Biology subjects

Ding, X.

Publications and source records attributed to Ding, X..

160 records · Page 9Linked to original sources

bioRxiv2019

Single cell RNA sequencing reveals cellular diversity of trisomy 21 retina

Retina is a crucial tissue for the capturing and processing of light stimulus. Characterization of the retina at single cell level is essential for the understanding of its biological functions. A variety of abnormalities in terms of morphology and function were reported in T21 retina. To evaluate the effects of chromosome aneuploidy on retina development, we characterized single cell transcriptional profiles of a T21 fetus and performed comprehensive bioinformatic analyses. Our data revealed the diversity and heterogeneity of cellular compositions in T21 retina. In total, we identified seven major cell types, and detected several subtypes within each cell type, followed by the detection of corresponding molecular markers including previously reported ones and a series of novel markers. Our analyses identified extensive communication networks between distinct cellular types, among which a few ligand-receptor interactions were associated with the development of retina and immunoregulatory interactions. Taken together, our data provided the first single cell transcriptome profile for human T21 retina which facilitates our understanding on the dosage effects of chromosome 21 on the development of retina.

cell biology↗

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

A practical computerized decision support system for predicting the severity of Alzheimer’s disease of an individual

Computerized clinical decision support systems can help to provide objective, standardized, and timely dementia diagnosis. However, current computerized systems are mainly based on the group analysis, discrete classification of disease stages, or expensive and not readily accessible biomarkers, while current clinical practice relies relatively heavily on cognitive and functional assessments (CFA). In this study, we developed a computational framework using a suite of machine learning tools for identifying key markers in predicting the severity of Alzheimers disease (AD) from a large set of biological and clinical measures. Six machine learning approaches, namely Kernel Ridge Regression (KRR), Support Vector Regression (SVR), and k-Nearest Neighbor (kNNreg) for regression and Support Vector Machine (SVM), Random Forest (RF), and k-Nearest Neighbor (kNNclass) for classification, were used for the development of predictive models. We demonstrated high predictive power of CFA. Predictive performance of models incorporating CFA was shown to be consistently higher accuracy than those based solely on biomarker modalities. We found that KRR and SVM were the best performing regression and classification methods respectively. The optimal SVM performance was observed for a set of four CFA test scores (FAQ, ADAS13, MoCA, MMSE) with multi-class classification accuracy of 83.0%, 95%CI = (72.1%, 93.8%) while the best performance of the KRR model was reported with combined CFA and MRI neuroimaging data, i.e., R2 = 0.874, 95%CI = (0.827, 0.922). Given the high predictive power of CFA and their widespread use in clinical practice, we then designed a data-driven and self-adaptive computerized clinical decision support system (CDSS) prototype for evaluating the severity of AD of an individual on a continuous spectrum. The system implemented an automated computational approach for data pre-processing, modelling, and validation and used exclusively the scores of selected cognitive measures as data entries. Taken together, we have developed an objective and practical CDSS to aid AD diagnosis.

neuroscience↗

bioRxiv2019

Characterization of pyruvate dehydrogenase complex E1 alpha and beta subunits of Mycoplasma synoviae

