Biology subjects

Gao, Y.

Publications and source records attributed to Gao, Y..

At least 55 records · Page 3Linked to original sources

bioRxiv2017

Urinary candidate biomarkers in an experimental autoimmune myocarditis rat model

Urine is a better source than plasma for biomarker studies, as it can accumulate all changes in the body. Various candidate urinary biomarkers of physiological conditions, kidney disease and even brain dysfunction, have been detected in urine; however, urine has rarely been used to reflect cardiac diseases. As the clinical presentations of myocarditis are heterogeneous, reliable and sensitive diagnostic biomarkers of myocarditis are very important. In this study, candidate urinary biomarkers in the myosin-induced autoimmune myocarditis rat models were characterized using the isobaric tandem mass tag labeling approach coupled with high-resolution mass spectrometry. Compared with controls, forty-six urinary proteins were significantly changed in the myocarditis rats; among them, ten had previously been associated with myocarditis, twelve corresponding gene products have been annotated as mainly cardiovascular network genes by the Ingenuity Pathway Analysis, and four urinary proteins were validated by western blot.

molecular biology↗

bioRxiv2017

Effects of regional differences on the urinary proteomes of healthy Chinese individuals

Urine is a promising biomarker source for clinical proteomics studies. Although regional physiological differences are common in multi-center clinical studies, the presence of significant differences in the urinary proteomes of individuals from different regions remains unknown. In this study, morning urine samples were collected from healthy urban residents in three regions of China and urinary proteins were preserved using a membrane-based method (Urimem). The urine proteomes of 27 normal samples were analyzed using LC-MS/MS and compared among the three regions. We identified 1,898 proteins from Urimem samples using label-free proteome quantification, of which 62 urine proteins were differentially expressed among the three regions. Hierarchical clustering analysis showed that inter-regional differences caused less significant changes in the urine proteome than inter-sex differences. Of the 62 differentially expressed proteins, 10 have been reported to be disease biomarkers in previous clinical studies. Urimem facilitates urinary protein storage for large-scale urine sample collection, and thus accelerates biobank development and urine biomarker studies employing proteomics approaches. Regional differences are a confounding factor influencing the urine proteome and should be considered in future multi-center biomarker studies.

physiology↗

bioRxiv2017

Stromal Reactivity Differentially Drives Tumor Cell Evolution and Prostate Cancer Progression

We implemented a hybrid multiscale model of carcinogenesis that merges data from biology and pathology on the microenvironmental regulation of prostate cancer (PCa) cell behavior. It recapitulates the biology of stromal influence in prostate cancer progression. Our data indicate that the interactions between the tumor cells and reactive stroma shape the evolutionary dynamics of PCa cells and explain overall tumor aggressiveness. We show that the degree of stromal reactivity, when coupled with the current clinical biomarkers, significantly improves PCa prognostication, both for death and recurrence, that may alter treatment decisions. We also show that stromal reactivity correlates directly with tumor growth but inversely modulates tumor evolution. This suggests that the aggressive stromal independent PCa may be an inevitable evolutionary result of poor stromal reactivity. It also suggests that purely tumor centric metrics of aggressiveness may be misleading in terms on clinical outcome.

cancer 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↗

bioRxiv2017

SWELL1 is a glucose sensor required for β-cell excitability and insulin secretion

Insulin secretion from the pancreatic {beta}-cell initiated by activation of voltage-gated Ca2+ channels (VGCC) to trigger Ca2+-mediated insulin vesicle fusion with the {beta}-cell plasma membrane. The firing of VGCC depends on the {beta}-cell membrane potential, which is in turn mediated by the balance of depolarizing (excitatory) and hyperpolarizing (inhibitory) ionic currents1-3. While much attention has focused on inhibitory potassium currents4-10 there is little knowledge about the excitatory currents required to depolarize the {beta}-cell, including the molecular identity of these excitatory currents3. Here we show that SWELL1 (LRRC8a) mediates a swell-activated, depolarizing chloride current (ICl,SWELL) in {beta}-cells. Hypotonic and glucose-stimulated {beta}-cell swelling activates SWELL1-mediated ICl,SWELL and this is required for both glucose-stimulated and hypotonic swell-mediated activation of VGCC-dependent intracellular calcium signaling in {beta}-cells. SWELL1 KO MIN6 cells and {beta}-cell targeted SWELL1 KO murine islets exhibit significantly impaired glucose-stimulated insulin secretion, with preserved insulin content in vitro. Tamoxifen-inducible {beta}-cell targeted SWELL1 KO mice have normal fasting insulin levels but display markedly impaired glucose-stimulated insulin secretion. Our results reveal a physiological role for SWELL1 as a glucose sensor - linking glucose-mediated {beta}-cell swelling to SWELL1-dependent activation of VGCC-triggered calcium signaling, and highlights SWELL1-mediated \"swell-secretion\" coupling as required for glucose-stimulated insulin secretion.

