Biology subjects

Tang, G.

Publications and source records attributed to Tang, G..

35 records · Page 2Linked to original sources

bioRxiv2023

Metagenomic analysis of individual mosquitos reveals the ecology of insect viruses

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Using a meta-transcriptomic approach, we analysed the virome of 2,438 individual mosquitos (79 species), spanning [~]4000 km along latitudes and longitudes in China. From these data we identified 393 core viral species associated with mosquitos, including seven (putative) arbovirus species. We identified potential species and geographic hotspots of viral richness and arbovirus occurrence, and demonstrated that host phylogeny had a strong impact on the composition of individual mosquito viromes. Our data revealed a large number of viruses shared among mosquito species or genera, expanding our knowledge of host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, possibly facilitated by long-distance mosquito migrations. Together, our results greatly expand the known mosquito virome, linked the viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the ecology of viruses of insect vectors.

ecology↗

bioRxiv2023

The DEAD-box helicase RCF1 plays roles in miRNA biogenesis and RNA splicing in Arabidopsis

RCF1 is a highly conserved DEAD-box helicase found in yeast, plants and mammals. Studies about the functions of RCF1 in plants are limited. Here we uncovered the functions of RCF1 in Arabidopsis thaliana as a player in pri-miRNA processing and splicing, as well as in pre-mRNA splicing. A mutant with miRNA biogenesis defects was isolated and the defect was traced to a recessive point mutation in RCF1 (rcf1-4). We show that RCF1 promotes D-body formation and facilitates the interaction between pri-miRNAs and HYL1. Finally, we show that intron-containing pri-miRNAs and pre-mRNAs exhibit a global splicing defect in rcf1-4. Together, this work uncovers roles for RCF1 in miRNA biogenesis and RNA splicing in Arabidopsis. One-sentence summaryRCF1 promotes not only the processing of pri-miRNAs, but also the splicing of intron-containing pri-miRNAs, therefore promotes miRNA biogenesis.

plant biology↗

bioRxiv2023

Single-cell transcriptome analysis on the anatomic positional heterogeneity of pig skin

Different anatomic locations of the body skin dermis come from different origins, and its positional hereditary information can be maintained in adults, while highly resolvable cellular specialization is less well characterized in different anatomical regions. Pig is regarded as excellent model for human research in view of its similar physiology to human. In this study, we performed single-cell RNA sequencing of six different anatomical skin regions from the Chenghua pig with superior skin thickness trait. We obtained 215,274 cells, representing seven cell types, among which we primarily characterized the heterogeneity of smooth muscle cells, endothelial cells and fibroblasts. We identified several phenotypes of smooth muscle cell and endothelial cell and presented genes expression of pathways such as the immune response in different skin regions. By comparing differentially expressed fibroblast genes among different skin regions, we considered TNN, COL11A1, and INHBA as candidate genes for facilitating ECM accumulation. These findings of heterogeneity in the main three cell types from different anatomic skin sites will contribute to a better understanding of hereditary information and places the potential focus on skin generation, transmission and transplantation, paving the foundation for human skin priming.

cell biology↗

bioRxiv2022

Robustness of a multivariate composite score when evaluating distress of animal models for gastrointestinal diseases

The fundament of an evidence-based severity assessment in laboratory animal science is reliable distress parameters. Many readouts are used to evaluate and determine animal distress and the severity of experimental procedures. Therefore, we analyzed four distinct parameters like the body weight, burrowing behavior, nesting, and distress score in the four gastrointestinal animal models (pancreatic ductal adenocarcinoma (PDA), pancreatitis, CCl4 intoxication, and bile duct ligation (BDL)). Further, we determined the parameters robustness in various experimental subgroups due to slight variations like drug treatment or telemeter implantations. We used non-parametric bootstrapping to get robust estimates and 95 % confidence intervals for the experimental groups. It was found that the performance of the readout parameters is model-dependent and that the distress score is prone to experimental variation. On the other hand, we also found that burrowing and nesting can be more robust than, e.g., the body weight when evaluating PDA. However, the body weight still was highly robust in BDL, pancreatitis, and CCl4 intoxication. To address the complex nature of the multi-dimensional severity space, we used the Relative Severity Assessment (RELSA) procedure to combine multiple distress parameters into a score and mapped the subgroups and models against a defined reference set obtained by telemeter implantation. This approach allowed us to compare the severity of individual animals in the experimental subgroups using the maximum achieved severity (RELSAmax). With this, the following order of severity was found for the animal models: CCl4 < PDA {approx} Pancreatitis < BDL. Furthermore, the robustness of the RELSA procedure and outcome was externally validated with a reference set from another laboratory also obtained from telemeter implantation. Since the RELSA procedure reflects the multi-dimensional severity information and is highly robust in estimating the quantitative severity within and between models, it can be deemed a valuable tool for laboratory animal severity assessment.