Mycoplasma synoviae (MS) is an important pathogen, causing enormous economic losses to the poultry industry worldwide every year. Therefore, the studies on MS will lay the foundation for diagnosis, prevention and treatment of MS infection. In this study, primers designed based on the sequences of pyruvate dehydrogenase complex (PDC) E1 alpha and beta subunit genes (pdhA and pdhB, respectively) of MS WVU1853 strain in GenBank were used to amplify the pdhA and pdhB genes of MS WVU1853 strain through PCR. Then the prokaryotic expression vectors pET-pdhA and pET-pdhB were constructed and were expressed in Escherichia coli BL21(DE3) cells. Subsequently, the recombinant proteins rMSPDHA and rMSPDHB were purified and anti-rMSPDHA and anti-rMSPDHB sera were prepared by immunizing rabbits, respectively. Finally, the subcellular localization of PDHA and PDHB in MS, binding activity of rMSPDHA and rMSPDHB to chicken plasminogen (Plg) and human fibronectin (Fn), complement-dependent mycoplasmacidal assays, and adherence and adherence inhibition assays were accomplished. The results showed that PDHA and PDHB were distributed both on the surface membrane and within soluble cytosolic fractions of MS cells. The rMSPDHA and rMSPDHB presented binding activity with chicken Plg and human Fn. The rabbit anti-rMSPDHA and anti-rMSPDHB sera had distinct mycoplasmacidal efficacy in the presence of guinea pig complement, and the adherence of MS to DF-1 cells pretreated with Plg was effectively inhibited by treatment with anti-rMSPDHA or anti-rMSPDHB sera. Hence, the study indicates that the surface-associated MSPDHA and MSPDHB are the adhesion-related factors of MS that contributes to bind to Plg/Fn and adhesion to DF-1 cells.

microbiology↗

bioRxiv2019

Spread of pathological α-synuclein from urogenital nerves initiates multiple system atrophy-like symptoms

Multiple system atrophy (MSA) is a fatal adult-onset movement disorder with autonomic failures, especially urogenital dysfunction. The neuropathological feature of MSA is the accumulation of misfolded -synuclein (-Syn) in the nervous system. Here, we show that misfolded -Syn exist in nerve terminals in detrusor (DET) and external urethral sphincter (EUS) of patients with MSA. Moreover, -Syn preformed fibrils inoculated into the EUS or DET in TgM83+/- mice initiated the transmission of misfolded -Syn from the lower urinary tract to brain, and these mice developed -Syn inclusion pathology through micturition reflex pathways along with urinary dysfunction and motor impairments. These findings indicate that spreading of misfolded -Syn from the autonomic control of the lower urinary tract to the brain via micturition reflex pathways induces autonomic failure and motor impairments. These results provide important new insights into the pathogenesis of MSA as well as highlight potential targets for early detection and therapeutics.

neuroscience↗

bioRxiv2018

Differential responses of antioxidants and dehydrin expression in two switchgrass (Panicum virgatum) cultivars contrasting in drought tolerance

Drought stress is a major limiting factor for plant growth and development in many regions of the world. This study was designed to investigate antioxidant metabolism and dehydrin expression responses to drought stress in two switchgrass cultivars (drought tolerant Alamo, and drought sensitive Dacotah) contrasting in drought tolerance. The plants were subjected to well-watered [100% evapotranspiration (ET)] or drought stress (30%-50% ET) conditions for up to 24 d in growth chambers. Drought stress decreased leaf relative water content (RWC), increased leaf electrolyte leakage (EL), leaf malondialdehyde (MDA) content in two cultivars, but Alamo exhibited higher leaf RWC level, lower leaf EL and MDA when compared to Dacotah at 24 d of drought treatment. Drought stress also increased superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) activities in two cultivars, Alamo had relatively higher SOD, CAT and APX activities and greater abundance of SOD and APX isozymes than Dacotah at 24 d of drought treatment. Alamo had higher abundance of 55 KDa and 18 KDa dehydrin accumulation than Dacotah under drought treatment. Relative genes expression level of PvCAT1, PvAPX2, PvERD and PvPIP1;5 in Alamo were significantly higher than Dacotah at 24 d of drought treatment. These results suggest that increase in antioxidant enzymes and accumulation of dehydrin were highly related with switchgrass drought tolerance. Antioxidant enzyme activity, isozyme expression and dehydrin abundance could provide a useful screening tool to identify relative drought tolerance in switchgrass cultivars.

plant biology↗

bioRxiv2018

Discover Stable Expression Hot Spot in Genome of Chinese Hamster Ovary Cells Using Lentivirus based Random Integration Method

