Biology subjects

Wei, L.

Publications and source records attributed to Wei, L..

At least 181 records · Page 10Linked to original sources

bioRxiv2019

Emodin Attenuates Renal Interstitial Fibrosis via Regulation of TIMP1/MM9 Pathway in Rats

Emodin has a variety of pharmacological functions including anti-bacterial infection, anti-inflammatory, anti-oxidation, anti-tumor, regulation of gastrointestinal activities and anti-hepatic and lung fibrosis. However, the role of emodin in the regulation of renal interstitial fibrosis(RIF) remains poorly understood. In this study, we investigated the regulation of emodin in RIF and revealed the underlying molecular mechanisms. We established a unilateral ureter obstruction(UUO) model to simulate renal interstitial fibrosis in rats. We found that UUO rats were observed a large amount of inflammatory cell infiltration, more fibroblast proliferation, collagen fiber proliferation. Furthermore, we demonstrated that the up-regulation of TIMP1 and down-regulation of MMP9 were related to renal fibrosis. However, those phenomena in emodin-treated UUO rats were ameliorated. Collectively, our results provide new insights into the treatment of RIF and suggest that the TIMP1/MM9 signaling axis may be a potential therapeutic target for RIF.

molecular biology↗

bioRxiv2019

DeepMicrobes: taxonomic classification for metagenomics with deep learning

Taxonomic classification is a crucial step for metagenomics applications including disease diagnostics, microbiome analyses, and outbreak tracing. Yet it is unknown what deep learning architecture can capture microbial genome-wide features relevant to this task. We report DeepMicrobes (https://github.com/MicrobeLab/DeepMicrobes), a computational framework that can perform large-scale training on > 10,000 RefSeq complete microbial genomes and accurately predict the species-of-origin of whole metagenome shotgun sequencing reads. We show the advantage of DeepMicrobes over state-of-the-art tools in precisely identifying species from microbial community sequencing data. Therefore, DeepMicrobes expands the toolbox of taxonomic classification for metagenomics and enables the development of further deep learning-based bioinformatics algorithms for microbial genomic sequence analysis.

bioinformatics↗

bioRxiv2019

Tumor Evolution Decoder (TED): Unveiling Tumor Evolution Based on Mutation Profiles of Subclones or Single Cells

Cancer cells constantly evolve accumulating somatic mutations. To describe the tumor evolution process, we develop the Tumor Evolution Decoder (TED), a novel algorithm for constructing phylogenetic tree based on somatic mutation profiles of tumor subclones or single cells. TED takes a unique strategy that reduces the total number of duplicated mutations and dropout mutations in the tumor evolution process, which has not been explored by previous phylogenetic tree methods. TED allows multiple types of somatic mutations as input, such as point mutations, copy number alterations, gene fusion, and their combinations. Theoretical properties of TED are derived while its numerical performance is examined using simulated data. We applied TED to analyze single-cell sequencing data from an essential thrombocythemia tumor and a clear cell renal cell carcinoma, to investigate the ancestral relationships between tumor cells, and found genes related to disease initialization and development mutated in the early steps of evolution. We also applied TED to the subclones of a breast invasive carcinoma and provided important insights on the evolution and metastasis of the tumor.

bioinformatics↗

bioRxiv2019

In Vitro Potent Activity of ε-poly-L-lysine against Candida albicans and the Underlying Mechanisms

