83 results on '"Quanyuan He"'
Search Results
2. Deep convolutional neural networks using an active learning strategy for cervical cancer screening and diagnosis
- Author
-
Xueguang Li, Mingyue Du, Shanru Zuo, Mingqing Zhou, Qiyao Peng, Ziyao Chen, Junhua Zhou, and Quanyuan He
- Subjects
cervical cancer ,CNN ,active learning strategy ,deep learning ,whole slide image ,Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
Cervical cancer (CC) is the fourth most common malignant tumor among women worldwide. Constructing a high-accuracy deep convolutional neural network (DCNN) for cervical cancer screening and diagnosis is important for the successful prevention of cervical cancer. In this work, we proposed a robust DCNN for cervical cancer screening using whole-slide images (WSI) of ThinPrep cytologic test (TCT) slides from 211 cervical cancer and 189 normal patients. We used an active learning strategy to improve the efficiency and accuracy of image labeling. The sensitivity, specificity, and accuracy of the best model were 96.21%, 98.95%, and 97.5% for CC patient identification respectively. Our results also demonstrated that the active learning strategy was superior to the traditional supervised learning strategy in cost reduction and improvement of image labeling quality. The related data and source code are freely available at https://github.com/hqyone/cancer_rcnn.
- Published
- 2023
- Full Text
- View/download PDF
3. The effects of the interaction between BMI and dyslipidemia on hypertension in adults
- Author
-
Na Tang, Jian Ma, Rongqin Tao, Zhijun Chen, Yide Yang, Quanyuan He, Yuan Lv, Zelong Lan, and Junhua Zhou
- Subjects
Medicine ,Science - Abstract
Abstract Body mass index (BMI) and dyslipidemia are indicators of human health and are often associated with high blood pressure. In this study,we explored the relationship between BMI or dyslipidemia and the risk of hypertension and further verified the possible interacting influences of BMI with dyslipidemia on the risk of hypertension. The aim is to explore the possible risk factors of hypertension and to provide scientific basis for the prevention and treatment of hypertension. Eligible subjects were selected from a cross-sectional survey in Changsha City, and we collected relevant data and clinical indicators for each participant. Body mass index (BMI) was calculated as weight (kg)/height2 (m2), and divided into four categories according to the Chinese standard. Dyslipidemia is defined according to Chinese guideline. Unconditional logistic regression models were used for dichotomous variables to determine the risk or protective factors of dependent variables. Multivariate Logistic model was used to study the influence of BMI and dyslipidemia on hypertension. The following indicators were used to assess the interaction effects: (1) Relative excess risk due to interaction (RERI); (2) Attributable proportion due to interaction(AP); (3) Synergy index (SI). SPSS software was used for statistical analysis. A total of 2740 eligible participants were enrolled in the cross-sectional study, of which 765 subjects (27.9%) were diagnosed with hypertension. Multivariate Logistic model showed that overweight (OR: 1.70, 95%CI: 1.39–2.09) or obese (OR: 2.60, 95%CI: 1.84–3.66) subjects had a significantly higher risk of hypertension than normal weight people, and underweight was a protective factor for hypertension(OR: 0.52, 95%CI: 0.29–0.93). People with dyslipidemia have a higher risk of hypertension than those with normal lipids (OR: 3.05, 95%CI: 2.36–3.90). In addition,there was a significant potentiating interaction effect between overweight or obesity and dyslipidemia(overweight: RERI (1.91, 95%CI: 0.17–3.66), AP (0.40, 95%CI:0.14–0.66), SI (2.03, 95%CI:1.11–3.74) and obesity: RERI (2.20, 95%CI:1.01–3.40), AP (0.38, 95%CI:0.18–0.58), SI (1.84, 95%CI:1.18–2.89), while no interaction was found between underweight and dyslipidemia. Low body weight is an independent protective factor for hypertension, but overweight, obesity and dyslipidemia are risk factors for hypertension, and dyslipidemia significantly shared interactions with overweight and obesity that influenced the risk of hypertension.
- Published
- 2022
- Full Text
- View/download PDF
4. A Quick Method to Synthesize Extrachromosomal Circular DNA In Vitro
- Author
-
Shanru Zuo, Xueguang Li, Yide Yang, Junhua Zhou, and Quanyuan He
- Subjects
extrachromosomal circular DNA ,minicircle ,PCR ,ligase reaction ,Organic chemistry ,QD241-441 - Abstract
Extrachromosomal circular DNA (eccDNA) is a special class of circular DNA in eukaryotes. Recent studies have suggested that eccDNA is the product of genomic instability and has important biological functions to regulate many downstream biological processes. While NGS (Next-Generation Sequencing)-based eccDNA sequencing has led to the identification of many eccDNAs in both healthy and diseased tissues, the specific biological functions of individual eccDNAs have yet to be clearly elucidated. Synthesizing eccDNAs longer than 1 kb with specific sequences remains a major challenge in the field, which has hindered our ability to fully understand their functions. Current methods for synthesizing eccDNAs primarily rely on chemical oligo synthesis, ligation, or the use of a specific gene editing and recombination systems. Therefore, these methods are often limited by the length of eccDNAs and are complex, expensive, as well as time-consuming. In this study, we introduce a novel method named QuickLAMA (Ligase-Assisted Minicircle Accumulation) for rapidly synthesizing eccDNAs up to 2.6 kb using a simple PCR and ligation approach. To validate the efficacy of our method, we synthesized three eccDNAs of varying lengths from cancer tissue and PC3 cells and confirmed successful circularization through sequencing and restriction enzyme digestion. Additional analyses have demonstrated that this method is highly efficient, cost-effective, and time-efficient, with good reproducibility. Using the method, a well-trained molecular biologist can synthesize and purify multiple eccDNAs within a single day, and it can be easily standardized and processed in a high-throughput manner, indicating the potential of the method to produce a wide range of desired eccDNAs and promote the translation of eccDNA research into clinical applications.
- Published
- 2023
- Full Text
- View/download PDF
5. Integrated genomic analysis reveals regulatory pathways and dynamic landscapes of the tRNA transcriptome
- Author
-
Zefang Sun, Jia Tan, Minqiong Zhao, Qiyao Peng, Mingqing Zhou, Shanru Zuo, Feilong Wu, Xueguang Li, Yangyang Dong, Ming Xie, Yide Yang, Junhua Zhou, Xianghua Liu, Quanze He, Zuping He, Xing Yu, and Quanyuan He
- Subjects
Medicine ,Science - Abstract
Abstract tRNAs and tRNA-derived RNA fragments (tRFs) play various roles in many cellular processes outside of protein synthesis. However, comprehensive investigations of tRNA/tRF regulation are rare. In this study, we used new algorithms to extensively analyze the publicly available data from 1332 ChIP-Seq and 42 small-RNA-Seq experiments in human cell lines and tissues to investigate the transcriptional and posttranscriptional regulatory mechanisms of tRNAs. We found that histone acetylation, cAMP, and pluripotency pathways play important roles in the regulation of the tRNA gene transcription in a cell-specific manner. Analysis of RNA-Seq data identified 950 high-confidence tRFs, and the results suggested that tRNA pools are dramatically distinct across the samples in terms of expression profiles and tRF composition. The mismatch analysis identified new potential modification sites and specific modification patterns in tRNA families. The results also show that RNA library preparation technologies have a considerable impact on tRNA profiling and need to be optimized in the future.
- Published
- 2021
- Full Text
- View/download PDF
6. Zbtb40 Deficiency Leads to Morphological and Phenotypic Abnormalities of Spermatocytes and Spermatozoa and Causes Male Infertility
- Author
-
Yinghong Cui, Mingqing Zhou, Quanyuan He, and Zuping He
- Subjects
Zbtb40 knockout ,ZBTB40 mutation ,spermatocytes ,spermatids ,telomere length ,male infertility ,Cytology ,QH573-671 - Abstract
Studies on the gene regulation of spermatogenesis are of unusual significance for maintaining male reproduction and treating male infertility. Here, we have demonstrated, for the first time, that a loss of ZBTB40 function leads to abnormalities in the morphological and phenotypic characteristics of mouse spermatocytes and spermatids as well as male infertility. We revealed that Zbtb40 was expressed in spermatocytes of mouse testes, and it was co-localized with γH2AX in mouse secondary spermatocytes. Interestingly, spermatocytes of Zbtb40 knockout mice had longer telomeres, compromised double-strand break (DSB) repair in the sex chromosome, and a higher apoptosis ratio compared to wild-type (WT) mice. The testis weight, testicular volume, and cauda epididymis body weight of the Zbtb40+/− male mice were significantly lower than in WT mice. Mating tests indicated that Zbtb40+/− male mice were able to mate normally, but they failed to produce any pups. Notably, sperm of Zbtb40+/− mice showed flagellum deformities and abnormal acrosome biogenesis. Furthermore, a ZBTB40 mutation was associated with non-obstructive azoospermia. Our results implicate that ZBTB40 deficiency leads to morphological and phenotypic abnormalities of spermatocytes and spermatids and causes male infertility. This study thus offers a new genetic mechanism regulating mammalian spermatogenesis and provides a novel target for gene therapy in male infertility.
- Published
- 2023
- Full Text
- View/download PDF
7. Hsa-miR-1908-3p Mediates the Self-Renewal and Apoptosis of Human Spermatogonial Stem Cells via Targeting KLF2
- Author
-
Wei Chen, Yinghong Cui, Bang Liu, Chunyun Li, Li Du, Ruiling Tang, Lulu Qin, Yiqun Jiang, Jian Li, Xing Yu, Quanyuan He, and Zuping He
- Subjects
hsa-miR-1908-3p ,human spermatogonial stem cells ,self-renewal ,apoptosis ,KLF2 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Spermatogenesis depends on precise epigenetic and genetic regulation of spermatogonial stem cells (SSCs). However, it remains largely unknown about the roles and mechanisms of small noncoding RNA in regulating the self-renewal and apoptosis of human SSCs. Notably, we have found that Homo sapiens-microRNA (hsa-miR)-1908-3p is expressed at a higher level in human spermatogonia than pachytene spermatocytes. MiR-1908-3p stimulated cell proliferation and DNA synthesis of the human SSC line. Allophycocyanin (APC) Annexin V and propidium iodide staining, determined by flow cytometric analysis and TUNEL assays, showed that miR-1908-3p inhibited early and late apoptosis of the human SSC line. Furthermore, Kruppel-like factor 2 (KLF2) was predicted and verified as the target of miR-1908-3p, and, significantly, KLF2 silencing resulted in the increase of proliferation and DNA synthesis, as well as reduction of apoptosis of the human SSC line. Moreover, KLF2 silencing ameliorated the decrease in the proliferation and DNA synthesis and the enhancement in the apoptosis of the human SSC line caused by miR-1908-3p inhibition. Collectively, these results implicate that miR-1908-3p stimulates the self-renewal and suppresses the apoptosis of human SSCs by targeting KLF2. This study thus provides a novel epigenetic regulatory mechanism underlying the fate determinations of human SSCs, and it offers new endogenous targets for treating male infertility.
