Biology subjects

Lu, H.

Publications and source records attributed to Lu, H..

306 records · Page 17Linked to original sources

bioRxiv2019

Comparative Population Genomics of Bread Wheat (Triticum aestivum) Reveals Its Cultivation and Breeding History in China

The evolution of bread wheat (Triticum aestivum) is distinctive in that domestication, natural hybridization, and allopolyploid speciation have all had significant effects on the diversification of its genome. Wheat was spread around the world by humans and has been cultivated in China for ~4,600 years. Here, we report a comprehensive assessment of the evolution of wheat based on the genome-wide resequencing of 120 representative landraces and elite wheat accessions from China and other representative regions. We found substantially higher genetic diversity in the A and B subgenomes than in the D subgenome. Notably, the A and B subgenomes of the modern Chinese elite cultivars were mainly derived from European landraces, while Chinese landraces had a greater contribution to their D subgenomes. The duplicated copies of homoeologous genes from the A, B, and D subgenomes were commonly found to be under different levels of selection. Our genome-wide assessment of the genetic changes associated with wheat breeding in China provides new strategies and practical targets for future breeding.

plant biology↗

bioRxiv2019

Genomic approaches reveal an endemic sub-population of gray wolves in Southern China

Despite being one of the most widely distributed terrestrial mammals, the history of gray wolves (Canis lupus) in China is not well understood as their habitats have been destroyed with growing economic development. Using six specimens from wolf skins in Chinese Natural History museums, we sequenced their genome using a modified ancient DNA procedure. Using whole genome sequence analysis, we showed that gray wolves from Southern China (SC) derive from a single lineage, distinct from gray wolves from the Tibetan Plateau (Canis lupus chanco) and Northern China, suggesting that SC gray wolves may form a distinct sub-population. Of SC gray wolves, one wolf from Zhejiang carries a genetic component from a canid that must have diverged earlier from other wolves than jackals did, perhaps through gene flow from a population related to or further diverged from wolves than the dhole, a species distributed in Southern China and Southeast Asia. This may indicate that interspecific gene flow likely played an important role in shaping the speciation patterns and population structure in the genus Canis. Our study is the first to survey museum genomes of gray wolves from Southern China, revealing the presence of an endemic population with ancient interspecific gene flow from a population related to the dhole, and highlighting how sequencing the paleogenome from museum specimens can help us to study extinct species.

evolutionary biology↗

bioRxiv2018

The Salivary Microbiome: Analysis of by Pyrosequencing and the Relationship with Helicobacter pylori Infection

AbstractsO_ST_ABSBackgroundsC_ST_ABSThere have been reports of Helicobacter pylori (H. pylori) in the oral cavity and it has been suggested that the oral cavity may be a reservoir for H. pylori reflux from the stomach.\n\nObjectivesHigh-throughput pyrosequencing was used to assess the structure and composition of oral microbiota communities in individuals with or without confirmed H. pylori infection.\n\nMethodsSaliva samples were obtained from 34 H. pylori infected and 24 H. pylori uninfected subjects. Bacterial genomic DNA was extracted and examined by pyrosequencing by amplification of the 16S rDNA V3-V4 hypervariable regions followed by bioinformatics analysis. Saliva sampling was repeated from 22 of the 34 H. pylori infected subjects 2 months after H. pylori eradication.\n\nResultsHigh-quality sequences (2,812,659) clustered into 95,812 operational taxonomic units (OTUs; 97% identity), representing 440 independent species belonging to 138 genera, 68 families, 36 orders, 21 classes, and 11 phyla. Species richness (alpha diversity) of H. pylori infected subjects was similar to that of uninfected subjects. Eradication treatment decreased saliva bacterial diversity. Beta diversity analysis showed that the salivary microbial community structure differed between H. pylori infected and uninfected subjects both before and after H. pylori eradication.\n\nConclusionsSalivary microbiota diversity was similar in H. pylori infected and uninfected individuals. Antibiotic therapy was associated with a decline in salivary bacterial diversity. Both H. pylori infection and its eradication caused the oral microbiota alterations in community and structure. The present of H. pylori in oral cavity was not related with its infection status in stomach.\n\nTrial registrationClinicalTrials.gov, Identifier: NCT03730766\n\nImportanceThe oral cavity plays a vital role in Helicobacter pylori transmission among human. High-throughput pyrosequencing of the 16S rDNA V3-V4 hypervariable regions was used to assess the structure and composition of oral microbiota communities in individuals with or without confirmed Helicobacter pylori infection. We show that both Helicobacter pylori infection and eradication cause microbiota alterations in the oral microbiota. Prior studies report detection of Helicobacter pylori in the oral cavity by polymerase chain reaction. We show that the presence of Helicobacter pylori in the oral cavity is unrelated with its infection status in the stomach.

