Biology subjects

Xu, J.

Publications and source records attributed to Xu, J..

At least 649 records · Page 36Linked to original sources

bioRxiv2021

Global Patterns in Culturable Soil Yeast Diversity

Yeasts, broadly defined as unicellular fungi, fulfill essential roles in soil ecosystems as decomposers and nutrition sources for fellow soil-dwellers. Broad-scale investigations of soil yeasts pose a methodological challenge as metagenomics are of limited use on this group of fungi. Here we characterize global soil yeast diversity using fungal DNA barcoding on 1473 yeasts cultured from 3826 soil samples obtained from nine countries in six continents. We identify mean annual precipitation and international air travel as two significant predictors of soil yeast community structure and composition worldwide. Anthropogenic influences on soil yeast communities, directly via travel and indirectly via altered rainfall patterns resulting from climate change, are concerning as we found common infectious yeasts frequently distributed in soil in several countries. Our discovery of 41 putative novel species highlights the need to revise the current estimate of ~1500 recognized yeast species. Our findings demonstrate the continued need for culture-based studies to advance our knowledge of environmental yeast diversity.

microbiology↗

bioRxiv2021

Soil chemistry determines whether defensive plant secondary metabolites promote or suppress herbivore growth

Specialized metabolites mediate important interactions in both the rhizosphere and the phyllosphere. How this compartmentalized multifunctionality influences plant-environment interactions is unknown. Here, we investigated how the dual role of maize benzoxazinoids as leaf defenses and root siderophores shapes the interaction between maize and a major global insect pest, the fall armyworm. We find that benzoxazinoids suppress fall armyworm growth in soils with low bioavailable iron but enhance growth in soils with higher bioavailable iron. Manipulation experiments confirm that benzoxazinoids suppress herbivore growth under iron-deficient conditions but enhance herbivore growth when iron is present in its free form. This reversal of the protective effect of benzoxazinoids is not associated with major changes in plant primary metabolism. Plant defense activation is modulated by the interplay between soil iron and benzoxazinoids but does not explain fall armyworm performance. Instead, increased iron supply to the fall armyworm by benzoxazinoids in the presence of free iron enhances larval performance. This work identifies soil chemistry as a decisive factor for the impact of plant secondary metabolites on herbivore growth. It also demonstrates how the multifunctionality of plant secondary metabolites drives interactions between abiotic and biotic factors, with major consequences for plant health in variable environments.

plant biology↗

bioRxiv2021

Distance-guided protein folding based on generalized descent direction

Advances in the prediction of the inter-residue distance for a protein sequence have increased the accuracy to predict the correct folds of proteins with distance information. Here, we propose a distance-guided protein folding algorithm based on generalized descent direction, named GDDfold, which achieves effective structural perturbation and potential minimization in two stages. In the global stage, random-based direction is designed using evolutionary knowledge, which guides conformation population to cross potential barriers and explore conformational space rapidly in a large range. In the local stage, locally rugged potential landscape can be explored with the aid of conjugate-based direction integrated into a specific search strategy, which can improve exploitation ability. GDDfold is tested on 347 proteins of a benchmark set, 24 FM targets of CASP13 and 20 FM targets of CASP14. Results show that GDDfold correctly folds (TM-score [≥] 0.5) 316 out of 347 proteins, where 65 proteins have TM-scores that are greater than 0.8, and significantly outperforms Rosetta-dist (distance-assisted fragment assembly method) and L-BFGSfold (distance geometry optimization method). On CASP FM targets, GDDfold is comparable with five state-of-the-art methods, namely, Quark, RaptorX, Rosetta, MULTICOM and trRosetta in the CASP 13 and 14 server groups.

bioinformatics↗

bioRxiv2021

The First High-Quality Reference Genome of Sika Deer Provides Insights for High-Tannin Adaptation

Sika deer are known to prefer oak leaves, which are rich in tannins and toxic to most mammals; however, the genetic mechanisms underlying their unique ability to adapt to living in the jungle are still unclear. In identifying the mechanism responsible for the tolerance of a highly toxic diet, we have made a major advancement in the elucidation of the genomics of sika deer. We generated the first high-quality, chromosome-level genome assembly of sika deer and measured the correlation between tannin intake and RNA expression in 15 tissues through 180 experiments. Comparative genome analyses showed that the UGT and CYP gene families are functionally involved in the adaptation of sika deer to high-tannin food, especially the expansion of UGT genes in a subfamily. The first chromosome-level assembly and genetic characterization of the tolerance toa highly toxic diet suggest that the sika deer genome will serve as an essential resource for understanding evolutionary events and tannin adaptation. Our study provides a paradigm of comparative expressive genomics that can be applied to the study of unique biological features in non-model animals.

