Biology subjects

Tian, B.

Publications and source records attributed to Tian, B..

43 records · Page 3Linked to original sources

bioRxiv2020

A Neutralizing Antibody-Conjugated Photothermal Nanoparticle Captures and Inactivates SARS-CoV-2

The outbreak of 2019 coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global pandemic. Despite intensive research including several clinical trials, currently there are no completely safe or effective therapeutics to cure the disease. Here we report a strategy incorporating neutralizing antibodies conjugated on the surface of a photothermal nanoparticle to actively capture and inactivate SARS-CoV-2. The photothermal nanoparticle is comprised of a semiconducting polymer core and a biocompatible polyethylene glycol surface decorated with neutralizing antibodies. Such nanoparticles displayed efficient capture of SARS-CoV-2 pseudoviruses, excellent photothermal effect, and complete inhibition of viral entry into ACE2-expressing host cells via simultaneous blocking and inactivating of the virus. This photothermal nanoparticle is a flexible platform that can be readily adapted to other SARS-CoV-2 antibodies and extended to novel therapeutic proteins, thus providing a broad range of protection against multiple strains of SARS-CoV-2. O_FIG O_LINKSMALLFIG WIDTH=192 HEIGHT=200 SRC="FIGDIR/small/404624v1_ufig1.gif" ALT="Figure 1"> View larger version (66K): org.highwire.dtl.DTLVardef@44a5a8org.highwire.dtl.DTLVardef@d7bcd5org.highwire.dtl.DTLVardef@1ae6e70org.highwire.dtl.DTLVardef@d4a4f5_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2020

StackRAM: a cross-species method for identifying RNA N6-methyladenosine sites based on stacked ensemble

N6-methyladenosine is a prevalent RNA methylation modification, which plays an important role in various biological processes. Accurate identification of the m6A sites is fundamental to deeply understand the biological functions and mechanisms of the modification. However, the experimental methods for detecting m6A sites are usually time-consuming and expensive, and various computational methods have been developed to identify m6A sites in RNA. This paper proposes a novel cross-species computational method StackRAM using machine learning algorithms to identify the m6A sites in S. cerevisiaeH. sapiens and A. thaliana. First, the RNA sequences features are extracted through binary encoding, chemical property, nucleotide frequency, k-mer nucleotide frequency, pseudo dinucleotide composition, and position-specific trinucleotide propensity, and the initial feature set is obtained by feature fusion. Secondly, the Elastic Net is used for the first time to filter redundant and noisy information and retain important features for m6A sites classification. Finally, the base-classifiers output probabilities are combined with the optimal feature subset corresponding to the Elastic Net, and the combination feature input the second-stage meta-classifier SVM. The jackknife test on training dataset S. cerevisiae indicates that the prediction performance of StackRAM is superior to the current state-of-the-art methods. StackRAM prediction accuracy for independent test datasets H. sapiens and A. thaliana reach 92.30% and 87.06%, respectively. Therefore, StackRAM has development potential in cross-species prediction and can be a useful method for identifying m6A sites. The source code and all datasets are available at https://github.com/QUST-AIBBDRC/StackRAM/.

bioinformatics↗

bioRxiv2019

Silicon Nanowires for Intracellular Optical Interrogation with Sub-Cellular Resolution

Current techniques for intracellular electrical interrogation are substrate bound and are technically demanding, or lack high spatial resolution. In this work, we use silicon nanowires, which are spontaneously internalized by many cell types, to achieve photo-stimulation with sub-cellular resolution. Myofibroblasts loaded with silicon nanowires remain viable and can undergo cell division. Stimulation of silicon nanowires at separate intracellular locations results in local calcium fluxes. We also show that nanowire-containing myofibroblasts can electrically couple to cardiomyocytes in co-culture and that photo-stimulation of the nanowires increases the spontaneous activation rate in neighboring cardiomyocytes. Finally, we demonstrate that this methodology can be extended to the interrogation of signaling in neuron-glia interactions using nanowire-containing oligodendrocytes.

bioengineering↗

bioRxiv2019

A novel antiviral lncRNA EDAL shields a T309 O-GlcNAcylation site to promote EZH2 degradation

The central nervous system (CNS) is vulnerable for viral infection, yet few host factors in the CNS are known to defend invasion by neurotropic viruses. We report here that multiple neurotropic viruses, including rabies virus (RABV), vesicular stomatitis virus (VSV), Semliki Forest virus (SFV) and herpes simplex virus 1 (HSV-1), elicit the neuronal expression of a host-encoded lncRNA EDAL. EDAL inhibits the replication of these neurotropic viruses in neuronal cells and RABV infection in mouse brains. EDAL binds to the conserved histone methyltransferase enhancer of zest homolog 2 (EZH2) and specifically causes EZH2 degradation via lysosomes, reducing the cellular H3K27me3 level. The antiviral function of EDAL resides in a 56-nt antiviral substructure through which its 18-nt helix-loop intimately contacts multiple EZH2 sites surrounding T309, a known O-GlcNAcylation site. EDAL positively regulate the transcription of Pcp4l1 encoding a 10 kDa peptide, which inhibits the replication of mutiple neurotropic viruses. Our findings proposed a model in which a neuronal lncRNA can exert an effective antiviral function via blocking a specific O-GlcNAcylation that determines EZH2 lysosomal degradation.