microbiology↗

bioRxiv2018

βVPE is involved in tapetal degradation and pollen development by activating proprotease maturation in Arabidopsis thaliana

Vacuolar processing enzyme (VPE) is responsible for the maturation and activation of vacuolar proteins in plants. We found that {beta}VPE was involved in tapetal degradation and pollen development by transforming proproteases into mature protease in Arabidopsis thaliana. {beta}VPE was expressed specifically in the tapetum from stages 5-8 of anther development. The {beta}VPE protein first appeared as a proenzyme and transformed into the mature enzyme before stages 7-8. The recombinant {beta}VPE protein self-cleaved and transformed to a 27-kD mature protein at pH 5.2. The mature {beta}VPE protein could induce the maturation of CEP1 in vitro. {beta}vpe mutants exhibited delayed vacuolar degradation and decreased pollen fertility. The maturation of CEP1, RD19A, and RD19C were seriously inhibited in {beta}vpe mutants. Our results indicate that {beta}VPE is a crucial processing enzyme that directly participates in the maturation of cysteine proteases before vacuolar degradation, and is indirectly involved in pollen development and tapetal cell degradation.\n\nHighlight{beta}VPE is a crucial processing enzyme that directly participates in the maturation of cysteine proteases before vacuolar degradation, and is indirectly involved in pollen development and tapetal cell degradation.

plant biology↗

bioRxiv2018

Network remodeling induced by transcranial brain stimulation: A computational model of tDCS-triggered cell assembly formation

Transcranial direct current stimulation (tDCS) is a variant of non-invasive neuro-modulation, which promises treatment for diseases like major depressive disorder or chronic pain for patients resistant to conventional therapies. In experiments, long lasting after-effects were observed, suggesting that plastic changes were induced. The exact mechanism underlying the emergence and maintenance of these after-effects, however, remains elusive. Here we propose a model to explain how transcranial stimulation triggers a homeostatic response of the network involving growth and decay of synapses. In our model, the cortical tissue underneath the electrodes is conceived as a recurrent network of excitatory and inhibitory neurons, in which excitatory-to-excitatory synapses are subject to structural plasticity. Various aspects of stimulation were tested via numerical simulations of such networks, including size and montage of the electrode, as well as intensity and duration of the stimulation. Our results suggest that stimulation indeed perturbs the homeostatic equilibrium and leads to cell assembly formation. Strong focal stimulation, for example, enhances the connectivity of new cell assemblies by increasing the rate of synaptic remodeling. Repetitive stimulation with well-chosen duty cycles increases the impact of stimulation as well. The long-term goal of our work is to optimize the impact of tDCS in clinical applications.

neuroscience↗

bioRxiv2018

SIP: An Interchangeable Pipeline for scRNA-seq Data Processing

Multiple steps of bioinformatics processing are needed to convert the raw scRNA-seq data to information that can be used in downstream analyses and in building cell atlases. Dozens of software packages have been developed and different labs tend to have different preferences on choices of the workflow. Such diversity can cause difficulties in future efforts of aggregating data from multiple labs, and also difficulties for new labs to start in this field. A few pipelines have been developed to help integrating multiple steps into a whole, but the fixed software architecture makes it hard for developers to add new features or exchange parts in the pipeline.\n\nWe presented SIP, a Single-cell Interchangeable Pipeline. It is a one-stop platform for the processing of scRNA-seq data from multiple platforms, and will also support for other types of data like scATAC-seq data. SIP utilizes container technology to solve the deployment dilemma when handling multiple packages and provides an easy-to-use interface for users to conduct the complicated multi-step process from raw data to final results with a single command. It also allows advanced users to assemble different versions of the pipeline by interchanging parts or adding new modules. SIP is available at https://github.com/XuegongLab/SIP under the GPL-3.0 license.