cell biology↗

bioRxiv2017

Insm1a regulates motor neuron development in zebrafish

Insulinoma-associated1a (Insm1a) is a zinc-finger transcription factor playing a series of functions in cell formation and differentiation of vertebrate central and peripheral nervous systems and neuroendocrine system. However, its roles on the development of motor neuron have still remained uncovered. Here, we provided evidences that insmla was a vital regulator of motor neuron development and provide a mechanistic understanding of how it contributes to this process. Firstly, we showed the localization of insmla in spinal cord and primary motor neurons (PMNs) of zebrafish embryos by in situ hybridization and imaging analysis of transgenic reporter line Tg(insmla: mCherry) ntu805. Then we demonstrated that the deficiency of insmla in zebrafish larvae lead to the defects of PMNs development, including the reduction of caudal primary motor neurons (CaP) and middle primary motor neurons (MiP), the excessive branching of motor axons, and the disorganized distance between adjacent CaPs. Additionally, knockout of insm1 impaired motor neuron differentiation in the spinal cord. Locomotion analysis showed that insmla-null zebrafish significantly reduced the swimming activity. Furthermore, we proved that the insmla loss of function significantly decreased the transcripts levels of both olig2 and nkx6.1. Microinjection of olig2 and nkx6.1 mRNA rescued the motor neuron defects in insmla deficient embryos. Taken together, these data indicate that insmla regulates the motor neuron development, at least in part, through modulation of the expressions of olig2 and nkx6.1.

developmental biology↗

bioRxiv2017

Engineering Cell Sensing and Responses Using a GPCR-Coupled CRISPR-Cas System

G-protein coupled receptors (GPCRs) are the largest and most diverse group of membrane receptors in eukaryotes, and detects a wide array of physiological cues in the human body. We describe a new molecular device that couples CRISPR-Cas9 programmed genome regulation to natural and synthetic extracellular signals via GPCRs. The design of our synthetic device, named CRISPR ChaCha, displays superior performance over an architecture proposed by the previously reported Tango system. Using a parsimonious mathematical model and gene-reporter assays, we find that CRISPR ChaCha can recruit and activate multiple Cas9 molecules for each GPCR molecule. We also characterize key molecular features that modulate CRISPR ChaCha performance. We adopt the design to diverse GPCRs that sense synthetic and natural ligands including chemokines, mitogens, and fatty acids, and observe efficient conversion of signals to customizable genetic programs in mammalian cells, including regulation of endogenous genes. The new class of CRISPR-coupled GPCRs provides a robust and efficient platform for engineering cells with novel behaviors in response to the diverse GPCR ligand repertoire.

synthetic biology↗

bioRxiv2017

Coupling effect of morphology and mechanical properties contributes to the tribological behaviors of snake scales

It is known that the tribological behaviors of snake skins are contributed by the synergistic action of multiple factors, such as surface morphology and mechanical properties, which has inspired fabrication of scale-like surface textures in recent years. However, the coupling effect and mechanism remain to be elucidated. In this work, the morphology and mechanical properties of the scales from different body sections (leading body half, middle trunk and trailing body half) and positions (dorsal, lateral and ventral) of Boa constrictor and Eryx tataricus have been characterized and compared to investigate the corresponding effects on the tribological behaviors and to probe the possible coupling mechanism. The morphological characterizations of scanning electron microscopy and atomic force microscopy have revealed significant differences between the two species with the roughness of scales from Boa constrictor being larger in general. The mechanical properties measured by nanoindentation have corroboratively demonstrated substantial differences in terms of elastic modulus and hardness. Meanwhile, tribological characterizations of scales in different body positions from the two species also exhibit evident anisotropy. Interestingly, the ventral scales manifest higher friction coefficients but lower surface roughness, together with relatively larger elastic modulus and hardness. A \"double-crossed\" hypothesis has been proposed to explain the observed coupling effect of the morphology and mechanical properties on friction, which may afford valuable insights for the design of materials with desirable tribological performance.

animal behavior and cognition↗

bioRxiv2017

Sugar metabolism changes in response to the ultraviolet B irradiation of peach (Prunus persica L.)