animal behavior and cognition↗

bioRxiv2022

An updated nomenclature for plant ribosomal protein genes

Ban et al. (2014) proposed a nomenclature for ribosomal proteins (r-proteins) that reflects the current understanding of ribosomal protein evolution. In the past few years, this nomenclature has been widely adopted among biomedical researchers and microbiologists. This homology-based r-protein nomenclature has not been as widely adopted among plant biologists, however, presumably because r-protein nomenclature is much more complicated in plants due to gene duplication. Here, we propose compatible upgrades to the homology-guided nomenclature proposed by Ban et al. (2014) so that this naming system can be adopted for widespread use in the plant biology community. We note that Lan et al. (2022) recently proposed updated nomenclature for plant cytosolic ribosomal proteins, focused on Arabidopsis and rice. The nomenclature outlined here is an extension of that proposed by Lan et al. (2022), expanding to include organellar ribosomes and additional species, with the intent that this nomenclature can serve as a template to guide future plant genome annotations. A more detailed comparison highlighting how this naming system builds on the Ban et al. (2014) and Lan et al. (2022) nomenclatures is offered below. At this time, we request community feedback on this proposed nomenclature so that the naming system ultimately chosen represents a broad consensus. Feedback can be communicated to the this working group at plantribosome@gmail.com before July 25th, 2022. Coauthors of this letter and anyone in the scientific community expressing significant interest will then discuss this feedback as a group, reach a consensus agreement, and communicate the updated nomenclature rules through a letter to the editor (expected to be published at The Plant Cell) and the databases at TAIR and MaizeGDB.

plant biology↗

bioRxiv2022

Single nuclei RNAseq analysis of HD mouse models and human brain reveals impaired oligodendrocyte maturation and potential role for thiamine metabolism

The complexity of affected brain regions and cell types is a challenge for Huntingtons disease (HD) treatment. Here we used single nucleus RNA sequencing (snRNAseq) to investigate mechanism of pathology in the cortex and striatum from R6/2 mice at 8 and 12w and in three regions of human HD post-mortem tissue. We identified cell type-specific and cell agnostic signatures and found changes suggesting oligodendrocytes (OLs) and oligodendrocyte precursors (OPCs) were arrested in intermediate maturation states. OL-lineage regulators OLIG1 and OLIG2 were negatively correlated with CAG length in human OPCs, and ATACseq analysis of HD mouse NeuN-negative cells showed decreased accessibility of sites regulated by OL maturation genes. Glucose and lipid metabolism were implicated in abnormal cell maturation and PRKCE and Thiamine Pyrophosphokinase 1 were identified as central genes. High dose thiamine/biotin treatment of R6/1 HD mice to target thiamine metabolism not only restored OL maturation, but also rescued pathology in neurons. These findings reveal insights into HD OL pathology that spans multiple brain regions and link OL maturation deficits to abnormal thiamine metabolism.

neuroscience↗

bioRxiv2022

Extensive neutralization against SARS-CoV-2 variants elicited by Omicron-specific subunit vaccine booster

The currently dominant variant of SARS-CoV-2 Omicron, carrying a great number of mutations, has been verified its strong capacity of immune escape in COVID-19 convalescents and vaccinated individuals. An increased risk of SARS-CoV-2 reinfection or breakthrough infection should be concerned. Here we reported higher humoral immune response elicited by Delta and Omicron variants after breaking through previous infection and cross-neutralization against VOCs, compared to the ancestral wild-type (WT) virus infection. To overcome the immune escape of Omicron, Omicron-specific vaccine was considered as a novel and potential strategy. Mouse models were used to verify whether Omicron-specific RBD subunit boost immune response by immunizing Omicron-RBD recombinant proteins. Three doses of Omicron-RBD immunization elicit comparable neutralizing antibody (NAb) titers with three doses of WT-RBD immunization, but the neutralizing activity was not cross-active. By contrast, two doses of WT-RBD with an Omicron-RBD booster increased the NAb geometric mean titers against Omicron by 9 folds. Moreover, an additional boost vaccination with Omicron-RBD protein could increase humoral immune response against both WT and current VOCs. These results suggest that the Omicron-specific subunit booster shows its advantages in the immune protection from both WT and current VOCs, and that SARS-CoV-2 vaccines administration using two or more virus lineages as antigens might improve the NAb response.