ObjectiveThis study aimed to examine the antifungal activity of {varepsilon}-poly-L-lysine ({varepsilon}-PL) against the planktonic cells or biofilms of Candida albicans and explore the underlying mechanism.\n\nMethodsThe minimal inhibitory concentration, minimum fungal concentration, and sessile minimal inhibitory concentration were estimated. The germ tube formation and yeast-to-hypha transformation of C. albicans in different media that induced mycelial growth were recorded. The effect of different concentrations of {varepsilon}-PL on the biofilm formation process and mature biofilm of C. albicans was determined. The reactive oxygen species (ROS) and malondialdehyde (MDA) contents of C. albicans after {varepsilon}-PL treatment were measured. The changes in major virulence genes and proteins of C. albicans were detected.\n\nResults{varepsilon}-PL (512 g/mL) exerted a strong inhibitory effect on C. albicans and biofilms. It blocked the yeast-to-hypha transition and reduced the germ tube formation and germ tube length of C. albicans. The MDA and ROS contents showed an upward trend, indicating a positive correlation with the concentration. Further, {varepsilon}-PL inhibited the high expression of virulence genes in oxidative stress induced by C. albicans. The main peak in the mass spectrum of C. albicans was found to be clear.\n\nConclusions{varepsilon}-PL exerted a significant antifungal effect on the phytoplankton and biofilm of C. albicans. High concentrations of {varepsilon}-PL significantly inhibited the main mycelium of C. albicans. {varepsilon}-PL induced ROS, released cytochrome C, attacked the C. albicans cell membrane to aggravate its lipid oxidation, and inhibited the expression of C. albicans-associated virulence genes and proteins, thereby exerting a bacteriostatic effect.\n\nImportanceThe last two decades have seen a growing trend toward the failure of current antifungal drugs attributed to Candida biofilms. Under appropriate conditions, adherence and colonization of planktonic cells on host tissues and medical devices initiate multicellular organization called biofilm, which is an organized heterogeneous mixture of yeast, hyphae, and pseudohyphal forms embedded in a complex extracellular matrix. Compared with the planktonic cells, biofilms show high resistance to a wide variety of antifungal agents and tolerance to harsh environments and host immune system. Moreover, the development of antifungal drugs is costly, long-term, and difficult. Thus, researchers turned their attention to natural antibacterial peptides, hoping to find an effective antifungal substance or enhance the sensitivity of the existing antifungal drugs to C. albicans.

microbiology↗

bioRxiv2019

De novo transcriptome sequencing of Serangium japonicum (Coleoptera: Coccinellidae) and application of two assembled unigenes

The ladybird beetle Serangium japonicum is an important predator of whiteflies. Although some ecological and biological characteristics of this predator have been studied, the only molecular data for the ladybird beetle at the NCBI website has been submitted by us. To yield gene sequences of the ladybird beetle, paired-end sequencing was used to sequence its transcriptome. Real-time PCR was used to validate differences in the quantity of RNA expressed by the Krueppel homolog 1 (Kr-h1) gene in summer versus winter samples. To find the effective molecular barcode, the annotated cytochrome c oxidase subunit I (COX1) gene fragments were amplified from several ladybird beetle populations. Analysis yielded 191,246 assembled unigenes, of which 127,016 (66.4%) were annotated. The differential expression of Kr-h1 in summer versus winter suggests that S. japonicum can successfully overwinter because the adults enter diapause. The annotated COX1 gene can be used to distinguish S. japonicum from other ladybird species. These gene sequences are currently available in the National Center for Biotechnology Information (NCBI), and will facilitate the study of molecular mechanism in S. japonicum.

zoology↗

bioRxiv2019

Dynamic chromosome rearrangements of the white-spotted bamboo shark shed light on cartilaginous fish diversification mechanisms

Cartilaginous fishes have a very high phenotypical diversity, a phenomenon for which the mechanisms have been largely unexplored. Here, we report the genome of the white-spotted bamboo shark as the first chromosome-level genome assembly of cartilaginous fish. Using this genome, we illustrated a dynamic chromosome rearrangement process in the bamboo shark, which resulted in the formation of 13 chromosomes, all of which were sparsely distributed with conserved genes and fast-evolving. We found the fast-evolving chromosomes to be enriched in immune-related genes with two chromosomes harboring the major genes for developing the single-chain antibody. We also found chromosome rearrangements to have resulted in the loss of two genes (p2rx3 and p2rx5) which we also showed were involved in cartilage development using a CRISPR/Cas9 approach in zebrafish. Our study highlighted the significance of chromosome rearrangements in the phenotypical evolution of cartilaginous fishes, providing clues to inform further studies on mechanisms for fish diversification.

