interacts with intra-flagellar transport protein 88 (IFT88) as well as the outer dense fibrous 2 (ODF2), and its depletion reduces the transportation of ODF2 to flagellum. Altogether, our results uncover the essential role of CCDC38 during sperm flagellum biogenesis, and suggesting the defects of these genes might be associated with male infertility in human being. Summary statementWe demonstrated that CCDC38, localizes on manchette and sperm tail, is crucial for male fertility.

developmental biology↗

bioRxiv2021

Efficient pre-processing of Single-cell ATAC-seq data

Single-cell and single-nucleus genomics assays are becoming increasingly complex, with multiple measurements of distinct modalities performed concurrently resulting in "multimodal" readouts. While multimodal single-cell and single-nucleus genomics offers the potential to better understand how distinct cellular processes are coordinated, there can be technical and cost tradeoffs associated with increasing the number of measurement modes. To assess some of the tradeoffs inherent in multimodal assays, we have developed snATAK for preprocessing sequencing-based high-throughput assays that measure single-nucleus chromatin accessibility. Coupled with kallisto bustools for single-nucleus RNA-seq preprocessing, the snATAK workflow can be used for uniform preprocessing of 10x Genomics Multiome and single-nucleus ATAC-seq, SHARE-seq, ISSAAC-seq, spatial ATAC-seq and other chromatin-related assays. Using snATAK, we are able to perform cross-platform comparisons and quantify some of the tradeoffs between Multiome and unregistered single-nucleus RNA-seq/ATAC-seq experiments. We also show that snATAK can be used to assess allele concordance between paired RNAseq and ATACseq. snATAK is available at https://github.com/pachterlab/snATAK/.

bioinformatics↗

bioRxiv2021

Neural decoding dissociates perceptual grouping between proximity and similarity in visual perception

Previous research on perceptual grouping primarily focused on the dynamics of single grouping principle in light of the Gestalt psychology. Yet, there has been comparatively little emphasis on the dissociation across two or more grouping principles. To tackle this issue, the current study aims at investigating how, when, and where the processing of two grouping principles (proximity and similarity) are established in the human brain by using a dimotif lattice paradigm and adjusting the strength of one grouping principle. Specifically, we measured the modulated strength of the other grouping principle, thus forming six visual stimuli. The current psychophysical results showed that similarity grouping effect was enhanced with reduced proximity effect when the grouping cues of proximity and similarity were presented simultaneously. Meanwhile, electrophysiological (EEG) response patterns were able to decode the specific pattern out of the six visual stimuli involving both principles in each trail by using time-resolved multivariate pattern analysis (MVPA). The onsets of the dissociation between the two grouping principles coincided within three time windows: the earliest proximity-defined local visual element arrangement in the middle occipital cortex, the middle-stage processing for feature selection modulating low-level visual cortex in the inferior occipital cortex and fusiform cortex, and the higher-level cognitive integration to make decisions for specific grouping preference in the parietal areas. In addition, brain responses were highly correlated with behavioral grouping. The results therefore provide direct evidence for a link between human perceptual space of grouping decision-making and neural space of these brain response patterns. Significance statementHow does our brain aggregate meaningless local elements to meaningful global patterns? Here, we used visual stimuli that can be perceived as a whole orientation from one of the two grouping cues (proximity and similarity) when they were presented simultaneously. Behavioral responses showed a trade-off between proximity and similarity. Further, time-resolved MVPA and source estimation results showed three stages for the processing of two grouping cues, involving an early stage in the low-level visual cortex, then the middle stage in the lateral visual cortex, and finally the late stage in the parietal areas. This was among the first attempt employing multivariate analysis to decode the dissociative processing of both proximity and similarity principles within one single study.

neuroscience↗