Biology subjects

Tan, X.

Publications and source records attributed to Tan, X..

At least 127 records · Page 7Linked to original sources

bioRxiv2020

Composition and Abundance of Drifting Fish Eggs on the Upper Reaches of Xijiang River, China, after the Formation of the Cascade Reservoirs

To develop effective management actions of riverine fisheries, it is important to monitor how fish resources (i.e., eggs) are recruited in the upper reaches of natural rivers, particularly where dams have been constructed, which potentially hinder life-history strategies. Here, we aimed to determine the State of drifting fish eggs resources, and the underlying environmental factors regulating the presence of fish eggs in the upper reaches of a river (Laibin section of Xijiang River, China). Based on surveys conducted over one spawning period (2016), we set out to: (1) describe the composition and abundance of drifting fish eggs in the 150 km Lainbin section under a dam control, and (2) analyze how the composition and distribution of fish eggs was correlated with environmental factors. A total of 15157 eggs belonging to two orders, four families, and 18 species were collected. Comparison of these data with historical records in the same area showed that the community structure of drifting eggs has changed considerably. Previously, the community was dominated by larger-bodied species, rather than the smaller species documented in 2016. Eggs were primarily detected between May and August. In the natural channel, the greatest abundance of eggs occurred during May and June. In comparison, the greatest abundance of eggs downstream of the dam was detected in July. The results of this study provide important information for water conservancy institutions towards managing regions containing dams to maintain the ecology of rivers and protect important fish resources.

ecology↗

bioRxiv2019

The Tung Tree (Vernicia Fordii) Genome Provides A Resource for Understanding Genome Evolution and Oil Improvement

Tung tree (Vernicia fordii) is an economically important woody oil plant that produces tung oil containing a high proportion of eleostearic acid ([~]80%). Here we report a high-quality, chromosome-scale tung tree genome sequence of 1.12 Gb with 28,422 predicted genes and over 73% repeat sequences. Tung tree genome was assembled by combining Illumina short reads, PacBio single-molecule real-time long reads and Hi-C sequencing data. Insertion time analysis revealed that the repeat-driven tung tree genome expansion might be due to long standing long terminal repeat (LTR) retrotransposon bursts and lack of efficient DNA deletion mechanisms. An electronic fluorescent pictographic (eFP) browser was generated based on genomic and RNA-seq data from 17 various tissues and developmental stages. We identified 88 nucleotide-binding site (NBS)-encoding resistance genes, of which 17 genes may help the tung tree resist the Fusarium wilt shortly after infection. A total of 651 oil-related genes were identified and 88 of them were predicted to be directly involved in tung oil biosynthesis. The fewer phosphoenolpyruvate carboxykinase (PEPC) genes, and synergistic effects between transcription factors and oil biosynthesis-related genes may contribute to high oil content in tung seeds. The tung tree genome should provide valuable resources for molecular breeding and genetic improvement.

bioinformatics↗

bioRxiv2019

SpaCell: integrating tissue morphology and spatial gene expression to predict disease cells

MotivationSpatial transcriptomics technology is increasingly being applied because it enables the measurement of spatial gene expression in an intact tissue along with imaging morphology of the same tissue. However, current analysis methods for spatial transcriptomics data do not use image pixel information, thus missing the quantitative links between gene expression and tissue morphology.\n\nResultsWe developed an user-friendly deep learning software, SpaCell, to integrate millions of pixel intensity values with thousands of gene expression measurements from spatially-barcoded spots in a tissue. We show the integration approach outperforms the use of gene count alone or imaging data alone to create deep learning models to identify cell types or predict labels of tissue images with high resolution and accuracy.\n\nAvailabilityThe SpaCell package is open source under a MIT license and it is available at https://github.com/BiomedicalMachineLearning/SpaCell\n\nContactquan.nguyen@uq.edu.au

bioinformatics↗

bioRxiv2019

Evolving a new protein-DNA interface via sequential introduction of permissive and specificity-switching mutations

