Biology subjects

Tang, L.

Publications and source records attributed to Tang, L..

104 records · Page 6Linked to original sources

bioRxiv2019

Measurement of organ-specific and acute-phase blood protein levels in early Lyme disease

Lyme disease results from infection of humans with the spirochete Borrelia burgdorferi. The first and most common clinical manifestation is the circular, inflamed skin lesion referred to as erythema migrans; later manifestations result from infections of other body sites. Laboratory diagnosis of Lyme disease can be challenging in patients with erythema migrans because of the time delay in the development of specific diagnostic antibodies against Borrelia. Reliable blood biomarkers for the early diagnosis of Lyme disease in patients with erythema migrans are needed. Here, we performed selected reaction monitoring, a targeted mass spectrometry-based approach, to measure selected proteins that 1) are known to be predominantly expressed in one organ (i.e., organ-specific blood proteins) and whose blood concentrations may change as a result of Lyme disease, or 2) are involved in acute immune responses. In a longitudinal cohort of 40 Lyme disease patients and 20 healthy controls, we identified 10 proteins with significantly altered serum levels in patients at the time of diagnosis, and we also developed a 10-protein panel identified through multivariate analysis. In an independent cohort of patients with erythema migrans, six of these proteins, APOA4, C9, CRP, CST6, PGLYRP2 and S100A9, were confirmed to show significantly altered serum levels in patients at time of presentation. Nine of the 10 proteins from the multivariate panel were also verified in the second cohort. These proteins, primarily innate immune response proteins or proteins specific to liver, skin or white blood cells, may serve as candidate blood biomarkers requiring further validation to aid in the laboratory diagnosis of early Lyme disease.

systems biology↗

bioRxiv2019

System-Level Quantification and Phenotyping of Early Embryonic Morphogenesis of Caenorhabditis elegans

Cell lineage consists of cell division timing, cell migration and cell fate, and is highly conserved during development of nematode species. An outstanding question is how differentiated cells are genetically and physically regulated in order to migrate to their precise destination among individuals. Here, we first generated a reference embryo using time-lapse 3 dimensional images of 222 wild-type C. elegans embryos at about 1.5-minute interval. This was achieved by automatic tracing and quantitative analysis of cellular phenotypes from 4- to 24-cell stage, including cell cycle duration, division orientation and migration trajectory. We next characterized cell division timing and cell kinematic state, which suggests that eight groups of cells can be clustered based on invariant and distinct division sequence. Cells may still be moving while others start to divide, indicating strong robustness against motional noise in developing embryo. We then devised a system-level phenotyping method for detecting mutant defect in global growth rate, cell cycle duration, division orientation and cell arrangement. A total of 758 genes were selected for perturbation by RNA interference followed by automatic phenotyping, which suggests a cryptic genetic architecture coordinating early morphogenesis spatially and temporally. The high-quality wild-type reference supports a conceptual close-packing model for cell arrangement during 4- to 8-cell stage, implying fundamental mechanical laws regulating the topological structure of early C. elegans embryo. Also, we observed a series of remarkable morphogenesis phenomena such as induced defect or recovery from defect in mutant embryo. To facilitate use of this quantification system, we built a software named STAR 1.0 for visualizing the wild-type reference and mutant phenotype. It also allows automatic phenotyping of new mutant embryo. Taken together, we not only provide a statistical wild-type reference with defined variability, but also shed light on both genetic and physical mechanisms coordinating early embryonic morphogenesis of C. elegans. The statistical reference permits a sensitive approach for mutant phenotype analysis, with which we phenotype a total of 1818 mutant embryos by depletion of 758 genes.\n\nHighlights & Graphical Abstract[bullet] Spatial-Temporal Wild-Type Reference for Early Embryonic Morphogenesis of C. elegans\n[bullet]Variability (Noise) of Division Timing, Division Orientation and Cell Arrangement\n[bullet]A Conceptual Close-Packing Model for Cell Arrangement Up to 8-Cell Stage\n[bullet]Quantitative Phenotyping Methods at Embryo and Cellular Level\n[bullet]Cellular Phenotypes of 1818 Mutant Embryos (758 Genes) Before Gastrulation\n[bullet]Categorized Phenotypes upon Gene Perturbation\n\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=134 SRC=\"FIGDIR/small/776062v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (37K):\norg.highwire.dtl.DTLVardef@2ec730org.highwire.dtl.DTLVardef@11732deorg.highwire.dtl.DTLVardef@ccbf4org.highwire.dtl.DTLVardef@2218d1_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2019

