Biology subjects

Xiao, B.

Publications and source records attributed to Xiao, B..

53 records · Page 3Linked to original sources

bioRxiv2021

Palaeogenomics reveal a hybrid origin of the world's largest Camelus species

The extinct Camelus knoblochi is known as the largest camel in genus Camelus, but its relationship to modern Camelus species remains unclear. In this study, we reported the first mitochondrial and nuclear analyses of seven Late Pleistocene C. knoblochi samples from Northeastern China. We found that they are inseparable to wild Bactrian camel on the matrilineal side, but belong to a distinct cluster on the biparental nuclear side. Further admixture proportion analyses suggested hybrid ancestry between both the ancestors of the modern wild and domesticated Bactrian camels, with ~65% contribution from the former and ~35% from the later. By calculating the coalescence time for three Camelus species above, we estimated the hybridization event occurred between approximately 0.8 and 0.33 Ma. We also used Bayesian skyline to reconstruct the maternal demographic trajectories for different Camelus to better compare their evolutionary histories. Our results provide molecular insights into C. knoblochi and fill in a vital piece in understanding the genus Camelus.

molecular biology↗

bioRxiv2021

TMEM120A contains a specific coenzyme A-binding site and might not mediate poking- or stretch-induced channel activities in cells

TMEM120A, a member of the Transmembrane protein 120 (TMEM120) family, has pivotal function in adipocyte differentiation and metabolism, and may also contribute to sensing mechanical pain by functioning as an ion channel named TACAN. Here we report that expression of TMEM120A is not sufficient in mediating poking- or stretch-induced currents in cells, and have solved cryo-EM structures of human TMEM120A (HsTMEM120A) in complex with an endogenous metabolic cofactor (coenzyme A, CoASH) and in the apo form. HsTMEM120A forms a symmetrical homodimer with each monomer containing an amino-terminal coiled-coil motif followed by a transmembrane domain with six membrane-spanning helices. Within the transmembrane domain, a CoASH molecule is hosted in a deep cavity and forms specific interactions with nearby amino acid residues. Mutation of a central tryptophan residue involved in binding CoASH dramatically reduced the binding affinity of HsTMEM120A with CoASH. HsTMEM120A exhibits distinct conformations at the states with or without CoASH bound. Our results suggest that TMEM120A may have alternative functional roles potentially involved in CoASH transport, sensing or metabolism.

biophysics↗

bioRxiv2021

The Nicotiana tabacum Mediator subunit MED25 regulates nicotine biosynthesis through interacting with the basic helix-loop-helix (bHLH) transcription factor NtMYC2s

Nicotine is one of the most important secondary metabolites in tobacco, and its biosynthesis can be induced by topping and jasmonic acid treatment. NtMYC2s play pivotal roles in the regulation of nicotine. The mediator server as a bridge betwen the transcription factors and RNA polymerase in order to facilitates transcription and functions in plants. However, the role of mediator in the regulation of nicotine biosynthesis remains unknown. In this study, we firstly identify the NtMED25 through homologous analysis. NtMED25 interacts with NtMYC2s through the MD region. Interestingly, the nicotine content is decreased in the the knock-down transgenic lines of NtMED25, and the expression levels of two nicotine biosynthesis genes, NtQPT2 and NtPMT2, are also reduced when compared with that in the wild-type plants. Furthermore, NtMED25 enhances the binding of NtMYC2a/ NtMYC2b to the promoter of NtPMT2 and NtQPT2, and then facilitates the nicotine biosynthesis. Therefore, our study revealed the function of mediator in the regulation of nicotine, and provide the insight role on the transcriptional regulation of plant secondary metabolites.

