Biology subjects

Song, Y.

Publications and source records attributed to Song, Y..

At least 289 records · Page 16Linked to original sources

bioRxiv2022

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

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

genomics↗

bioRxiv2022

Rapid GPR183-mediated recruitment of eosinophils to the lung after Mycobacterium tuberculosis infection

Influx of eosinophils into the lungs is typically associated with type-II responses during allergy, fungal and parasitic infections. However, we previously reported that eosinophils accumulate in lung lesions during type-I inflammatory responses to Mycobacterium tuberculosis (Mtb) in humans, macaques, and mice where they contribute to host resistance. Here we show eosinophils migrate into the lungs of macaques and mice as early as one week after Mtb-exposure. In mice this influx was CCR3 independent and instead required cell-intrinsic expression of the oxysterol-receptor GPR183, which is highly expressed on human and macaque eosinophils. Murine eosinophils interacted directly with bacilli-laden alveolar macrophages, which upregulated the oxysterol-synthesizing enzyme Ch25h, and eosinophil recruitment was impaired in Ch25h deficient mice. Our findings show that eosinophils are among the first cells from circulation to sense and respond to Mtb infection of alveolar macrophages and reveal a novel role for GPR183 in the migration of eosinophils into lung tissue. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/480919v1_ufig1.gif" ALT="Figure 1"> View larger version (105K): org.highwire.dtl.DTLVardef@e8cd29org.highwire.dtl.DTLVardef@1f5769borg.highwire.dtl.DTLVardef@3dce9borg.highwire.dtl.DTLVardef@1c75587_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSIn mice and macaques eosinophils accumulate early in Mtb-infected lungs preceding neutrophils Eosinophils interact with Mtb-infected cells in the alveoli in mice Early pulmonary eosinophil migration occurs independently of CCR3 in mice Early lung migration in mice requires Ch25h and eosinophil-intrinsic GPR183 expression

immunology↗

bioRxiv2022

Endometriotic Organoids as an In Vitro Model of Endometriotic Lesion Development.

The development and progression of endometriotic lesions are poorly understood, but immune cell dysfunction and inflammation are closely associated with the pathophysiology of endometriosis. A lack of suitable 3D in vitro models permitting the study of interactions between cell types and the microenvironment is a contributing factor. To address this limitation, we developed endometriotic organoids (EO) to explore the role of epithelial-stromal interactions and model peritoneal cell invasion associated with lesion development. Using a non-adherent microwell culture system, spherical organoids were generated with endometriotic epithelial cells (12Z) combined with immortalized endometriotic stromal cells (iEc-ESC) or immortalized uterine stromal cells (iHUF). Organoids self-organized with stromal cells occupying the center and epithelial cells on the periphery of the organoid. Endometriotic organoids (EO), containing iEc-ESC, resulted in the development of stratified 12Z epithelial cells compared to those with iHUF where the 12Z cells developed as a single layered epithelium. Transcriptomic analysis found 4,522 differentially expressed genes (DEG) between EO and 12Z/iHUF organoids, and the top DEG included increased expression of interleukins and prostaglandin synthase enzymes. An overlap of the EO DEG with baboon endometriotic lesions was highly significant. Finally, to mimic invasion of endometrial tissue into the peritoneum, a model was developed using EO and extracellular matrix containing human peritoneal mesothelial cells (LP9). Invasion of EO into the extracellular matrix-LP9 layer was increased in presence of estrogen or THP1-derived proinflammatory macrophages. Taken together, our results strongly support the concept that EO are an appropriate model for dissecting mechanisms that contribute to endometriotic lesion development. One Sentence SummaryEndometriotic organoids are an appropriate model to study epithelial-stromal interactions and model cell invasion associated with lesion development.

cell biology↗

bioRxiv2022

Impact of Nosema ceranae invasion on sucrose solution consumption, midgut epithelial cell structure, and lifespan of Apis cerana cerana workers

