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Biology subjects

Yu, P.

Publications and source records attributed to Yu, P..

At least 73 records · Page 4Linked to original sources

Control of Leaf Width by the APC/CTAD1-WL1-NAL1 Pathway in Rice

Leaf morphology is one of the most important features of the ideal plant architecture. However, the genetic and molecular mechanisms controlling leaf morphology in crops remain largely unknown, despite their central importance. Here we demonstrate that the APC/CTAD1-WL1-NAL1 pathway regulates leaf width in rice, and mutation of WL1 leads to width leaf variation. WL1 interacts with TAD1 and is degraded by APC/CTAD1, with the loss of TAD1 function resulting in narrow leaves. The WL1 protein directly binds to the regulatory region of NAL1 and recruits the corepressor TOPLESS-RELATED PROTEIN to inhibit NAL1 expression by down-regulating the level of histone acetylation of chromatin. Furthermore, biochemical and genetic analyses revealed that TAD1, WL1, and NAL1 function in a common pathway to control leaf width. Our study establishes an important framework for the APC/CTAD1-WL1-NAL1 pathway-mediated control of leaf width in rice and introduces novel perspectives for using this regulatory pathway for improving crop plant architecture.

plant biology↗

Alkaliphilus flagellata sp. nov., Butyricicoccus intestinisimiae sp. nov., Clostridium mobile sp. nov., Clostridium simiarum sp. nov., Dysosmobacter acutus sp. nov., Paenibacillus brevis sp. nov., Peptoniphilus ovalis sp. nov., and Tissierella simiarum sp. nov., isolated from monkey feces

Non-human primates harbor diverse microbiomes in their guts. As a part of China Microbiome Initiatives, we cultivated and characterized the gut microbiome of cynomolgus monkeys (Macaca fascicularis). In this report, we communicate the characterization and taxonomy of 8 bacterial strains that were obtained from fecal samples of captive cynomolgus monkeys. The results revealed that they represented 8 novel bacterial species. The proposed names of the 8 novel species are Alkaliphilus flagellate (type strain MSJ-5T =CGMCC 1.45007T=KCTC 15974T), Butyricicoccus intestinisimiae MSJd-7T (type strain MSJd-7T =CGMCC 1.45013T =KCTC 25112T), Clostridium mobile (type strain MSJ-11T =CGMCC 1.45009T=KCTC 25065T), Clostridium simiarum (type strain MSJ-4T =CGMCC 1.45006T =KCTC 15975T), Dysosmobacter acutus (type strain MSJ-2T =CGMCC 1.32896T=KCTC 15976T), Paenibacillus brevis MSJ-6T (type strain MSJ-6T =CGMCC 1.45008T=KCTC 15973T), Peptoniphilus ovalis (type strain MSJ-1T =CGMCC 1.31770T=KCTC 15977T), and Tissierella simiarum (type strain MSJ-40T =CGMCC 1.45012T=KCTC 25071T).

microbiology↗

Constitutive expression of JASMONATE RESISTANT 1 elevates content of several jasmonates and primes Arabidopsis thaliana to better withstand drought

Jasmonates have a well-documented role in balancing the trade-off between plant growth and defense against biotic stresses. However, the role of jasmonate signaling under abiotic stress is less well studied. Here, we investigated the function of JASMONATE RESISTANT 1 (JAR1) in drought stress in Arabidopsis thaliana. JAR1 converts jasmonic acid (JA) to jasmonyl-L-isoleucine (JA-Ile), the major bioactive form of jasmonates. Comparison of a newly generated over-expression line (JAR1-OE) with jar1-11, a T-DNA insertion line in the JAR1 locus, and Col-0 revealed that constitutively increased JA-Ile production results in stunted growth and a delay in flowering. Upon water limitation, JAR1-OE plants retained more water in their leaves, showed reduced wilting and recovered better from drought stress than the wild type. By contrast, jar1-11 mutant plants were hypersensitive to drought. RNA-seq analysis and hormonal profiling of plants under control and drought stress conditions provided insight into the molecular reprogramming caused by the alteration in JA-Ile content. Especially JAR1-OE plants were affected in many adaptive systems related to drought stress, including stomatal density, stomatal aperture or the formation of reactive oxygen species (ROS). Overall, our data suggest that constitutively increased expression of JAR1 can prime Arabidopsis towards improved drought tolerance. One sentence summaryConstitutive expression of JAR1primes Arabidopsis thaliana to better withstand drought stress

plant biology↗

Dynamic surveillance of mosquitoes and their viromes in Wuhan during 2020.