genomics↗

bioRxiv2019

Cell BLAST: Searching large-scale scRNA-seq database via unbiased cell embedding

An effective and efficient cell-querying method is critical for integrating existing scRNA-seq data and annotating new data. Herein, we present Cell BLAST, an accurate and robust cell-querying method. Powered by a well-curated reference database and a user-friendly Web server, Cell BLAST (http://cblast.gao-lab.org) provides a one-stop solution for real-world scRNA-seq cell querying and annotation.

bioinformatics↗

bioRxiv2019

Notch signaling restricts FGF pathway activation in parapineal cells to promote their collective migration

Coordinated migration of cell collectives is important during embryonic development and relies on cells integrating multiple mechanical and chemical cues. Recently, we described that focal activation of the FGF pathway promotes the migration of the parapineal in the zebrafish epithalamus. How FGF activity is restricted to leading cells in this system is, however, unclear. Here, we address the role of Notch signaling in modulating FGF activity within the parapineal. While Notch loss-of-function results in an increased number of parapineal cells activating the FGF pathway, global activation of Notch signaling decreases it; both contexts result in defects in parapineal migration and specification. Decreasing or increasing FGF signaling in a Notch loss-of-function context respectively rescues or aggravates parapineal migration defects without affecting parapineal cells specification. We propose that Notch signaling controls the migration of the parapineal through its capacity to restrict FGF pathway activation to a few leading cells.

cell biology↗

bioRxiv2019

3D cell culture stimulates the secretion of in vivo like exosomes

For studying cellular communications ex-vivo, a two-dimensional (2D) cell culture model is currently used as the "gold standard". 2D culture models are also widely used in the study of RNA expression profiles from tumor cells secreted extracellular vesicles (EVs) for tumor biomarker discovery. Although the 2D culture system is simple and easily accessible, the culture environment is unable to represent in vivo extracellular matrix (ECM) microenvironment. Our study observed that 2D culture-derived EVs showed significantly different profiles in terms of secretion dynamics and essential signaling molecular contents (RNAs and DNAs), when compared to the three-dimensional (3D) culture-derived EVs. By performing small RNA next-generation sequencing (NGS) analysis of cervical cancer cells and their EVs compared with cervical cancer patient plasma EV-derived small RNAs, we observed that 3D culture-derived EV small RNAs differ from their parent cell small RNA profile which may indicate a specific sorting process. Most importantly, the 3D culture derived EV small RNA profile exhibited a much higher similarity (~96%) to in vivo circulating EVs derived from cervical cancer patient plasma. However, 2D culture derived EV small RNA profile correlated better with only their parent cells cultured in 2D. On the other hand, DNA sequencing analysis suggests that culture and growth conditions do not affect the genomic information carried by EV secretion. This work also suggests that tackling EV molecular alterations secreted into interstitial fluids can provide an alternative, non-invasive approach for investigating 3D tissue behaviors at the molecular precision. This work could serve as a foundation for building precise models employed in mimicking in vivo tissue system with EVs as the molecular indicators or transporters. Such models could be used for investigating tumor biomarkers, drug screening, and understanding tumor progression and metastasis.

bioengineering↗

bioRxiv2019

Multi-immersion open-top light-sheet microscope for high-throughput imaging of cleared tissues

Recent advances in optical clearing and light-sheet microscopy have provided unprecedented access to structural and molecular information from intact tissues. However, current light-sheet microscopes have imposed constraints on the size, shape, number of specimens, and compatibility with various clearing protocols. Here we present a multi-immersion open-top light-sheet microscope that enables simple mounting of multiple specimens processed with a variety of protocols, which will facilitate wider adoption by preclinical researchers and clinical laboratories. One Sentence SummaryGlaser et al. describe a multi-immersion open-top light-sheet microscope that enables simple and high-throughput imaging of large numbers of preclinical and clinical specimens prepared with a variety of clearing protocols.

bioengineering↗

bioRxiv2019

PRISM: a comprehensive 3D structure database for post-translational modifications and mutations with functional impact