Nosema ceranae is an intracellular fungal parasite for honeybees, leading to chronic disease named bee nosemosis with worldwide distribution. Asian honeybee (Apis cerana) is the original host for N. ceranae, but the impact of N. ceranae infection on A. cerana physiology is largely unknown. In this current work, workers of Apis cerana cerana, a subspecies of Asian honeybee, were artificially inoculated with N. ceranae spores and reared under lab conditions, followed by detection of fungal spore load as well as host sucrose solution consumption, midgut epithelial cell structure, and lifespan. The result of spore counting suggested that the spore load in the host midgut decreased significantly during 1 dpi-2 dpi, whereas that displayed an elevated trend among 2 dpi-13 dpi. The sucrose solution consumption of workers in N. ceranae-inoculated groups among 1 dpi-20 dpi was always higher than that of workers in un-inoculated groups; additionally, the difference of sucrose solution consumption between these two groups at 4 dpi, 5 dpi, and 13 dpi was of significance. Based on microscopic observation of paraffin sections, darkly stained parasites were clearly detected in the midgut epithelial cells of N. ceranae-inoculated workers at 7 dpi-10 dpi, whereas no parasite was observed in those of un-inoculated workers. In addition, the boundaries of un-inoculated host epithelial cells were intact and the darkly stained nucleus were clear, while the boundaries of midgut epithelial cells of N. ceranae-inoculated workers were blurred, the nucleus were almost disappeared, and the nucleic acid substances were diffused. Moreover, the survival rates of workers in both N. ceranae-inoculated groups and un-inoculated groups at 1 dpi-5 dpi were pretty high and then started to decrease at 5 dpi; the survival rate of workers in N. ceranae-inoculated groups was always lower than that in un-inoculated groups, with significant difference between these two groups during 11 dpi-20 dpi. These results together indicate that the quantity of fungal spores continuously elevated with the microsporidian multiplication, causing energetic stress for workers and host cell structure damage, which further negatively affected the host lifespan. Our findings offer a solid basis not only for exploring the molecular mechanism underlying N. ceranae infection but also for investigating the interaction between N. ceranae and eastern honeybee.

molecular biology↗

bioRxiv2021

Importance of linear combination modeling for quantification of Glutathione and GABA levels using Hadamard-edited MRS

PurposeTwo main approaches are used for spectral analysis of edited data: simple peak fitting and linear combination modeling (LCM) with a simulated basis set. Recent consensus recommended LCM as the method of choice for the spectral analysis of edited data. The aim of this study is to compare the performance of simple peak fitting and LCM in a test-retest dataset, hypothesizing that the more sophisticated LCM approach will improve quantification of HERMES data compared with simple peak fitting. MethodsA test-retest dataset was re-analyzed using Gannet (simple peak fitting) and Osprey (LCM). These data were obtained from the dorsal anterior cingulate cortex of twelve healthy volunteers, with TE 80 ms for HERMES and TE 120 ms for MEGA-PRESS of glutathione (GSH). Within-subject coefficients of variance (CVs) were calculated to quantify between-scan reproducibility of each metabolite estimate. ResultsThe reproducibility of HERMES GSH estimates was substantially improved using LCM compared to simple peak fitting, from a CV of 19.0% to 9.9%. For MEGA-PRESS data, the GSH reproducibility was similar using LCM and simple peak fitting, with CVs of 7.3% and 8.8% respectively. ConclusionLinear combination modeling with simulated basis functions substantially improves the reproducibility of GSH quantification for HERMES data.

biophysics↗

bioRxiv2021

The first sheep graph pan-genome reveals the spectrum of structural variations and their effects on different tail phenotypes

Structural variations (SVs) are a major contributor to genetic diversity and phenotypic variations, but their prevalence and functions in domestic animals are largely unexplored. Here, we assembled 26 haplotype-resolved genome assemblies from 13 genetically diverse sheep using PacBio HiFi sequencing. We constructed a graph-based ovine pan-genome and discovered 142,422 biallelic insertions and deletions, 7,028 divergent alleles and 13,419 multiallelic variations. We then used a graph-based approach to genotype the biallelic SVs in 684 individuals from 45 domestic breeds and two wild species. Integration with RNA-seq data allows to identify candidate expression-associated SVs. We demonstrate a direct link of SVs and phenotypes by localizing the putative causative insertion in HOXB13 gene responsible for the long-tail trait and identifying multiple large SVs associated with the fat-tail. Beyond generating a benchmark resource for ovine structural variants, our study highlights that animal genetic research will greatly benefit from using a pan-genome graph rather than a single reference genome.

genomics↗

bioRxiv2021

New insights into colorectal cancer liver metastasis carcinogenesis and its effect with moxibustion