- Published
- 2020
- Full Text
- View/download PDF
8. BCREval: a computational method to estimate the bisulfite conversion ratio in WGBS
- Author
-
Junhua Zhou, Minqiong Zhao, Zefang Sun, Feilong Wu, Yucong Liu, Xianghua Liu, Zuping He, Quanze He, and Quanyuan He
- Subjects
DNA methylation ,Whole genome bisulfite sequencing (WGBS) ,Bisulfite conversion ratio (BCR) ,Telomere ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background Whole genome bisulfite sequencing (WGBS) also known as BS-seq has been widely used to measure the methylation of whole genome at single-base resolution. One of the key steps in the assay is converting unmethylated cytosines into thymines (BS conversion). Incomplete conversion of unmethylated cytosines can introduce false positive methylation call. Developing a quick method to evaluate bisulfite conversion ratio (BCR) is benefit for both quality control and data analysis of WGBS. Results Here we provide a computational method named “BCREval” to estimate the unconverted rate (UCR) by using telomeric repetitive DNA as native spike-in control. We tested the method by using public WGBS data and found that it is very stable and most of BS conversion assays can achieve> 99.5% efficiency. The non-CpG DNA methylation at telomere fits a binomial model and may result from a random process with very low possibility (the ratio
- Published
- 2020
- Full Text
- View/download PDF
9. Extrachromosomal Circular DNA (eccDNA): From Chaos to Function
- Author
-
Shanru Zuo, Yihu Yi, Chen Wang, Xueguang Li, Mingqing Zhou, Qiyao Peng, Junhua Zhou, Yide Yang, and Quanyuan He
- Subjects
eccDNA ,circulome ,biogenesis ,cancer ,biomarker ,Biology (General) ,QH301-705.5 - Abstract
Extrachromosomal circular DNA (eccDNA) is a type of double-stranded circular DNA that is derived and free from chromosomes. It has a strong heterogeneity in sequence, length, and origin and has been identified in both normal and cancer cells. Although many studies suggested its potential roles in various physiological and pathological procedures including aging, telomere and rDNA maintenance, drug resistance, and tumorigenesis, the functional relevance of eccDNA remains to be elucidated. Recently, due to technological advancements, accumulated evidence highlighted that eccDNA plays an important role in cancers by regulating the expression of oncogenes, chromosome accessibility, genome replication, immune response, and cellular communications. Here, we review the features, biogenesis, physiological functions, potential functions in cancer, and research methods of eccDNAs with a focus on some open problems in the field and provide a perspective on how eccDNAs evolve specific functions out of the chaos in cells.
- Published
- 2022
- Full Text
- View/download PDF
10. Structural and Functional Insight Into the Glycosylation Impact Upon the HGF/c-Met Signaling Pathway
- Author
-
Xinyue Hu, Feiyu Tang, Peilin Liu, Taowei Zhong, Fengyan Yuan, Quanyuan He, Mark von Itzstein, Hao Li, Liang Weng, and Xing Yu
- Subjects
HGF ,c-Met ,glycosylation ,cancer ,application ,Biology (General) ,QH301-705.5 - Abstract
Upon interactions with its specific ligand hepatocyte growth factor (HGF), the c-Met signal is relayed to series of downstream pathways, exerting essential biological roles. Dysregulation of the HGF-c-Met signaling pathway has been implicated in the onset, progression and metastasis of various cancers, making the HGF-c-Met axis a promising therapeutic target. Both c-Met and HGF undergo glycosylation, which appears to be biologically relevant to their function and structural integrity. Different types of glycoconjugates in the local cellular environment can also regulate HGF/c-Met signaling by distinct mechanisms. However, detailed knowledge pertaining to the glycosylation machinery of the HGF-c-Met axis as well as its potential applications in oncology research is yet to be established. This mini review highlights the significance of the HGF-c-Met signaling pathway in physiological and pathological context, and discusses the molecular mechanisms by which affect the glycosylation of the HGF-c-Met axis. Owing to the crucial role played by glycosylation in the regulation of HGF/c-Met activity, better understanding of this less exploited field may contribute to the development of novel therapeutics targeting glycoepitopes.
- Published
- 2020
- Full Text
- View/download PDF
11. Zebrafish as a model system to study the physiological function of telomeric protein TPP1.
- Author
-
Yiying Xie, Dong Yang, Quanyuan He, and Zhou Songyang
- Subjects
Medicine ,Science - Abstract
Telomeres are specialized chromatin structures at the end of chromosomes. Telomere dysfunction can lead to chromosomal abnormalities, DNA damage responses, and even cancer. In mammalian cells, a six-protein complex (telosome/shelterin) is assembled on the telomeres through the interactions between various domain structures of the six telomere proteins (POT1, TPP1, TIN2, TRF1, TRF2 and RAP1), and functions in telomere maintenance and protection. Within the telosome, TPP1 interacts directly with POT1 and TIN2 and help to mediate telosome assembly. Mechanisms of telomere regulation have been extensively studied in a variety of model organisms. For example, the physiological roles of telomere-targeted proteins have been assessed in mice through homozygous inactivation. In these cases, early embryonic lethality has prevented further studies of these proteins in embryogenesis and development. As a model system, zebrafish offers unique advantages such as genetic similarities with human, rapid developmental cycles, and ease of manipulation of its embryos. In this report, we detailed the identification of zebrafish homologues of TPP1, POT1, and TIN2, and showed that the domain structures and interactions of these telosome components appeared intact in zebrafish. Importantly, knocking down TPP1 led to multiple abnormalities in zebrafish embryogenesis, including neural death, heart malformation, and caudal defect. And these embryos displayed extensive apoptosis. These results underline the importance of TPP1 in zebrafish embryogenesis, and highlight the feasibility and advantages of investigating the signaling pathways and physiological function of telomere proteins in zebrafish.
- Published
- 2011
- Full Text
- View/download PDF
12. Correction: Zebrafish as a Model System to Study the Physiological Function of Telomeric Protein TPP1.
- Author
-
Yiying Xie, Dong Yang, Quanyuan He, and Zhou Songyang
- Subjects
Medicine ,Science - Published
- 2011
- Full Text
- View/download PDF
13. Matrix recruitment and calcium sequestration for spatial specific otoconia development.
- Author
-
Hua Yang, Xing Zhao, Yinfang Xu, Lili Wang, Quanyuan He, and Yunxia Wang Lundberg
- Subjects
Medicine ,Science - Abstract
Otoconia are bio-crystals anchored to the macular sensory epithelium of the utricle and saccule in the inner ear for motion sensing and bodily balance. Otoconia dislocation, degeneration and ectopic calcification can have detrimental effects on balance and vertigo/dizziness, yet the mechanism underlying otoconia formation is not fully understood. In this study, we show that selected matrix components are recruited to form the crystal matrix and sequester Ca(2+) for spatial specific formation of otoconia. Specifically, otoconin-90 (Oc90) binds otolin through both domains (TH and C1q) of otolin, but full-length otolin shows the strongest interaction. These proteins have much higher expression levels in the utricle and saccule than other inner ear epithelial tissues in mice. In vivo, the presence of Oc90 in wildtype (wt) mice leads to an enrichment of Ca(2+) in the luminal matrices of the utricle and saccule, whereas absence of Oc90 in the null mice leads to drastically reduced matrix-Ca(2+). In vitro, either Oc90 or otolin can increase the propensity of extracellular matrix to calcify in cell culture, and co-expression has a synergistic effect on calcification. Molecular modeling and sequence analysis predict structural features that may underlie the interaction and Ca(2+)-sequestering ability of these proteins. Together, the data provide a mechanism for the otoconial matrix assembly and the role of this matrix in accumulating micro-environmental Ca(2+) for efficient CaCO(3) crystallization, thus uncover a critical process governing spatial specific otoconia formation.
- Published
- 2011
- Full Text
- View/download PDF
14. Machine Learning Prediction Model of Tuberculosis Incidence Based on Meteorological Factors and Air Pollutants
- Author
-
Na Tang, Maoxiang Yuan, Zhijun Chen, Jian Ma, Rui Sun, Yide Yang, Quanyuan He, Xiaowei Guo, Shixiong Hu, and Junhua Zhou
- Subjects
machine learning ,tuberculosis ,Health, Toxicology and Mutagenesis ,Public Health, Environmental and Occupational Health ,random forest regression ,forecasting ,support vector regression ,neural networks - Abstract
Background: Tuberculosis (TB) is a public health problem worldwide, and the influence of meteorological and air pollutants on the incidence of tuberculosis have been attracting interest from researchers. It is of great importance to use machine learning to build a prediction model of tuberculosis incidence influenced by meteorological and air pollutants for timely and applicable measures of both prevention and control. Methods: The data of daily TB notifications, meteorological factors and air pollutants in Changde City, Hunan Province ranging from 2010 to 2021 were collected. Spearman rank correlation analysis was conducted to analyze the correlation between the daily TB notifications and the meteorological factors or air pollutants. Based on the correlation analysis results, machine learning methods, including support vector regression, random forest regression and a BP neural network model, were utilized to construct the incidence prediction model of tuberculosis. RMSE, MAE and MAPE were performed to evaluate the constructed model for selecting the best prediction model. Results: (1) From the year 2010 to 2021, the overall incidence of tuberculosis in Changde City showed a downward trend. (2) The daily TB notifications was positively correlated with average temperature (r = 0.231), maximum temperature (r = 0.194), minimum temperature (r = 0.165), sunshine duration (r = 0.329), PM2.5 (r = 0.097), PM10 (r = 0.215) and O3 (r = 0.084) (p < 0.05). However, there was a significant negative correlation between the daily TB notifications and mean air pressure (r = −0.119), precipitation (r = −0.063), relative humidity (r = −0.084), CO (r = −0.038) and SO2 (r = −0.034) (p < 0.05). (3) The random forest regression model had the best fitting effect, while the BP neural network model exhibited the best prediction. (4) The validation set of the BP neural network model, including average daily temperature, sunshine hours and PM10, showed the lowest root mean square error, mean absolute error and mean absolute percentage error, followed by support vector regression. Conclusions: The prediction trend of the BP neural network model, including average daily temperature, sunshine hours and PM10, successfully mimics the actual incidence, and the peak incidence highly coincides with the actual aggregation time, with a high accuracy and a minimum error. Taken together, these data suggest that the BP neural network model can predict the incidence trend of tuberculosis in Changde City.
- Published
- 2023
- Full Text
- View/download PDF
15. Nuclear Factor Related to KappaB Binding Protein (NFRKB) Is a Telomere-Associated Protein and Involved in Liver Cancer Development
- Author
-
Yucong Liu, Mingqing Zhou, Quanze He, Shanru Zuo, Quanyuan He, Qiyao Peng, Junhua Zhou, Xing Yu, Yide Yang, Xueguang Li, and Zuping He
- Subjects
Mechanism (biology) ,Binding protein ,Genetics ,medicine ,Cell Biology ,General Medicine ,Biology ,Homologous recombination ,Liver cancer ,medicine.disease ,Molecular Biology ,Cell biology ,Telomere - Abstract
Alternative lengthening of telomeres (ALT) is a homologous recombination-based telomere maintenance mechanism activated in 10–15% of human cancers. Although significant progress has been made, the ...