bioinformatics↗

bioRxiv2018

Mcidas mutant mice reveal a two-step process for the specification and differentiation of multiciliated cells in mammals

Motile cilia on multiciliated cells (MCCs) function in fluid clearance over epithelia. Studies with Xenopus embryos and patients with the congenital respiratory disorder reduced generation of multiple motile cilia, have implicated the nuclear protein MCIDAS (MCI), in the transcriptional regulation of MCC specification and differentiation. Recently, a paralogous protein, GMNC, was also shown to be required for MCC formation. Surprisingly, and in contrast to the presently held view, we find that Mci mutant mice can specify MCC precursors. However, these precursors cannot produce multiple basal bodies, and mature into single ciliated cells. We show that MCI is required specifically to induce deuterosome pathway components for the production of multiple basal bodies. Moreover, GMNC and MCI associate differentially with the cell-cycle regulators E2F4 and E2F5, which enables them to activate distinct sets of target genes (ciliary transcription factor genes versus genes for basal body generation). Our data establish a previously unrecognized two-step model for MCC development: GMNC functions in the initial step for MCC precursor specification. GMNC induces Mci expression, which then drives the second step of basal body production for multiciliation.\n\nSUMMARY STATEMENTWe show how two GEMININ family proteins function in mammalian multiciliated cell development: GMNC regulates precursor specification and MCIDAS induces multiple basal body formation for multiciliation.

developmental biology↗

bioRxiv2018

Analysis of contributory gut microbiota and lauric acid against necrotic enteritis in Clostridium perfringens and Eimeria side-by-side challenge model

Gut microbiota has been demonstrated to be involved in intestinal nutrition, defense, and immunity, as well as participating in disease progression. This study was to investigate gut microbiota changes in chickens challenged with netB-positive Clostridium perfringens strain 1 (CP1) and/or the predisposing Eimeria species (Eimeria). In addition, the effects of lauric acid, a medium-chain fatty acid (MCFA), on NE reduction and modulation of microbiota were evaluated. The results demonstrated that microbial communities in the jejunum were distinct from those in the cecum, and the microbial community change was more significant in jejunum. Challenge of CP1 in conjunction with Eimeria significantly reduced species diversity in jejunal microbiota, but cecal microbiota remained stable. In the jejunum, CP1 challenge increased the abundance of the genera of Clostridium sensu stricto 1, Escherichia Shigella, and Weissella, but significantly decreased the population of Lactobacillus. Eimeria infection on its own was unable to promote NE, demonstrating decrements of Clostridium sensu stricto 1 and Lactobacillus. Co-infection with CP1 and Eimeria reproduced the majority of NE lesions with significant increment of Clostridium sensu stricto 1 and reduction in Lactobacillus. The changes of these two taxa increased the severity of NE lesions. Further analyses of metagenomeSeq, STAMP, and LEfSe showed significant overgrowth of Clostridium sensu stricto 1 was associated with NE and Eimeria infection than C. perfringens challenge alone. The supplementation of lauric acid did not reduce NE incidence and severity but decreased the relative abundance of Escherichia Shigella. In conclusion, significant overgrowth of Clostridium sensu stricto 1 in the jejunm is the major microbiota contributory to NE. Controlling proliferation of this taxon in the jejunum should be the niche for developing effective strategies against NE.

microbiology↗

bioRxiv2018

Fast, versatile, and quantitative annotation of complex images

We report a generic smartphone app for quantitative annotation of complex images. The app is simple enough to be used by children, and annotation tasks are distributed across app users, contributing to efficient annotation. We demonstrate its flexibility and speed by annotating >30,000 images, including features of rice root growth and structure, stem cell aggregate morphology, and complex worm (C. elegans) postures, for which we show that the speed of annotation is >130-fold faster than state-of-the-art techniques with similar accuracy.