microbiology↗

bioRxiv2019

System-Level Quantification and Phenotyping of Early Embryonic Morphogenesis of Caenorhabditis elegans

Cell lineage consists of cell division timing, cell migration and cell fate, and is highly conserved during development of nematode species. An outstanding question is how differentiated cells are genetically and physically regulated in order to migrate to their precise destination among individuals. Here, we first generated a reference embryo using time-lapse 3 dimensional images of 222 wild-type C. elegans embryos at about 1.5-minute interval. This was achieved by automatic tracing and quantitative analysis of cellular phenotypes from 4- to 24-cell stage, including cell cycle duration, division orientation and migration trajectory. We next characterized cell division timing and cell kinematic state, which suggests that eight groups of cells can be clustered based on invariant and distinct division sequence. Cells may still be moving while others start to divide, indicating strong robustness against motional noise in developing embryo. We then devised a system-level phenotyping method for detecting mutant defect in global growth rate, cell cycle duration, division orientation and cell arrangement. A total of 758 genes were selected for perturbation by RNA interference followed by automatic phenotyping, which suggests a cryptic genetic architecture coordinating early morphogenesis spatially and temporally. The high-quality wild-type reference supports a conceptual close-packing model for cell arrangement during 4- to 8-cell stage, implying fundamental mechanical laws regulating the topological structure of early C. elegans embryo. Also, we observed a series of remarkable morphogenesis phenomena such as induced defect or recovery from defect in mutant embryo. To facilitate use of this quantification system, we built a software named STAR 1.0 for visualizing the wild-type reference and mutant phenotype. It also allows automatic phenotyping of new mutant embryo. Taken together, we not only provide a statistical wild-type reference with defined variability, but also shed light on both genetic and physical mechanisms coordinating early embryonic morphogenesis of C. elegans. The statistical reference permits a sensitive approach for mutant phenotype analysis, with which we phenotype a total of 1818 mutant embryos by depletion of 758 genes.\n\nHighlights & Graphical Abstract[bullet] Spatial-Temporal Wild-Type Reference for Early Embryonic Morphogenesis of C. elegans\n[bullet]Variability (Noise) of Division Timing, Division Orientation and Cell Arrangement\n[bullet]A Conceptual Close-Packing Model for Cell Arrangement Up to 8-Cell Stage\n[bullet]Quantitative Phenotyping Methods at Embryo and Cellular Level\n[bullet]Cellular Phenotypes of 1818 Mutant Embryos (758 Genes) Before Gastrulation\n[bullet]Categorized Phenotypes upon Gene Perturbation\n\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=134 SRC=\"FIGDIR/small/776062v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (37K):\norg.highwire.dtl.DTLVardef@2ec730org.highwire.dtl.DTLVardef@11732deorg.highwire.dtl.DTLVardef@ccbf4org.highwire.dtl.DTLVardef@2218d1_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2018

PCF11 connects alternative polyadenylation to formation and spontaneous regression of neuroblastoma

Diversification at the transcriptome 3end is an important and evolutionarily conserved layer of gene regulation associated with differentiation and dedifferentiation processes. However the underlying mechanisms and functional consequences are poorly defined. Here, we identify extensive transcriptome-3end-alterations in neuroblastoma, a tumour entity with a paucity of recurrent somatic mutations and an unusually high frequency of spontaneous regression. Utilising extensive RNAi-screening we reveal the landscape and drivers of transcriptome-3end-diversification, discovering PCF11 as critical regulator, directing alternative polyadenylation (APA) of hundreds of transcripts including a differentiation RNA-operon. PCF11 shapes inputs converging on WNT-signalling, and governs cell cycle, proliferation, apoptosis and neurodifferentiation. Postnatal PCF11 down-regulation induces a neurodifferentiation program, and low-level PCF11 in neuroblastoma associates with favourable outcome and spontaneous tumour regression. Our findings document a critical role for APA in tumourigenesis and describe a novel mechanism for cell fate reprogramming in neuroblastoma with important clinical implications. An interactive data repository of transcriptome-wide APA covering >170 RNAis, and an APA-network map with regulatory hubs is provided.

developmental biology↗

bioRxiv2018

Covalent Modification and Regulation of the Nuclear Receptor Nurr1 by a Dopamine Metabolite

Nurr1, a nuclear receptor essential for the development, maintenance, and survival of midbrain dopaminergic neurons, is a potential therapeutic target for Parkinsons disease, a neurological disorder characterized by the degeneration of these same neurons. Efforts to identify Nurr1 agonists have been hampered by the recognition that it lacks several classic regulatory elements of nuclear receptor function, including the canonical ligand-binding pocket. Here we report that the dopamine metabolite 5,6-dihydroxyindole (DHI) binds directly to and modulates the activity of Nurr1. Using biophysical assays and x-ray crystallography we show that DHI binds to the ligand binding domain within a non-canonical pocket, forming a covalent adduct with Cys566. In cultured cells and zebrafish, DHI stimulates Nurr1 activity, including the transcription of target genes underlying dopamine homeostasis. These findings suggest avenues for developing synthetic Nurr1 ligands to ameliorate the symptoms and progression of Parkinsons disease.

biophysics↗