Infection of Borrelia burgdorferi sensu lato of small mammals in Yunnan Province, China

BackgroundLyme disease is caused by Borrelia burgdorferisensulato (BBSL) which is usually found in wild and domestic mammals worldwide. Human cases of B. burgdorferi infections have been identified in China, but little direct surveillance of potential rodent reservoirs has been performed in Yunnan Province, Southwestern China. Yunnan Province is a tropical area with a diverse topographic range and sustains a high biodiversity of small mammals that could potentially play an important role in the transmission of a variety of B. burgdorferigenospecies.\n\nMethods3659 small mammals were captured in 159 sample siteslocated 23 countries inYunnan Province and screened for BBSL infection by nested PCR based on 5S-23S rRNA intergenic spacer gene of BBSL.Univariate and multivariate forward stepwise logistic regression analysis was used to access the association between infections and related risk factors.\n\nResultsInfection with BBSL was confirmed in 3.99%(146/3659) of small mammals. Significant differences in prevalence rates of BBSL were observed at varying landscape types and altitudes.Small mammals in forested areas had higher prevalence rates than other landscape types as did small mammals found at altitudes greater than 2500 meters. The 5S-23S rRNA intergenic spacergene revealed that there were 5 genotype of BBSL, including B. afzelii, B. burgdorferisensustricto, B.japonica, B.gariniiand B.valaisiana, which demonstrate the genetic diversity and regional distribution.\n\nConclusionsThere exists a wide distribution and genetic diversity of endemic BBSL in Southwestern China, warranting further investigations and monitoring of clinical disease in individuals presenting with symptoms of Lyme disease in these areas.\n\nAuthor summaryLyme disease is caused by Borrelia burgdorferi sensu lato (BBSL) which is usually found in wild and domestic mammals worldwide. Human cases of Borrelia burgdorferi sensu lato infections have been identified in China, but little direct surveillance of potential rodent reservoirs has been performed in Southwestern China. This study documents potential small mammal reservoir hosts collected from a large of sample sites from different landscape types and altitudes, with PCR and sequencing identifying the wide distribution and genetic diversity of endemic Borrelia burgdorferi sensu lato in Southwestern China. This was the first report that B. japonica was detected in Apodemus draco and Niviventer excelsior in China. This study adds to body of literature on Borrelia burgdorferi sensu lato in China. This work will provide insight regarding small mammals to target for surveillance and we access the association between gender, developmental stage of rodents, environmental landscape and altitude to better prevent human exposure.

epidemiology↗

bioRxiv2019

Alteration of Gut Microbiome in Lung Cancer Patients

Lung cancer is the leading cause of cancer death. Better understanding of factors and pathways involved in lung cancer is needed to improve diagnose and treatment strategies. Recent studies have provided insights into the possible correlation between intestinal dysbiosis and cancer development. Although the immunological relationship between gut and lung had been suggested by many researches, however, to date, no study had investigated the characterization of gut microbiome in treatment naive lung cancer patients, whether it is distinct from that of health individuals and contribute to the onset and development of lung cancer remain unclear. In this study, we investigated whether gut microbiome of lung cancer patients (LC, n=28) is altered compare with that of matched healthy individuals (HC, n=19) by high throughout sequencing of the V3-V4 regions of 16S rDNA in their fecal samples. We also identified microbiota signatures specific for different histological types of lung cancer, including SSC, ADC, and SCLC. The gut microbiome of lung cancer patients is characterized by decreased relative abundance of Prevotella, and increased bacteria groups such as Actinomyces, and Streptococcus, etc. We also detected a mild structural shift in gut microbiome between ADC and SCLC patients. Our results showed that the gut microbiome of lung cancer patients altered significantly compared with healthy individuals. However, the association between microbial dysbiosis and lung cancer is not clearly understood, future studies involving larger cohorts and metagenomics, or metabolomics, may elucidate the correlations between gut microbiota and lung cancer development.\n\nIMPORTANCEThis is the first report to show the alteration of gut microbiome in lung cancer patients. Our results showed that the gut microbiome of lung cancer patients altered significantly compared with healthy individuals.

microbiology↗

bioRxiv2019

Clinical pattern of antibiotic overuse and misuse in primary healthcare hospitals in the southwest of China