bioengineering↗

bioRxiv2018

Improving Whole-Brain Neural Decoding of fMRI with Domain Adaptation

In neural decoding, there has been a growing interest in machine learning on whole-brain functional magnetic resonance imaging (fMRI). However, the size discrepancy between the feature space and the training set poses serious challenges. Simply increasing the number of training examples is infeasible and costly. In this paper, we proposed a domain adaptation framework for whole-brain fMRI (DawfMRI) to improve whole-brain neural decoding on target data leveraging pre-existing source data. DawfMRI consists of three steps: 1) feature extraction from whole-brain fMRI, 2) source and target feature adaptation, and 3) source and target classifier adaptation. We evaluated its eight possible variations, including two non-adaptation and six adaptation algorithms, using a collection of seven task-based fMRI datasets (129 unique subjects and 11 cognitive tasks in total) from the OpenNeuro project. The results demonstrated that appropriate source domain can help improve neural decoding accuracy for challenging classification tasks. The best-case improvement is 8.94% (from 78.64% to 87.58%). Moreover, we discovered a plausible relationship between psychological similarity and adaptation effectiveness. Finally, visualizing and interpreting voxel weights showed that the adaptation can provide additional insights into neural decoding.

neuroscience↗

bioRxiv2018

Effects of vitamin D on inflammatory and oxidative stress responses of human bronchial epithelial cells exposed to particulate matter.

BackgroundParticulate matter (PM) pollutant exposure, which induces oxidative stress and inflammation, and vitamin D insufficiency, which compromises immune regulation, are detrimental in asthma.\n\nObjectivesMechanistic cell culture experiments were undertaken to ascertain whether vitamin D abrogates PM-induced inflammatory responses of human bronchial epithelial cells (HBECs) through enhancement of antioxidant pathways.\n\nMethodsTranscriptome analysis, PCR and ELISA were undertaken to delineate markers of inflammation and oxidative stress; with comparison of expression in primary HBECs from healthy and asthmatic donors cultured with reference urban PM in the presence/absence of vitamin D.\n\nResultsTranscriptome analysis identified over 500 genes significantly perturbed by PM-stimulation, including multiple pro-inflammatory cytokines. Vitamin D altered expression of a subset of these PM-induced genes, including suppressing IL6. Addition of vitamin D suppressed PM-stimulated IL-6 production, although to significantly greater extent in healthy versus asthmatic donor cultures. Vitamin D also differentially affected PM-stimulated GM-CSF, with suppression in healthy HBECs and enhancement in asthmatic cultures. Vitamin D increased HBEC expression of the antioxidant pathway gene G6PD, increased the ratio of reduced to oxidised glutathione, and in PM-stimulated cultures decreased the formation of 8-isoprostane. Pre-treatment with vitamin D decreased CXCL8 and further decreased IL-6 production in PM-stimulated cultures, an effect abrogated by inhibition of G6PD with DHEA, supporting a role for this pathway in the anti-inflammatory actions of vitamin D.\n\nConclusionsIn a study using HBECs from 18 donors, vitamin D enhanced HBEC antioxidant responses and modulated the immune response to PM, suggesting that vitamin D may protect the airways from pathological pollution-induced inflammation.

immunology↗

bioRxiv2018

Deconvolution of single-cell multi-omics layers reveals regulatory heterogeneity

Integrative analysis of multi-omics layers at single cell level is critical for accurate dissection of cell-to-cell variation within certain cell populations. Here we report scCAT-seq, a technique for simultaneously assaying chromatin accessibility and the transcriptome within the same single cell. We show that the combined single cell signatures enable accurate construction of regulatory relationships between cis-regulatory elements and the target genes at single-cell resolution, providing a new dimension of features that helps direct discovery of regulatory patterns specific to distinct cell identities. Moreover, we generated the first single cell integrated maps of chromatin accessibility and transcriptome in human pre-implantation embryos and demonstrated the robustness of scCAT-seq in the precise dissection of master transcription factors in cells of distinct states during embryo development. The ability to obtain these two layers of omics data will help provide more accurate definitions of \"single cell state\" and enable the deconvolution of regulatory heterogeneity from complex cell populations.