Traditional construction method for stable expression cell line was mainly achieved by using random integration method. However, target gene might be integrated into heterochromatin region or unstable region of chromatin by using this method, and thus required multiple rounds of selection to obtain desirable expression cell lines with stable expression level of target proteins. Rational cell line construction method can overcome this shortcoming by integrating transgenes into stable hot spot within genome specifically. Thus, to discover novel effective hot spot would be critical for this new cell line construction method. Here we reported one practical method to discover new stable hot spot by using lentivirus infection and random integration. One such hot spot located at NW_006880285.1 was thoroughly investigated in this article. The expression stability of this hot spot was verified by detecting Zsgreen1 reporter gene expression for over 50 passages. When cells were adapted to suspension culture, they successfully kept expressing Zsgreen1 reporter gene. In addition, this suspension cell line could keep expressing reporter gene stably for another 50 passages. In summary, this research offered an easy new method for researchers to identify their own stable hot spots within CHO genome, and would contribute to the development of site-specific integration study in the future.

bioengineering↗

bioRxiv2018

Single-cell RNA-seq reveals dynamic transcriptome profiling in human early neural differentiation

BackgroundInvestigating cell fate decision and subpopulation specification in the context of the neural lineage is fundamental to understanding neurogenesis and neurodegenerative diseases. The differentiation process of neural-tube-like rosettes in vitro is representative of neural tube structures, which are composed of radially organized, columnar epithelial cells and give rise to functional neural cells. However, the underlying regulatory network of cell fate commitment during early neural differentiation remains elusive.\n\nResultsIn this study, we investigated the genome-wide transcriptome profile of single cells from six consecutive reprogramming and neural differentiation time points and identified cellular subpopulations present at each differentiation stage. Based on the inferred reconstructed trajectory and the characteristics of subpopulations contributing the most towards commitment to the central nervous system (CNS) lineage at each stage during differentiation, we identified putative novel transcription factors in regulating neural differentiation. In addition, we dissected the dynamics of chromatin accessibility at the neural differentiation stages and revealed active c/s-regulatory elements for transcription factors known to have a key role in neural differentiation as well as for those that we suggest are also involved. Further, communication network analysis demonstrated that cellular interactions most frequently occurred among embryoid body (EB) stage and each cell subpopulation possessed a distinctive spectrum of ligands and receptors associated with neural differentiation which could reflect the identity of each subpopulation.\n\nConclusionsOur study provides a comprehensive and integrative study of the transcriptomics and epigenetics of human early neural differentiation, which paves the way for a deeper understanding of the regulatory mechanisms driving the differentiation of the neural lineage.

developmental biology↗

bioRxiv2018

A computational observer model of spatial contrast sensitivity: Effects of wavefront-based optics, cone mosaic structure, and inference engine

We present a computational observer model of the human spatial contrast sensitivity (CSF) function based on the Image Systems EngineeringTools for Biology (ISETBio) simulation framework. We demonstrate that ISETBio-derived CSFs agree well with CSFs derived using traditional ideal observer approaches, when the mosaic, optics, and inference engine are matched. Further simulations extend earlier work by considering more realistic cone mosaics, more recent measurements of human physiological optics, and the effect of varying the inference engine used to link visual representations to psy-chohysical performance. Relative to earlier calculations, our simulations show that the spatial structure of realistic cone mosaics reduces upper bounds on performance at low spatial frequencies, whereas realistic optics derived from modern wavefront measurements lead to increased upper bounds high spatial frequencies. Finally, we demonstrate that the type of inference engine used has a substantial effect on the absolute level of predicted performance. Indeed, the performance gap between an ideal observer with exact knowledge of the relevant signals and human observers is greatly reduced when the inference engine has to learn aspects of the visual task. ISETBio-derived estimates of stimulus representations at different stages along the visual pathway provide a powerful tool for computing the limits of human performance.

neuroscience↗

bioRxiv2018

Chicken uric acid elimination via the uric acid transporters BCRP and MRP4 in the liver, kidneys, and intestines