microbiology↗

bioRxiv2021

A protein-trap allele reveals roles for Drosophila ATF4 in photoreceptor degeneration, oocyte maturation and wing development

Metazoans have evolved various stress response mechanisms to cope with cellular stress inflicted by external and physiological conditions. The Integrated Stress Response (ISR) is an evolutionarily conserved pathway that mediates adaptation to cellular stress via the transcription factor, ATF4. Loss of function of Drosophila ATF4, encoded by the gene cryptocephal (crc), results in lethality during pupal development. The roles of crc in Drosophila disease models and adult tissue homeostasis thus remain poorly understood. Here, we report that a protein-trap MiMIC insertion in the crc locus generates a crc-GFP fusion protein that allows visualization of crc activity in vivo, and acts as a hypomorphic mutant that uncovers previously unknown roles for crc. Specifically, the crc protein-trap line shows crc-GFP induction in a Drosophila model for Retinitis Pigmentosa (RP). This crc allele renders photoreceptors more vulnerable to age-dependent retinal degeneration. crc mutant adult animals also show greater susceptibility to amino acid deprivation and reduced levels of known crc transcriptional targets. Furthermore, this mutant allele shows defects in wing veins and oocyte maturation, uncovering previously unknown roles for crc in the development of these tissues. Together, our data establish physiological and pathological functions of crc-mediated ISR in adult Drosophila tissues.

genetics↗

bioRxiv2021

An integral genomic signature approach for tailored cancer targeted therapy using genome-wide sequencing data

With the advent of low-cost sequencing, transcriptome and genome sequencing is expected to become clinical routine and transform precision oncology within next decade. However, viable genome-wide modeling methods that can facilitate rational selection of patients for tailored intervention while tolerating sequencing biases are far lacking. Here we propose an integral genomic signature (iGenSig) analysis as a new class of transparent, interpretable, and resilient methods for precision oncology based on multiple types of genome-wide sequencing data. We postulate that the redundant high-dimensional genomic features, which are typically eliminated during multi-omics modeling, may help overcome the sequencing biases. We thus conceive a novel method that models the therapeutic response using the high-dimensional transcriptional and mutational features predictive of tumor response, which we termed as an integral genomic signature (iGenSig), and then algorithmically resolve the feature redundancy tailored for each patient subject. Using genomic dataset of chemical perturbations, we developed the iGenSig models for predicting targeted therapy responses, and applied selected models to independent datasets for cancer cell lines, patient-derived xenografts, and patient subjects. iGenSig models exhibit outstanding cross-dataset performance compared to artificial intelligence methods, with exceptional resilience against simulated errors in genomic features. In particular, the iGenSig model for the EGFR inhibitor Erlotinib significantly predicted the responses of patient-derived xenografts and patients from a clinical trial, biological interpretation of which led to new insights into the predictive signature pathways with clinical relevance. Together, iGenSig will provide a computational infrastructure to empower tailored cancer intervention based on genome-wide sequencing data.

bioinformatics↗

bioRxiv2021

CTCF association with episomal HPV16 genomes regulates viral oncogene transcription and splicing

Human papillomavirus 16 (HPV16) is a high-risk alphapapillomavirus that is associated with cancers of mucosal epithelia. The virus genome exists in cells as an episome but can integrate and overexpress the E6 and E7 viral oncogenes. In related high-risk family members HPV18 and HPV31, host proteins including CTCF, an insulator, and SMC1A, a component of the cohesion complex, are known to interact with the viral genome and alter transcriptional activity, splicing patterns and episome amplification. However, the roles of these two proteins during HPV16 infection has not yet been fully examined. Here, we show during differentiation of the episomal HPV16-containing W12 cell line that CTCF association increases with the virus genome at the known E2 binding site, whilst additional CTCF binding now occurs at the putative L2 binding site, with SMC1A association occurring unchanged here. While expression of virus late transcripts (E4^L1, L2, L1) is stimulated, early transcript levels decrease by 48 hours, with the exception of the E6*IV spliced transcript. Conversely, in undifferentiated, monolayer W12 cells, CTCF knockdown increases the level of all early transcripts, whereas E6*IV level increases. Additionally, CTCF ablation as well as SMC1A knockdown results in decreases to HPV16 genome copy number. Taken together, this supports the model that while CTCF and SMC1A have a role in HPV16 genome maintenance, CTCF plays a greater part in regulating HPV16 oncogene splicing and expression during the natural lifecycle of the virus, and may be involved in a reduced risk of cancer development during episomal HPV16 infections.

cancer biology↗

bioRxiv2020

Cloning and Functional characterization of seed-specific LEC1A promoter from peanut (Arachis hypogaea L.)