plant biology↗

bioRxiv2020

Piezo2 mediates ultrasonic hearing via cochlear outer hair cells in mice

Ultrasonic hearing is exploited for hunting and navigation as in echolocation by microbats and bottleneck dolphins, and for social communication like ultrasonic vocalization by mice and rats. However, the molecular and cellular basis for ultrasonic hearing is not known yet. Here we show that knockout of the mechanosensitive ion channel PIEZO2 in cochlea disrupts the ultrasonic hearing but not the low-frequency hearing in mice, as shown by audiometry and acoustically-associative freezing behavior. Deletion of Piezo2 in the outer hair cells specifically abolishes the associative learning of the mice upon hearing the ultrasonic frequency. Ex vivo cochlear Ca2+ imaging revealed that the ultrasonic transduction requires both PIEZO2 and the hair-cell mechanotransduction channel. Together, our study demonstrates that the outer hair cells are the effector cells with PIEZO2 as an essential molecule for ultrasonic hearing in mice. Significance StatementSome animals have evolved an incredible ability for vocalizing and hearing ultrasonic frequencies that is inaudible for humans (> 20 kHz). For many years, it has been considered that animals hear ultrasonic frequencies with their cochlear hair cells, using the identical set of mechanotransduction molecules in the hair bundles for hearing audible frequencies. Here, we show that the mice lacking the mechanosensitive ion channel PIEZO2 hardly hear ultrasonic frequencies, while can still be sensitive to audible frequencies. Thus, animals may use a partially different mechanism for sensing physiological ultrasound.

neuroscience↗

bioRxiv2020

RiceLncPedia: a comprehensive database of rice long non-coding RNAs

Long non-coding RNAs (lncRNAs) play significant functions in various biological processes including differentiation, development and adaptation to different environments. Although multi research focused on lncRNAs in rice, the systematic identification and annotation of lncRNAs expressed in different tissues, developmental stages under diverse conditions are still scarce. This impacts the elucidation of their functional significance and the further research on them. Here, RiceLncPedia (http://218.199.68.191:10092/) is constructed including rice lncRNAs explored from 2313 publically available rice RNA-seq libraries and characterize them with multi-omics data sets. In the current version, RiceLncPedia shows 6978 lncRNAs with abundant features: (i) expression profile across 2313 rice RNA-seq libraries; (ii) an online genome browser for rice lncRNAs; (iii) genome SNPs in lncRNA transcripts; (iv) lncRNA associations with phenotype; (v) overlap of lncRNAs with transposons; and (vi) LncRNA-miRNA interactions and lncRNAs as the precursors of miRNAs. In total, RiceLncPedia imported numerous of rice lncRNAs during development under various environments as well as their features extracted from multi-omics data and thus serve as a fruitful resource for rice-related research communities. RiceLncPedia will be further updated with experimental validation, functions association and epigenetic characteristics to greatly facilitate future investigation on rice lncRNAs.

bioinformatics↗

bioRxiv2020

Tethering Piezo channels to the actin cytoskeleton for mechanogating via the E-cadherin-β-catenin mechanotransduction complex

The mechanically activated Piezo channel plays a versatile role in conferring mechanosensitivity to various cell types. However, how it incorporates its intrinsic mechanosensitivity and cellular components to effectively sense long-range mechanical perturbation across a cell remains elusive. Here we show that Piezo1 is biochemically and functionally tethered to the actin cytoskeleton via the E-cadherin-{beta}-catenin mechanotransduction complex, whose perturbation significantly impairs Piezo1-mediated responses. Mechanistically, the adhesive extracellular domain of E-cadherin interacts with the cap domain of Piezo1 that controls the transmembrane gate, while its cytosolic tail might interact with the cytosolic domains of Piezo1 that are in close proximity to its intracellular gates, allowing a direct focus of adhesion-cytoskeleton-transmitted force for gating. Specific disruption of the intermolecular interactions prevents cytoskeleton-dependent gating of Piezo1. Thus, we propose a force-from-filament model to complement the previously suggested force-from-lipids model for mechanogating of Piezo channels, enabling them to serve as versatile and tunable mechanotransducers. HighlightsO_LIRevealed biochemical and functional interactions between Piezo1 and the E-cadherin-{beta}-catenin-F-actin mechanotransduction complex. C_LIO_LIIdentified critical mechanogating domains of Piezo1 as E-cadherin binding domains. C_LIO_LISpecific disruption of the intermolecular interactions between Piezo1 and E-cadherin prevents cytoskeleton-dependent gating of Piezo1. C_LIO_LIProposed a tether model for mechanogating of Piezo channels. C_LI