genomics↗

bioRxiv2021

Dual functions of ZmGI1 in the photoperiodic flowering pathway and salt stress responses in maize

The circadian clock perceives photoperiodic changes and initiates processes leading to floral transition. GIGANTEA (GI) primarily functions as a principal clock component that integrates environmental cues into regulation of growth and development in Arabidopsis. However, it is unclear whether ZmGIs regulate photoperiodic flowering and abiotic stress response. Here, we demonstrated that the expression of ZmGI1 depicted a typical circadian pattern and was differentially expressed under LDs and SDs in photoperiodic sensitive and insensitive maize lines. The transcription level was significantly and positively correlated with days to silking and photoperiodic sensitivity in maize. Moreover, natural variation in ZmGI1 was associated with maize photoperiod response and the fine-tuning of plant development traits. Overexpression of ZmGI1Huangzao4 induced early flowering and enhanced salt tolerance in Arabidopsis relative to the wild-type and gi mutants. ZmGI1 formed a protein complex with ZmFKF1 and acted as a positive regulator of flowering time by regulating CONSTANS transcription in the photoperiod pathway. The ZmGI1/ZmThox complex regulates oxidative stress induced by salt stress via a redox balance pathway. Over all, we have provided compelling evidence to suggest that ZmGI1 is a pleotropic gene whose expression depicts a typical circadian rhythmic pattern and regulates flowering time and confers salt stress tolerance.

developmental biology↗

bioRxiv2021

Somatic genetics analysis of sleep in adult mice

Classical forward and reverse mouse genetics approaches require germline mutations and, thus, are unwieldy to study sleep functions of essential genes or redundant pathways. It is also time-consuming to conduct electroencephalogram/electromyogram-based mouse sleep screening owning to labor-intensive surgeries and genetic crosses. Here, we describe a highly accurate SleepV (video) system and adeno-associated virus (AAV)-based adult brain chimeric (ABC)- expression/knockout (KO) platform for somatic genetics analysis of sleep in adult mice. A pilot ABC-expression screen identifies CREB and CRTC1, of which constitutive or inducible expression significantly reduces quantity and quality of non-rapid eye movement sleep. Whereas ABC-KO of exon 13 of Sik3 by AAV-Cre injection in Sik3-E13flox/flox adult mice phenocopies Sleepy (Sik3Slp/+) mice, ABC-CRISPR of Slp/Sik3 reverses hypersomnia of Sleepy mice, indicating a direct role of SLP/SIK3 kinase in sleep regulation. Multiplex ABC-CRISPR of both orexin/hypocretin receptors causes narcolepsy-like episodes, enabling one-step analysis of redundant genes in adult mice. Finally, ABC-expression/KO screen identifies Ankrd63 and NR1 as two potentially new sleep regulators. Therefore, this somatic genetics approach should facilitate high-throughput analysis of sleep regulatory genes, especially for essential or redundant genes, in adult mice by skipping the mouse development and genetic crosses.

neuroscience↗

bioRxiv2021

Mapping the Central and Peripheral Projections of Lung Innervating Sensory Neurons

While best known as the gas exchange organ, the lung is also critical for sensing and responding to the aerosol environment in part through interaction with the nervous system. The rich diversity of lung innervating neurons remains poorly understood. Here, we interrogated the cell body location, projection pattern and targets of lung-innervating sensory neurons. Retrograde tracing from the lung labeled neurons primarily in the vagal ganglia, in a spatially distributed population expressing markers including Vglut2, Trpv1, Tac1, Calb1 or Piezo2. Centrally, they project to the nucleus of the solitary tract in the brainstem. Peripherally, they project along the branching airways and terminate on airway smooth muscles, vasculature including lymphatics, and selected alveoli. Notably, a discrete population of Calb1+ neurons preferentially innervate pulmonary neuroendocrine cells, a demonstrated airway sensor population. This comprehensive illustration of the properties of lung innervating sensory neurons serves as a foundation for understanding their function in lung.

cell biology↗

bioRxiv2021

Loss of Smad4 promotes aggressive lung cancer metastasis by de-repression ofPAK3 via miRNA regulation