Mosquitoes are medically important arthropod vectors and harbor a great variety of viruses. The population density, species and virome of mosquitoes varies according to geography and climate. To investigate the dynamic changes in the species composition and diversity of mosquitoes and their viromes in Wuhan, China, a total of 2,345 adult mosquitoes collected from different habitats including an urban residential area, two hospitals, a scenic area, and a pig farm in a rural region from April to October 2020 were subjected to morphological identification, RT-qPCR and metagenomic sequencing. The results indicated that the dominant presence of Culex mosquitoes was observed in both urban regions (90.32%, 1538/1703) and the pig farm (54.98%, 353/642). Viromes of Culex showed dynamic changes during the collection time. Several viruses, such as Culex flavivirus, Alphamesonivirus 1, Hubei mosquito virus 2 and Hubei mosquito virus 4, had seasonal changes and unimodal increases or declines. Other viruses, such as Wuhan mosquito virus 6, Hubei virga-like virus 2 and Zhejiang mosquito virus 3, were stable in all collected Culex and should be potential members of "core viromes". This study improves the understanding of the dynamic composition of mosquitoes and the viromes they carry and provides useful information for informing mosquito control and mosquito-borne disease prevention strategies.

microbiology↗

Precision Genome and Base Editing by Regulating mRNA Nuclear Export Using Selective Inhibitors of Nuclear Export

CRISPR-based genome engineering tools are associated with off-target effects that constitutively active Cas9 protein may instigate. In the present study, we screened for irreversible small molecule off-switches of CRISPR-Cas9 and discovered that selective inhibitors of nuclear export (SINEs) could inhibit the cellular activity of CRISPR-Cas9 by interfering with the nuclear export of Cas9 mRNA. We subsequently found that SINEs, including an FDA-approved anticancer drug KPT330, could improve the specificities of CRISPR-Cas9-based genome and base editing tools in human cells.

biochemistry↗

Spike Protein Targeting "Nano-Glue" that Captures and Promotes SARS-CoV-2 Elimination

The global emergency caused by the SARS-CoV-2 pandemics can only be solved with adequate preventive and therapeutic strategies, both currently missing. The electropositive Receptor Binding Domain (RBD) of SARS-CoV-2 spike protein with abundant {beta}-sheet structure serves as target for COVID-19 therapeutic drug design. Here, we discovered that ultrathin 2D CuInP2S6 (CIPS) nanosheets as a new agent against SARS-CoV-2 infection, which also able to promote viral host elimination. CIPS exhibits extremely high and selective binding capacity with the RBD of SARS-CoV-2 spike protein, with consequent inhibition of virus entry and infection in ACE2-bearing cells and human airway epithelial organoids. CIPS displays nano-viscous properties in selectively binding with spike protein (KD < 1 pM) with negligible toxicity in vitro and in vivo. Further, the CIPS-bound SARS-CoV-2 was quickly phagocytosed and eliminated by macrophages, suggesting CIPS could be successfully used to capture and facilitate the virus host elimination with possibility of triggering anti-viral immunization. Thus, we propose CIPS as a promising nanodrug for future safe and effective anti-SARS-CoV-2 therapy, as well as for use as disinfection agent and surface coating material to constrain the SARS-CoV-2 spreading.

immunology↗

CoVac501, a self-adjuvanting peptide vaccine conjugated with TLR7 agonists, against SARS-CoV-2 induces protective immunity

Safe, economical and effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to achieve adequate herd immunity and halt the pandemic. We have constructed a novel SARS-CoV-2 vaccine, CoVac501, which is a self-adjuvanting peptide vaccine conjugated with Toll-like receptor 7 (TLR7) agonists. The vaccine contains two immunodominant peptides screened from receptor-binding domain (RBD) and is fully chemically synthesized. And the vaccine has optimized nanoemulsion formulation, outstanding stability and safety. In non-human primates (NHPs), CoVac501 elicited high and persistent titers of RBD-specific and protective neutralizing antibodies (NAbs), which were also effective to RBD mutations. CoVac501 was found to elicit the increase of memory T cells, antigen-specific CD8+ T cell responses and Th1-biased CD4+ T cell immune responses in NHPs. More importantly, the sera from the immunized NHPs can prevent infection of live SARS-CoV-2 in vitro. One-Sentence SummaryA novel SARS-CoV-2 vaccine we developed, CoVac501, which is a fully chemically synthesized and self-adjuvanting peptides conjugated with TLR7 agonists, can induce high-efficient humoral and cellular immune responses against SARS-CoV-2.