The protected cultivation of peach (Prunuspersica L.) trees is more economical and efficient than traditional cultivation, resulting in increased farmers incomes, but the peach sugar contents are lower than in open planting. In the greenhouse, a high-sugar variety of peach Lumi 1 was irradiated with 1.44 KJ{middle dot}m-2.d-1 intensity ultraviolet B radiation. The soluble sugar contents in fruit, peel and leaf were quantified using liquid chromatography. Overall, sucrose and sorbitol increased before the second fruit-expansion period. To further understand the mechanisms regulating sucrose and sorbitol accumulation in peach fruit, expression profiles of genes involved in sugar metabolism and transport were measured. The activity and translocation protein contents of these enzymes were measured by enzyme-linked immunosorbent assay. The increased sucrose synthase activity and sucrose transporter level in the pericarp promoted the synthesis of sucrose and intake of sucrose into fruit. Sorbitol transport into fruit was promoted by the increased sorbitol transporter protein levels in leaves. In summary, greenhouse the sucrose and sorbitol contents were increased when supplemented with 1.44 kJ{middle dot}m-2{middle dot}d-1 ultraviolet B radiation before the second fruit-expansion period of peach.

plant biology↗

bioRxiv2017

Collection And Preservation Of Urinary Proteins Using A Fluff Pulp Diaper

Change is the most fundamental property of biomarker. Contrast to the blood, which is under homeostatic controls, urine reflects changes in the body earlier and more sensitive therefore is a better biomarker source. And drawing blood from infants and toddlers is hard and less tolerated. For patients limited by language, giving chief complaint is difficult. Thus, monitoring biomarkers in urine can provide valuable clues for diagnosis of diseases, especially pediatric diseases. Collecting urine from young children and some adult patients is more challenging than collecting it from healthy adults. Here, we propose a method that uses a fluff pulp diaper to collect urine. Urinary proteins were then eluted and adsorbed onto a piece of nitrocellulose membrane, which can be dried and stored in a vacuumed bag. SDS-PAGE and LC-MS/MS analysis indicated that this method is reproducible, and similar proteins were identified as those obtained using an acetone precipitation method. With this simple economical method, it is possible to collect and preserve urine samples from infants, toddlers, and patients with special needs, even for large-scale biomarker studies.

molecular biology↗

bioRxiv2017

A Dry Method For Preserving Tear Samples

Tears covering the ocular surface is an important bio-fluid containing thousands of molecules, including proteins, lipids, metabolites, nucleic acids, and electrolytes. Tears are valuable resources for biomarker research of ocular and even systemic diseases. For application in biomarker studies, tear samples should ideally be stored using a simple, low-cost, and efficient method along with the patients medical records. For this purpose, we developed a novel Schirmers strip-based dry method that allows for storage of tear samples in vacuum bags at room temperature. Using this method, tear protein patterns can also be preserved. Liquid chromatography-mass spectrometry/mass spectrometry analysis of proteins recovered from the dry method and traditional wet method showed no significant difference. Some tissue/organ enriched proteins were identified in tear, thus tear might be a good window for monitoring the change of these tissues or organs. This dry method facilitates sample transportation and enables the storage of tear samples on a large scale, increasing the availability of samples for studying disease biomarkers in tears.

biochemistry↗

bioRxiv2017

Effects of the glucocorticoid drug prednisone on urinary proteome and candidate biomarkers