Over 85% of lung cancer patients harbor overt or subclinical metastases at diagnosis, and therefore most patients die of progressive metastatic disease despite aggressive local and systemic therapies. Somatic mutations in the Smad4 gene have been found in non-small-cell lung cancer, but the underlying mechanism by which Smad4 loss-of-function (LOF) accelerates lung cancer metastasis is yet to be elucidated. Here, we generated a highly aggressive lung cancer mouse model bearing conditional KrasG12D, p53fl/fl LOF and/or Smad4 fl/fl LOF mutations. The Smad4fl/fl; p53 fl/fl; KrasG12D (SPK) mutant mice manifested a much higher incidence of tumor metastases than the p53 fl/fl; KrasG12D (PK) mice. Molecularly, PAK3 was identified as a novel downstream effector of Smad4, mediating metastatic signal transduction via the PAK3-JNK-Jun pathway. Upregulation of PAK3 by Smad4 LOF in SPK mice was achieved by attenuating Smad4-dependent transcription of miR-495 and miR-543. These microRNAs (miRNAs) directly bind to the PAK3 3UTR for blockade of PAK3 production, ultimately regulating lung cancer metastasis. An inverse correlation between Smad4 and PAK3 pathway components suggests clinical use of Smad4 LOF as a potential marker for prognosis in human lung cancer. Our study highlights the Smad4-PAK3 regulation as a point of potential therapy in metastatic lung cancer.

cancer biology↗

bioRxiv2021

Nasal BCG Exposure Accelerates Dural Lymphatics Development via Macrophages' Role in Newborn Mice

The dural lymphatics develop mainly during the first postnatal month. Lymphatics may be shaped by immune activation when bacterial infection happens. BCG, a strong immune activator, is widely injected to newborns. Moreover, human beings are nasally exposed in daily life to bacterial stimuli. These background prompted us to investigate whether neonatal BCG injection combined with nasally exposure exerts an influence on dural lymphatics develop. Here, mice received a single dose intracutaneous (i.c.) BCG injection immediately after birth followed by repeated nasal BCG challenge once a day (i.c./nasal group). These mice had an accelerated dural lymphatics growth and increased levels of several cytokines and VEGFR-3. Furthermore, macrophages were identified as a key mediator of these alterations. Mice that received mere one dose i.c. BCG injection showed no significant alterations in these indexes. Additionally, mere repeated nasal BCG challenge induced similar effects to i.c./nasal challenge but with a slighter extent. Taken together, these findings show that repeated nasal BCG vaccination accelerates dural lymphatics development in neonatal mice, especially in the presence of neonatal i.c. BCG injection.

neuroscience↗

bioRxiv2021

Variations in soil nutrient dynamics and bacterial communities in long-term tea monoculture production systems

Long-term monoculture agriculture systems could lead to soil degradation and yield decline. The ways in which soil microbiotas interact with one another, particularly in response to long-term tea monoculture systems are currently unclear. In this study, through the comparison of three independent tea plantations across eastern China composed of varying stand ages (from 3 years to 90 years after conversion from forest), we found that long-term tea monoculture led to significant increases in soil total organic carbon (TOC) and microbial nitrogen (MBN). Additionally, the structure, function and co-occurrence network of soil microbial communities were investigated by pyrosequencing 16S rRNA genes. The pyrosequencing analysis revealed that structures and functions of soil bacterial communities were significantly affected by different stand ages of tea plantations, but sampling sites and land-use conversion (from forest to tea plantation) still outcompeted stand age to control the diversity and structure of soil bacterial communities. Further RDA analysis revealed that the C and N availability improvement in tea plantation soils led to variation of structure and function in soil microbial communities. Moreover, co-occurrence network analysis of soil bacterial communities also demonstrated that interactions among soil bacteria taxa were strengthened with the increasing stand age of respective tea stands. Overall, this study provides a comprehensive understanding of the impact of long-term monoculture stand age on soil nutrient dynamics and bacterial communities in tea production.

ecology↗

bioRxiv2021

Multi-tissue integrative analysis of personal epigenomes

Understanding how genetic variants impact molecular phenotypes is a key goal of functional genomics, currently hindered by reliance on a single haploid reference genome. Here, we present the EN-TEx resource of personal epigenomes, for [~]25 tissues and >10 assays in four donors (>1500 open-access functional genomic and proteomic datasets, in total). Each dataset is mapped to a matched, diploid personal genome, which has long-read phasing and structural variants. The mappings enable us to identify >1 million loci with allele-specific behavior. These loci exhibit coordinated epigenetic activity along haplotypes and less conservation than matched, non-allele-specific loci, in a fashion broadly paralleling tissue-specificity. Surprisingly, they can be accurately modelled just based on local nucleotide-sequence context. Combining EN-TEx with existing genome annotations reveals strong associations between allele-specific and GWAS loci and enables models for transferring known eQTLs to difficult-to-profile tissues. Overall, EN-TEx provides rich data and generalizable models for more accurate personal functional genomics.