immunology↗

Phage Peptides Mediate Precision Base Editing with Focused Targeting Window

Cytidine base editors (CBE) are novel genome engineering tools that can generate C-to-T nucleotide substitutions without introducing double-stranded breaks (DSBs). Instead of generating single-point mutations, CBEs induce nucleotide substitutions at wobble positions within the 20-nucleotide target site. A variety of strategies have been developed to improve the targeting scope and window of CBEs. Among these strategies, molecular switches that can temporally control CBE activities represent compelling options. In this study, we investigated the feasibility of using a bacteriophage-derived peptide, referred to as G8PPD, as the off-switch of CBEs. We showed that G8PPD could be employed to control the activities of and improve the targeting window of A3A and BE3 CBEs and adenine base editor 7.10 (ABE7.10). Notably, in a cell-based disease model of Marfan syndrome, G8PPD facilitated A3A CBE-based gene correction with a more focused targeting window and improved the percentage of perfectly edited gene alleles from less than 4% to more than 38% of the whole population. Our study presents the first peptide off-switch that can improve the targeting scope of CBEs, thus highlighting the importance of the temporal control of BE activity for precision base editing.

genomics↗

AIBP-CAV1-VEGFR3 axis dictates lymphatic cell fateand controls lymphangiogenesis

The lymphatics are essential for the maintenance of tissue fluid homeostasis. Accordingly, lymphatic dysfunction contributes to lymphedema. In development, lymphangiogenesis often requires lymphatic endothelial cell (LEC) lineage specification from the venous ECs and subsequent LEC proliferation and migration, all of which are regulated by the VEGFC/VEGFR3 signaling. Cholesterol is essential for proper cell functions and organ development, yet the molecular mechanism by which cholesterol metabolism controls lymphangiogenesis is unknown. We show that the secreted protein, ApoA1 binding protein (AIBP), dictates lymphatic vessel formation by accelerating cholesterol efflux. Loss of Aibp2, the human paralog in zebrafish, impairs LEC progenitor specification and impedes lymphangiogenesis. Mechanistically, we found that caveolin-1 (CAV-1) suppresses VEGFR3 activation in LECs, and that AIBP-regulated cholesterol efflux disrupts lipid rafts/caveolae and reduces CAV-1 bioavailability, which abolishes the CAV-1 inhibition of VEGFR3 signaling, thereby augmenting VEGFR3 activation and increasing lymphangiogenesis. Enhancement of cholesterol efflux with ApoA1 overexpression or inhibition of cholesterol biosynthesis using atorvastatin restores proper lymphangiogenesis in Aibp2 mutant zebrafish. Loss of Cav-1 increases LEC progenitor specification in zebrafish, and rescues lymphangiogenesis in Aibp2-deficient animals. Recombinant AIBP supplement confers profound LEC fate commitment in the mouse embryonic stem cells (mESC) to LEC differentiation model. Furthermore, enhancement of AIBP-CAV-1-VEGFR3 signaling axis promotes VEGFC-engaged adult lymphangiogenesis in mice. Consistent with these data, AIBP expression is reduced in the epidermis of human lymphedematous skin. These studies identify that AIBP-mediated cholesterol efflux is a critical contributor for lymphangiogenesis. Our studies will provide a new therapeutic avenue for the treatment of lymphatic dysfunctions. One Sentence SummaryOur studies identify that AIBP-CAV-1-VEGFR3 axis enhances VEGFC-elicited lymphangiogenesis, which will guide a new therapeutic strategy for the treatment of lymphatic dysfunctions.

developmental biology↗

Adsorption mechanism of bacteria onto a Na-montmorillonite surface with organic and inorganic calcium

The adsorption of bacteria onto the Na-montmorillonite (Na-MMT) was studied as a function of time, bacterial concentration, temperature and pH with the introduction of the organic and inorganic calcium sources. The results indicated that albeit revealing the same adsorption mechanism, the organic calcium (i.e., Ca(CH3COO)2) proposed in this study is more beneficial and environmentally friendly than the inorganic calcium (i.e., CaCl2) in terms of the adsorption of bacteria onto the Na-MMT surface, which can be ascribed to the formation of the denser aggregates in the Na-MMT with Ca(CH3COO)2. Meanwhile, the adsorption kinetics and isotherms followed the pseudo-second-order kinetic model and Langmuir Equation for both two calcium sources. Meanwhile, the adsorption bands of the water molecules on the minerals were observed to shift significantly after the bacterial adsorption, showing that the hydrogen bonding on the Na-MMT surface played an important role during this process. A value of {Delta}H0 > 0 indicated that the bacterial adsorption was affected by van der Waals force and hydrophobic interaction. Finally, the negative zeta potentials of the Na-MMT increased with the addition of Ca2+ ions, and the experimental data also showed that the adsorption of bacteria onto the Na-MMT was mainly determined by the electrostatic and non-electrostatic forces.