- Published
- 2021
16. [Association between regional fat mass and risk of nonalcoholic fatty liver disease in overweight/obese adults]
- Author
-
Yuan, Zeng, Shuqian, Yuan, Ming, Xie, Tianli, Xiao, Zehua, Huang, Junhua, Zhou, Quanyuan, He, Yide, Yang, and Jun, Ma
- Subjects
Adult ,Male ,Young Adult ,Cross-Sectional Studies ,Non-alcoholic Fatty Liver Disease ,Risk Factors ,Humans ,Female ,Obesity ,Middle Aged ,Overweight ,Waist Circumference ,Body Mass Index - Abstract
To explore the relationship between fat distribution and non-alcoholic fatty liver(NAFLD) in overweight/obese adults.This cross-sectional study included 736(190 men and 546 women) 19-56 years old overweight/obese people in Beijing were selected by convenient sampling. Their age and body mass index(BMI) distribution were 36(31-46) years old and 28.0(26.2-30.7), respectively. The body fat mass and regional fat mass were measured by dual energy X-ray absorptiometry(DXA), and Logistic regression model was used to analyze the association between regional fat mass and the risk of NAFLD.The prevalence of NAFLD was 70.0%(515/736) in overweight/obese population. In the multivariate Logistic model, after adjusting for age, gender, BMI, hypertension and body fat mass, waist circumference(WC), thigh fat mass and android fat mass were significantly association with NAFLD risk(Plt;0.05), but no association was found between arms, trunk and gynoid fat mass and NAFLD risk. There were interactions between thigh fat mass and age(P_(interaction)lt;0.001) and BMI group(P_(interaction)=0.001). Subgroup analysis showed that thigh fat mass and NAFLD risk were significantly associated in ≤36-year-old(OR=0.62, 95%CI 0.48-0.81), male(OR=0.32, 95%CI 0.16-0.64) and overweight(OR=0.48, 95%CI 0.36-0.64) groups, but in thegt;36-year-old, female and the obesity group this association was not statistically significant. There was an interaction between trunk fat mass and age group(P_(interaction)=0.009). There was a positive correlation between trunk fat mass and NAFLD risk ingt;36-year-old group(OR=1.63, 95%CI 1.35-1.97), but no association was found in ≤36-year-old group. In addition, we also found that a significant interaction between gynoid fat mass and BMI group on NAFLD(P_(interaction)lt;0.001). In overweight, gynoid fat mass was negatively correlated with the risk of NAFLD(OR=0.12, 95% CI 0.06-0.25), but in the obesity group, the association was not statistically significant. There were no statistically significant interactions between WC, arms fat mass and android mass and age, sex and BMI groups.WC, android fat mass and thigh fat mass are associated with the risk of NAFLD. Thigh fat mass has a significant interaction with age and BMI group on the risk of NAFLD(only in ≤36-year-old group, male and overweight group a significant protective effect of thigh fat on NAFLD was found, but not ingt;36-year-old group, female and obesity group). Trunk fat mass had an interaction with age(the association between trunk fat mass and NAFLD was significant ingt;36-year-old group). Gynoid fat mass and BMI group also have a significant interaction on NAFLD(the detrimental effect of gynoid fat on NAFLD is much more profound in the obesity group).
- Published
- 2022
17. Extrachromosomal Circular DNA (eccDNA): From Chaos to Function
- Author
-
Shanru Zuo, Yihu Yi, Chen Wang, Xueguang Li, Mingqing Zhou, Qiyao Peng, Junhua Zhou, Yide Yang, and Quanyuan He
- Subjects
Cell and Developmental Biology ,QH301-705.5 ,cancer ,biomarker ,Cell Biology ,Review ,eccDNA ,Biology (General) ,biogenesis ,Developmental Biology ,circulome - Abstract
Extrachromosomal circular DNA (eccDNA) is a type of double-stranded circular DNA that is derived and free from chromosomes. It has a strong heterogeneity in sequence, length, and origin and has been identified in both normal and cancer cells. Although many studies suggested its potential roles in various physiological and pathological procedures including aging, telomere and rDNA maintenance, drug resistance, and tumorigenesis, the functional relevance of eccDNA remains to be elucidated. Recently, due to technological advancements, accumulated evidence highlighted that eccDNA plays an important role in cancers by regulating the expression of oncogenes, chromosome accessibility, genome replication, immune response, and cellular communications. Here, we review the features, biogenesis, physiological functions, potential functions in cancer, and research methods of eccDNAs with a focus on some open problems in the field and provide a perspective on how eccDNAs evolve specific functions out of the chaos in cells.
- Published
- 2021
18. Nuclear Factor Related to KappaB Binding Protein (
- Author
-
Qiyao, Peng, Mingqing, Zhou, Shanru, Zuo, Yucong, Liu, Xueguang, Li, Yide, Yang, Quanze, He, Xing, Yu, Junhua, Zhou, Zuping, He, and Quanyuan, He
- Subjects
Carcinoma, Hepatocellular ,Carcinogenesis ,Liver Neoplasms ,Hep G2 Cells ,Telomere ,DNA-Binding Proteins ,HEK293 Cells ,Biomarkers, Tumor ,Hepatocytes ,MCF-7 Cells ,Humans ,K562 Cells ,HeLa Cells ,Protein Binding - Abstract
Alternative lengthening of telomeres (ALT) is a homologous recombination-based telomere maintenance mechanism activated in 10-15% of human cancers. Although significant progress has been made, the key regulators of the ALT pathway and its role in cancer development remain elusive. Bioinformatics methods were used to predict novel telomere-associated proteins (TAPs) by analysis of large-scale ChIP-Seq data. Immunostaining and fluorescence
- Published
- 2021
19. Bend family proteins mark chromatin boundaries and synergistically promote early germ cell differentiation
- Author
-
Jingran Zhang, Pengguihang Zeng, Junfeng Su, Zhou Songyang, Junjie Pang, Xiya Zhang, Yuanyan Xiong, Junjun Ding, Guang Shi, Dan Liu, Quanyuan He, Jingwen Wang, Junjiu Huang, Wenbin Ma, and Yaofu Bai
- Subjects
Homeobox protein NANOG ,Cell Differentiation ,Cell Biology ,Biology ,Biochemistry ,Embryonic stem cell ,Chromatin ,Cell biology ,Bimolecular fluorescence complementation ,Mice ,medicine.anatomical_structure ,Germ Cells ,SOX2 ,KLF4 ,Drug Discovery ,medicine ,Animals ,Developmental biology ,Germ cell ,Embryonic Stem Cells ,Germ Layers ,Biotechnology - Abstract
Understanding the regulatory networks for germ cell fate specification is necessary to developing strategies for improving the efficiency of germ cell production in vitro. In this study, we developed a coupled screening strategy that took advantage of an arrayed bi-molecular fluorescence complementation (BiFC) platform for protein-protein interaction screens and epiblast-like cell (EpiLC)-induction assays using reporter mouse embryonic stem cells (mESCs). Investigation of candidate interaction partners of core human pluripotent factors OCT4, NANOG, KLF4 and SOX2 in EpiLC differentiation assays identified novel primordial germ cell (PGC)-inducing factors including BEN-domain (BEND/Bend) family members. Through RNA-seq, ChIP-seq, and ATAC-seq analyses, we showed that Bend5 worked together with Bend4 and helped mark chromatin boundaries to promote EpiLC induction in vitro. Our findings suggest that BEND/Bend proteins represent a new family of transcriptional modulators and chromatin boundary factors that participate in gene expression regulation during early germline development.
- Published
- 2021
20. The roles and mechanisms of Leydig cells and myoid cells in regulating spermatogenesis
- Author
-
Yiqun Jiang, Rui Zhou, Wei Chen, Quanyuan He, Bang Liu, Jingrouzi Wu, Zuping He, and Jian Li
- Subjects
Male ,endocrine system ,Cell type ,Somatic cell ,Biology ,Male infertility ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Stroma ,medicine ,Humans ,Spermatogenesis ,Molecular Biology ,Transcription factor ,Infertility, Male ,Testosterone ,Pharmacology ,0303 health sciences ,Sertoli Cells ,urogenital system ,030302 biochemistry & molecular biology ,Leydig Cells ,Cell Biology ,Seminiferous Tubules ,Sertoli cell ,medicine.disease ,Cell biology ,medicine.anatomical_structure ,Molecular Medicine - Abstract
Spermatogenesis is fundamental to the establishment and maintenance of male reproduction, whereas its abnormality results in male infertility. Somatic cells, including Leydig cells, myoid cells, and Sertoli cells, constitute the microenvironment or the niche of testis, which is essential for regulating normal spermatogenesis. Leydig cells are an important component of the testicular stroma, while peritubular myoid cells are one of the major cell types of seminiferous tubules. Here we addressed the roles and mechanisms of Leydig cells and myoid cells in the regulation of spermatogenesis. Specifically, we summarized the biological features of Leydig cells and peritubular myoid cells, and we introduced the process of testosterone production and its major regulation. We also discussed other hormones, cytokines, growth factors, transcription factors and receptors associated with Leydig cells and myoid cells in mediating spermatogenesis. Furthermore, we highlighted the issues that are worthy of further studies in the regulation of spermatogenesis by Leydig cells and peritubular myoid cells. This review would provide novel insights into molecular mechanisms of the somatic cells in controlling spermatogenesis, and it could offer new targets for developing therapeutic approaches of male infertility.
- Published
- 2019
21. Integrated genomic analysis reveals regulatory pathways and dynamic landscapes of the tRNA transcriptome
- Author
-
Mingqing Zhou, Qiyao Peng, Quanyuan He, Shanru Zuo, Quanze He, Ming Xie, Zefang Sun, Zuping He, Feilong Wu, Junhua Zhou, Yide Yang, Xianghua Liu, Xing Yu, Yangyang Dong, Xueguang Li, Minqiong Zhao, and Jia Tan
- Subjects
0301 basic medicine ,Transcription, Genetic ,RNA library ,Science ,Computational biology ,Article ,Gene regulatory networks ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,RNA, Transfer ,Cancer genomics ,Cyclic AMP ,Protein biosynthesis ,Humans ,RNA-Seq ,Multidisciplinary ,biology ,Genome, Human ,RNA ,Genomics ,Human cell ,Gene regulation ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Histone ,Acetylation ,Protein Biosynthesis ,Transfer RNA ,biology.protein ,Medicine ,Algorithms ,030217 neurology & neurosurgery - Abstract
tRNAs and tRNA-derived RNA fragments (tRFs) play various roles in many cellular processes outside of protein synthesis. However, comprehensive investigations of tRNA/tRF regulation are rare. In this study, we used new algorithms to extensively analyze the publicly available data from 1332 ChIP-Seq and 42 small-RNA-Seq experiments in human cell lines and tissues to investigate the transcriptional and posttranscriptional regulatory mechanisms of tRNAs. We found that histone acetylation, cAMP, and pluripotency pathways play important roles in the regulation of the tRNA gene transcription in a cell-specific manner. Analysis of RNA-Seq data identified 950 high-confidence tRFs, and the results suggested that tRNA pools are dramatically distinct across the samples in terms of expression profiles and tRF composition. The mismatch analysis identified new potential modification sites and specific modification patterns in tRNA families. The results also show that RNA library preparation technologies have a considerable impact on tRNA profiling and need to be optimized in the future.
- Published
- 2021
22. ATP2B1 gene polymorphisms rs2681472 and rs17249754 are associated with susceptibility to hypertension and blood pressure levels: A systematic review and meta-analysis
- Author
-
Chanjuan Zheng, Quanyuan He, Yanhui Dong, Ming Xie, Shuqian Yuan, Yide Yang, and Yuan Zeng
- Subjects
Adult ,Male ,medicine.medical_specialty ,hypertension ,Population ,Blood Pressure ,ATP2B1 ,polymorphism ,03 medical and health sciences ,Plasma Membrane Calcium-Transporting ATPases ,0302 clinical medicine ,Asian People ,Polymorphism (computer science) ,Internal medicine ,Genetic model ,Odds Ratio ,Medicine ,Humans ,Genetic Predisposition to Disease ,030212 general & internal medicine ,Allele ,education ,gene ,education.field_of_study ,Polymorphism, Genetic ,business.industry ,General Medicine ,Publication bias ,Middle Aged ,meta-analysis ,Blood pressure ,Phenotype ,030220 oncology & carcinogenesis ,Meta-analysis ,Female ,Gene polymorphism ,business ,Systematic Review and Meta-Analysis ,Research Article - Abstract
Objective: The present study aimed to conduct a systematic review and meta-analysis to evaluate the relationships between ATP2B1 gene polymorphisms with blood pressure (BP) level and susceptibility to hypertension. Methods: PubMed, Web of Science, Embase and China National Knowledge Infrastructure (CNKI) Databases were systematically searched by 2 independent researchers to screen studies on ATP2B1 gene polymorphisms and BP related phenotypes. The records retrieval period was limited from the formation of the database to March 4, 2021. Pooled odds rations (ORs) or β and their 95% confidence intervals (95%CI) were calculated to assess the association between ATP2B1 gene polymorphisms and the risk of hypertension or BP levels. Publication bias and sensitivity analysis were conducted to find potential bias. All the statistical analysis were conducted with Stata version 11.0 software. Results: A total of 15 articles were ultimately included in the present study, including 15 polymorphisms of ATP2B1 gene. Nine articles (N = 65,362) reported the polymorphism rs17249754, and 7 articles(N = 91,997) reported rs2681472 (both loci were reported in 1 article). Meta-analysis showed that rs17249754 (G/A) and rs2681472 (A/G) were associated with the susceptibility to hypertension (rs17249754: OR = 1.19, 95%CI: 1.10–1.28; rs2681472: OR = 1.15, 95%CI: 1.12–1.17), and were positively associated with systolic BP (SBP) and diastolic blood pressure (DBP) (rs17249754: SBP, β=1.01, 95%CI: 0.86–1.16, DBP, β=0.48, 95%CI: 0.30–0.66; rs2681472: SBP, β=0.92, 95%CI: 0.77–1.07, DBP, β=0.50, 95%CI: 0.42–0.58) in the additive genetic model. Subgroup analysis stratified by race, population, sample size, and BP measurement method revealed that the association between A allele in rs2681472 polymorphism and risk of hypertension was slightly stronger in European (EUR) populations (OR = 1.16, 95%CI: 1.13–1.20) than in East Asians (OR = 1.14, 95%CI: 1.10–1.17). While in East Asians, relation between rs17249754 with risk of hypertension (OR = 1.19, 95%CI: 1.10–1.28) is stronger than rs2681472 (OR = 1.14, 95%CI: 1.10–1.17). Conclusions: Our study demonstrated that ATP2B1 gene polymorphism rs2681472 and rs17249754 were associated with BP levels and the susceptibility to hypertension.