Urine is a good source of biomarkers for clinical proteomics studies. However, one challenge in the use of urine biomarkers is that outside factors can affect the urine proteome. Prednisone is a commonly prescribed glucocorticoid used to treat various diseases in the clinic. To evaluate the possible impact of glucocorticoid drugs on the urine proteome, specifically disease biomarkers, this study investigated the effects of prednisone on the rat urine proteome. Urine samples were collected from control rats and prednisone-treated rats after drug administration. The urinary proteome was analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and proteins were identified using label-free proteome quantification. Differentially expressed proteins and their human orthologs were analyzed with bioinformatics methods. A total of 523 urinary proteins were identified in rat urine. Using label-free quantification, 27 urinary proteins showed expression changes after prednisone treatment. A total of 16 proteins and/or their human orthologs have been previously annotated as disease biomarkers. After functional analysis, we found that the pharmacological effects of prednisone were reflected in the urine proteome. Thus, urinary proteomics has the potential to be a powerful drug efficacy monitoring tool in the clinic. Meanwhile, alteration of the urine proteome due to prednisone treatment should be considered in future disease biomarker studies.

molecular biology↗

bioRxiv2017

Profiling Of Lysine-Acetylated Proteins In Human Urine

Biomarker is the measurable change associated with a physiological or pathophysiological process, its nature is change. Contrast to the blood which is under homeostatic controls, urine reflects changes in the body earlier and more sensitive therefore is a better biomarker source. Lysine acetylation is an abundant and highly regulated post-translational modification. It plays a pivotal role in modulating diverse biological processes and is associated with various important diseases. Enrichment or visualization of proteins with specific post-translational modifications provides a method for sampling the urinary proteome and reducing sample complexity. In this study, we used anti-acetyllysine antibody-based immunoaffinity enrichment combined with high-resolution mass spectrometry to profile lysine-acetylated proteins in normal human urine. A total of 629 acetylation sites on 315 proteins were identified, including some very low-abundance proteins. This is the first proteome-wide characterization of lysine acetylation proteins in normal human urine. Our dataset provides a useful resource for the further discovery of the lysine acetylated proteins as biomarker in urine.

molecular biology↗

bioRxiv2017

Early urinary candidate biomarker discovery in a rat thioacetamide-induced liver fibrosis model

Biomarker is the change associated with the disease. Blood is relatively stable because of the homeostatic mechanisms of the body. However, urine accumulates changes of the body, which makes it a better early biomarker source. Liver fibrosis, which results from the deposition of extracellular matrix (ECM) components, is a reversible pathological condition, whereas cirrhosis, the end-stage of liver fibrosis, is irreversible. Consequently, noninvasive early biomarkers for fibrosis are desperately needed. In this study, differential urinary proteins were identified in the thioacetamide (TAA) liver fibrosis rat model using tandem mass tagging and two-dimensional liquid chromatography tandem mass spectrometry (2DLC-MS/MS). A total of 766 urinary proteins were identified, 143 and 118 of which were significantly changed in the TAA 1-week and 3-week groups, respectively. Multiple reaction monitoring (MRM)-targeted proteomics was used to further validate the abundant differentially expressed proteins in the TAA 1-week, 3-week, 6-week and 8-week groups. A total of 40 urinary proteins were statistically significant (fold change >2 and p<0.05), 15 of which had been previously reported as biomarkers of liver fibrosis, cirrhosis or other related diseases and 10 of which had been reported to be associated with the pathology and mechanism of liver fibrosis. These differential proteins were detected in urine before the alanine aminotransferase (ALT) and aspartate transaminase (AST) changes in the serum and before fibrosis was observed upon hematoxylin and eosin (HE) and Massons staining.

molecular biology↗

bioRxiv2017

Developmental And Genetic Regulation Of The Human Cortex Transcriptome In Schizophrenia

GWAS have identified 108 loci that confer risk for schizophrenia, but risk mechanisms for individual loci are largely unknown. Using developmental, genetic, and illness-based RNA sequencing expression analysis, we characterized the human brain transcriptome around these loci and found enrichment for developmentally regulated genes with novel examples of shifting isoform usage across pre- and post-natal life. We found widespread expression quantitative trait loci (eQTLs), including many with transcript specificity and previously unannotated sequence that were independently replicated. We leveraged this eQTL database to show that 48.1% of risk variants for schizophrenia associated with nearby expression. Within patients and controls, we implemented a novel algorithm for RNA quality adjustment, and identified 237 genes significantly associated with diagnosis that replicated in an independent case-control dataset. These genes implicated synaptic processes and were strongly regulated in early development (p < 10-20). These data offer new targets for modeling schizophrenia risk in cellular systems.