PurposeOveruse and misuse of antibiotics are the primary risk factors for antibiotics resistance. Inadequate professional competence of primary care physicians might exacerbate these problems in China. This retrospective study aims to document the clinical pattern of antibiotics use and its overuse and misuse rates in rural primary care institutions, and to evaluate the association between antibiotics use and characteristics of the physicians and their patients.\n\nMethodsMedical records from 16 primary care hospitals in rural areas of Guizhou province, China were obtained from the Health Information System in 2018. Classification of incorrect and/or unnecessary use, escalated use and combined antibiotics use was based on the Guiding Principle of Clinical Use of Antibiotics (2015, China) and the standard of USA Centers for Disease Control and Prevention. Generalized Estimating Equations were employed to determine predictive factors for inappropriate antibiotics use.\n\nResultsA total of 74,648 antibiotics prescriptions were retrieved. Uncomplicated respiratory infection was the most common disease accounting for 58.6% of all prescriptions. The main antibiotic group used was penicillins (51.5%) followed by cephalosporins and macrolides (14% each). Of 57,009 patient visits, only 8.7% of the antibiotic prescriptions were appropriate. Combined, escalated, and incorrect and/or unnecessary antibiotics use was found in 7.8%, 6.2% and 77.3% of patient visits, respectively, of which 28.7% were given intravenously. Antibiotics misuse was significantly more likely among newly employed physicians with lower levels of professional education. Adult patients and those who had public insurance had a higher risk of being prescribed incorrect and/or unnecessary antibiotics.\n\nConclusionOveruse of antibiotics for uncomplicated respiratory infection and use of cephalosporins, macrolides and injection antibiotics in primary care are the major problems of clinical practice in rural areas of Guizhou.

epidemiology↗

bioRxiv2019

Layer 5 circuits in V1 differentially control visuomotor behavior

Sensory areas of the mammalian neocortex are thought to act as distribution hubs, transmitting information about the external environment to various cortical and subcortical structures in order to generate adaptive behavior. However, the exact role of cortical circuits in sensory perception remains unclear. Within primary visual cortex (V1), various populations of pyramidal neurons (PNs) send axonal projections to distinct targets, suggesting multiple cellular networks that may be independently engaged during the generation of behavior. Here, we investigated whether PN subpopulations differentially support sensory-guided performance by training mice in a visual detection task based on eyeblink conditioning. Applying 2-photon calcium imaging and optogenetic manipulation of anatomically-defined PNs in behaving animals, we show that layer 5 corticopontine neurons strongly encode task information and are selectively necessary for performance. These results contrast with recent observations of operant behavior showing a limited role for the neocortex in sensory detection. Instead, our findings support a model in which target-specific cortical subnetworks form the basis for adaptive behavior by directing relevant information to downstream brain areas. Overall, this work highlights the potential for neurons to form physically interspersed but functionally segregated networks capable of parallel, independent control of perception and behavior.

neuroscience↗

bioRxiv2018

Construction of an index system for big data application in health care enterprises: A study based on the Delphi method

This study explored the theory of medical enterprise management and big data. Based on the Delphi method, two rounds of expert opinions were consulted on the capability of a health care enterprise big data application index system covering 11 dimensions, 46 first-level indicators and 111 second-level indicators. The index system includes two categories of input and capacity. The input category includes five dimensions: human resources, material resources, financial resources, government policies, and social service system or social environment. The capabilities category includes six dimensions: data integration capabilities, service capabilities, data analysis capabilities, information security, profitability, and innovation capabilities. This index system aims to appraise the application capability of big data scientifically and systematically, and fills the gaps of such research in China so far, which has positive significance for further research in the future.

scientific communication and education↗

bioRxiv2018

Combined use of Candida Utilis and Idesia polycarpa var. Vestita Fruit Improve the Production Performance of Laying Quail