- Published
- 2020
23. BCREval: a computational method to estimate the bisulfite conversion ratio in WGBS
- Author
-
Quanze He, Junhua Zhou, Xianghua Liu, Minqiong Zhao, Quanyuan He, Zuping He, Feilong Wu, Yucong Liu, and Zefang Sun
- Subjects
Computer science ,Bisulfite sequencing ,Computational biology ,lcsh:Computer applications to medicine. Medical informatics ,Biochemistry ,Genome ,Cytosine ,03 medical and health sciences ,0302 clinical medicine ,Structural Biology ,Humans ,Sulfites ,lcsh:QH301-705.5 ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,DNA methylation ,Whole Genome Sequencing ,Methodology Article ,Applied Mathematics ,Computational Biology ,High-Throughput Nucleotide Sequencing ,DNA ,Methylation ,Bisulfite conversion ratio (BCR) ,Telomere ,Computer Science Applications ,lcsh:Biology (General) ,030220 oncology & carcinogenesis ,lcsh:R858-859.7 ,DNA microarray ,Whole genome bisulfite sequencing (WGBS) ,Whole genome bisulfite sequencing ,Algorithms - Abstract
Background Whole genome bisulfite sequencing (WGBS) also known as BS-seq has been widely used to measure the methylation of whole genome at single-base resolution. One of the key steps in the assay is converting unmethylated cytosines into thymines (BS conversion). Incomplete conversion of unmethylated cytosines can introduce false positive methylation call. Developing a quick method to evaluate bisulfite conversion ratio (BCR) is benefit for both quality control and data analysis of WGBS. Results Here we provide a computational method named “BCREval” to estimate the unconverted rate (UCR) by using telomeric repetitive DNA as native spike-in control. We tested the method by using public WGBS data and found that it is very stable and most of BS conversion assays can achieve> 99.5% efficiency. The non-CpG DNA methylation at telomere fits a binomial model and may result from a random process with very low possibility (the ratio Conclusion Our method is a simple but robust method to QC and speculates BCR for WGBS experiments to make sure it achieves acceptable level. It is faster and more efficient than current tools and can be easily integrated into presented WGBS pipelines.
- Published
- 2020
24. Additional file 1 of BCREval: a computational method to estimate the bisulfite conversion ratio in WGBS
- Author
-
Junhua Zhou, Minqiong Zhao, Zefang Sun, Feilong Wu, Yucong Liu, Xianghua Liu, Zuping He, Quanze He, and Quanyuan He
- Abstract
Additional file 1: Figure S1. The location of N7 telomeric (TTAGGG)7 repeats in hg38 genome. Table S1. Detailed analysis results.
- Published
- 2020
- Full Text
- View/download PDF
25. Prevalence and risk factors for hyperhomocysteinemia: a population-based cross-sectional study from Hunan, China
- Author
-
Yide Yang, Yuan Zeng, Shuqian Yuan, Ming Xie, Yanhui Dong, Jian Li, Quanyuan He, Xiangli Ye, Yuan Lv, Carl-Friedrich Hocher, Bernhard K Kraemer, Xiuqin Hong, and Berthold Hocher
- Subjects
Male ,congenital, hereditary, and neonatal diseases and abnormalities ,China ,Epidemiology ,Hyperhomocysteinemia ,nutritional and metabolic diseases ,General Medicine ,Middle Aged ,risk management ,Cross-Sectional Studies ,Risk Factors ,adult cardiology ,Prevalence ,Humans ,Female ,Homocysteine - Abstract
ObjectivesHyperhomocysteinemia is an independent risk factor for cardiovascular diseases. We aimed to investigate the prevalence and risk factors for hyperhomocysteinemia, especially modifiable lifestyle factors, such as smoking behaviour and dietary factors.DesignPopulation-based cross-sectional study.SettingHunan Province, ChinaParticipantsA total of 4012 participants completed the study, between July 2013 and March 2014. The median age is 55 (interquartile range: 45–63) years, with 1644 males (41%) and 2368 females (59%).Main outcome measuresHomocysteine level were measured by the microplate enzyme immunoassay method. Hyperthomocysteinemia was defined as ≥15 µmol/L. Questionnaire was used to investigate potential risk factors of hyperhomocysteinemia. Crude odd ratio (OR) or adjusted OR with 95% CI were determined by using univariable or multivariable logistic regression models.ResultsThe prevalence of hyperhomocysteinemia is 35.4% (45.4% vs 28.5% for men, women, respectively). One-year increase in age is significantly associated with 2% higher risk of hyperhomocysteinemia (OR=1.02, 95% CI: 1.01 to 1.03). One unit increase of BMI is associated with 5% higher risk of hyperhomocysteinemia (OR=1.05, 95% CI: 1.03 to 1.07). Compared with the non-smoker, smoking participants have a 24% higher risk of hyperhomocysteinemia (OR=1.24, 95% CI: 1.006 to 1.53), while the risk for those quitting smoking are not significantly different (OR=1.14, 95% CI: 0.85 to 1.54). compared with those consuming fruit and vegetable at least once every day, those consuming less than once every day had a significantly higher risk of hyperhomocysteinemia (OR=1.29, 95% CI:1.11 to 1.50). In addition, we found there were significant sex interaction with education level or alcohol drinking on the risk of hyperhomocysteinemia (pinteractionConclusionsHigher BMI and older age are potential risk factors for hyperhomocysteinemia. Current smoking but not quitting smoking is associated with higher risk of hyperhomocysteinemia. Fruit and vegetable consumption may have protective effect against hyperhomocysteinemia. Alcohol consumption or education level might interact to influence the risk of hyperhomocysteinemia.
- Published
- 2021
26. Prevalence of Hyperhomocysteinemia in China: An Updated Meta-Analysis
- Author
-
Shuqian Yuan, Yide Yang, Haokai Tang, Junhua Zhou, Yuan Zeng, Feifei Li, Julien S. Baker, Quanyuan He, and Yanhui Dong
- Subjects
China ,Hyperhomocysteinemia ,medicine.medical_specialty ,education.field_of_study ,General Immunology and Microbiology ,QH301-705.5 ,Public health ,prevalence ,Population ,updated meta-analysis ,Subgroup analysis ,Biology ,medicine.disease ,Random effects model ,General Biochemistry, Genetics and Molecular Biology ,Confidence interval ,Meta-analysis ,medicine ,Systematic Review ,Biology (General) ,hyperhomocysteinemia ,General Agricultural and Biological Sciences ,education ,Demography - Abstract
Simple Summary Hyperhomocysteinemia has been defined as an elevated serum concentration of homocysteine exceeding 15 μmol/L and has been proven to play an important role in the pathogenesis of cerebrovascular disease. The prevalence of hyperhomocysteinemia in China has been outlined in a previous meta-analysis. Considering the key role of homocysteine in the process of vascular injury, more studies have been conducted to prevent hyperhomocysteinemia by nutritional supplements such as folic acid or other treatments. Additionally, studies have shown that the prevalence of hyperhomocysteinemia increases over time; therefore, it was necessary to provide an update from the previous meta-analysis on homocysteine status in China. This was needed to understand the prevalence, the trend in changes over time, and its determinants. The results highlight that the prevalence of hyperhomocysteinemia is increasing in China, especially among the elderly, men, and residents in the north, inland areas, and rural areas of China. Abstract We conducted a meta-analysis to systematically assess the prevalence of hyperhomocysteinemia (HHcy) in China, its change over time, and its determinants. Literature searches were conducted using English databases (PubMed, Embase, and Web of Science) and Chinese databases (CNKI, CBM, VIP, and Wanfang). The time ranges were from Jan 2014 to Mar 2021 in China. We adopted the random effects model to estimate the pooled positive rates of HHcy and corresponding 95% confidence intervals (95% CI). To find the sources of heterogeneity, we performed subgroup analysis and meta-regression. A total of 29 related articles were identified involving 338,660 participants with 128,147 HHcy cases. The estimated prevalence of HHcy in China was 37.2% (95% CI: 32.6–41.8%, I2 = 99.8%, p for heterogeneity < 0.001). The trend of HHcy prevalence was gradually upward over time, with increases during 2015–2016 (comparison to 2013–2014, p < 0.001), but steady between 2015–2016 and 2017–2018. Subgroup analysis showed that the prevalence was higher in the elderly over 55 years old, males, and residents in the north, inland, and rural China (for each comparison, p < 0.001). Meta-regression analysis revealed that age and area of study contributed to 42.3% of the heterogeneity between studies. The current meta-analysis provides strong evidence that the prevalence of HHcy is increasing in China, and varies substantially across different ages, genders, and geographic distribution. Accordingly, high-risk population groups should be focused on, and public health policies and strategies should be carried out to prevent and control HHcy in China.
- Published
- 2021
27. Design and application of time series algorithm model in information assisted sensing system of nursing measurement in neurology
- Author
-
Quanyuan He, Miaoxia Wang, Mingyuan Yin, and Meirong Liu
- Subjects
Index (economics) ,Series (mathematics) ,Computer science ,Applied Mathematics ,Exponential smoothing ,Condensed Matter Physics ,Nursing ,Software deployment ,Information system ,Limit (mathematics) ,Electrical and Electronic Engineering ,Time series ,Instrumentation ,Algorithm ,Smoothing - Abstract
Objective This paper studies the measurement indicators of nursing workload in neurology department, discusses the development and development law of nursing workload, provides scientific basis for nursing staff deployment, and guarantees high-quality and safe nursing services. Methods By using time series algorithm model, the paper calculates the nursing workload of neurology department and establishes the measurement index of nursing workload of neurology department. Improve the nursing workload information system, automatically generate and extract daily nursing workload, and construct a time series model of daily nursing workload. Results Through literature search and on-site observation, preliminary measurement of nursing workload measurement indicators, consultation with expert meetings to develop an expert consultation form for nursing workload measurement indicators, and application of SPSS 19.0 for time series analysis to construct a time series model for daily nursing workload. Results The best fit models of the time series of the two wards in neurology department were both exponential smoothing models. The predictive value of the ward A smoothing model for the total nursing workload from January 1 to 3, 2014 was 317.39. 316.14, 295.94 points (upper limit: 366.39, 375.95, 364.88 points; lower limit: 268.40, 256.33, 227.00 points). The prediction value of the B Ward Index Smoothing Model for the total nursing workload from January 1 to 3, 2014 is 450.03, 449.38, 445.58 points (upper limit: 503.76, 512.04, 515.05 points; lower limit: 396.30, 386.71, 375.11 points). Conclusion Time series analysis can predict the nursing workload on the one hand, and adjust the number of nurses on the day of work according to the short-term predicted value of the nursing workload on the time series model; on the other hand, it can evaluate the rationality of the existing manpower allocation strategy.