genomics↗

bioRxiv2021

Dual adhesive unipolar polysaccharides synthesized by overlapping biosynthetic pathways in Agrobacterium tumefaciens

Agrobacterium tumefaciens, is a member of the Alphaproteobacteria that pathogenizes plants, and associates with biotic and abiotic surfaces via a single cellular pole. A. tumefaciens produces the unipolar polysaccharide (UPP) at the site of surface contact. UPP production is normally surface-contact inducible, but elevated levels of the second messenger cyclic diguanylate monophosphate (cdGMP) bypass this requirement. Multiple lines of evidence suggest that the UPP has a central polysaccharide component. Using an A. tumefaciens derivative with elevated cdGMP and mutationally disabled for other dispensable polysaccharides, a series of related genetic screens have identified a large number of genes involved in UPP biosynthesis, most of which are Wzx-Wzy-type polysaccharide biosynthetic components. Extensive analyses of UPP production in these mutants have revealed that the UPP is comprised of two genetically, chemically and spatially discrete forms of polysaccharide, and that each requires a specific Wzy-type polymerase. Other important biosynthetic, processing and regulatory functions for UPP production are also revealed, some of which are common to both polysaccharides, and a subset of which are specific to each species. Many of the UPP genes identified are conserved among diverse rhizobia, whereas others are more lineage specific. Plain language summaryBacteria attach to a wide variety of surfaces including host tissues, via externalized structures described as adhesins. We define a large set of genes involved in synthesis of a complex unipolar adhesin comprised of two distinct polysaccharides, that is required for surface attachment by the plant-associated pathogen Agrobacterium tumefaciens.

microbiology↗

bioRxiv2021

Role of PARP1 in oligodendrocyte differentiation during developmental myelination and remyelination after myelin damage

The function of poly(ADP-ribosyl) polymerase 1 (PARP1) in myelination and remyelination of the central nervous system (CNS) remain enigmatic. Here we report that PARP1 is an intrinsic driver for oligodendroglial development and myelination. Genetic PARP1 depletion impairs the differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes and impedes CNS myelination. Mechanistically, PARP1-mediated PARylation activity is not only necessary but also sufficient for OPC differentiation. At the molecular level, we identify the RNA-binding protein Myef2 as a novel PARylated target which we show controls OPC differentiation through PARylation-modulated de-repression of myelin protein expression. Furthermore, PARP1s enzymatic activity is necessary for oligodendrocyte and myelin regeneration after demyelination. Together, our findings suggest that PARP1-mediated PARylation activity may be a potential therapeutic target for promoting OPC differentiation and remyelination in neurological disorders characterized by arrested OPC differentiation and remyelination failure such as multiple sclerosis.

neuroscience↗

bioRxiv2021

Identifying Oscillatory Hyperconnectivity andHypoconnectivity Networks in Major DepressionUsing Coupled Tensor Decomposition

Previous researches demonstrate that major depression disorder (MDD) is associated with widespread network dysconnectivity, and the dynamics of functional connectivity networks are important to delineate the neural mechanisms of MDD. Cortical electroencephalography (EEG) oscillations act as coordinators to connect different brain regions, and various assemblies of oscillations can form different networks to support different cognitive tasks. Studies have demonstrated that the dysconnectivity of EEG oscillatory networks is related with MDD. In this study, we investigated the oscillatory hyperconnectivity and hypoconnectivity networks in MDD under a naturalistic and continuous stimuli condition of music listening. With the assumption that the healthy group and the MDD group share similar brain topology from the same stimuli and also retain individual brain topology for group differences, we applied the coupled nonnegative tensor decomposition algorithm on two adjacency tensors with the dimension of time x frequency x connectivity x subject, and imposed double-coupled constraints on spatial and spectral modes. The music-induced oscillatory networks were identified by a correlation analysis approach based on the permutation test between extracted temporal factors and musical features. We obtained three hyperconnectivity networks from the individual features of MDD and three hypoconnectivity networks from common features. The results demonstrated that the dysfunction of oscillation-modulated networks could affect the involvement in music perception for MDD patients. Those oscillatory dysconnectivity networks may provide promising references to reveal the pathoconnectomics of MDD and potential biomarkers for the diagnosis of MDD.

neuroscience↗

bioRxiv2021

Protein visualization and manipulation in Drosophila through the use of epitope tags recognized by nanobodies