neuroscience↗

bioRxiv2017

Urine Glucose Levels Are Disordered Before Blood Glucose Levels Increase In Zucker Diabetic Fatty Rats

Diabetes mellitus is a type of metabolic disease marked by hyperglycemia, and 90% of diabetes cases are type 2 diabetes mellitus. More than half of patients are not diagnosed at all or are diagnosed too late to be effectively treated, resulting in nonspecific symptoms and a long period of incubation of the disease. Pre-diabetes mellitus, also known as impaired glucose regulation, is an early warning signal of diabetes, which has long been determinated by impaired fasting glucose and impaired glucose tolerance. In this study, Zucker diabetic fatty (ZDF) rats were used to test if there were changes in urine glucose before blood glucose increases. Six 8-week-old male ZDF rats (fa/fa) and Zucker lean (ZL) rats (fa/+) were fed with Purina 5008 high-fat diet and tested for fasting blood glucose and urine glucose. After 12 weeks of feeding, the urine glucose values of the ZL rats were normal (0-10 mmol/L), but the values of the ZDF model rats increased 10 weeks before their blood glucose levels elevated. The urine glucose values of the ZDF model rats showed a state of disorder that was frequently elevated (>10 mmol/L) and occasionally normal (0-10 mmol/L). This finding may provide an easy early diagnosis. Screening for human diabetes can be considered by frequently monitoring urine glucose levels: pre-diabetes may be revealed by frequently disordered urine glucose levels over a period.

molecular biology↗

bioRxiv2017

Early Candidate Biomarkers Found From Urine Of Astrocytoma Rat Before Changes In MRI

Astrocytoma is the most common aggressive glioma and its early diagnosis remains difficult. Biomarkers are changes associated with the disease. Urine, which is not regulated by homeostatic mechanisms, accumulates changes and therefore is a better source for biomarker discovery. In this study, C6 cells were injected into Wistar rats brain as astrocytoma model. Urine samples were collected at day 2, day 6, day 10 and day 13 after injection, and the urinary proteomes were analyzed. On the 10th day, lesions appeared in magnetic resonance imaging. On the 13th day, clinical symptoms started. But differential urinary proteins were changed with the development of the astrocytoma, and can provide clues even on the 2nd and 6th day. Twenty-seven differential proteins with human orthologs had been reported to associate with astrocytoma. Thirty-nine proteins were verified in four more rats as candidate biomarkers of astrocytoma using multiple-reaction monitoring. A panel of differential urinary proteins may provide early biomarkers for diagnose of astrocytoma.

biochemistry↗

bioRxiv2017

Comparative Transcriptome Profiling Conferring Of Resistance To Fusarium Oxysporum Infection Between Resistant And Susceptible Tomato

ABASTRCATTomato Fusarium wilt caused by Fusarium oxysporum f. sp. lycopersici (FOL) is a destructive disease of tomato worldwide which causes severe yield loss of the crops. As exploring gene expression and function approaches constitute an initial point for investigating pathogen-host interaction, we performed a transcriptional analysis to unravel regulated genes in tomato infected by FOL. Differentially expressed genes (DEG) upon inoculation with FOL were presented at twenty-four hours post-inoculation including four treatments: Moneymaker_H2O, Moneymaker_FOL, Motelle_H2O and Motelle_FOL. A total of more than 182.6 million high quality clean reads from the four libraries were obtained. A large overlap was found in DEGs between susceptible tomato cultivar Moneymaker and resistant tomato cultivar Motelle. All Gene Ontology terms were mainly classified into catalytic activity, metabolic process and binding. However, Gene Ontology enrichment analysis evidenced specific categories in infected Motelle. Statistics of pathway enrichment of DEGs resulted that the taurine and hypotaurine metabolism, the stibenoid, diarylheptanoid and gingerol biosynthesis, the starch and sucrose metabolism were the top three pathway affected in both groups. Interestingly, plant-pathogen pathway was greatly regulated in Motelle treated with FOL. Combining with qRT-PCR facilitated the identification of regulated pathogenicity associated genes upon infected resistant or susceptible tomato. Our data showed that a coordinated machinery played a critical role in prompting the response, which could help in generating models of mediated resistance responses with assessment of genomic gene expression patterns.

pathology↗