- Published
- 2020
28. Systematic analysis of human telomeric dysfunction using inducible telosome/shelterin CRISPR/Cas9 knockout cells
- Author
-
Dan Liu, Jun Xu, Feng Li, Quanyuan He, Nagireddy Putluri, Feng Jin, Tingting Deng, Hyeung Kim, Zhou Songyang, and Cristian Coarfa
- Subjects
0301 basic medicine ,Genetics ,Gene knockdown ,telomere ,Cas9 ,Cell Biology ,Biology ,Shelterin ,Biochemistry ,Article ,Telomere ,telosome/shelterin ,03 medical and health sciences ,030104 developmental biology ,inducible knockout ,Conditional gene knockout ,POT1 isoform ,CRISPR ,Human genome ,Molecular Biology ,Gene ,CRISPR/Cas9 ,metabolism - Abstract
CRISPR/Cas9 technology enables efficient loss-of-function analysis of human genes using somatic cells. Studies of essential genes, however, require conditional knockout (KO) cells. Here, we describe the generation of inducible CRISPR KO human cell lines for the subunits of the telosome/shelterin complex, TRF1, TRF2, RAP1, TIN2, TPP1 and POT1, which directly interact with telomeres or can bind to telomeres through association with other subunits. Homozygous inactivation of several subunits is lethal in mice, and most loss-of-function studies of human telomere regulators have relied on RNA interference-mediated gene knockdown, which suffers its own limitations. Our inducible CRISPR approach has allowed us to more expediently obtain large numbers of KO cells in which essential telomere regulators have been inactivated for biochemical and molecular studies. Our systematic analysis revealed functional differences between human and mouse telomeric proteins in DNA damage responses, telomere length and metabolic control, providing new insights into how human telomeres are maintained.
- Published
- 2017
29. SGK3 is associated with estrogen receptor expression in breast cancer
- Author
-
Lei Huo, Jun Xu, Xiaoyong Fu, Rachel Schiff, Roland L. Bassett, Chad J. Creighton, Ma Wan, Quanyuan He, Feng-Tao Shi, Albert C. Chen, and Dan Liu
- Subjects
Adult ,Cancer Research ,Gene Expression ,Estrogen receptor ,Breast Neoplasms ,Disease ,Protein Serine-Threonine Kinases ,Biology ,Article ,Disease-Free Survival ,Breast cancer ,Cell Line, Tumor ,Immunochemistry ,medicine ,Humans ,Protein kinase B ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,Kinase ,Carcinoma, Ductal, Breast ,Middle Aged ,Prognosis ,medicine.disease ,Primary tumor ,Logistic Models ,Receptors, Estrogen ,Oncology ,Multivariate Analysis ,Cancer research ,Immunohistochemistry ,Female - Abstract
While breast cancer mortality rate has seen a steady decline in the last few decades, advances in better treatment and diagnostic tools remain important as we come into the age of personalized therapy. In this report, we describe our studies of SGK3's role in breast cancer. SGK3 (also known as CISK) is a member of the AGC family of kinases. Our previous work indicates that SGK3 functions downstream of the PI 3-kinase cascade and shares molecular and biochemical similarities with Akt. Here, we show that SGK3 expression is linked to estrogen receptor (ER) both in breast caner cell lines and in primary tumor samples. Our analysis also indicated a positive correlation between SGK3 expression and tumor prognosis. Importantly, our immunochemistry analysis of human tumor samples established a clinical link between SGK3 expression and ER+ tumors. These findings implicate SGK3 as an additional component to a complex and heterogeneous disease, and point to the potential benefits of incorporating SGK3 into the process of breast cancer diagnosis and treatment.
- Published
- 2012
30. TIN2 Protein Dyskeratosis Congenita Missense Mutants Are Defective in Association with Telomerase
- Author
-
Dong Yang, Quanyuan He, Zhou Songyang, Hyeung Kim, and Wenbin Ma
- Subjects
Telomere-binding protein ,Telomerase ,Mutation ,Telomere-Binding Proteins ,Mutation, Missense ,Cell Biology ,Telomere ,Biology ,medicine.disease ,medicine.disease_cause ,Biochemistry ,Molecular biology ,Dyskeratosis Congenita ,Shelterin Complex ,Cell Line ,Telomerase RNA component ,Cancer research ,medicine ,Humans ,Telomerase reverse transcriptase ,Ectopic expression ,Molecular Biology ,Dyskeratosis congenita - Abstract
Dyskeratosis congenita (DC) is a progressive and heterogeneous congenital disorder that affects multiple systems and is characterized by bone marrow failure and a triad of abnormal skin pigmentation, nail dystrophy, and oral leukoplakia. One common feature for all DC patients is abnormally short telomeres and defects in telomere biology. Most of the known DC mutations have been found to affect core components of the telomerase holoenzyme. Recently, multiple mutations in the gene encoding the telomeric protein TIN2 have been identified in DC patients with intact telomerase genes, but the molecular mechanisms underlying TIN2 mutation-mediated DC remain unknown. Here, we demonstrate that ectopic expression of TIN2 with DC missense mutations in human cells led to accelerated telomere shortening, similar to the telomere phenotypes found in DC patients. However, this telomere shortening was not accompanied by changes in total telomerase activity, localization of TIN2, or telomere end protection status. Interestingly, we found TIN2 to participate in the TPP1-dependent recruitment of telomerase activity. Furthermore, DC mutations in TIN2 led to its decreased ability to associate with TERC and telomerase activity. Taken together, our data suggest that TIN2 mutations in DC may compromise the telomere recruitment of telomerase, leading to telomere shortening and the associated pathogenesis.
- Published
- 2011
31. Human telomeric proteins occupy selective interstitial sites
- Author
-
Yumei Li, Zhou Songyang, Hyeung Kim, Quanyuan He, Dong Yang, Yuanyan Xiong, and Rui Chen
- Subjects
Transcriptional Activation ,Telomere-binding protein ,Chromatin Immunoprecipitation ,Binding Sites ,Base Sequence ,Genome, Human ,Telomere-Binding Proteins ,Cell Biology ,Plasma protein binding ,Telomere ,Biology ,Molecular biology ,Shelterin Complex ,Cell Line ,ChIP-sequencing ,Transcription (biology) ,Humans ,Original Article ,Telomeric Repeat Binding Protein 2 ,Rap1 ,Molecular Biology ,Gene ,Chromatin immunoprecipitation ,Protein Binding - Abstract
Human telomeres are bound and protected by protein complexes assembled around the six core telomeric proteins RAP1, TRF1, TRF2, TIN2, TPP1, and POT1. The function of these proteins on telomeres has been studied extensively. Recently, increasing evidence has suggested possible roles for these proteins outside of telomeres. However, the non-canonical (extra-telomeric) function of human telomeric proteins remains poorly understood. To this end, we systematically investigated the binding sites of telomeric proteins along human chromosomes, by performing whole-genome chromatin immunoprecipitation (ChIP) for RAP1 and TRF2. ChIP sequencing (ChIP-seq) revealed that RAP1 and TRF2 could be found on a small number of interstitial sites, including regions that are proximal to genes. Some of these binding sites contain short telomere repeats, suggesting that telomeric proteins could directly bind to interstitial sites. Interestingly, only a small fraction of the available interstitial telomere repeat-containing regions were occupied by RAP1 and TRF2. Ectopically expressed TRF2 was able to occupy additional interstitial telomere repeat sites, suggesting that protein concentration may dictate the selective targeting of telomeric proteins to interstitial sites. Reducing RAP1 and TRF2 expression by RNA interference led to altered transcription of RAP1- and TRF2-targeted genes. Our results indicate that human telomeric proteins could occupy a limited number of interstitial sites and regulate gene transcription.
- Published
- 2011
32. Systematic analysis of gene expression level with tissue-specificity, function and protein subcellular localization in human transcriptome
- Author
-
Long Yu, Qiang Li, Yichen Ling, Lei Hu, Yanhua Wu, Quanyuan He, Xianmei Yang, and Xianghua Liu
- Subjects
Organelles ,TBX1 ,Cytoplasm ,Gene Expression Profiling ,Cell Membrane ,Pair-rule gene ,Gene Expression ,Proteins ,General Medicine ,Biology ,Subcellular localization ,Protein subcellular localization prediction ,Extracellular Matrix ,Cell biology ,Evolution, Molecular ,Gene expression profiling ,Genes ,Membrane protein ,Organ Specificity ,HSPA2 ,Gene expression ,Genetics ,Humans ,Molecular Biology - Abstract
Recent studies have shown that, in mammals, the highly expressed genes have shorter gene length and their protein products have relatively lower evolutionary rates. However, the global relationship between genes' expression level and their features such as tissue-specificity, function and protein subcellular localization has not been investigated extensively, especially in mammalian. In order to solve it, we analysed 8,570 genes across 46 human tissues. Our results suggest that widely expressed genes have higher mean expression levels than tissue-specific ones and genes encoding zinc-finger proteins have low expression levels similar to that of DNA-binding proteins. In the analysis of protein subcellular localization, it is shown that nuclear and Golgi apparatus proteins have lower mean expression levels than those of mitochondria, endoplasmic reticulum and membrane proteins, while genes encoding cytoplasm and extracellular components display the highest expression levels. When comparing the gene expression levels and the number of expressed genes in different tissues, we found that some tissues have less active genes while single gene encodes relatively more transcripts. Taken together, gene expression levels are clearly correlated with their tissue-specificity, function and protein subcellular localization, and are highly conserved during evolution.
- Published
- 2010
33. ATDB 2.0: A database integrated toxin-ion channel interaction data
- Author
-
Quanze He, Wenjun Han, Songping Liang, Ping Chen, Quanyuan He, Jingjing Zhang, Yong Lin, and Linju Huo
- Subjects
Databases, Factual ,Database ,Computer science ,Sequence analysis ,Toxin ,Computational Biology ,Resource (Windows) ,Toxicology ,computer.software_genre ,medicine.disease_cause ,Ion Channels ,Sequence pattern ,Protein Structure, Tertiary ,User-Computer Interface ,Sequence Analysis, Protein ,Interaction network ,medicine ,Animal toxin ,computer ,Ion channel ,Toxins, Biological - Abstract
We have developed an updated version of the Animal Toxin Database (ATDB 2.0) that provides a new bioinformatics resource for analyzing toxin-channel (T-C) interactions. Data on more than 54,000 T-C interactions, including 9193 high-confidence interactions, has been extracted, formatted and mapped to toxin and ion channel databases. The interaction data can be accessed easily through a new network browser on the website at http://protchem.hunnu.edu.cn/toxin. This resource may be useful for sequence pattern recognition and prediction of the function of new toxins.