genomics↗

bioRxiv2018

Recruitment of Two Dyneins to an mRNA-Dependent Bicaudal D Transport Complex

We investigated the role of binding partners of full-length Drosophila Bicaudal D (BicD) in the activation of dynein-dynactin motility for mRNA transport on microtubules. In single-molecule assays, full-length BicD robustly activated dynein-dynactin only when both the mRNA binding protein Egalitarian (Egl), and K10 mRNA cargo were present. Electron microscopy showed that both Egl and mRNA were needed to disrupt an auto-inhibited, looped BicD conformation that sterically prevents dynein-dynactin binding. In vitro reconstituted messenger ribonucleoprotein (mRNP) complexes with two Egl molecules showed faster speeds and longer run lengths than mRNPs with one Egl, suggesting that cargo binding enhances dynein recruitment. Labeled dynein showed that BicD can recruit two dimeric dyneins to the mRNP, resulting in faster speeds and longer run lengths than with one dynein. The fully reconstituted mRNP provides a model for understanding how adaptor proteins and cargo cooperate to confer optimal transport properties to a dynein-driven transport complex.

biophysics↗

bioRxiv2017

Identification of methylation and hydroxymethylation haplotype blocks as distal regulatory elements aids in deconvolution of heterogeneous brain tissues

5-Hydroxymethylcytosine (5hmC) is an oxidation product of 5-methylcytosine (5mC), and adjacent CpG sites in the mammalian genome can be co-methylated and co-hydroxymethylated due to the processivity of DNMT and TET enzymes. We applied TAB-seq and oxBS-seq to selectively detect 5hmC and 5mC, respectively, at base resolution in the mouse cortex, olfactory bulb and cerebellum tissues. We found that majority of the called 5hmC CpG sites frequently had 5mC modification simultaneously and enriched in gene body regions of neuron development related genes in brain tissues. These results supported a prominent role of oxidizing 5mC to 5hmC as new epigenetic mark. Strikingly, by a systematic search of regions that show highly coordinated methylation and hydroxymethylation (MHBs and hMHBs), we found that MHBs significantly overlapped with hMHBs in gene body regions which further supported that oxidized 5mC to 5hmC co-ordinately in a subset of cells within heterogeneous brain tissues. Consistently, using a metric called methylation haplotype load, we defined a subset of 1,361 tissue-specific MHBs and 3,818 shared MHBs which were predominantly regulatory elements, and aids in deconvolution of heterogeneous brain tissues. Our results provide new insights into the role of co-ordinately oxidized 5mC to 5hmC as distal regulatory elements may involve in regulating tissue identity.

genetics↗

bioRxiv2017

SPIN1 promotes tumorigenesis by blocking the uL18-MDM2-p53 pathway

Ribosomal proteins (RPs) play important roles in modulating the MDM2-p53 pathway. However, less is known about the upstream regulators of the RPs. Here we identify SPIN1 (Spindlin 1) as a novel binding partner of human RPL5/uL18 that is important for this pathway. SPIN1 ablation activates p53, suppresses cell growth, reduces clonogenic ability, and induces apoptosis of cancer cells by sequestering uL18 in the nucleolus, preventing it from interacting with MDM2, and thereby alleviating uL18-mediated inhibition of MDM2 ubiquitin ligase activity towards p53. SPIN1 deficiency increases ribosome-free uL18 and uL5 (human RPL11), which are required for SPIN1 depletion-induced p53 activation. Analysis of cancer genomic databases suggests that SPIN1 is highly expressed in several human cancers, and its overexpression is positively correlated with poor prognosis in cancer patients. Altogether, our findings reveal that the oncogenic property of SPIN1 is highly attributed to its negative regulation of uL18, leading to p53 inactivation.