Although Idesia polycarpa oil has been wildly explored as a raw material for biodiesel, the reports studying the by-product Idesia polycarpa fruit residues (IPR) are few. This study aimed to evaluate the effect of the Idesia polycarpa fruit residues fermented feed additive (IPFF) on the egg production of laying quails. The egg production and related performances include egg quality, yolk cholesterol, yolk fatty acid, quails jejunum morphology, and relative gene expression were determined in this study. Compared to the standard diet group, birds fed the 1% IPFF showed a higher egg production (87.7% on average, 11.5% above the control; P<0.01). The yolk fatty acid composition and n6/n3 ratio were affected by IPFF or IPR. Compared to the standard diet group, the egg cholesterol content was lower in both IPFF and IPR groups, and the yolk n6/n3 ratio in the 5% IPFF group (10.3; P<0.01) was more reasonable. Meanwhile, birds under IPFF dietary supplement showed a thicker jejunum wall, higher villus, and deeper crypt than the standard diet group. In addition, the altered mRNA expression of four genes involved in cholesterol and fatty acids metabolism (SREBP-1, SREBP-2, ADGL, APOVLDL-II) in the 1% IPFF group and 5% IPR group indicated that the lipids metabolism and transportation were enhanced in the interclavicular fat pad and liver, relative to the standard diet group. HIGHLIGHTSEgg production was higher in IPFF groups Egg cholesterol was lower in IPFF groups Lipid metabolism and transportation was enhanced in IPFF groups Intestine wall was thicker in IPFF groups

microbiology↗

bioRxiv2018

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

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

molecular biology↗

bioRxiv2018

Dynamic Regulation of RNA Structure in Mammalian Cells

RNA structure is intimately connected to each step of gene expression. Recent advances have enabled transcriptome-wide maps of RNA secondary structure, termed RNA structuromes. However, previous whole-cell analyses lacked the resolution to unravel the dynamic regulation of RNA structure across subcellular states. Here we reveal the RNA structuromes in three compartments -- chromatin, nucleoplasm and cytoplasm. The cytotopic structuromes substantially expand RNA structural information, and enable detailed investigation of the central role of RNA structure in linking transcription, translation, and RNA decay. Through comparative structure analysis, we develop a resource to visualize the interplay of RNA-protein interactions, RNA chemical modifications, and RNA structure, and predict both direct and indirect reader proteins of RNA modifications. We validate the novel role of the RNA binding protein LIN28A as an N6-methyladenosine (m6A) modification \"anti-reader\". Our results highlight the dynamic nature of RNA structures and its functional significance in gene regulation.

molecular biology↗

bioRxiv2018

Multi-omics analysis of AML cells treated with azacitidine reveals highly variable cell surface proteome remodeling

Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are diseases of abnormal hematopoietic differentiation with aberrant epigenetic alterations. Azacitidine (AZA) is a DNA methyltransferase inhibitor (DNMTi) widely used to treat MDS and AML, yet the impact of AZA on the cell surface proteome has not been defined. To identify potential therapeutic targets for use in combination with AZA in AML patients, we investigated the effects of AZA treatment on four AML cell lines (KG1a, HL60, HNT34, and AML193), representing different stages of differentiation. The effect of AZA treatment on these cell lines was characterized at three levels: the DNA methylome (methylation array), the transcriptome (gene expression array), and the cell surface proteome (glycoprotein capture with SILAC labeling). Untreated AML cell lines showed substantial overlap in their methylomes, transcriptomes, and cell surface proteomes. AZA treatment globally reduced DNA methylation in all cell lines, but changes in the transcriptome and surface proteome were subtle and differed among the cell lines. Transcriptome analysis identified five commonly up-regulated coding genes upon AZA treatment in all four cell lines, TRPM4 being the only gene encoding a surface protein, and surface proteomics analysis found no commonly regulated proteins. Gene Set Enrichment Analysis (GSEA) of differentially-regulated RNA and surface proteins showed a decrease in metabolism pathways and an increase in immune defense response pathways. As such, AZA treatment in four AML cell lines had diverse effects at the individual gene and protein level, but converged to regulation of metabolism and immune response at the pathway level. Given the heterogeneous response of AZA in the four cell lines at the gene and protein level, we discuss potential therapeutic strategies for combinations with AZA.

cancer biology↗

bioRxiv2018

Notch3 Promotes Prostate Cancer-Induced Bone Osteoblastic Metastasis in an MMP-3-Dependent Manner