neuroscience↗

bioRxiv2020

Measurement of the torque in braided DNAs using a thermodynamic Maxwell relation

Braided DNAs are significant structural intermediates in cellular processes, yet little has been experimentally demonstrated about their higher-order structure and twisting torques. We use magnetic tweezers to measure braid extensions at forces ranging from 0.3 to 8 piconewtons, and then apply a thermodynamic Maxwell relation to calculate the torque. Experimentally inferred torques in unbuckled braids take on values up to 76 pN{middle dot}nm, which depends on force, and inter-tether distance. As predicted using a statistical mechanical model, the twist modulus of the braids increases with catenation prior to buckling or formation of plectoneme, and is comparable to that of single DNA.

biophysics↗

bioRxiv2020

Single cell atlas of trisomy 21 cerebral cortex

Down syndrome (DS) is one of the most common human birth defects caused by trisomy 21 (T21), leading to a variety of cognitive impairments. The cellular composition of human brain has been explored using single cell RNA sequencing in both physiological and pathological conditions. However, the cellular heterogeneity of human brain with chromosome aneuploidy is largely unknown. Here, we profiled the transcriptome of 36046 cells in cerebral cortex of T21 human fetus, covering frontal lobe, parietal lobe, occipital lobe and temporal lobe. Intriguingly, we detected several genes positively associated with neurons maturation was dysregulated in T21 frontal cortex (HIC2, POU2F2, ZGLP1 and FOXK1). To share, explore and utilized the data resources of T21 cerebral cortex, we developed a comprehensive platform named T21atlas, composing of two functional modules (T21cluster and T21talk). Overall, our study provides, as far as we know, the first single cell atlas for T21 cerebral cortex, which could promote our understanding of the molecular mechanism of DS at an unprecedented resolution and could potentially facilitate the development of novel clinical therapeutics against T21.

neuroscience↗

bioRxiv2019

Genome-wide Association Study of Pediatric Obsessive-Compulsive Traits: Shared Genetic Risk between Traits and Disorder

ObjectiveTo identify genetic variants associated with obsessive-compulsive (OC) traits and test for sharing of genetic risks between OC traits and obsessive-compulsive disorder (OCD). MethodsWe conducted a genome-wide association analysis of OC traits using the Toronto Obsessive-Compulsive Scale (TOCS) in 5018 unrelated Caucasian children and adolescents from the community (Spit for Science sample). We tested the hypothesis that genetic variants associated with OC traits from the community would be associated with clinical OCD using a meta-analysis of three OCD case-controls samples (cases=3384, controls=8363). Shared genetic risk was examined between OC traits and OCD in the respective samples using polygenic risk score and genetic correlation analyses. ResultsA locus tagged by rs7856850 in an intron of PTPRD (protein tyrosine phosphatase {delta}) was significantly associated with OC traits at the genome-wide significance level (p=2.48x10-8). The rs7856850 locus was also associated with OCD in a meta-analysis of three independent OCD case/control genome-wide datasets (p=0.0069). Polygenic risk scores derived from OC traits were significantly associated with OCD in a sample of childhood-onset OCD and vice versa (ps<0.01). OC traits were highly but not significantly genetically correlated with OCD (rg=0.83, p=0.07). ConclusionsWe report the first validated genome-wide significant variant for OC traits. OC traits measured in the community sample shared genetic risk with OCD case/control status. Our results demonstrate the importance of the type of measure used to measure traits as well as the feasibility and power of using trait-based approaches in community samples for genetic discovery.

genomics↗

bioRxiv2019

Effect of Geometric Sharpness on Translucent Material Perception

When judging optical properties of a translucent object, humans often look at sharp geometric features such as edges and thin parts. Analysis of the physics of light transport shows that these sharp geometries are necessary for scientific imaging systems to be able to accurately measure the underlying material optical properties. In this paper, we examine whether human perception of translucency is likewise affected by the presence of sharp geometry, by confounding our perceptual inferences about an objects optical properties. We employ physically accurate simulations to create visual stimuli of translucent materials with varying shapes and optical properties under different illuminations. We then use these stimuli in psychophysical experiments, where human observers are asked to match an image of a target object by adjusting the material parameters of a match object with different geometric sharpness, lighting geometry, and 3D geometry. We find that the level of geometric sharpness significantly affects perceived translucency by the observers. These findings generalize across a few illuminations and object shapes. Our results suggest that the perceived translucency of an object depends on both the underlying material optical parameters and 3D shape. We also conduct analyses using computational metrics including (luminance-normalized) L2, structural similarity index (SSIM), and Michelson contrast. We find that these image metrics cannot predict perceptual results, suggesting low level image cues are not sufficient to explain our results.