Breast cancer resistance protein (BCRP) and multidrug resistance protein 4 (MRP4) are involved in uric acid excretion in humans and mice. Despite evidence suggesting that chicken renal proximal tubular epithelial cells participate in uric acid secretion, the roles of BCRP and MRP4 in chickens remain unclear. This study evaluated the relationship between chicken BCRP and MRP4 expression and renal function in the liver, kidneys, and intestines. Sixty 20-day-old Isa brown laying hens were randomly divided into four groups: a control group (NC) and groups provided with sulfonamide-treated drinking water (SD), a diet supplemented with fishmeal (FM), and an intraperitoneal injection of uric acid (IU). Serum uric acid, creatinine, and blood urea nitrogen (BUN) levels were significantly higher in the SD and IU groups than in the NC group. BCRP and MRP4 levels in the SD and IU groups were significantly increased in the kidneys and ileum and decreased in the liver. In the FM group, BCRP and MRP4 were significantly increased in the kidneys and slightly increased in the ileum. These results demonstrate that chicken BCRP and MRP4 are involved in renal and intestinal uric acid excretion. When renal function is impaired, serum uric acid increased and BCRP and MRP4 in the liver, kidneys, and ileum exhibit compensatory increases; when renal function is normal, serum uric acid changes have no effect on ileum BCRP and MRP4 expression. Therefore, this study may provide the references to the uric acid regulation in human.

physiology↗

bioRxiv2018

Exploration of miRNA-mediated fertility regulation network of cytoplasmic male sterility during flower bud development in soybean

Cytoplasmic male sterility (CMS) plays an important role in the production of soybean hybrid seeds. MicroRNAs (miRNAs) are a class of non-coding endogenous ~21 nt small RNAs that play crucial roles in flower and pollen development by targeting genes in plants. Here, two small RNA libraries and two degradome libraries were constructed from the flower buds of the soybean CMS line NJCMS1A and its restorer (Rf) line NJCMS1C. Following high-throughput sequencing, 558 known miRNAs, 103 novel miRNAs on the other arm of known pre-miRNAs, 10 novel miRNAs, and a number of base-edited miRNAs were identified. Among the identified miRNAs, 76 differentially expressed miRNAs were discovered with greater than two-fold changes between NJCMS1A and NJCMS1C. By degradome analysis, a total of 466 distinct transcripts targeted by 200 miRNAs and 122 distinct transcripts targeted by 307 base-edited miRNAs were detected. Further integrated analysis of transcriptome and small RNA found some miRNAs and their targets expression patterns showing a negative correlation, such as miR156b-GmSPL and miR4413b-GmPPR. Previous reports showed that these targets might be related to flower bud development, suggesting that miRNAs might act as regulators of soybean CMS fertility. These findings may provide a better understanding of the miRNA-mediated regulatory networks in CMS mechanisms of soybean.

genomics↗

bioRxiv2018

Computational-Observer Analysis of Illumination Discrimination

The spectral properties of the ambient illumination provide useful information about time of day and weather. We study the perceptual representation of illumination by analyzing measurements of how well people discriminate between illuminations across scene configurations. More specifically, we compare human performance to a computational-observer analysis that evaluates the information available in the isomerizations of the cones in a model human photoreceptor mosaic. Some patterns of human performance are predicted by the computational observer, other aspects are not. The analysis clarifies which aspects of performance require additional explanation in terms of the action of visual mechanisms beyond the isomerization of light by the cones.

neuroscience↗

bioRxiv2017

Improving the calling of non-invasive prenatal testing on 13-/18-/21-trisomy by support vector machine discrimination

With the advance of next-generation sequencing technologies, non-invasive prenatal testing (NIPT) has been developed and employed in fetal aneuploidy screening on 13-/18-/21-trisomies through detecting cell-free fetal DNA (cffDNA) in maternal blood. Although Z test is widely used in NIPT nowadays, there is still necessity to improve its accuracy for removing a) false negatives and false positives, and b) the ratio of unclassified data, so as to reduce the potential harm to patients caused by these inaccuracies as well as the induced cost of retests.\n\nEmploying multiple Z tests with machine-learning algorithm could provide a better prediction on NIPT data. Combining the multiple Z values with indexes of clinical signs and quality control, features were collected from the known samples and scaled for model training in support vector machine (SVM) discrimination. The trained model was applied to predict the unknown samples, which showed significant improvement. In 4752 qualified NIPT data, our method reached 100% accuracies on all three chromosomes, including 151 data that were grouped as unclassified by one-Z-value based method. Moreover, four false positives and four false negatives were corrected by using this machine-learning model.\n\nTo our knowledge, this is the first study to employ support vector machine in NIPT data analysis. It is expected to replace the current one-Z-value based NIPT analysis in clinical use.