biochemistry↗

Recombinant SARS-CoV-2 RBD molecule with a T helper epitope as a built in adjuvant induces strong neutralization antibody response

Without approved vaccines and specific treatment, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading around the world with above 20 million COVID-19 cases and approximately 700 thousand deaths until now. An efficacious and affordable vaccine is urgently needed. The Val308 - Gly548 of Spike protein of SARS-CoV-2 linked with Gln830 - Glu843 of Tetanus toxoid (TT peptide) (designated as S1-4) and without TT peptide (designated as S1-5), and prokaryotic expression, chromatography purification and the rational renaturation of the protein were performed. The antigenicity and immunogenicity of S1-4 protein was evaluated by Western Blotting (WB) in vitro and immune responses in mice, respectively. The protective efficiency of it was measured by virus neutralization test in Vero E6 cells with SARS-CoV-2. S1-4 protein was prepared to high homogeneity and purity by prokaryotic expression and chromatography purification. Adjuvanted with Alum, S1-4 protein stimulated a strong antibody response in immunized mice and caused a major Th2-type cellular immunity compared with S1-5 protein. Furthermore, the immunized sera could protect the Vero E6 cells from SARS-CoV-2 infection with neutralization antibody GMT 256. The candidate subunit vaccine molecule could stimulate strong humoral and Th1 and Th2-type cellular immune response in mice, giving us solid evidence that S1-4 protein could be a promising subunit vaccine candidate.

bioengineering↗

FGFR Signaling Coordinates the Balance Between Glycolysis and Fatty Acid β-Oxidation in Lymphatic Endothelial Cells

The balance between glycolysis and oxidative phosphorylation is believed to be critical for maintaining cellular bioenergetics, yet the regulation of such balance in lymphatic endothelial cells (LECs) remains unclear. Here we found that chemical inhibition of fibroblast growth factor receptor (FGFR) activity or knockdown of FGFR1, which has been shown to suppress glycolysis and consequently ATP production, induces substantial upregulation of fatty acid {beta}-oxidation (FAO), but not glucose oxidation or glutamine oxidation in LECs. Mechanistically, blockade of FGFR-AKT signaling promotes the expression of CPT1A, a rate-limiting enzyme of FAO, in a PPAR-dependent manner. Metabolic analysis further showed that CPT1A depletion impairs ATP generation in FGFR1-deficient rather than wild-type LECs. This result suggests that FAO, which makes a minor contribution to cellular energy under normal conditions, can compensate for energy deficiency caused by FGFR inhibition. Consequently, CPT1A silencing potentiates the effect of FGFR1 knockdown on impeding LEC proliferation and migration. Collectively, our study identified an FGFR-regulated metabolic balance that is important for LEC growth.

cell biology↗

A Rapid COVID-19 RT-PCR Detection Assay for Low Resource Settings

Quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay is the gold standard recommended to test for acute SARS-CoV-2 infection. It has been used by the Centers for Disease Control and Prevention (CDC) and several other companies in their Emergency Use Authorization (EUA) assays. RT-qPCR requires expensive equipment such as RNA isolation instruments and real-time PCR thermal cyclers, which are not available in many low resource settings and developing countries. As a pandemic, COVID-19 has quickly spread to the rest of the world. Many underdeveloped and developing counties do not have the means for fast and accurate COVID-19 detection to control this outbreak. Using COVID-19 positive clinical specimens, we demonstrated that RT-PCR assays can be performed in as little as 12 minutes using untreated samples, heat-inactivated samples, or extracted RNA templates. Rapid RT-PCR was achieved using thin-walled PCR tubes and a setup including sous vide immersion heaters/circulators. Our data suggest that rapid RT-PCR can be implemented for sensitive and specific molecular diagnosis of COVID-19 in situations where sophisticated laboratory instruments are not available.

molecular biology↗

CREB1 contributes colorectal cancer cell plasticity by regulating lncRNA CCAT1 and NF-κB pathways