neuroscience↗

bioRxiv2019

Lung tumour cell-derived exosomes promote the expansion of MDSC through miR-21a/PDCD4/IL-6/STAT3 pathway

The percentage of MDSC population in peripheral blood is significantly increased in lung cancer patients. The accumulation of MDSC contributes to the development of a tumour-associated immune suppressive environment. But the mechanism mediating MDSC accumulation in lung cancer patients is elusive. We found that exosomes from Lewis lung cancer cells (LLC-Exo) can be taken up by the mice bone marrow cells and then promote MDSC expansion, which enhance tumour growth. Mechanistically, during the induction of MDSC from the bone marrow cells, miR-21a from LLC-Exo can stimulate BM cells to produce more IL-6 by inhibiting pdcd4 expression post-transcriptionally. Autocrine IL-6 induces tyrosine 705(Y705) of STAT3 to be phosphorylated during MDSC expansion. LLC-Exo with miR-21a deletion lost its ability to stimulate IL-6 production, STAT3 activation and MDSC expansion. These results demonstrate that lung cancer cell-derived exosomes promote functional MDSC expansion through activation of miR-21a/PDCD4/IL-6/STAT3 pathway.

cancer biology↗

bioRxiv2019

Manipulating patterns of dynamic deformation elicits the impression of cloth with varying stiffness

Cloth is a common material and humans can visually estimate its mechanical properties by observing how it deforms under external forces. Here we ask whether, and how, dynamic deformation can affect the perception of mechanical properties of cloth. In Experiment 1, we find that both intrinsic mechanical properties and optical properties affect stiffness perception when the stimuli are presented as images. By contrast, in videos, humans can partially discount the effect of optical appearances and exhibit higher sensitivity to stiffness. We further identified an idiosyncratic deformation pattern (i.e., movement uniformity) to differentiate stiffness, which can be reliably measured by six optical flow features. In Experiment 2, we isolate the deformation by creating dynamic dot stimuli from the 3D mesh of the cloth. We directly alter the movement pattern by manipulating the uniformity of the displacement vectors on the dot stimuli, and show that changing the pattern of dynamic deformation alone can alter the perceived stiffness of cloth in a variety of scene set-ups. Furthermore, by analyzing optical flow fields extracted from the manipulated dynamic dot stimuli, we confirmed the same six optical flow features can be diagnostic of the degree of stiffness of moving cloth across different scenes. Overall, our study demonstrates that manipulating patterns of dynamic deformation alone can elicit the impression of cloth with varying stiffness, suggesting that human visual system might rely on the idiosyncratic pattern of dynamic deformation for estimating stiffness.