- Published
- 2010
34. Proteomic Screen for Multiprotein Complexes in Synaptic Plasma Membrane from Rat Hippocampus by Blue Native Gel Electrophoresis and Tandem Mass Spectrometry
- Author
-
Songping Liang, Xuanwen Li, Jianglin Li, Yan Li, Ping Chen, Rui Cao, Quanyuan He, Yong Lin, Chunliang Xie, Mingjun Liu, and Qihui Jin
- Subjects
Male ,Proteomics ,Synapsin I ,ATPase ,Immunoblotting ,Neurotransmission ,Tandem mass spectrometry ,Hippocampus ,Models, Biological ,Biochemistry ,Mass Spectrometry ,Animals ,Syntaxin ,Integral membrane protein ,Neurons ,biology ,Cell Membrane ,Computational Biology ,General Chemistry ,Hydrogen-Ion Concentration ,Molecular biology ,Rats ,Cell biology ,Membrane ,Microscopy, Fluorescence ,biology.protein ,Electrophoresis, Polyacrylamide Gel ,Subcellular Fractions - Abstract
Neuronal synapses are specialized sites for information exchange between neurons. Many diseases, such as addiction and mood disorders, likely result from altered expression of synaptic proteins, or altered formation of synaptic complexes involved in neurotransmission or neuroplasticity. A detailed description of native multiprotein complexes in synaptic plasma membranes (PM) is therefore essential for understanding biological mechanisms and disease processes. For the first time in this study, two-dimensional Blue Native/SDS-PAGE electrophoresis, combined with tandem mass spectrometry, was used to screen multiprotein complexes in synaptic plasma membranes from rat hippocampus. As a result, 514 unique proteins were identified, of which 36% were integral membrane proteins. In addition, 19 potentially novel and known heterooligomeric multiprotein complexes were found, such as the SNARE and ATPase complexes. A potentially novel protein complex, involving syntaxin, synapsin I and Na+/K+ ATPase alpha-1, was further confirmed by co-immunoprecipitation and immunofluorescence staining. As demonstrated here, Blue Native-PAGE is a powerful tool for the separation of hydrophobic membrane proteins. The combination of Blue Native-PAGE and mass spectrometry could systematically identify multiprotein complexes.
- Published
- 2009
35. An in Vivo Membrane Density Perturbation Strategy for Identification of Liver Sinusoidal Surface Proteome Accessible from the Vasculature
- Author
-
Quanyuan He, Chunliang Xie, Songping Liang, Qihui Jin, Rui Cao, Jia Cao, Ping Chen, Yong Lin, Xianchun Wang, and Xuanwen Li
- Subjects
Proteomics ,Proteome ,Biology ,Tandem mass spectrometry ,Biochemistry ,Mass Spectrometry ,Cell membrane ,In vivo ,medicine ,Animals ,Cell Membrane ,Computational Biology ,Endothelial Cells ,Membrane Proteins ,General Chemistry ,Protein composition ,Cellular Structures ,Rats ,Cell biology ,Membrane ,medicine.anatomical_structure ,Liver ,Membrane protein ,Blood Vessels ,Electrophoresis, Polyacrylamide Gel ,Chromatography, Liquid - Abstract
Liver sinusoidal endothelial cells (LSEC), the predominant nonparenchyma cells in liver, play critical roles in many important physiological and pathological processes by virtue of their unique location at the blood-tissue interface. To uncover the protein composition of LSEC plasma membrane (PM) comprehensively and give implications for the tissue microenvironment heterogeneity, we have developed an in vivo modified membrane density perturbation method for purification of the PM fraction. The proteins were separated and identified by SDS-PAGE combined with LC-MS/MS (GeLC-MS/MS). A total of 837 nonredundant proteins were identified, including a number of proteins previously reported to be localized to the PM of LSEC, as well as others not described. A diversity of membrane proteins involved in signaling, traffic, transporting and adhesion functions were identified. Our results demonstrated that the in vivo membrane density perturbation was an effective strategy to purify LSEC PM.
- Published
- 2008
36. Molecular diversity and evolution of cystine knot toxins of the tarantula Chilobrachys jingzhao
- Author
-
Liping Jiang, Jinjun Chen, Quanyuan He, Z. Liao, Meichun Deng, Mingqiang Rong, E. Meng, and Songping Liang
- Subjects
Models, Molecular ,Spider Venoms ,Molecular Sequence Data ,Gating ,Bioinformatics ,Chilobrachys jingzhao ,Evolution, Molecular ,Cellular and Molecular Neuroscience ,Phylogenetics ,Ganglia, Spinal ,Animals ,Amino Acid Sequence ,Molecular Biology ,Ion channel ,Neurons ,Pharmacology ,Tarantula ,Genetics ,Expressed sequence tag ,biology ,Cystine knot ,Genetic Variation ,Spiders ,Cell Biology ,biology.organism_classification ,Rats ,Amino Acid Substitution ,Structural Homology, Protein ,Molecular Medicine ,Cystine Knot Motifs ,Sequence Alignment - Abstract
Cystine knot toxins (CKTs) in spider venoms represent a rich source of novel ligands for varied ion channels. Here, we identified 95 novel putative CKT precursors by analyzing expressed sequence tags of the tarantula Chilobrachys jingzhao venom gland. Phylogenetics analyses revealed one orphan family and six families with sequence similarity to known toxins. To further investigate the relationships of their structures, functions and evolution, we assayed 10 representative toxins for their effect on ion channels, and performed structure model comparisons, evolution analysis and toxin distribution analysis. This study revealed two major types of CKTs: pore-blocking toxins and gating modifier toxins. A few blockers were observed with relatively high abundance and wide distribution, which may be a category of original toxins that block channels conserved in various preys with relatively high specificity. The gating modifier families contain advanced toxins, usually have many members and interact with diverse regulatory components of channels.
- Published
- 2008
37. Development and Application of a Two-Phase, On-Membrane Digestion Method in the Analysis of Membrane Proteome
- Author
-
Songping Liang, Jianying Shen, Yong Lin, Ping Chen, Xing-Can Deng, Quanyuan He, Jian Zhou, and Xianchun Wang
- Subjects
Proteomics ,Biochemistry ,Rats, Sprague-Dawley ,1-Butanol ,Tandem Mass Spectrometry ,Animals ,Trypsin ,Integral membrane protein ,Chemistry ,Hydrolysis ,Methanol ,Extraction (chemistry) ,Membrane Proteins ,Reproducibility of Results ,General Chemistry ,Transmembrane protein ,Rats ,Bicarbonates ,Transmembrane domain ,Membrane ,Liver ,Membrane protein ,Proteome ,Digestion ,Chromatography, Liquid - Abstract
Analysis of membrane proteins, particularly integral membrane proteins, still presents a great challenge due to their poor water solubility and low abundance though much effort has been devoted to the solubilization and enrichment of the protein class. In this paper, a two-phase, on-membrane digestion method was developed and applied in the analysis of rat liver membrane proteome. The two-phase system was constituted by mixing n-butanol and 25 mM NH4HCO3. Comparative experiments indicated that the proteins on membranes could be digested in the two-phase system more efficiently than in both 60% methanol and 25 mM NH4HCO3 solutions under the same conditions, thereby improving the identification of the membrane proteins. When the established two-phase system and CapLC-MS/MS was used to analyze rat liver membrane proteome, a total of 411 membrane proteins were identified, more than 80% of which were transmembrane proteins with 1-12 mapped transmembrane domains (TMDs). Because of its extraction and dissolution actions, the two-phase on-membrane digestion system we developed could efficiently improve the digestion and removal of adsorbed nonmembrane proteins, and remarkably increase the number and coverage of identified membrane proteins, particularly the transmembrane proteins. Using our procedure to identify a complementary protein set from all fractions of the two-phase system could achieve a higher coverage of the membrane proteome.
- Published
- 2008
38. Dataset of the plasma membrane proteome of nasopharyngeal carcinoma cell line HNE1 for uncovering protein function
- Author
-
Zhen Liu, Songping Liang, Xiaofang Jia, Ni Shi, Peng-Fei Zhang, Tingting Sheng, Jixian Xiong, Quanyuan He, Xia Peng, Rui Cao, Lijun Zhang, and Xiaohui Liu
- Subjects
Proteome ,Molecular Sequence Data ,Biophysics ,Biology ,Tandem mass spectrometry ,Biochemistry ,Protein–protein interaction ,Western blot ,Cell Line, Tumor ,Biomarkers, Tumor ,medicine ,Humans ,Amino Acid Sequence ,Databases, Protein ,Integral membrane protein ,Gel electrophoresis ,medicine.diagnostic_test ,Cell Membrane ,Peripheral membrane protein ,Membrane Proteins ,Nasopharyngeal Neoplasms ,General Medicine ,Molecular biology ,Neoplasm Proteins ,Membrane protein - Abstract
Nasopharyngeal carcinoma (NPC) is a commonly occurring tumor in southern China and Southeast Asia. The current study focused on developing an extensive analysis method for the peripheral and integral proteins of NPC cell line HNE1. The peripheral membrane proteins were extracted by biotinylated enrichment, 0.1 M Na2CO3, and H2O. Integral or total plasma membrane fractions were prepared using 30% Percoll density grade centrifugation with or without 0.1 M Na2CO3 treatment and evaluated by Western blot analysis. The proteins were subjected to two-dimensional electrophoresis combined with tandem mass spectrometry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis combined with tandem mass spectrometry, and shotgun analysis. We identified 371, 180, and 702 proteins from peripheral, integral, and total plasma membrane fractions, respectively. In all, 848 non-redundant proteins (534 groups) were identified. Binding, catalytic, and structural molecules were the major classes. In addition to the known cell surface markers of NPC cells, the analysis revealed 311 proteins involved in multiple cell-signaling pathways and 25 proteins in disease pathways that are characteristic of cancer cells. By searching the Differentially Expressed Protein Database (http://protchem.hunnu.edu.cn/depd/index.jsp), 199 proteins were found to be differentially expressed in previous cancer proteome research. A 671 protein-protein interaction network was obtained, including 178 identified proteins in this work. The plasma membrane localization of five proteins was confirmed by immunological techniques, validating this proteomic strategy. Our study could offer some help for understanding the molecular mechanism of NPC.
- Published
- 2008
39. A proteomic study reveals the diversified distribution of plasma membrane-associated proteins in rat hepatocytes
- Author
-
Chunliang Xie, Rui Cao, Xuanwen Li, Jia Cao, Ping Chen, Quanyuan He, Qihui Jin, Jixian Xiong, Songping Liang, and Xianchun Wang
- Subjects
Proteomics ,Spectrometry, Mass, Electrospray Ionization ,Carbonates ,Biology ,Tandem mass spectrometry ,Biochemistry ,Mass Spectrometry ,Annexin ,Radixin ,medicine ,Animals ,Molecular Biology ,Integral membrane protein ,Differential centrifugation ,Cell Membrane ,Computational Biology ,Membrane Proteins ,Cell Biology ,Protein Structure, Tertiary ,Rats ,Blot ,Transmembrane domain ,medicine.anatomical_structure ,Hepatocyte ,Hepatocytes ,Electrophoresis, Polyacrylamide Gel ,Chromatography, Liquid ,Subcellular Fractions - Abstract
To investigate the heterogeneous protein composition of highly polarized hepatocyte plasma membrane (PM), three PM-associated subfractions were obtained from freshly isolated rat hepatocytes using density gradient centrifugation. The origins of the three subfractions were determined by morphological analysis and western blotting. The proteins were subjected to either one-dimensional (1-D) SDS–PAGE or two-dimensional (2-D) benzyldimethyl-n-hexadecylammonium chloride (BAC)/SDS–PAGE before nano-Liquid Chromatography-Electrospray Ionization—tandem mass spectrometry analysis (LC-ESI-MS/MS). A total of 613 non-redundant proteins were identified, among which 371 (60.5%) proteins were classified as PM or membrane-associated proteins according to GO annotations and the literatures and 32.4% had transmembrane domains. PM proteins from microsomal portion possessed the highest percentage of transmembrane domain, about 46.5% of them containing at least one transmembrane domain. In addition to proteins known to be located at polarized liver PM regions, such as asialoglycoprotein receptor 2, desmoplakin and bile salt export pump, several proteins which had the potential to become novel subfraction-specific proteins were also identified, such as annexin a6, pannexin and radixin. Our analysis also evaluated the application of 1-D SDS–PAGE and 2-D 16-BAC/SDS–PAGE on the separation of integral membrane proteins. J. Cell. Biochem. 104: 965–984, 2008. © 2008 Wiley-Liss, Inc.