Specific interactions between proteins and DNA are essential to many biological processes. Yet it remains unclear how the diversification in DNA-binding specificity was brought about, and what were the mutational paths that led to changes in specificity. Using a pair of evolutionarily related DNA-binding proteins, each with a different DNA preference (ParB and Noc: both having roles in bacterial chromosome maintenance), we show that specificity is encoded by a set of four residues at the protein-DNA interface. Combining X-ray crystallography and deep mutational scanning of the interface, we suggest that permissive mutations must be introduced before specificity-switching mutations to reprogram specificity, and that mutational paths to a new specificity do not necessarily involve dual-specificity intermediates. Overall, our results provide insight into the possible evolutionary history of ParB and Noc, and in a broader context, might be useful in understanding the evolution of other classes of DNA-binding proteins.

microbiology↗

bioRxiv2019

ProGeo-neo: a Customized Proteogenomic Workflow for Neoantigen Prediction and Selection

Neoantigens can be differentially recognized by T cell receptor (TCR) as these sequences are derived from mutant proteins and are unique to the tumor. The discovery of neoantigens is the first key step for tumor-specific antigen (TSA) based immunotherapy. Based on high-throughput tumor genomic analysis, each missense mutation can potentially give rise to multiple neopeptides, resulting in a vast total number, but only a small percentage of these peptides may achieve immune-dominant status with a given major histocompatibility complex (MHC) class I allele. Specific identification of immunogenic candidate neoantigens is consequently a major challenge. Currently almost all neoantigen prediction tools are based on genomics data. Here we report the construction of proteogenomics prediction of neoantigen (ProGeo-neo) pipeline, which incorporates the following modules: mining tumor specific antigens from next-generation sequencing genomic and mRNA expression data, predicting the binding mutant peptides to class I MHC molecules by latest netMHCpan (v.4.0), verifying MHC-peptides by MaxQuant with mass spectrometry proteomics data searched against customized protein database, and checking potential immunogenicity of T-cell-recognization by additional screening methods. ProGeo-neo pipeline achieves proteogenomics strategy and the neopeptides identified were of much higher quality as compared to those identified using genomic data only. The pipeline was constructed based on the genomics and proteomics data of Jurkat leukemia cell line but is generally applicable to other solid cancer research. With massively parallel sequencing and proteomics profiling increasing, this proteogenomics workflow should be useful for neoantigen oriented research and immunotherapy.

bioinformatics↗

bioRxiv2019

PsyMuKB: A De Novo Variant Knowledge Base Integrating Transcriptional and Translational Information to Identify Isoform-specific Mutations in Developmental Disorders

De novo variants (DNVs) are one of the most significant contributors to severe early-onset genetic disorders such as autism spectrum disorder, intellectual disability, and other developmental and neuropsychiatric (DNP) disorders. Currently, a plethora of DNVs have being identified through the use of next-generation sequencing and much effort has been made to understand their impact at the gene level; however, there has been little exploration of the impact at the isoform level. The brain contains a high level of alternative splicing and regulation, and exhibits a more divergent splicing program than other tissues; therefore, it is crucial to explore variants at the transcriptional regulation level to better interpret the mechanisms underlying DNP disorders. To facilitate better usage and improve the isoform-level interpretation of variants, we developed the PsyMuKB (NeuroPsychiatric Mutation Knowledge Base), a knowledge base containing a comprehensive, carefully curated list of DNVs with transcriptional and translational annotations to enable identification of isoform-specific mutations. PsyMuKB allows a flexible search of genes or variants and provides both table-based descriptions and associated visualizations, such as expression, transcript genomic structures, protein interactions, and the mutation sites mapped on the protein structures. It also provides an easy-to-use web interface, allowing users to rapidly visualize the locations and characteristics of mutations and the expression patterns of the impacted genes and isoforms. PsyMuKB thus constitutes a valuable resource for identifying tissue-specific de novo mutations for further functional studies of related disorders. PsyMuKB is freely accessible at http://psymukb.net.

bioinformatics↗

bioRxiv2019

Characterization of Rhodopseudomonas palustris population dynamics on tobacco phyllosphere and induction of plant resistance to Tobacco mosaic virus i

Although many biocontrol bacteria can be used to improve plant tolerance to stresses and to promote plant growth, the hostile environmental conditions on plant phyllosphere and the limited knowledge on bacterial colonization on plant phyllosphere minimized the beneficial effects produced by the biocontrol bacteria. Rhodopseudomonas palustris strain GJ-22 is known as a phyllosphere biocontrol agent. In this paper we described detailed processes of strain GJ-22 colony establishment at various colonization stages. We have shown that the preferable location sites of bacterial aggregates on leaf phyllosphere are grooves between plant epidermal cells. In this study, we categorized bacterial colonies into four phases. Analyses of expressions of plant defense-related genes showed that, starting from Phase III, bacterial cells in the Type 3 and Type 4 colonies started produce unidentified signals to induce host defense again Tobacco mosaic virus infection. To our knowledge, this is the first report focused on the colonization process of a phyllosphere biocontrol agent.