Post-translational modifications (PTMs) play very important roles in various cell signalling pathways and biological process. Due to PTMs extremely important roles, many major PTMs have been thoroughly studied, while the functional and mechanical characterization of major PTMs is well-documented in several databases. However, most currently available databases mainly focus on protein sequences, while the real 3D structures of PTMs have been largely ignored. Therefore, studies of PTMs 3D structural signatures have been severely limited by the deficiency of the data. Here, we develop PRISMOID, a novel publicly available and free 3D structure database for a wide range of PTMs. PRISMOID represents an up-to-date and interactive online knowledge base with specific focus on 3D structural contexts of PTMs sites and mutations that occur on PTMs and in the close proximity of PTM sites with functional impact. The first version of PRISMOID encompasses 17,145 non-redundant modification sites on 3,919 related protein 3D structure entries pertaining to 37 different types of PTMs. Our entry web page is organized in a comprehensive manner, including detailed PTM annotation on the 3D structure and biological information in terms of mutations affecting PTMs, secondary structure features and per-residue solvent accessibility features of PTM sites, domain context, predicted natively disordered regions and sequence alignments. In addition, high-definition JavaScript packages are employed to enhance information visualization in PRISMOID. PRISMOID equips a variety of interactive and customizable search options and data browsing functions; these capabilities allow users to access data via keyword, ID, and advanced options combination search in an efficient and user-friendly way. A download page is also provided to enable users to download the SQL file, computational structural features, and PTM sites data. We anticipate PRISMOID will swiftly become an invaluable online resource, assisting both biologists and bioinformaticians to conduct experiments and develop applications supporting discovery efforts in the sequence-structural-functional relationship of PTMs and providing important insight into mutations and PTM sites interaction mechanisms. The PRISMOID database is freely accessible at http://prismoid.erc.monash.edu/. The database and web interface are implemented in MySQL, JSP, JavaScript, and HTML with all major browsers supported.

bioinformatics↗

bioRxiv2018

Somatic LINE-1 retrotransposition in cortical neurons of Rett patients and healthy individuals

Mounting evidence supports that LINE-1 (L1) retrotransposition can occur postzygotically in healthy and diseased human tissues, contributing to genomic mosaicism in the brain and other somatic tissues of an individual. However, the genomic distribution of somatic L1Hs (Human-specific LINE-1) insertions and their potential impact on carrier cells remain unclear. Here, using a PCR-based targeted bulk sequencing approach, we profiled 9,181 somatic insertions from 20 postmortem tissues from five Rett patients and their matched healthy controls. We identified and validated somatic L1Hs insertions in both cortical neurons and non-brain tissues. In Rett patients, somatic insertions were significantly depleted in exons--mainly contributed by long genes--than healthy controls, implying that cells carrying MECP2 mutations might be defenseless against a second exonic L1Hs insertion. We observed a significant increase of somatic L1Hs insertions in the brain compared with non-brain tissues from the same individual. Compared to germline insertions, somatic insertions were less sense-depleted to transcripts, indicating that they underwent weaker selective pressure on the orientation of insertion. Our observations demonstrate that somatic L1Hs insertions contribute to genomic diversity and MECP2 dysfunction alters their genomic patterns in Rett patients. Author SummaryHuman-specific LINE-1 (L1Hs) is the most active autonomous retrotransposon family in the human genome. Mounting evidence supports that L1Hs retrotransposition occurs postzygotically in the human brain cells, contributing to neuronal genomic diversity, but the extent of L1Hs-driven mosaicism in the brain is debated. In this study, we profiled genome-wide L1Hs insertions among 20 postmortem tissues from Rett patients and matched controls. We identified and validated somatic L1Hs insertions in both cortical neurons and non-brain tissues, with a higher jumping activity in the brain. We further found that MECP2 dysfunction might alter the genomic pattern of somatic L1Hs in Rett patients.

genomics↗

bioRxiv2018

Single cell transcriptomes reveal characteristics of miRNA in gene expression noise reduction