- Published
- 2008
40. Proteomic analysis of rat hippocampal plasma membrane: characterization of potential neuronal-specific plasma membrane proteins
- Author
-
Zhen Liu, Xuanwen Li, Jinyun Xie, Yalan Sun, Quanyuan He, Meichi Wang, Xianchun Wang, Rui Cao, Ping Chen, Songping Liang, and Jixian Xiong
- Subjects
Proteomics ,Chemical Phenomena ,Electrospray ionization ,Nerve Tissue Proteins ,Hippocampal formation ,Tandem mass spectrometry ,Hippocampus ,Biochemistry ,Chromatography, Affinity ,Mass Spectrometry ,Cellular and Molecular Neuroscience ,Affinity chromatography ,Databases, Genetic ,medicine ,Animals ,Polyacrylamide gel electrophoresis ,Cells, Cultured ,Chromatography, High Pressure Liquid ,Neurons ,Chromatography ,Chemistry, Physical ,Chemistry ,Cell Membrane ,Membrane Proteins ,Trypsin ,Rats ,Membrane protein ,Electrophoresis, Polyacrylamide Gel ,Subcellular Fractions ,medicine.drug - Abstract
The hippocampus is a distinct brain structure that is crucial in memory storage and retrieval. To identify comprehensively proteins of hippocampal plasma membrane (PM) and detect the neuronal-specific PM proteins, we performed a proteomic analysis of rat hippocampus PM using the following three technical strategies. First, proteins of the PM were purified by differential and density-gradient centrifugation from hippocampal tissue and separated by one-dimensional electophoresis, digested with trypsin and analyzed by electrospray ionization (ESI) quadrupole time-of-flight (Q-TOF) tandem mass spectrometry (MS/MS). Second, the tryptic peptide mixture from PMs purified from hippocampal tissue using the centrifugation method was analyzed by liquid chromatography ion-trap ESI-MS/MS. Finally, the PM proteins from primary hippocampal neurons purified by a biotin-directed affinity technique were separated by one-dimensional electrophoresis, digested with trypsin and analyzed by ESI-Q-TOF-MS/MS. A total of 345, 452 and 336 non-redundant proteins were identified by each technical procedure respectively. There was a total of 867 non-redundant protein entries, of which 64.9% are integral membrane or membrane-associated proteins. One hundred and eighty-one proteins were detected only in the primary neurons and could be regarded as neuronal PM marker candidates. We also found some hypothetical proteins with no functional annotations that were first found in the hippocampal PM. This work will pave the way for further elucidation of the mechanisms of hippocampal function.
- Published
- 2006
41. Abstract 4437: Small non-coding RNA profiling from prostate cancer plasma by deep sequencing
- Author
-
Xianghua Liu, Annemarie Benton, Mark Miglarese, Gerri Ortiz, Quanyuan He, Vaishali Pannu, Nick Xiao, Qing Zhang, David Spetzler, and Andrew Hunter
- Subjects
Cancer Research ,Small RNA ,cDNA library ,RNA ,Biology ,Non-coding RNA ,Bioinformatics ,medicine.disease ,Molecular biology ,Deep sequencing ,Fold change ,Prostate cancer ,Oncology ,microRNA ,medicine - Abstract
Background: Prostate cancer (PCa) is the most common non-skin cancer among American men. MicroRNAs (miRNAs) are critical post-transcriptional regulators and involved in prostate cancer tumorigenesis. The aim of this study is to identify a PCa-specific expression profile of miRNAs from plasma to guide prostate cancer diagnosis and therapeutic treatment. Methods: Plasma was collected from 5 PCa patients and 5 normal men. Circulating RNA was extracted from 1) 200ul plasma or 2) the pellets of anti-Ago2 immunoprecipitations from 500ul plasma using the miRNeasy Serum/Plasma kit (Qiagen), with addition of glycogen as a carrier. Small RNA libraries were constructed using the NEBNext Multiplex Small RNA Prep Set for Illumina® (New England. BioLabs). The cDNA library fragments were purified by Blue Pippin (Sage Science) for extraction of 140-160 bp size fraction containing small RNA inserts. Equimolar amounts of cDNA library samples were pooled and were sequenced in a single flowcell on an Illumina HiSeq2500 with 50 cycle kit and rapid run model. Bioinformatics analysis: Adaptor was firstly removed from the raw reads, and the sequences were mapped to several small RNA databases by using bowtie1 with 1 mismatch. The multiple aligned reads were weighted to the mapped small RNAs based on their unique mapped reads counts. We then calculated the RPM (reads per million) as indicator of the expression levels of the small RNA. To get confident analysis results, we discarded the small RNAs whose averages of the raw reads counts in cancer and normal groups are smaller than 25 and only focus on the mature microRNAs. The moderate t-test is applied to find the differently expressed (DE) microRNAs between normal and cancer group. Results: Two major small RNA classes identified from total plasma are miRNA (47.7%) and yRNA (35.0%). The percentage of miRNA increased to 85.3% by Ago2-IP method. The compositions of categories of small RNAs in cancer and normal samples are similar. We identified 28 and 22 differential miRNAs (>2 fold change between cancer and normal group) by total plasma and Ago-2 IP methods respectively. Conclusions: We discovered a unique expression profile of miRNA detectable in the plasma from prostate cancer patients. Extracted RNA from the pellets of anti-Ago2 immunoprecipitations can enhance the detection of miRNA. Expand study to confirm these findings are needed. Citation Format: Xianghua Liu, Andrew Hunter, Qing Zhang, Quanyuan He, Annemarie Benton, Gerri Ortiz, Vaishali Pannu, Nick Xiao, Mark Miglarese, David Spetzler. Small non-coding RNA profiling from prostate cancer plasma by deep sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4437. doi:10.1158/1538-7445.AM2017-4437
- Published
- 2017
42. Genome-wide prediction of cancer driver genes based on SNP and cancer SNV data
- Author
-
Quanze, He, Quanyuan, He, Xiaohui, Liu, Youheng, Wei, Suqin, Shen, Xiaohui, Hu, Qiao, Li, Xiangwen, Peng, Lin, Wang, and Long, Yu
- Subjects
Original Article ,human activities - Abstract
Identifying cancer driver genes and exploring their functions are essential and the most urgent need in basic cancer research. Developing efficient methods to differentiate between driver and passenger somatic mutations revealed from large-scale cancer genome sequencing data is critical to cancer driver gene discovery. Here, we compared distinct features of SNP with SNV data in detail and found that the weighted ratio of SNV to SNP (termed as WVPR) is an excellent indicator for cancer driver genes. The power of WVPR was validated by accurate predictions of known drivers. We ranked most of human genes by WVPR and did functional analyses on the list. The results demonstrate that driver genes are usually highly enriched in chromatin organization related genes/pathways. And some protein complexes, such as histone acetyltransferase, histone methyltransferase, telomerase, centrosome, sin3 and U12-type spliceosomal complexes, are hot spots of driver mutations. Furthermore, this study identified many new potential driver genes (e.g. NTRK3 and ZIC4) and pathways including oxidative phosphorylation pathway, which were not deemed by previous methods. Taken together, our study not only developed a method to identify cancer driver genes/pathways but also provided new insights into molecular mechanisms of cancer development.
- Published
- 2014
43. Ten-Eleven Translocation 1 (Tet1) Is Regulated by O-Linked N-Acetylglucosamine Transferase (Ogt) for Target Gene Repression in Mouse Embryonic Stem Cells*
- Author
-
Ma Wan, Quanyuan He, Margaret A. Goodell, Hyeung Kim, Feng-Tao Shi, Weisi Lu, Zhou Songyang, and Dan Liu
- Subjects
Pluripotent Stem Cells ,Glycosylation ,Immunoprecipitation ,Repressor ,Biology ,N-Acetylglucosaminyltransferases ,Biochemistry ,Cell Line ,Mice ,Proto-Oncogene Proteins ,Gene expression ,SIN3A ,Animals ,Genes, Developmental ,Molecular Biology ,Embryonic Stem Cells ,Gene Expression Regulation, Developmental ,Cell Biology ,Molecular biology ,Chromatin ,DNA-Binding Proteins ,Repressor Proteins ,DNA demethylation ,DNA methylation ,Ectopic expression ,Protein Binding - Abstract
As a member of the Tet (Ten-eleven translocation) family proteins that can convert 5-methylcytosine (5mC) to 5-hydroxylmethylcytosine (5hmC), Tet1 has been implicated in regulating global DNA demethylation and gene expression. Tet1 is highly expressed in embryonic stem (ES) cells and appears primarily to repress developmental genes for maintaining pluripotency. To understand how Tet1 may regulate gene expression, we conducted large scale immunoprecipitation followed by mass spectrometry of endogenous Tet1 in mouse ES cells. We found that Tet1 could interact with multiple chromatin regulators, including Sin3A and NuRD complexes. In addition, we showed that Tet1 could also interact with the O-GlcNAc transferase (Ogt) and be O-GlcNAcylated. Depletion of Ogt led to reduced Tet1 and 5hmC levels on Tet1-target genes, whereas ectopic expression of wild-type but not enzymatically inactive Ogt increased Tet1 levels. Mutation of the putative O-GlcNAcylation site on Tet1 led to decreased O-GlcNAcylation and level of the Tet1 protein. Our results suggest that O-GlcNAcylation can positively regulate Tet1 protein concentration and indicate that Tet1-mediated 5hmC modification and target repression is controlled by Ogt.
- Published
- 2013
44. The trithorax group protein Ash2l is essential for pluripotency and maintaining open chromatin in embryonic stem cells
- Author
-
Dan Liu, Weisi Lu, Yuanyan Xiong, Jiancong Liang, Quanyuan He, Feng-Tao Shi, Ma Wan, Dong Yang, Yi Zhang, Michelle Craig Barton, Rui Chen, and Zhou Songyang
- Subjects
Pluripotent Stem Cells ,Chromatin Immunoprecipitation ,animal structures ,Biology ,Biochemistry ,environment and public health ,Methylation ,Models, Biological ,Chromatin remodeling ,Histones ,Mice ,Histone H1 ,hemic and lymphatic diseases ,Histone code ,Animals ,Molecular Biology ,neoplasms ,ChIA-PET ,Embryonic Stem Cells ,Genetics ,Genome ,fungi ,Gene Expression Regulation, Developmental ,Nuclear Proteins ,Cell Differentiation ,Cell Biology ,Chromatin ,DNA-Binding Proteins ,Histone ,Microscopy, Fluorescence ,biology.protein ,RNA Interference ,Chromatin immunoprecipitation ,Myeloid-Lymphoid Leukemia Protein ,Bivalent chromatin ,Transcription Factors - Abstract
Embryonic stem (ES) cells exhibit general characteristics of open chromatin, a state that may be necessary for ES cells to efficiently self-renew while remaining poised for differentiation. Histone H3K4 and H3K9 trimethylation associate as a general rule, with open and silenced chromatin, respectively, for ES cell pluripotency maintenance. However, how histone modifications are regulated to maintain open chromatin in ES cells remains largely unknown. Here, we demonstrate that trithorax protein Ash2l, homologue of the Drosophila Ash2 (absent, small, homeotic-2) protein, is a key regulator of open chromatin in ES cells. Consistent with Ash2l being a core subunit of mixed lineage leukemia methyltransferase complex, RNAi knockdown of Ash2l was sufficient to reduce H3K4 methylation levels and drive ES cells to a silenced chromatin state with high H3K9 trimethylation. Genome-wide ChIP-seq analysis indicated that Ash2l is recruited to target loci through two distinct modes and enriched at a family of genes implicated in open chromatin regulation, including chromatin remodeler Cdh7, transcription factor c-Myc, and H3K9 demethylase Kdm4c. Our results underscore the importance of Ash2l in open chromatin regulation and provide insight into how the open chromatin landscape is maintained in ES cells.