microbiology↗

bioRxiv2019

Laser Recording of Subcellular Neuron Activities

Advances in imaging and recording of neural activities with a single neuron resolution have played a significant role in understanding neurological diseases in the past decade. Conventional methods relying on patch-clamp and electrodes are regarded as invasive, whereas fluorescence-based imaging tools are useful but still suffer from a low signal-to-noise ratio and low sensitivity. Here we developed a novel optical imaging and recording system by employing laser emissions to record the action potentials in single neurons and neuronal networks caused by subtle transients (Ca2+ concentration) in primary neurons in vitro with a subcellular and single-spike resolution. By recording the laser emissions from neurons, we discovered that lasing emissions could be biologically modulated by intracellular activities and extracellular stimulation with >100-fold improvement in detection sensitivity over traditional fluorescence-based measurement. Finally, we showed that ultrasound can wirelessly activate neurons adsorbed with piezoelectric BaTiO3 nanoparticles, in which the neuron laser emissions were modulated by ultrasound. Our findings show that ultrasound stimulation can significantly increase the lasing intensity and neuron network response. This work not only opens the door to laser emission recording of intracellular dynamics in neuronal networks but may provide an ultra-sensitive detection method for brain-on-chip applications, optogenetics, and neuro-analysis.

bioengineering↗

bioRxiv2019

Bacterial Glycogen as a Durable Energy Reserve Contributing to Persistence: An Updated Bibliography and Mathematical Model

Glycogen is conventionally viewed as a transient energy reserve that can be rapidly synthesized for glucose accumulation or mobilized for ATP production and blood glucose homeostasis in higher organisms. However, this understanding is not completely applicable to prokaryotes due to glycogen structural heterogeneity. A number of studies have noted that glycogen with short average chain length gc in bacteria has the potential to degrade slowly, which might prolong bacterial survival in the environment and thus enhance potential for transmission to new hosts. This phenomenon has been examined over the past few years and called the durable energy storage mechanism hypothesis (DESM). In this updated bibliography, we summarize recent progress and provide a mathematical model of glycogen as a durable energy reserve.

microbiology↗

bioRxiv2019

Transketolase is involved in the control of Sigma B during chronic infection by Staphylococcus aureus

Staphylococcus aureus is a leading cause of both acute and chronic infections in humans. The importance of the pentose phosphate pathway (PPP) during S. aureus infection is currently largely unexplored. Here, we focused on one key PPP enzyme, transketolase. We showed that inactivation of the unique gene encoding transketolase activity in S. aureus USA300 ({triangleup}tkt) led to drastic metabolomic changes. Using time-lapse video imaging and mice infection, we observed a major defect of the {triangleup}tkt strain compared to wild-type strain in early intracellular proliferation and in the ability to colonise kidneys. Transcriptional activity of the two master regulators Sigma B and RpiRc was drastically reduced in the {triangleup}tkt mutant during host cells invasion. The concomitant increased RNAIII transcription, suggests that TKT-or a functional PPP-strongly influences the ability of S. aureus to proliferate within host cells by modulating key transcriptional regulators.

microbiology↗

bioRxiv2019

The HIV-1 ribonucleoprotein dynamically regulates its condensate behavior and drives acceleration of protease activity through membrane-less granular phase-separation