Isogenic cells growing in identical environments show cell-to-cell variations because of stochastic gene expression. The high level of variation or noise could disrupt robust gene expression and result in tremendous consequences on cell behaviors. In this work, we showed evidence that microRNAs (miRNAs) could reduce gene expression noise in mRNA level of mouse cells based on single-cell RNA-sequencing data analysis. We identified that miRNA expression level, number of targets, targets pool abundance and interaction strength of miRNA with its targets are the key features contributing to noise repression. MiRNAs tend to work together as cooperative sub-networks to repress target noise synergistically in a cell type specific manner. Using a physical model of post-transcriptional regulation, we demonstrated that the accelerated degradation with elevated transcriptional activation of miRNA target provides resistance to extrinsic fluctuations. Together, through the integration analysis of single-cell RNA and miRNA expression profiles. We demonstrated that miRNAs are important post-transcriptional regulators for reducing gene expression noise and conferring robustness to biological processes.

bioinformatics↗

bioRxiv2018

Cytologic, Genetic, and Proteomic Analysis of a Yellow Leaf Mutant of Sesame (Sesamum indicum L.), Siyl-1

Leaf color mutation in sesame always affects the growth and development of plantlets, and their yield. To clarify the mechanisms underlying leaf color regulation in sesame, we analyzed a yellow-green leaf mutant. Genetic analysis of the mutant selfing revealed 3 phenotypes--YY, light-yellow (lethal); Yy, yellow-green; and yy, normal green--controlled by an incompletely dominant nuclear gene, Siyl-1. In YY and Yy, the number and morphological structure of the chloroplast changed evidently, with disordered inner matter, and significantly decreased chlorophyll content. To explore the regulation mechanism of leaf color mutation, the proteins expressed among YY, Yy, and yy were analyzed. All 98 differentially expressed proteins (DEPs) were classified into 5 functional groups, in which photosynthesis and energy metabolism (82.7%) occupied a dominant position. Our findings provide the basis for further molecular mechanism and biochemical effect analysis of yellow leaf mutants in plants.

genetics↗

bioRxiv2018

Regulatory networks of gene expression in maize (Zea mays) under drought stress and re-watering

Drought can severely limit plant growth and production. However, few studies have investigated gene expression profiles in maize during drought/re-watering. We compared drought-treated and water-sufficient maize plants by measuring their leaf relative water content, superoxide dismutase and peroxidase activities, proline content, and leaf gas exchange parameters (photosynthetic rates, stomatal conductance, and transpiration rates). We conducted RNA sequencing analyses to elucidate gene expression profiles and identify miRNAs that might be related to drought resistance. A GO enrichment analysis showed that the common DEGs (differently expressed genes) between drought-treated and control plants were involved in response to stimulus, cellular process, metabolic process, cell part, and binding and catalytic activity. Analyses of gene expression profiles revealed that 26 of the DEGs under drought encoded 10 enzymes involved in proline synthesis, suggesting that increased proline synthesis was a key part of the drought response. We also investigated cell wall-related genes and transcription factors regulating abscisic acid-dependent and -independent pathways. The expression profiles of the miRNAs miR6214-3p, miR5072-3p, zma-miR529-5p, zma-miR167e-5p, zma-miR167f-5p, and zma-miR167j-5p and their relevant targets under drought conditions were analyzed. These results provide new insights into the molecular mechanisms of drought tolerance, and may identify new targets for breeding drought-tolerant maize lines.\n\nAbbreviationsleaf relative water content: RWC, superoxide dismutase activity: SOD, peroxidase activity: POD, proline content: Pro, photosynthetic rates: Pn, stomatal conductance: Cond, transpiration rates: Tr.; quantitative real-time polymerase chain reaction: qPCR; abscisic acid; ABA; polyethylene glycol :PEG; Principal component analysis :PCA; polyacrylamide gel electrophoresis :PAGE\n\nHighlightThe study of physiology and molecular mechanism of maize laid a theoretical foundation for drought resistance breeding under drought stress and re-watering.