Prostate cancer metastases primarily localize in the bone where they induce a unique osteoblastic response. Elevated Notch activity is associated with high-grade disease and metastasis. To address how Notch affects prostate cancer bone lesions, we manipulated Notch expression in mouse tibia xenografts and monitored tumor growth, lesion phenotype, and the bone microenvironment. Prostate cancer cell lines that induce mixed osteoblastic lesions in bone expressed 5-6 times more Notch3, than tumor cells that produce osteolytic lesions. Expression of active Notch3 (NICD3) in osteolytic tumors reduced osteolytic lesion area and enhanced osteoblastogenesis, while loss of Notch3 in osteoblastic tumors enhanced osteolytic lesion area and decreased osteoblastogensis. This was accompanied by a respective decrease and increase in the number of active osteoclasts and osteoblasts at the tumor-bone interface, without any effect on tumor proliferation. Conditioned medium from NICD3-expressing cells enhanced osteoblast differentiation and proliferation in vitro, while simultaneously inhibiting osteoclastogenesis. MMP-3 was specifically elevated and secreted by NICD3-expressing tumors, and inhibition of MMP-3 rescued the NICD3-induced osteoblastic phenotypes. Clinical osteoblastic bone metastasis samples had higher levels of Notch3 and MMP-3 compared to patient matched visceral metastases or osteolytic metastasis samples. We identified a Notch3-MMP-3 axis in human prostate cancer bone metastases that contributes to osteoblastic lesion formation by blocking osteoclast differentiation, while also contributing to osteoblastogenesis. These studies define a new role for Notch3 in manipulating the tumor microenvironment in bone metastases.

cancer biology↗

bioRxiv2017

ATRX, DAXX or MEN1 mutant pancreatic neuroendocrine tumors are a distinct alpha-cell signature subgroup

The most commonly mutated genes in pancreatic neuroendocrine tumors (PanNETs) are ATRX, DAXX, and MEN1. Little is known about the cells-of-origin for non-functional neuroendocrine tumors. Here, we genotyped 64 PanNETs for mutations in ATRX, DAXX, and MEN1 and found 37 tumors (58%) carry mutations in these three genes (A-D-M mutant PanNETs) and this correlates with a worse clinical outcome than tumors carrying the wild-type alleles of all three genes (A-D-M WT PanNETs). We performed RNA sequencing and DNA-methylation analysis on 33 randomly selected cases to reveal two distinct subgroups with one group consisting entirely of A-D-M mutant PanNETs. Two biomarkers differentiating A-D-M mutant from A-D-M WT PanNETs were high ARX gene expression and low PDX1 gene expression with PDX1 promoter hyper-methylation in the A-D-M mutant PanNETs. Moreover, A-D-M mutant PanNETs had a gene expression signature related to that of alpha cells (pval < 0.009) of pancreatic islets including increased expression of HNF1A and its transcriptional target genes. This gene expression profile suggests that A-D-M mutant PanNETs originate from or transdifferentiate into a distinct cell type similar to alpha cells.

cancer biology↗

bioRxiv2017

Demoralization among cancer patients in mainland China: validity of the Demoralization Scale (DS)

Demoralization, characterized by hopelessness, helplessness, and loss of meaning and purpose, reflects existential distress. The objectives is To assess the validity of a Mainland Chinese versions of the demoralization scale (MC-DS) for using with Mainland Chinese cancer patients. In-patients sequentially recruited from a specialist tertiary-level cancer hospital in Beijing between January 2016-April 2016 completed Demoralization Scale, (DS) Patient Health Questionnaire-9 (PHQ-9), Revised Life Orientation Test (CLOT-R), Beck Hopelessness Scale (BHS), and provided sociodemographic and clinical information. We determined DS factor structure and convergent and divergent validity. 296/424 (70.0%) participants reported mean DS score=30.42(SD=13.00). EFA identified 3-factors explaining 21.4%, 17.8%, and 10.6% respectively of observed variance. Respective Cronbach Alphas were 0.88, 0.84, and 0.64 (0.90 full-scale). Convergent was shown by PHQ-9 scores correlating with Factor 2 (r=0.606), and BHS and C-LOT-R scores correlating (r=0.632,r=0.407 respectively) with Factor 1. Dichotomizing demoralization (high >30, low[less double equals]30) cross-tabulated against PHQ-9 score (mood) scores revealed 47% of patients exceeded demoralization cut-off, 60% of whom were not depressed. Using mean value{+/-}SD indicated demoralization cutoffs at <17.4 (low), 17.4-43.4 (medium) and >43.4 (high). Overall 71% met criteria for medium demoralization, and 15% for high demoralization. Sixty percent of all medium demoralization patients were not depressed, but only 5% of high demoralization patients were not depressed. The conclusion is that the Mainland Chinese Demoralization Scale is useful for detecting mild-to-moderate demoralization in cancer patients but at higher scores has poor specificity against depression.

epidemiology↗