A growing number of studies indicate that mRNAs and long ncRNAs can affect protein populations by assembling dynamic ribonucleoprotein (RNP) granules. These phase separated molecular sponges, stabilized by quinary (transient and weak) interactions, control proteins involved in numerous biological functions. Retroviruses such as HIV-1 form by self-assembly when their genomic RNA (gRNA) traps Gag and GagPol polyprotein precursors. Infectivity requires extracellular budding of the particle followed by maturation, an ordered processing of ~2400 Gag and ~120 GagPol by viral protease (PR). This leads to a condensed gRNA-NCp7 nucleocapsid and a CAp24-self-assembled capsid surrounding the RNP. The choreography by which all of these components dynamically interact during virus maturation is one of the missing milestones to fully depict the HIV life cycle. Here, we describe how HIV-1 has evolved a dynamic RNP granule with successive weak-strong-moderate quinary NC-gRNA networks during the sequential processing of the GagNC domain. We also reveal two palindromic RNA-binding triads on NC, KxxFxxQ and QxxFxxK, that provide quinary NC-gRNA interactions. Consequently, the nucleocapsid complex appears properly aggregated for capsid reassembly and reverse transcription, mandatory processes for viral infectivity. We show that PR is sequestered within this RNP and drives its maturation/condensation within minutes, this process being most effective at the end of budding. We anticipate such findings will stimulate further investigations of quinary interactions and emergent mechanisms in crowded environments throughout the wide and growing array of RNP granules.

molecular biology↗

bioRxiv2019

In Vivo Monitoring of Rare Circulating Tumor Cell and Cluster Dissemination in a Multiple Myeloma Xenograft Model

We recently developed Diffuse in vivo Flow Cytometry (DiFC), a new pre-clinical research tool for enumerating extremely rare fluorescently-labeled circulating cells directly in vivo. In this paper, we developed a green fluorescent protein (GFP) compatible version of DiFC, and used it to non-invasively monitor the circulating tumor cell (CTC) burden over time in a multiple myeloma disseminated xenograft model. We show that DiFC allowed counting of CTCs at estimated concentrations below 1 cell per mL in peripheral blood with a negligible false alarm rate. DiFC also revealed the presence of CTC clusters in circulation to our knowledge for the first time in this model, and allowed us to calculate their size, kinetics, and frequency of shedding. We anticipate that the unique capabilities of DiFC will have many applications in the study of hematogenous metastasis, and as a powerful complementary methodology to liquid biopsy assays.

bioengineering↗

bioRxiv2018

The third-generation tetracycline, KBP-7072, exploits and reveals a new potential of the primary tetracycline binding pocket

Antibiotic resistance is a growing threat to human health requiring the discovery or development of new anti-infectives. As such, KBP-7072 is a novel tetracycline derivative that exhibits broad-spectrum activity against Gram-positive and -negative bacterial strains. To determine the mechanism of action of KBP-7072 and understand how its unique C9 extension can be used to combat the growing problem of antibiotic resistance we determined the structure of KBP-7072 bound to the bacterial 30S ribosomal subunit, the inhibitory target of typical tetracyclines. We show that KBP-7072 binds to the primary tetracycline binding site on the 30S ribosomal subunit consistent with it acting as a protein synthesis inhibitor that blocks A-site occupation. Moreover, the unique chemical nature of KBP-7072{acute}s C9 extension leads to a distinctive interaction pattern with the 30S subunit that distinguishes KBP-7072 from the third-generation tetracycline, Tigecycline, and thus expands the interaction potential of the primary tetracycline binding pocket.

biochemistry↗

bioRxiv2018

Co-Expression Network-based Analysis associated with potato initial resistance

RNA sequencing (RNA-seq) providing genome-wide expression datasets has been successfully used to study gene expression patterns and regulation mechanism among multiple samples. Gene co-expression networks (GCNs) studies within or across species showed that coordinated genes in expression patterns are often functionally related. For potatoes, a large amount of publicly available transcriptome datasets have been generated but an optimal GCN detecting expression patterns in different genotypes, tissues and environmental conditions, is lacking. We constructed a potato GCN using 16 published RNA-Seq datasets covering 11 cultivars from native habitat worldwide. The correlations of gene expression were assessed pair-wisely and biologically meaningful gene modules which are highly connected in GCN were identified. One of the primitively native-farmer-selected cultivars in the Andes, ssp.Andigena, had relative far distance in gene expression patterns with other modern varieties. GCN in further enriched 134 highly and specifically co-expressed genes in ssp.Andigena associated with potato disease and stress resistance, which underlying the dramatic shift in evolutionary pressures during potato artificial domestication. In total, the network was consisted of into 14 gene models that involves in a variety of plant processes, which sheds light on how gene modules organized intra- and inter-varieties in the context of evolutionary divergence and provides a basis of information resource for potato gene functional studies.