genomics↗

bioRxiv2018

Klebsiella huaxiensis sp. nov., recovered from human urine

A Klebsiella strain, WCHKl090001, was recovered from a human urine sample in China in 2017. Phylogenetic analysis based on gyrA and rpoB housekeeping genes revealed that the strain was distinct from any previously described species of the genus Klebsiella though it was clustered with the Klebsiella oxytoca phylogroup including Klebsiella grimontii, Klebsiella michiganensis, and Klebsiella oxytoca. The whole genome sequence of strain WCHKl090001 has an up to 87.18% average nucleotide identity with those of type strains of all known Klebsiella species. In silico DNA-DNA hybridization (isDDH) values between strain WCHKl090001 and type strains of all known Klebsiella species range from 22.3 to 35.2%. Strain WCHKl090001 could be distinguished from species of the Klebsiella oxytoca phylogroup by its negative Voges-Proskauer reaction. Genotypic and phenotypic characteristics from this study indicate that strain WCHKl090001 should be considered to represent a novel species of the genus Klebsiella, for which the name Klebsiella huaxiensis sp. nov. is proposed. The type strain is WCHKl090001T (=GDMCC1.1379T = CCTCC AB 2018106 T).

microbiology↗

bioRxiv2018

Distinctive types of postzygotic single-nucleotide mosaicisms in healthy individuals revealed by genome-wide profiling of multiple organs

Postzygotic single-nucleotide mosaicisms (pSNMs) have been extensively studied in tumors and are known to play critical roles in tumorigenesis. However, the patterns and origin of pSNMs in normal organs of healthy humans remain largely unknown. Using whole-genome sequencing and ultra-deep amplicon re-sequencing, we identified and validated 164 pSNMs from 27 postmortem organ samples obtained from five healthy donors. The mutant allele fractions ranged from 1.0% to 29.7%. Inter- and intra-organ comparison revealed two distinctive types of pSNMs, with about half originating during early embryogenesis (embryonic pSNMs) and the remaining more likely to result from clonal expansion events that had occurred more recently (clonal expansion pSNMs). Compared to clonal expansion pSNMs, embryonic pSNMs had higher proportion of C>T mutations with elevated mutation rate at CpG sites. We observed differences in replication timing between these two types of pSNMs, with embryonic and clonal expansion pSNMs enriched in early- and late-replicating regions, respectively. An increased number of embryonic pSNMs were located in open chromatin states and topologically associating domains that transcribed embryonically. Our findings provide new insights into the origin and spatial distribution of postzygotic mosaicism during normal human development.\n\nAuthor SummaryGenomic mosaicism led by postzygotic mutation is the major cause of cancers and many non-cancer developmental disorders. Theoretically, postzygotic mutations should be accumulated during the developmental process of healthy individuals, but the genome-wide characterization of postzygotic mosaicisms across many organ types of the same individual remained limited. In this study, we identified and validated two types of postzygotic mosaicism from the whole-genomes of 27 organs obtained from five healthy donors. We further found that the postzygotic mosaicisms arising during early embryogenesis and later clonal expansion events show distinct genomic patterns in mutation spectrum, replication timing, and chromatin status.

genomics↗

bioRxiv2018

Multidirectional digital scanned light-sheet microscopy enables uniform fluorescence excitation and contrast-enhanced imaging

Light-sheet fluorescence microscopy (LSFM) has emerged as a powerful method for rapid and optically efficient 3D microscopy. Initial LSFM designs utilized a static sheet of light, termed selective plane illumination microscopy (SPIM), which exhibited shadowing artifacts and deteriorated contrast due to light scattering. These issues have been addressed, in part, by multidirectional selective plane illumination microscopy (mSPIM), in which rotation of the light sheet is used to mitigate shadowing artifacts, and digital scanned light-sheet microscopy (DSLM), in which confocal line detection is used to reject scattered light. Here we present a simple passive multidirectional digital scanned light-sheet microscopy (mDSLM) architecture that combines the benefits of mSPIM and DSLM. By utilizing an elliptical Gaussian beam with increased angular diversity in the imaging plane, mDSLM provides shadow-free contrast-enhanced imaging of fluorescently labeled samples.\n\nOne Sentence SummaryGlaser et al. describe a light-sheet microscopy architecture that enables passive multidirectional illumination with confocal line detection to enable both uniform fluorescence excitation and contrast-enhanced imaging of fluorescently labeled samples.

bioengineering↗