BackgroundChemotherapeutic drugs creates severe adverse reactions for colorectal cancer. Moxibustion confers clinical benefits for postoperative patients undergoing chemotherapy, it will fill the blank period of western medicine treatment and provide useful help for tumor patients to prevent recurrence and metastasis, but the physiological mechanisms behind the antitumor effects are unclear. This study was aimed to determine the effect and characterize the differential cytokines and gene expression profiles in intrasplenic transplanted GFP-HCT-116 cells-induced tumors model by Pre-Mox, Post-Mox and Pre-Post-Mox intervention. MethodsHuman CRC cells with GFP fluorescence were implanted via intrasplenic injection into Balb/c nude mice spleens. Moxibustion stimulation was applied to the BL18 and ST36 acupoints. The model control (MC) group were given no treatment. Pre-Mox mice were received moxibustion for 2 weeks before HCT-116 cell injection. Post-Mox mice received moxibustion for 3 weeks after CRC cell injection. Pre-Post-Mox mice received moxibustion for 5 weeks (2 weeks before and 3 weeks after CRC cell injection). Peripheral bloods were collected, pooled and assayed using a RayBio(R) mouse inflammation antibody array. Multi-Analyte Suspension Array was opted for verification. RNA isolated from liver paracancerous tissues from the control group and the experimental groups was subjected to RNA-seq, and then screened out significant differences for in-depth verification. RESULTSThe results showed that moxibustion stimulation increased the survival rate and decreased CRC liver metastasis. With the help of Multi-Analyte Suspension Array and RNA-seq, we screened significant differential expression of cytokines and RNA, then further verified them. The metastasis rate decreased significantly from 100% (10/10, MC group) to 50% (6/12, Pre-Mox group), to 46% (6/13, Post-Mox group), and further to 25% (3/12, Pre-Post-Mox group). Cytokine chips were used significant differences were found in MIP-3, MDC, IL-6, and IL-1a. Transcriptomic analysis suggested that the low-dose combination of Pre-Mox and Post-Mox modulated larger gene sets than the single treatment. We identified a small subset of genes, like APOA4, IGFBP5, IGFBP6, TIMP1, and MGP, as potential molecular targets involved in the preventive action of the combination of Pre-Mox and Post-Mox. ConclusionsTaken together, the current results provide the first evidence in support of the chemopreventive effect of a combination of Pre-Mox and Post-Mox in CRC. Moreover, the cytokines and transcriptional profile obtained in our study may provide a framework for identifying the mechanisms underlying the carcinogenesis process from colonic cancer to liver metastasis as well as the cancer inhibitory effects and potential molecular targets of Pre-Post-Mox.

cancer biology↗

bioRxiv2021

Evolution and Genetic Diversity of the Retroviral Envelope in Anamniotes

Retroviruses are widely distributed in all vertebrates, as are their endogenous form, endogenous retrovirus (ERV), which serves as "fossil" evidence to trace the ancient origins and history of virus-host interactions over millions of years. The retroviral envelope (Env) plays a significant role in host range determination, but major information on genetic diversification in anamniotes is lacking. Here, by incorporating multiple-round in silico similarity search and phylogenomic analysis, 25498 ERVs with gamma-type Env (GTE), covalently associated Env, were discovered by searching against all 974 available fish and 19 amphibian genomes, but no beta-type Env (BTE), noncovalently associated Env, were found. Furthermore, a nine-type classification system of anamniote GTE was proposed by combining phylogenetic and domain/motif analyses. The elastic genomic organization and overall phylogenetic incongruence between anamniotic Env and its neighboring polymerase (Pol) implied that early retroviral diversification in anamniotic vertebrates was facilitated by frequent recombination. At last, host opioid growth factor receptor (OGFr) gene capturing by anamniotic ERVs with GTE was reported for the first time. Overall, our findings overturn traditional Pol genotyping and reveal a complex evolutionary history of anamniotic retroviruses inferred by Env evolution. Author summaryAlthough the retroviral envelope (Env) protein in amniotes has been well studied, its evolutionary history in anamniotic vertebrates is ambiguous. By analyzing more than 25000 ERVs with gamma-type Env (GTE) in anamniotes, several important evolutionary features were identified. First, GTE were found to be widely distributed among different amphibians and fish. Second, nine types of GTE were discovered, revealing the great genetic diversity. Third, GTE-containing ERVs have rampantly proliferated in certain amphibians such as Ambystoma mexicanum, and the copy number was found to be markedly higher than 10000. Fourth, the incongruence between the Env and Pol phylogenies suggested that frequent recombination shaped the early evolution of anamniote retroviruses. Fifth, an ancient horizontal gene transfer event was discovered from anamniotes to ERVs with GTE. These findings reveal a complex evolution pattern for retroviral Env in anamniotes.