Expansion of the available repertoire of reagents for visualization and manipulation of proteins will help understand their function. Short epitope tags linked to proteins of interest and recognized by existing binders such as nanobodies facilitate protein studies by obviating the need to isolate new antibodies directed against them. Nanobodies have several advantages over conventional antibodies, as they can be expressed and used as tools for visualization and manipulation of proteins in vivo. Here, we characterize two short (<15 aa) NanoTag epitopes, 127D01 and VHH05) and their corresponding high-affinity nanobodies. We demonstrate their use in Drosophila for in vivo protein detection and re-localization, direct and indirect immunofluorescence, immunoblotting, and immunoprecipitation. We further show that CRISPR-mediated gene targeting provides a straightforward approach to tagging endogenous proteins with the NanoTags. Single copies of the NanoTags, regardless of their location, suffice for detection. This versatile and validated toolbox of tags and nanobodies will serve as a resource for a wide array of applications, including functional studies in Drosophila and beyond.

genetics↗

bioRxiv2021

Reduced graphene oxide membrane as supporting film for high-resolution cryo-EM

Although single-particle cryogenic electron microscopy (cryo-EM) has been applied extensively for elucidating many crucial biological mechanisms at the molecular level, this technique still faces critical challenges, the major one of which is to prepare the high-quality cryo-EM specimen. Aiming to achieve a more reproducible and efficient cryo-EM specimen preparation, novel supporting films including graphene-based two-dimensional materials have been explored in recent years. Here we report a robust and simple method to fabricate EM grids coated with single- or few-layer reduced graphene oxide (RGO) membrane in large batch for high-resolution cryo-EM structural determination. The RGO membrane has decreased interlayer space and enhanced electrical conductivity in comparison to regular graphene oxide (GO) membrane. Moreover, we found that the RGO supporting film exhibited nice particle-absorption ability, thus avoiding the air-water interface problem. More importantly, we found that the RGO supporting film is particularly useful in cryo-EM reconstruction of sub-100 kDa biomolecules at near-atomic resolution, as exemplified by the study of RBD-ACE2 complex and other small protein molecules. We envision that the RGO membranes can be used as a robust graphene-based supporting film in cryo-EM specimen preparation.

biophysics↗

bioRxiv2021

Class II LBD genes ZmLBD5 and ZmLBD33 regulate gibberellin and abscisic acid biosynthesis

Lateral organ boundaries domain (LBD) proteins are plant-specific transcription factors. Class I LBD members are widely reported to be pivotal for organ development, however, the role of class II members is unknown in cereal crops. Class II LBD proteins are distinguished from class I by the lack of a Gly-Ala-Ser (GAS) peptide and leucine-zipper-like coiled-coil domain, which is thought to be essential for protein dimerization. In this study, ZmLBD5 and ZmLBD33 form homo- and hetero-dimers, like class I members. At seedling stage, ZmLBD5 promoted biomass accumulation (shoot dry weight and root dry weight), root development (root length, root number, and root volume), and organ expansion (leaf area), while ZmLBD33 repressed these processes and display a dwarf phenotype. Both ZmLBD5 and ZmLBD33 displayed negative roles in drought tolerance mainly by increasing stomatal density and stomatal aperture. RNA sequencing, gene ontology enrichment analysis, and transient luciferase expression assays indicated that ZmLBD5 and ZmLBD33 are mainly involved in the regulation of the TPS-KS-GA2ox gene module, which comprises key enzymatic genes upstream of GA and ABA biosynthesis. GA1 content increased in ZmLBD5-overexpressing seedlings, while GA3 and abscisic acid content decreased in both transgenic seedlings. Consequently, exogenous GA1 or GA3 undoubtedly rescued the dwarf phenotype of ZmLBD33-overexpressing plants, with GA1 performing better. The study of ZmLBD5 and ZmLBD33 sheds light on the function of the class II LBD gene family in maize.

plant biology↗

bioRxiv2021

Deep oncopanel sequencing reveals fixation time- and within block position-dependent quality degradation in FFPE processed samples

Clinical laboratories routinely use formalin-fixed paraffin-embedded (FFPE) tissue or cell block cytology samples in oncology panel sequencing to identify mutations that can predict patient response to targeted therapy. To understand the technical error due to FFPE processing, a robustly characterized normal cell line was used to create FFPE samples with four different pre-tissue processing formalin fixation times. A total of 96 FFPE sections were then distributed to different laboratories for targeted sequencing analysis by four oncopanels, and variants resulting from technical error were identified. Tissue sections that failed more frequently showed low cellularity, lower than recommended library preparation DNA input, or target sequencing depth. Importantly, sections from block surfaces were more likely to show FFPE-specific errors, akin to "edge effects" seen in histology, and the depth of formalin damage was related to fixation time. To assure reliable results, we recommend avoiding the block surface portion and restricting mutation detection to genomic regions of high confidence.

cancer biology↗