neuroscience↗

bioRxiv2018

Penaeidins are a novel family of antiviral effectors against WSSV in shrimp

Penaeidins are members of a family of key effectors with broad anti-bacterial activities in penaeid shrimp. However, the function of penaeidins in antiviral immunity is rarely reported and remains largely unknown. Herein, we uncovered that penaeidins are a novel family of antiviral effectors against white spot syndrome virus (WSSV). Firstly, RNAi in vivo mediated knockdown of each penaeidin from four identified penaeidins from Litopenaeus vannamei resulted in elevated viral loads and rendered shrimp more susceptible to WSSV, whilst the phenotype of survival rate in penaeidin-silenced shrimp can be rescued via the injection of recombinant penaeidin proteins. Moreover, pull-down assays demonstrated the conserved PEN domain of penaeidin was able to interact with WSSV structural proteins. Furthermore, we observed that colloidal gold-labeled penaeidins were located on the outer surface of the WSSV virion. By infection-blocking assay, we observed that hemocytes had lower viral infection rates in the group of WSSV preincubated with penaeidins than those of control group. Phagocytic activity analysis further showed that penaeidins were able to inhibit phagocytic activity of hemocytes against WSSV Taken together, these results suggest that penaeidins specifically binds to WSSV virion by interacting with its structural proteins, thus preventing viral infection that confers host against WSSV. In addition, dual-luciferase assay and EMSA assay demonstrated that penaeidins were regulated by Dorsal and Relish, two transcription factors of the canonical Toll and IMD pathway, respectively. To our best knowledge, this is the first report on uncovering the antiviral function of penaeidins in the innate immune system of shrimp.\n\nImportancesWhite spot syndrome, caused by white spot syndrome virus (WSSV), is the most serious disease in shrimp aquaculture, which has long been a scourge of cultured shrimp industry. Herein, we provided some substantial evidences to indicate that penaeidins are a novel family of effectors with antiviral activity against WSSV in shrimp. Penaeidins such as BigPEN, PEN2 and PEN3 were able to interact with the outer surface of WSSV virion via binding to viral structural proteins, and thus preventing viral entry host cells. In addition, we demonstrated that the Toll and IMD signaling pathways can regulate the transcriptional expression of penaeidins, which may suggest an important role of the conserved innate signaling pathways in antiviral immunity. This is the first report of the antiviral mechanism of penaeidins in shrimp, which may provide some new insights into strategies to control WSSV infection in shrimp farms.

immunology↗

bioRxiv2018

RNAi screening identifies a new Toll from shrimp that restricts WSSV infection through activating Dorsal to induce antimicrobial peptides

The function of Toll pathway defense against bacterial infection has been well established in shrimp, however how this pathway responds to viral infection is still largely unknown. In this study, we report the Toll4-Dorsal-AMPs cascade restricts the white spot syndrome virus (WSSV) infection of shrimp. A total of nine Tolls from Litopenaeus vannamei namely Toll1-9 are identified, and RNAi screening in vivo reveals the Toll4 is important for shrimp to oppose WSSV infection. Knockdown of Toll4 results in elevated viral loads and renders shrimp more susceptible to WSSV. Furthermore, Toll4 could be a one of upstream pattern recognition receptor (PRR) to detect WSSV, and thereby leading to nuclear translocation and phosphorylation of Dorsal, the known NF-{kappa}B transcription factor of the canonical Toll pathway. More importantly, silencing of Toll4 and Dorsal contributes to impaired expression of a specific set of antimicrobial peptides (AMPs) such as anti-LPS-factor (ALF) and lysozyme (LYZ) family, which exert potent anti-WSSV activity. Two AMPs of ALF1 and LYZ1 as representatives are demonstrated to have the ability to interact with several WSSV structural proteins. Taken together, we therefore identify the Toll4-Dorsal pathway mediates strong resistance to WSSV infection by inducing some specific AMPs.\n\nAuthor summaryThe TLR pathway mediated antiviral immune response is well identified in mammals, yet, Toll pathway governing this protection in invertebrates remains unknown. In the present study, we uncover that a shrimp Toll4 from a total of nine Tolls in L. vannamei confers resistance to WSSV thought inducing the NF-{kappa}B transcription factor Dorsal to inspiring the production of some antimicrobial peptides (AMPs) with antiviral activity. The anti-LPS-factor (ALF) and lysozyme (LYZ) family are identified as the Toll4-Dorsal pathway targeted genes with the ability to interact with viral structural proteins in response to WSSV infection. These results suggest that the Toll receptor induces the expression of AMPs with antiviral activity could be a general antiviral mechanism in invertebrates and Toll pathway established antiviral defense could be conserved during evolution.

immunology↗

bioRxiv2018

Interaction between static visual cues and force-feedback on the perception of mass of virtual objects