plant biology↗

bioRxiv2018

In Vivo Flow Cytometry of Extremely Rare Circulating Cells

Circulating tumor cells (CTCs) are of great interest in cancer research, but methods for their enumeration remain far from optimal. We developed a new small animal research tool called \"Diffuse in vivo Flow Cytometry\" (DiFC) for detecting extremely rare fluorescently-labeled circulating cells directly in the bloodstream. The technique exploits near-infrared diffuse photons to detect and count cells flowing in large superficial arteries and veins without drawing blood samples. DiFC uses custom-designed, dual fiber optic probes that are placed in contact with the skin surface approximately above a major vascular bundle. In combination with a novel signal processing, algorithm DiFC allows counting of individual cells moving in arterial or venous directions, as well as measurement of their speed and depth. We show that DiFC allows sampling of the entire circulating blood volume of a mouse in under 10 minutes, while maintaining a false alarm rate of 0.014 per minute. Hence, the unique capabilities of DiFC are highly suited to biological applications involving very rare cell types such as the study of hematogenic cancer metastasis.

bioengineering↗

bioRxiv2018

Integrative analysis of Zika virus genome RNA structure reveals critical determinants of viral infectivity

Since its outbreak in 2007, Zika virus (ZIKV) has become a global health threat that causes severe neurological conditions. Here we perform a comparative in vivo structural analysis of the RNA genomes of two ZIKV strains to decipher the regulation of their infection at the RNA level. Our analysis identified both known and novel functional RNA structural elements. We discovered a functional long-range intramolecular interaction specific for the Asian epidemic strains, which contributes to their infectivity. Our findings illuminate the structural basis of ZIKV regulation and provide a rich resource for the discovery of RNA structural elements that are important for ZIKV infection.

molecular biology↗

bioRxiv2018

Genotyping by sequencing of 393 Sorghum bicolor BTx623 x IS3620C recombinant inbred lines improves sensitivity and resolution of QTL detection

We describe a genetic map with a total of 381 bins of 616 genotyping by sequencing (GBS)-based SNP markers in a F6-F8 recombinant inbred line (RIL) population of 393 individuals derived from crossing S. bicolor BTx623 to S. bicolor IS3620C, a guinea line substantially diverged from BTx623. Five segregation distorted regions were found with four showing enrichment for S. bicolor alleles, suggesting possible selection during formation of this RIL population. A quantitative trait locus (QTL) study with this number of individuals, tripled relative to prior studies of this cross, provided resources, validated previous findings, and demonstrated improved power to detect plant height and flowering time related QTLs relative to other published studies. An unexpected low correlation between flowering time and plant height permitted us to separate QTLs for each trait and provide evidence against pleiotropy. Ten non-random syntenic regions conferring QTLs for the same trait suggest that those QTLs may represent alleles at genes functioning in the same manner since the 96 million year ago genome duplication that created these syntenic relationships, while syntenic regions conferring QTLs for different trait may suggest sub-functionalization after duplication. Collectively, this study provides resources for marker-assisted breeding, as well as a framework for fine mapping and subsequent cloning of major genes for important traits such as plant height and flowering time in sorghum.

genetics↗

bioRxiv2018

Discrimination Exposure and DNA Methylation of Stress-Related Genes in Latina Mothers

Latina mothers, who have the highest fertility rate among all ethnic groups in the US, are often exposed to discrimination. The biological impacts of this discrimination are unknown. This study is the first to explore the relationship between discrimination and DNA methylation of stress regulatory genes in Latinas. Our sample was Latina women (n = 147) with a mean age of 27.6 years who were assessed at 24-32 weeks gestation (T1) and 4-6 weeks postpartum (T2) and reside in the U.S. Blood was collected at T1, and the Everyday Discrimination Scale (EDS) was administered at T1 and T2. DNA Methylation at candidate gene regions was determined by bisulphite pyrosequencing. Associations between EDS and DNA methylation were assessed via zero-inflated Poisson models, adjusting for covariates and multiple-test comparisons. Discrimination was negatively associated with methylation at CpG sites within the glucocorticoid receptor (NR3C1) and brain-derived neurotrophic factor (BDNF) genes that were consistent over time. In addition, discrimination was negatively associated with methylation of a CpG in the glucocorticoid binding protein (FKBP5) at T1 but not at T2. This study underscores the complex biological pathways between discrimination and epigenetic modification in Latina women that warrant further investigation to better understand the genetic and psychopathological impact of discrimination on Latino mothers and their families.

genomics↗