microbiology↗

bioRxiv2021

Diversity, function and evolution of aquatic vertebrate genomes

Aquatic vertebrates consist of jawed fish (cartilaginous fish and bony fish), aquatic mammals, reptiles and amphibians. Here, we present a comprehensive analysis of 630 aquatic vertebrate genomes to generate a standardized compendium of genomic data. We demonstrate its value by assessing their genome features as well as illuminating gene families related to the transition from water to land, such as Hox genes and olfactory receptor genes. We found that LINEs are the major transposable element (TE) type in cartilaginous fish and aquatic mammals, while DNA transposons are the dominate type in bony fish. To our surprise, TE types are not fixed in amphibians, the first group that transitioned to living on land. These results illustrate the value of a unified resource for comparative genomic analyses of aquatic vertebrates. Our data and strategy are likely to support all evolutionary and ecological research on vertebrates.

genomics↗

bioRxiv2021

Neural network models for spinal implementation of muscle synergies

Muscle synergies have been proposed as functional modules to simplify the complexity of body motor control; however, their neural implementation is still unclear. Converging evidence suggests that output projections of the spinal premotor interneurons (PreM-INs) underlie the formation of muscle synergies, but they exhibit a substantial variation across neurons and exclude standard models assuming a small number of unitary "modules" in the spinal cord. Here we compared neural network models for muscle synergies to seek a biologically plausible model that reconciles previous clinical and electrophysiological findings. We examined three neural network models: one with random connections (non-synergy model), one with a small number of spinal synergies (simple synergy model), and one with a large number of spinal neurons representing muscle synergies with a certain variation (population synergy model). We found that the simple and population synergy models emulate the robustness of muscle synergies against cortical stroke observed in human stroke patients. Furthermore, the size of the spinal variation of the population synergy matched well with the variation in spinal PreM-INs recorded in monkeys. These results suggest that a spinal population with moderate variation is a biologically plausible model for the neural implementation of muscle synergies.

neuroscience↗

bioRxiv2021

CircSry regulates spermatogenesis by enhancing γH2AX expression via sponging miR-138-5p

Sry on the Y chromosome is the master switch in sex determination in mammals. It has been well established that Sry encodes a transcription factor that is transiently expressed in somatic cells of male gonad, inducing a series of events that lead to the formation of testes. In the testis of adult mice, Sry is expressed as a circular RNA (circRNA) transcript, a type of noncoding RNA that forms a covalently linked continuous loop. However, the physiological function of this Sry circRNA (circSry) remains unknown since its discovery in 1993. Here we show that circSry is mainly expressed in the spermatocytes, but not in mature sperms and Sertoli cells. Loss of circSry led to the reduction of sperm number and the defect of germ cell development. The expression of {gamma}H2AX was decreased and failure of XY body formation was noted in circSry KO germ cells. Further study demonstrates that circSry regulates H2AX mRNA indirectly in pachytene spermatocytes through sponging miR-138-5p. Our study demonstrates that, in addition to its well-known sex-determination function, Sry also plays important role in spermatogenesis as a circRNA.

developmental biology↗

bioRxiv2021

ADAR2-repressed RNA editing: a novel mechanism contributing to t (8:21) AML leukemogenesis

In the past decade, adenosine to inosine (A-to-I) RNA editing, which is catalyzed by adenosine deaminases acting on RNA (ADAR) family of enzymes ADAR1 and ADAR2, has been shown to contribute to the development and progression of multiple cancers; however, very little is known about its role in acute myeloid leukemia (AML) - the second most common type of leukemia making up 31% of all adult leukemia cases. Here, we found that ADAR2, but not ADAR1 and ADAR3, is specifically downregulated in core binding factor (CBF) AML with t(8;21) or inv(16). In t(8;21) AML, RUNX1-driven transcription of ADAR2 transcripts was found to be repressed by the RUNX1-ETO fusion protein. Forced overexpression of two ADAR2-regulated RNA editing targets COPA and COG3 indeed inhibits clonogenic growth of human t(8;21) AML cells. Further in vivo animal studies confirmed that ADAR2 could suppress leukemogenesis of t(8;21) AML through its RNA binding and editing capabilities. Our results suggest a novel RNA editing-mediated mechanism leading to t(8,12) AML. Key pointsO_LIADAR2, but not ADAR1 and ADAR3, was specifically downregulated in CBF-AML C_LIO_LIRUNX1-ETO suppresses ADAR2 transcription in t(8;21) AML through binding on its promoter C_LIO_LIRNA editing capability of ADAR2 is essential for its repression of leukemogenesis in an AE9a mouse model C_LI

cancer biology↗

bioRxiv2021

Golgi structural defect impairs glycosaminoglycan synthesis, sulfation, and secretion