LEAFY COTYLEDON1 (LEC1) is a HAP3 subunit of CCAAT-binding transcription factor, which controls several aspects of embryo and postembryo development, including embryo morphogenesis, storage reserve accumulation and skotomorphogenesis. Herein, using the method of chromosomal walking, a 2707bp upstream sequence from the ATG initiation codon site of AhLEC1A which is a homolog of Arabidopsis LEC1 was isolated in peanut. Its transcriptional start site confirmed by 5 RACE was located at 82 nt from 5 upstream of ATG. The bioinformatics analysis revealed that there existed many tissue-specific elements and light responsive motifs in its promoter. To identify the functional region of the AhLEC1A promoter, seven plant expression vectors expressing the GUS ({beta}-glucuronidase) gene, driven by 5 terminal series deleted fragments of AhLEC1A promoter, were constructed and transformed into Arabidopsis. Results of GUS histochemical staining showed that the regulatory region containing 82bp of 5 UTR and 2228bp promoter could facilitate GUS to express preferentially in the embryos at different development periods of Arabidopsis. Taken together, it was inferred that the expression of AhLEC1A during seed development of peanut might be controlled positively by several seed-specific regulatory elements, as well as negatively by some other regulatory elements inhibiting its expression in other organs. Moreover, the GUS expression pattern of transgenic seedlings in darkness and in light was relevant to the light-responsive elements scattered in AhLEC1A promoter segment, implying that these light-responsive elements harbored in the AhLEC1A promoter regulate skotomorphogenesis of peanut seeds, and AhLEC1A expression was inhibited after the germinated seedlings were transferred from darkness to light.

molecular biology↗

bioRxiv2020

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↗

bioRxiv2020

Biochar effect - mediated ammonium transporter genes and GDH may be the core of improvement nitrogen assimilation in cotton seedling

Biochar enhancement of nitrogen efficiency in crops is highly essential not only to reduce costs of agricultural production but also to conserve resources, lower energy consumption for products of these fertilizers, strengthen soil health, and eventually helps in slowing climate change; however nitrogen efficiency physiology by biochar effects is not clear. Here, we reported on the morphological, nitrogen metabolism and cytokinin, at seedling stage, under different layers of biochar and limited urea conditions grown in soil culture. Expression profile of miRNAs and AOB was further studied in fine and medium roots. It showed active root absorption area, fresh weight, and nitrogen agronomic efficiency responded significantly under biochar and reduction by 20% urea condition in the surface soil layer. Also, NR and GPT activity in fine roots remarkably increased with cytokinin, but decreased significantly in medium roots, meanwhile both NR and GDH activity did so. GOGAT activity was to be dependent with biochar and urea locations. In addition, AMT1;1, gdh3 and gdh2 in fine roots showed their up-regulation with reduction 20% urea and biochar. It revealed that co-expression of gdh3 and gdh2 in fine roots significantly affected nitrogen assimilation under reduction 20% urea with biochar on surface soil at seedling stage. HighlightsThe co-expression of ammonium transporter gene and GDH induced by biochar effect improves nitrogen efficiency and seedling growth. These data emphasizes the importance of effects of cytokinin on nitrate reductase activity closely related to the position under biochar condition, which is a key element of enhancement nitrogen assimilation efficiency in cotton seedling. Biochar addition applied into 0 to 10cm soil had a more positive effect on seedling growth than that into 10 to 20cm soil layers.

plant biology↗

bioRxiv2020

Integrated profiling of single cell epigenomic and transcriptomic landscape of Parkinson's disease mouse brain

Parkinsons disease (PD) is a neurodegenerative disease leading to the impairment of execution of movement. PD pathogenesis has been largely investigated, but either restricted in bulk level or at certain cell types, which failed to capture cellular heterogeneity and intrinsic interplays among distinct cell types. To overcome this, we applied single-nucleus RNA-seq and single cell ATAC-seq on cerebellum, midbrain and striatum of PD mouse and matched control. With 74,493 cells in total, we comprehensively depicted the dysfunctions under PD pathology covering proteostasis, neuroinflammation, calcium homeostasis and extracellular neurotransmitter homeostasis. Besides, by multi-omics approach, we identified putative biomarkers for early stage of PD, based on the relationships between transcriptomic and epigenetic profiles. We located certain cell types that primarily contribute to PD early pathology, narrowing the gap between genotypes and phenotypes. Taken together, our study provides a valuable resource to dissect the molecular mechanism of PD pathogenesis at single cell level, which could facilitate the development of novel methods regarding diagnosis, monitoring and practical therapies against PD at early stage.