bioinformatics↗

bioRxiv2017

Forward-reverse mutation cycles between stages of cancer development

Earlier, prominent occurrences of interstitial loss-of-heterozygosities (LOHs) were found in different cancers as a type of single-nucleotide-variations (SNVs), at rates far exceeding those of the commonly investigated gain-of-heterozygosities (GOHs) type of SNVs. Herein, such co-occurrences of LOHs and GOHs were confirmed in 102 cases of four cancer types analyzed with three different next-generation sequencing platforms, comparing non-tumor, paratumor, and tumor tissues with white-blood-cell controls; and in 246 pan-cancer cases of whole-genome tumor-control pairs. Unexpectedly, large numbers of SNVs enriched with CG>TG GOHs and copy-number-variations (CNVs) proximal to these GOHs were detected in the non-tumor tissues, which were extensively reversed in paratumors showing prominent TG>CG LOHs with proximal CNVs, and less so in tumors to form forward-reverse mutation cycles. Lineage effects in the reversions, likely resulting from directional selection, supported a sequential rather than parallel mode of evolution as described in a Stage Specific Populations model of cancer development.

cancer biology↗

bioRxiv2017

A plant receptor-like kinase promotes cell-to-cell spread of RNAi and is targeted by a virus

RNA interference (RNAi) in plants can move from cell to cell, allowing for systemic spread of an anti-viral immune response. How this cell-to-cell spread of silencing is regulated is currently unknown. Here, we describe that the C4 protein from Tomato yellow leaf curl virus has the ability to inhibit the intercellular spread of RNAi. Using this viral protein as a probe, we have identified the receptor-like kinase (RLK) BARELY ANY MERISTEM 1 (BAM1) as a positive regulator of the cell-to-cell movement of RNAi, and determined that BAM1 and its closest homologue, BAM2, play a redundant role in this process. C4 interacts with the intracellular domain of BAM1 and BAM2 at the plasma membrane and plasmodesmata, the cytoplasmic connections between plant cells, interfering with the function of these RLKs in the cell-to-cell spread of RNAi. Our results identify BAM1 as an element required for the cell-to-cell spread of RNAi and highlight that signalling components have been co-opted to play multiple functions in plants.

plant biology↗

bioRxiv2017

Species composition and environmental adaptation of indigenous Chinese cattle

Indigenous Chinese cattle combine taurine and indicine origins and occupy a broad range of different environments. By 50K SNP genotyping we found a discontinuous distribution of taurine and indicine cattle ancestries with extremes of less than 10% indicine cattle in the north and more than 90% in the far south and southwest China. Model-based clustering and f4-statistics indicate introgression of both banteng and gayal into southern Chinese cattle while the sporadic yak influence in cattle in or near Tibetan area validate earlier findings of mitochondrial DNA analysis. Geographic patterns of taurine and indicine mitochondrial and Y-chromosomal DNA diversity largely agree with the autosomal cline. The geographic distribution of the genomic admixture of different bovine species is proposed to be the combined effect of prehistoric immigrations, gene flow, major rivers acting as genetic barriers, local breeding objectives and environmental adaptation. Whole-genome scan for genetic differentiation and association analyses with both environmental and morphological covariables are remarkably consistent with previous studies and identify a number of genes implicated in adaptation, which include TNFRSF19, RFX4, SP4 and several coat color genes. We propose indigenous Chinese cattle as a unique and informative resource for gene-level studies of climate adaptation in mammals.

evolutionary biology↗