We use force-feedback device and a game engine to measure the effects of material appearance on the perception of mass of virtual objects. We discover that the perceived mass is mainly determined by the ground-truth mass output by the force-feedback device. Different from the classic Material Weight Illusion (MWI), however, heavy-looking objects (e.g. steel) are consistently rated heavier than light-looking ones (e.g. fabric) with the same ground-truth mass. Analysis of the initial accelerated velocity of the movement trajectories of the virtual probe shows greater acceleration for materials with heavier rated mass. This effect is diminished when the participants lift the object for the second time, meaning that the influence of visual appearance disappears in the movement trajectories once it is calibrated by the force-feedback. We also show how the material categories are affected by both the visual appearance and the weight of the object. We conclude that visual appearance has a significant interaction with haptic force-feedback on the perception of mass and also affects the kinematics of how participants manipulate the object.\n\nCCS CONCEPTS* Human-centered computing [->] Empirical studies in HCI; Empirical studies in interaction design; Empirical studies in visualization;\n\nACM Reference FormatWenyan Bi, Jonathan Newport, and Bei Xiao. 2018. Interaction between static visual cues and force-feedback on the perception of mass of virtual objects. In Proceedings of. ACM, New York, NY, USA, 5 pages.

neuroscience↗

bioRxiv2018

Estimating mechanical properties of cloth from videos using dense motion trajectories: human psychophysics and machine learning

Humans can visually estimate the mechanical properties of deformable objects (e.g. cloth stiffness). While much of the recent work on material perception has focused on static image cues (e.g., textures and shape), little is known whether humans can integrate information over time to make a judgment. Here, we investigate the effect of spatiotemporal information across multiple frames (multi-frame motion) on estimating the bending stiffness of cloth. Using high-fidelity cloth animations, we first examined how the perceived bending stiffness changed as a function of the physical bending stiffness defined in the simulation model. Using maximum likelihood difference scaling methods (MLDS) we found that the perceived stiffness and the physical bending stiffness were highly correlated. A second experiment in which we scrambled the frame sequences diminished this correlation. This suggests that multi-frame motion plays an important role. To provide further evidence for this finding, we extracted dense motion trajectories from the videos across 15 consecutive frames and used the trajectory descriptors to train a machine-learning model with the measured perceptual scales. The model can predict human perceptual scales in new videos with varied winds, optical properties of cloth, and scene setups. When the correct multi-frame was removed (using either scrambled videos or 2-frame optical flow to train the model), the predictions significantly worsened. Our findings demonstrate that multi-frame motion information is important for both humans and machines to estimate the mechanical properties. In addition, we show that dense motion trajectories are effective features to build a successful automatic cloth estimation system.

neuroscience↗

bioRxiv2018

Utility of Attention-Deficit/Hyperactivity Disorder Trait Measure in Population Genetics: A Polygenic Risk Study

BackgroundValid and genetically-informative trait measures of psychopathology collected in the general population would provide a powerful complement to case/control genetic designs. We report the convergent, predictive and discriminant validity of the parent- and the self-report versions of the Strengths and Weaknesses of ADHD Symptoms and Normal Behavior Rating Scale (SWAN) for attention-deficit/hyperactivity disorder (ADHD) traits. We tested if SWAN ADHD scores were associated with ADHD diagnosis, ADHD polygenic risk, as well as with traits and polygenic risk for co-occurring disorders such as anxiety and obsessive-compulsive disorder (OCD).\n\nMethodsWe collected parent- and self-report SWAN scores in a community sample (n=15,560; 6-18 years of age) and created norms. Sensitivity-specificity analyses determined SWAN cut-points that discriminated those with a community ADHD diagnosis (n=972) from those without a community diagnosis. We validated cut-points from the community sample in a clinical sample (266 ADHD cases; 36 controls). We tested if SWAN scores were associated with anxiety and obsessive-compulsive (OC) traits and polygenic risk for ADHD, OCD and anxiety disorders.\n\nResultsBoth the parent- and the self-report SWAN measures showed high convergent validity with established ADHD measures and distinguished ADHD participants with high sensitivity and specificity in the community sample. Cut-points established in the community sample discriminated ADHD clinic cases from controls with a sensitivity of 86% and specificity of 94%. High parent- and self-report SWAN scores and scores above the community-based cut-points were associated with polygenic risk for ADHD. High ADHD traits were associated with high anxiety traits, but not OC traits. SWAN scores were not associated with OCD or anxiety disorder polygenic risk.\n\nConclusionThe parent- and self-report SWAN are potentially useful in genetic research because they predict ADHD diagnoses and are associated with ADHD polygenic risk.

genetics↗