cancer biology↗

bioRxiv2017

Synthesizing developmental trajectories

Dynamical processes in biology are studied using an ever-increasing number of techniques, each of which brings out unique features of the system. One of the current challenges is to develop systematic approaches for fusing heterogeneous datasets into an integrated view of multivariable dynamics. We demonstrate that heterogeneous data fusion can be successfully implemented within a semi-supervised learning framework that exploits the intrinsic geometry of high-dimensional datasets. We illustrate our approach using a dataset from studies of pattern formation in Drosophila. The result is a continuous trajectory that reveals the joint dynamics of gene expression, subcellular protein localization, protein phosphorylation, and tissue morphogenesis. Our approach can be readily adapted to other imaging modalities and forms a starting point for further steps of data analytics and modeling of biological dynamics.

developmental biology↗

bioRxiv2017

Reverse-Correlation Analysis of Mechanosensation Circuit in C. elegans Reveals Temporal and Spatial Encoding

Animals must integrate the activity of multiple mechanoreceptors to navigate complex environments. In Caenorhabditis elegans, the general roles of the mechanosensory neurons have been defined, but most studies involve end-point or single-time-point measurements, and thus lack dynamical information. Here, we formulate a set of unbiased quantitative characterizations of the mechanosensory system by using reverse correlation analysis on behavior. We use a custom tracking, selective illumination, and optogenetics platform to compare two mechanosensory systems: the gentle-touch (TRNs) and harsh-touch (PVD) circuits. This method yields characteristic linear filters that allow for prediction of behavioral responses. The resulting filters are consistent with previous findings, and further provide new insights on the dynamics and spatial encoding of the systems. Our results suggest that the tiled network of the gentle-touch neurons has better resolution for spatial encoding than the harsh-touch neurons. Additionally, linear-nonlinear models accurately predict behavioral responses based only on sensory neuron activity. Our results capture the overall dynamics of behavior induced by the activation of sensory neurons, providing simple transformations that quantitatively characterize these systems. Furthermore, this platform can be extended to capture the behavioral dynamics induced by any neuron or other excitable cells in the animal.\n\nAuthor SummaryAnimals constantly integrate the activity of neurons throughout their bodies to choose the most appropriate behavior. A key goal in quantitative neuroscience is to characterize and predict how neuronal circuits control and modulate behavior. C. elegans, a nematode with a fully mapped connectome, is an ideal model organism for elucidating the links between neuronal circuits and behavior. However, many studies relating activity in neurons to behavior rely on spontaneous behavior and lack information about their dynamics. In this study, we formulate unbiased quantitative characterizations of sensory neurons in C. elegans using with reverse correlation analysis with a white noise stimulus. We use optogenetics to stimulate body touch sensory neurons in freely moving worms, and provide quantitative descriptions that capture the dynamic transformations between sensory neuron activity and behavioral outputs. Our results are consistent with previous findings, and additionally provide new insights on the spatial encoding of these systems. Our system provides a simple platform for characterizing the behavioral output due to specific neurons, and can be extended to any excitable cell in the animal.

bioengineering↗

bioRxiv2017

High-Throughput Controlled Mechanical Stimulation and Functional Imaging In Vivo

Understanding mechanosensation and other sensory behavior in genetic model systems such as C. elegans is relevant to many human diseases. These studies conventionally require immobilization by glue and manual delivery of stimuli, leading to low experimental throughput and high variability. Here we present a microfluidic platform that delivers precise mechanical stimuli robustly. The system can be easily used in conjunction with functional imaging and optical interrogation techniques, as well as other capabilities such as sorting or more sophisticated fluid delivery schemes. The platform is fully automated, thereby greatly enhancing the throughput and robustness of experiments. We show that behavior of the well-known gentle and harsh touch neurons and their receptive fields can be recapitulated in our system. Using calcium dynamics as a readout, we demonstrate the ability to perform a drug screen in vivo. Furthermore, using an integrated chip platform that can deliver both mechanical and chemical stimuli, we examine sensory integration in interneurons in response to multimodal sensory inputs. We envision that this system will be able to greatly accelerate the discovery of genes and molecules involved in mechanosensation and multimodal sensory behavior, as well as the discovery of therapeutics for related diseases.

bioengineering↗