- Published
- 2012
45. Matrix recruitment and calcium sequestration for spatial specific otoconia development
- Author
-
Yinfang Xu, Quanyuan He, Yunxia Wang Lundberg, Hua Yang, Xing Zhao, and Lili Wang
- Subjects
Pathology ,medicine.medical_specialty ,Blotting, Western ,lcsh:Medicine ,Otolithic membrane ,Biology ,Calcium Carbonate ,Extracellular matrix ,03 medical and health sciences ,Ectopic calcification ,Mice ,Otolithic Membrane ,0302 clinical medicine ,Developmental Neuroscience ,Utricle ,Molecular Cell Biology ,medicine ,Animals ,Immunoprecipitation ,Inner ear ,Saccule and Utricle ,lcsh:Science ,030304 developmental biology ,Otolith ,0303 health sciences ,Extracellular Matrix Proteins ,Multidisciplinary ,Reverse Transcriptase Polymerase Chain Reaction ,lcsh:R ,Calcium-Binding Proteins ,Epithelial Cells ,medicine.disease ,Sensory Systems ,Cell biology ,Cochlea ,medicine.anatomical_structure ,Auditory System ,NIH 3T3 Cells ,lcsh:Q ,Calcium ,Saccule ,sense organs ,Cellular Types ,030217 neurology & neurosurgery ,Calcification ,Protein Binding ,Research Article ,Neuroscience - Abstract
Otoconia are bio-crystals anchored to the macular sensory epithelium of the utricle and saccule in the inner ear for motion sensing and bodily balance. Otoconia dislocation, degeneration and ectopic calcification can have detrimental effects on balance and vertigo/dizziness, yet the mechanism underlying otoconia formation is not fully understood. In this study, we show that selected matrix components are recruited to form the crystal matrix and sequester Ca(2+) for spatial specific formation of otoconia. Specifically, otoconin-90 (Oc90) binds otolin through both domains (TH and C1q) of otolin, but full-length otolin shows the strongest interaction. These proteins have much higher expression levels in the utricle and saccule than other inner ear epithelial tissues in mice. In vivo, the presence of Oc90 in wildtype (wt) mice leads to an enrichment of Ca(2+) in the luminal matrices of the utricle and saccule, whereas absence of Oc90 in the null mice leads to drastically reduced matrix-Ca(2+). In vitro, either Oc90 or otolin can increase the propensity of extracellular matrix to calcify in cell culture, and co-expression has a synergistic effect on calcification. Molecular modeling and sequence analysis predict structural features that may underlie the interaction and Ca(2+)-sequestering ability of these proteins. Together, the data provide a mechanism for the otoconial matrix assembly and the role of this matrix in accumulating micro-environmental Ca(2+) for efficient CaCO(3) crystallization, thus uncover a critical process governing spatial specific otoconia formation.
- Published
- 2011
46. Zebrafish as a Model System to Study the Physiological Function of Telomeric Protein TPP1
- Author
-
Zhou Songyang, Yiying Xie, Dong Yang, and Quanyuan He
- Subjects
Gerontology ,Physiological function ,Multidisciplinary ,biology ,business.industry ,Science ,lcsh:R ,Correction ,lcsh:Medicine ,Library science ,Model system ,biology.organism_classification ,Medicine ,lcsh:Q ,lcsh:Science ,business ,Zebrafish - Abstract
The 2nd affiliation for the 4th author was not indicated. Zhou Songyang is affiliated with both 1 State Key laboratory for Biocontrol, Sun Yat-Sen University, Guangzhou, People's Republic of China, and 2 Verna and Marrs McLean Department of Biochemistry and Molecular biology, Baylor College of Medicine, Houston, Texas, United States of America.
- Published
- 2011
47. Zebrafish as a model system to study the physiological function of telomeric protein TPP1
- Author
-
Dong Yang, Yiying Xie, Quanyuan He, and Zhou Songyang
- Subjects
Macromolecular Assemblies ,Embryo, Nonmammalian ,Morpholino ,Heart malformation ,ved/biology.organism_classification_rank.species ,Molecular Sequence Data ,Telomere-Binding Proteins ,Embryonic Development ,lcsh:Medicine ,Biochemistry ,Protein Chemistry ,Shelterin Complex ,Animals, Genetically Modified ,03 medical and health sciences ,0302 clinical medicine ,Chemical Biology ,Animals ,Humans ,Amino Acid Sequence ,Model organism ,Protein Interactions ,lcsh:Science ,Zebrafish ,Biology ,030304 developmental biology ,Genetics ,Telomere-binding protein ,0303 health sciences ,Multidisciplinary ,biology ,Base Sequence ,Sequence Homology, Amino Acid ,ved/biology ,lcsh:R ,Proteins ,Genomics ,Zebrafish Proteins ,Shelterin ,biology.organism_classification ,Chromatin ,Telomere ,Gene Knockdown Techniques ,Models, Animal ,Structural Genomics ,lcsh:Q ,030217 neurology & neurosurgery ,Research Article - Abstract
Telomeres are specialized chromatin structures at the end of chromosomes. Telomere dysfunction can lead to chromosomal abnormalities, DNA damage responses, and even cancer. In mammalian cells, a six-protein complex (telosome/shelterin) is assembled on the telomeres through the interactions between various domain structures of the six telomere proteins (POT1, TPP1, TIN2, TRF1, TRF2 and RAP1), and functions in telomere maintenance and protection. Within the telosome, TPP1 interacts directly with POT1 and TIN2 and help to mediate telosome assembly. Mechanisms of telomere regulation have been extensively studied in a variety of model organisms. For example, the physiological roles of telomere-targeted proteins have been assessed in mice through homozygous inactivation. In these cases, early embryonic lethality has prevented further studies of these proteins in embryogenesis and development. As a model system, zebrafish offers unique advantages such as genetic similarities with human, rapid developmental cycles, and ease of manipulation of its embryos. In this report, we detailed the identification of zebrafish homologues of TPP1, POT1, and TIN2, and showed that the domain structures and interactions of these telosome components appeared intact in zebrafish. Importantly, knocking down TPP1 led to multiple abnormalities in zebrafish embryogenesis, including neural death, heart malformation, and caudal defect. And these embryos displayed extensive apoptosis. These results underline the importance of TPP1 in zebrafish embryogenesis, and highlight the feasibility and advantages of investigating the signaling pathways and physiological function of telomere proteins in zebrafish.
- Published
- 2011
48. Genome-wide YFP Fluorescence Complementation Screen Identifies New Regulators for Telomere Signaling in Human Cells*
- Author
-
Amin Safari, Hyeung Kim, Hwa Jin Baek, Zhou Songyang, Dong Yang, Jiancong Liang, Dan Liu, Heekyung Kate Chae, Quanyuan He, Liuh-Yow Chen, and Ok Hee Lee
- Subjects
Regular Issue ,Proteome ,Ubiquitin-Protein Ligases ,Telomere-Binding Proteins ,Computational biology ,Biology ,Biochemistry ,Interactome ,Genome ,Shelterin Complex ,Analytical Chemistry ,Ubiquitin ,Bacterial Proteins ,Protein Interaction Mapping ,Humans ,Molecular Biology ,Genetics ,Telomere-binding protein ,Genetic Complementation Test ,Proteins ,Telomere ,Flow Cytometry ,Luminescent Proteins ,Retroviridae ,biology.protein ,Rap1 ,Signal Transduction - Abstract
Detection of low-affinity or transient interactions can be a bottleneck in our understanding of signaling networks. To address this problem, we developed an arrayed screening strategy based on protein complementation to systematically investigate protein-protein interactions in live human cells, and performed a large-scale screen for regulators of telomeres. Maintenance of vertebrate telomeres requires the concerted action of members of the Telomere Interactome, built upon the six core telomeric proteins TRF1, TRF2, RAP1, TIN2, TPP1, and POT1. Of the ∼12,000 human proteins examined, we identified over 300 proteins that associated with the six core telomeric proteins. The majority of the identified proteins have not been previously linked to telomere biology, including regulators of post-translational modifications such as protein kinases and ubiquitin E3 ligases. Results from this study shed light on the molecular niche that is fundamental to telomere regulation in humans, and provide a valuable tool to investigate signaling pathways in mammalian cells.
- Published
- 2010
49. Improvement of hydrophobic integral membrane protein identification by mild performic acid oxidation-assisted digestion
- Author
-
Songping Liang, Yi-Song Liu, Ping Chen, Quanyuan He, Tingting Sheng, Xianchun Wang, Qin Song, Rui Cao, Rong Lv, and Yin Wang
- Subjects
Formates ,Biophysics ,Biochemistry ,Mass Spectrometry ,chemistry.chemical_compound ,Methionine ,Cell Line, Tumor ,polycyclic compounds ,Humans ,heterocyclic compounds ,Cysteine ,Solubility ,Molecular Biology ,Integral membrane protein ,Performic acid ,Membrane Proteins ,Cell Biology ,biochemical phenomena, metabolism, and nutrition ,enzymes and coenzymes (carbohydrates) ,Transmembrane domain ,chemistry ,bacteria ,Digestion ,Peptides ,Hydrophobic and Hydrophilic Interactions ,Oxidation-Reduction - Abstract
Integral membrane proteins (IMPs) are critical for the maintenance of biological systems and represent important targets for the treatment of disease. The hydrophobicity and low abundance of IMPs make them difficult to analyze. In proteomic analyses, hydrophobic peptides including transmembrane domains are often underrepresented, and this reduces the sequence coverage and reliability of the identified IMPs. Here we report a new strategy, mild performic acid oxidation treatment (mPAOT), for improvement of IMP identification. In the mPAOT strategy, the hydrophobicity of IMPs is significantly decreased by oxidizing their methionine and cysteine residues with performic acid, thereby improving the solubility and enzymolysis of these proteins. The application of the mPAOT strategy to the analysis of IMPs from human nasopharyngeal carcinoma CNE1 cell line demonstrated that many IMPs, including those with high hydrophobicity, could be reliably identified.
- Published
- 2010
50. Liverbase: a comprehensive view of human liver biology
- Author
-
Wei Guan, Quanyuan He, Aihua Sun, Dong Li, Fuchu He, Yulin Sun, Xiaohang Zhao, Songping Liang, Chao Geng, Ying Jiang, Ping Chen, Yanping Song, Yunping Zhu, Dong Yun, Qijun Liu, Hao Li, Xiaoyan Yuan, Yang Xu, Fan Zhong, Yunwei Hao, Yixue Li, Hong Yu, Liang Shi, Xuequn Zhang, Siqi Liu, Dong Yang, Wei Tong, Chengzhao Lin, and Xue Wang
- Subjects
Proteome ,Systems biology ,Gene Expression Profiling ,Biological database ,General Chemistry ,Computational biology ,Biology ,Biochemistry ,Transcriptome ,Gene expression profiling ,World Wide Web ,User-Computer Interface ,Protein Annotation ,Liver ,Humans ,KEGG ,Databases, Protein ,Function (biology) ,Subcellular Fractions - Abstract
The Liverbase ( http://liverbase.hupo.org.cn ) integrates information on the human liver proteome, including the function, abundance, and subcellular localization of proteins as well as associated disease information. The overall objective of the Liverbase is to provide a unique public resource for the liver community by providing comprehensive functional annotation of proteins implicated in liver development and disease. The central database features are manually annotated proteins localized in or functionally associated with human liver. In this first version of Liverbase, the associated data includes the human liver proteome (6788 proteins) and transcriptome (11205 significantly expressed genes: 10224 from CHIP and 5422 from MPSS, respecively) from the Chinese human liver proteome project (CNHLPP). As a database made publicly available through the Web site, Liverbase provides browsing and searching capabilities and a compilation of external links to other databases and homepages. Liverbase enables (i) the establishment of liver GO slim with 51 nonredundant items; (ii) systematic searches for proteins within specific functional or metabolic pathways; (iii) systematic searches that aim to find the proteins that underlie common and rare liver diseases; and (iv) the integration of detailed protein annotations derived from the literature. Liverbase also contains an external links page with links to other biological databases and homepages, including GO, KEGG, pfam, SWISS-PROT, and GNF databases. Liverbase users can utilize all these information to conduct systems biology research on liver.
- Published
- 2009
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.