The CREB1 gene encodes a pleiotropic transcription factor that frequently dysregulated in cancers. CREB1 can regulates tumour cell status of proliferation or migration, however, the molecular basis for this switch involvement in cell plasticity has not been fully understood. Here, we show that knocking out CREB1 triggered a remarkable effect of epithelial-mesenchymal transition (EMT) and led to the occurrence of inhibited proliferation and enhanced motility in cancer cells. Mechanistically, CREB1-knockout cells showed arrest in the G0/G1 phase as a result of impaired CREB1-dependent transcription of CCAT1 and E2F1. Interestingly, the competition between the coactivator CBP/p300 for CREB1 and p65 leads to the activation of the NF-{kappa}B pathway in cells with CREB1 disrupted, which induces an EMT phenotype and enhances motility. These studies identified previously unknown mechanisms of CREB1 in cell plasticity via its lncRNA and protein effector pathways, revealing an important feature that should be considered in CREB1-targeted tumour therapies.

cell biology↗

Integrated analysis of a compendium of RNA-Seq datasets for splicing factors

A vast amount of public RNA-sequencing datasets have been generated and used widely to study transcriptome mechanisms. These data offer precious opportunity for advancing biological research in transcriptome studies such as alternative splicing. We report the first large-scale integrated analysis of RNA-Seq data of splicing factors for systematically identifying key factors in diseases and biological processes. We analyzed 1,321 RNA-Seq libraries of various mouse tissues and cell lines, comprising more than 6.6 TB sequences from 75 independent studies that experimentally manipulated 56 splicing factors. Using these data, RNA splicing signatures and gene expression signatures were computed, and signature comparison analysis identified a list of key splicing factors in Rett syndrome and cold-induced thermogenesis. We show that cold-induced RNA-binding proteins rescue the neurite outgrowth defects in Rett syndrome using neuronal morphology analysis, and we also reveal that SRSF1 and PTBP1 are required for energy expenditure in adipocytes using metabolic flux analysis. Our study provides an integrated analysis for identifying key factors in diseases and biological processes and highlights the importance of public data resources for identifying hypotheses for experimental testing.

bioinformatics↗

Rhesus macaques can be effectively infected with SARS-CoV-2 via ocular conjunctival route

The outbreak of Corona Virus Disease 2019 caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) is highly transmitted. The potential extra-respiratory transmission routes remain uncertain. Five rhesus macaques were inoculated with 1x106 TCID50 of SARS-CoV-2 via conjunctival (CJ), intratracheal (IT), and intragastric (IG) routes, respectively. Remarkably, the CJ inoculated-macaques developed mild interstitial pneumonia and viral load was detectable in the conjunctival swabs at 1 days post-inoculation (dpi). Only via IT inoculation, viral load was detected in the anal swab at 1-7 dpi and macaque showed weight loss. However, viral load was undetectable after IG inoculation. Comparatively, viral load was higher in the nasolacrimal system but lesions of lung were relatively mild and local via CJ inoculation compared with that via IT inoculation, demonstrating distinct characteristics of virus dispersion. Both the two routes affected the alimentary tract. Therefore the clinicians need to protect eye while working with patients.

microbiology↗

Reinfection could not occur in SARS-CoV-2 infected rhesus macaques

A global pandemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is ongoing spread. It remains unclear whether the convalescing patients have a risk of reinfection. Rhesus macaques were rechallenged with SARS-CoV-2 during an early recovery phase from initial infection characterized by weight loss, interstitial pneumonia and systemic viral dissemination mainly in respiratory and gastrointestinal tracts. The monkeys rechallenged with the identical SARS-CoV-2 strain have failed to produce detectable viral dissemination, clinical manifestations and histopathological changes. A notably enhanced neutralizing antibody response might contribute the protection of rhesus macaques from the reinfection by SARS-CoV-2. Our results indicated that primary SARS-CoV-2 infection protects from subsequent reinfection. One Sentence SummaryNeutralizing antibodies against SARS-CoV-2 might protect rhesus macaques which have undergone an initial infection from reinfection during early recovery days.

microbiology↗

brt: An R package for integrating biological relevance with p value in omics data

Summaryp-value as an indicator of statistical significance is commonly used in biological data. However, considering p-value alone neglects the importance of effect size (i.e., the mean difference between groups) in determining the biological relevance of a "significant" difference. Here, we present a novel algorithm for computing a new statistic, the biological relevance testing (BRT) index, in the frequentist hypothesis testing framework to address this problem. We also show that the results from the BRT procedure provided a promising way to select biologically relevant features by applying it to microarray-type data. Availability and ImplementationFreely available on the web at https://CRAN.R-project.org/package=brt. Contactpengyu.bio@gmail.com

bioinformatics↗