cell biology↗

bioRxiv2019

Single cell atlas of domestic pig brain illuminates the conservation and divergence of cell types at spatial and species levels

Domestic pig (Sus scrofa domesticus) has drawn much attention from researchers worldwide due to its implications in evolutionary biology, regenerative medicine and agriculture. The brain atlas of Homo sapiens (primate), Mus musculus (rodent), Danio rerio (fish) and Drosophila melanogaster (insect) have been constructed at single cell resolution, however, the cellular compositions of pig brain remain largely unexplored. In this study, we investigated the single-cell transcriptomic profiles of five distinct regions of domestic pig brain, from which we identified 21 clusters corresponding to six major cell types, characterized by unique spectrum of gene expression. By spatial comparison, we identified cell types enriched or depleted in certain brain regions. Inter-species comparison revealed cell-type similarities and divergences in hypothalamus between mouse and pig, providing invaluable resources for the evolutionary exploration of brain functions at single cell level. Besides, our study revealed cell types and molecular pathways closely associated with several diseases (obesity, anorexia, bulimia, epilepsy, intellectual disability, and autism spectrum disorder), bridging the gap between gene mutations and pathological phenotypes, which might be of great use to the development precise therapies against neural system disorders. Taken together, we reported, so far as we know, the first single cell brain atlas of Sus scrofa domesticus, followed by comprehensive comparisons across brain region and species, which could throw light upon future evo-devo, regenerative medicine, and agricultural studies.

bioinformatics↗

bioRxiv2019

Transcriptional Differences of Peanut (Arachis hypogaea L.) Seeds in the Fresh-harvest, After-ripened and Just-germinated States: insights into regulatory networks of seed dormancy-release and germination

Seed dormancy and germination are the two important traits related to plant survival and reproduction, and crop yield. To understand their regulation mechanism, it is crucial to clarify which genes or which pathways participate in the regulation of these processes. However, little information is available during the procedure of seed dormancy and germination in peanut. In this study, the seeds of the variety Luhua No.14 with non-deep dormancy were selected and its transcriptional changes at three developmental stages: the fresh-harvest (FS), the after-ripened (DS) and the just-germinated seeds (GS), were investigated by comparative transcriptomics analysis. The results showed that genes with increased transcription in DS vs FS comparison were overrepresented for oxidative phosphorylation, glycolysis pathway and tricarboxylic acid cycle (TCA), suggesting that after a period of drying storage, the intermediates stored in dry seeds were rapidly mobilized by glycolysis, TCA cycle, glyoxylate cycle, etc.; the electron transport chain accompanying with respiration has been reactivated to provide ATP for mobilization of other reserves and seed germination. In GS vs DS pairwise, dozens of the up-regulated genes were related to plant hormone biosynthesis and signal transduction, including the majority of components in auxin signal pathway, and brassinosteroid biosynthesis and signal transduction, and some GA and ABA signal transduction genes. During seeds germination, the expression of some EXPANSIN and XYLOGLUCAN ENDOTRANSGLYCOSYLASE was also significantly enhanced. To investigate the effect of different hormone during the procedure of seed germination, the contents and the differential distribution of ABA, GA, BR and IAA in cotyledon, hypocotyl and radicle, and plumule of three seed sections at different developmental stages were also detected. Combining with previous data in other species, a model of regulatory network related to peanut seed germination was developed. This model will helpful to gain further understanding of the mechanisms controlling seed dormancy and germination.

plant biology↗

bioRxiv2018

Widespread Alterations in Translation Elongation in the Brain of Juvenile Fmr1 Knock-Out Mice

FMRP is a polysome-associated RNA-binding protein encoded by Fmr1 that is lost in Fragile X syndrome. Increasing evidence suggests that FMRP regulates both translation initiation and elongation, but the gene-specificity of these effects is unclear. To elucidate the impact of Fmr1 loss on translation, we used ribosome profiling for genome-wide measurements of ribosomal occupancy and positioning in the cortex of 24 day-old Fmr1 knock-out mice. We found a remarkably coherent reduction in ribosome footprint abundance per mRNA for previously identified, high-affinity mRNA binding partners of FMRP, and an increase for terminal oligo-pyrimidine (TOP) motif-containing genes canonically controlled by mTOR-4EBP-eIF4E signaling. Amino acid motif- and gene-level analyses both showed a widespread reduction of translational pausing in Fmr1 knock-out mice. Our findings are consistent with a model of FMRP-mediated regulation of both translation initiation through eIF4E and elongation that is disrupted in Fragile X syndrome.

molecular biology↗