Synthesis of glycosaminoglycans such as heparan sulfate (HS) and chondroitin sulfate (CS) occurs in the lumen of the Golgi but the relationship between Golgi structural integrity and glycosaminoglycan synthesis is not clear. In this study, we disrupted the Golgi structure by knocking out GRASP55 and GRASP65 and determined its effect on the synthesis, sulfation, and secretion of HS and CS. We found that GRASP depletion increased HS synthesis while decreasing CS synthesis in cells, altered HS and CS sulfation, and reduced both HS and CS secretion. Using proteomics, RNA-seq and biochemical approaches, we identified EXTL3, a key enzyme in the HS synthesis pathway, whose level is upregulated in GRASP knockout cells; while GalNacT1, an essential CS synthesis enzyme, is robustly reduced. In addition, we found that GRASP depletion decreased HS sulfation via the reduction of PAPSS2, a bifunctional enzyme in HS sulfation. Our study provides the first evidence that Golgi structural defect may significantly alter the synthesis and secretion of glycosaminoglycans.

cell biology↗

bioRxiv2021

SARS-CoV-2 hijacks neutralizing dimeric IgA for enhanced nasal infection and injury

Robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) accounts for high viral transmissibility, yet whether neutralizing IgA antibodies can control it remains unknown. Here, we evaluated receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1 and B8-dIgA2 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparably potent neutralization against authentic virus by competing with human angiotensin converting enzyme-2 (ACE2) receptor for RBD binding. While reducing viruses in lungs, pre-exposure intranasal B8-dIgA1 or B8-dIgA2 led to 81-fold more infectious viruses and severer damage in NT than placebo. Virus-bound B8-dIgA1 and B8-dIgA2 could engage CD209 as an alternative receptor for entry into ACE2-negative cells and allowed viral cell-to-cell transmission. Cryo-EM revealed B8 as a class II neutralizing antibody binding trimeric RBDs in 3-up or 2-up/1-down conformation. Therefore, RBD-specific neutralizing dIgA engages an unexpected action for enhanced SARS-CoV-2 nasal infection and injury in Syrian hamsters.

microbiology↗

bioRxiv2021

Single-cell RNA-seq analysis reveals aberrant CSF1 expression in disease-causing synovial fibroblasts of pigmented villonodular synovitis

ObjectivesAlthough the role of the CSF1/CSF1R axis in pigmented villonodular synovitis (PVNS) has been confirmed, the cells that express CSF1 and CSF1R and the underlying mechanism remain unclear. Single-cell RNA sequencing (scRNA-seq) of PVNS obtained through biopsies depicted the cellular diversity of PVNS, revealed specific CSF1/CSF1R-expressing cells and further identified novel gene expression that is associated with the development of PVNS. MethodsscRNA-seq was performed on tissues obtained from the 6 biopsies of 3 patients with PVNS. Flow cytometry, immunofluorescence and western blot validated the transcriptional results, while co-culture systems revealed the cross talk between fibroblasts and macrophages. Results8 subsets of fibroblasts and 5 subsets of macrophages were identified from the synovium of patients with PVNS and were found to be related to distinct signaling pathways. The cellular components of localized and diffuse PVNS are overall similar. Moreover, the synovium and nodule of PVNS share similar composition. The specific cells expressing CSF1/CSF1R were also identified. Other than that, unique CXCL12+CSF1+ fibroblasts were revealed to attract macrophages as disease-causing synovial fibroblasts, leading to the formation of masses in PVNS. ConclusionsPVNS consists of macrophages, fibroblasts, T cells, endothelial cells and mast cells. Among them, the CSF1-expressing fibroblasts appeared to be tumor-like cells that attract macrophages, subsequently forming tumor-like mass in PVNS. This paves the path for novel treatments of PVNS by targeting CXCL12+CSF1+ fibroblasts and the CXCL12-CXCR4 axis.

molecular biology↗

bioRxiv2021

Open Imputation Server provides secure Imputation services with provable genomic privacy

SummaryAs DNA sequencing data is available for personal use, genomic privacy is becoming a major challenge. Nevertheless, high-throughput genomic data analysis outsourcing is performed using pipelines that tend to overlook these challenges. ResultsWe present a client-server-based outsourcing framework for genotype imputation, an important step in genomic data analyses. Genotype data is encrypted by the client and encrypted data are used by the server that never observes the data in plain. Cloud-based framework can benefit from virtually unlimited computational resources while providing provable confidentiality. We demonstrate servers utility from several aspects using genotype dataset from the 1000 Genomes datasets. First, we benchmark the accuracy of common variant imputation in comparison to BEAGLE, a state-of-the-art imputation method. We also provide the detailed time requirements of the server to showcase scaling of time usage in different steps of imputation. We also present a simple correlation metric that can be used to estimate imputation accuracy using only the reference panels. This is important for filtering the variants in downstream analyses. As a further demonstration and a different use case, we performed a simulated genomewide association study (GWAS) using imputed and known genotypes and highlight potential utility of the server for association studies. Overall, our study present multiple lines of evidence for usability of secure imputation service. AvailabilityServer is publicly available at https://www.secureomics.org/OpenImpute. Users can anonymously test and use imputation server without registration. ContactArif.O.Harmanci@uth.tmc.edu

bioinformatics↗

bioRxiv2021

Real-world size of objects serves as an axis of object space

Our mind can represent various objects from the physical world metaphorically into an abstract and complex high-dimensional object space, with a finite number of orthogonal axes encoding critical object features. Previous fMRI studies have shown that the middle fusiform sulcus in the ventral temporal cortex separates the real-world small-size map from the large-size map. Here we asked whether the feature of objects real-world size constructed an axis of object space with deep convolutional neural networks (DCNNs) based on three criteria of sensitivity, independence and necessity that are impractical to be examined altogether with traditional approaches. A principal component analysis on features extracted by the DCNNs showed that objects real-world size was encoded by an independent component, and the removal of this component significantly impaired DCNNs performance in recognizing objects. By manipulating stimuli, we found that the shape and texture of objects, rather than retina size, co-occurrence and task demands, accounted for the representation of the real-world size in the DCNNs. A follow-up fMRI experiment on humans further demonstrated that the shape, but not the texture, was used to infer the real-world size of objects in humans. In short, with both computational modeling and empirical human experiments, our study provided the first evidence supporting the feature of objects real-world size as an axis of object space, and devised a novel paradigm for future exploring the structure of object space. TeaserThis work provides the first evidence illuminating the feature of objects real-world size as an axis of the object space for object recognition with a mutually-inspired paradigm of computational modelling and biological observation.

neuroscience↗

bioRxiv2021

A screen for mutants deficient in coronatine-mediated suppression of root immunity identifies Arabidopsis SDA1 as a novel integrator of immunity and phytohormone signaling

Despite the importance of the root immune system in the interaction with rhizosphere microbes, the majority of genetic screens for immunity regulators have been performed in leaves. A previous screen identified 27 hsm (hormone-mediated suppression of MAMP-triggered immunity) mutants that are impaired in jasmonic acid (JA)-mediated suppression of pattern-triggered immunity (PTI) in roots. Here we characterized 16 of the hsm mutants that retain JA sensitivity and are potential negative regulators of root immunity. We found that the majority of hsm mutants show enhanced resistance to Fusarium, a root fungal pathogen; however, only a subset are more resistant to a foliar pathogen. Surprisingly, 12 of 16 hsm mutants are also impaired in abscisic acid (ABA)-mediated suppression of PTI, suggesting a largely shared pathway between JA- and ABA-mediated immune suppression in roots. Although all hsm mutants are insensitive to JA-mediated suppression of root immunity, hsm4 shows hypersensitivity to JA-mediated root growth inhibition and JA-induced gene expression. Consistently, hsm4 is more resistant to leaf pathogens, suggesting that HSM4 is a negative regulator of both root and leaf immunity. Hsm4 was mapped to a mutation in a conserved ARM-repeat protein homologous to yeast SDA1, which has been reported to regulate 60S ribosome biogenesis. As translational reprogramming is a critical layer of immune regulation, this work suggests that AtSDA1 is a novel negative translational regulator of immunity. Additionally, a comprehensive characterization of all 16 hsm mutants provides a genetic toolkit to identify novel mechanisms that regulate root immunity.

plant biology↗