An in Cellulo-Derived Structure of PAK4 in Complex with Its Inhibitor Inka1
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Screening Differentially Expressed Genes of Pancreatic Cancer Between Mongolian and Han People Using Bioinformatics Technology
Screening differentially expressed genes of pancreatic cancer between Mongolian and Han people using bioinformatics technology Jiasheng Xu First Aliated Hospital of Nanchang University Kaili Liao Second Aliated Hospital of Nanchang University ZHONGHUA FU First Aliated Hospital of Nanchang University ZHENFANG XIONG ( [email protected] ) The First Aliated Hospital of Nanchang University https://orcid.org/0000-0003-2062-9204 Research article Keywords: Pancreatic ductal cell carcinoma; Affymetrix gene expression prole; Gene differential expression; GO analysis; Pathway analysis; Mongolian Posted Date: October 14th, 2019 DOI: https://doi.org/10.21203/rs.2.11118/v2 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Version of Record: A version of this preprint was published at BMC Cancer on April 9th, 2020. See the published version at https://doi.org/10.1186/s12885-020-06722-7. Page 1/19 Abstract Objective: To screen and analyze differentially expressed genes in pancreatic carcinoma tissues taken from Mongolian and Han patients by Affymetrix Genechip. Methods: Pancreatic ductal cell carcinoma tissues were collected from the Mongolian and Han patients undergoing resection in the Second Aliated Hospital of Nanchang University from March 2015 to May 2018 and the total RNA was extracted. Differentially expressed genes were selected from the total RNA qualied by Nanodrop 2000 and Agilent 2100 using Affymetrix and a cartogram was drawn; The gene ontology (GO) analysis and Pathway analysis were used for the collection and analysis of biological information of these differentially expressed genes. Finally, some differentially expressed genes were veried by real-time PCR. Results: Through the microarray analysis of gene expression, 970 differentially expressed genes were detected by comparing pancreatic cancer tissue samples between Mongolian and Han patients. -
Phospho-PAK4 (Ser474)/PAK5 (Ser602)/PAK6 (Ser560) Antibody Detects Endogenous 12
Revision 1 C 0 2 - t Phospho-PAK4 (Ser474)/PAK5 a e r o t (Ser602)/PAK6 (Ser560) Antibody S Orders: 877-616-CELL (2355) [email protected] Support: 877-678-TECH (8324) 1 4 Web: [email protected] 2 www.cellsignal.com 3 # 3 Trask Lane Danvers Massachusetts 01923 USA For Research Use Only. Not For Use In Diagnostic Procedures. Applications: Reactivity: Sensitivity: MW (kDa): Source: UniProt ID: Entrez-Gene Id: WB H M GP Endogenous 72 (PAK4). 82 Rabbit Q9NQU5, Q9P286, O96013 56924, 57144, 10298 (PAK6). 90 (PAK5). p y g y p y Product Usage Information pivotal role in regulating the activity and function of PAK4 (10). PAK family members are widely expressed, and often overexpressed in human cancer (11,12). Application Dilution 1. Knaus, U.G. and Bokoch, G.M. (1998) Int. J. Biochem. Cell Biol. 30, 857-62. 2. Daniels, R.H. et al. (1998) EMBO J. 17, 754-64. Western Blotting 1:1000 3. King, C.C. et al. (2000) J. Biol. Chem. 275, 41201-9. 4. Manser, E. et al. (1997) Mol. Cell. Biol. 17, 1129-43. Storage 5. Gatti, A. et al. (1999) J. Biol. Chem. 274, 8022-8. 6. Lei, M. et al. (2000) Cell 102, 387-97. Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM NaCl, 100 µg/ml BSA and 50% 7. Chong, C. et al. (2001) J. Biol. Chem. 276, 17347-53. glycerol. Store at –20°C. Do not aliquot the antibody. 8. Zhao, Z. et al. (2000) Mol. Cell. Biol. 20, 3906-17. 9. -
Screening of Potential Genes and Transcription Factors Of
ANIMAL STUDY e-ISSN 1643-3750 © Med Sci Monit, 2018; 24: 503-510 DOI: 10.12659/MSM.907445 Received: 2017.10.08 Accepted: 2018.01.01 Screening of Potential Genes and Transcription Published: 2018.01.25 Factors of Postoperative Cognitive Dysfunction via Bioinformatics Methods Authors’ Contribution: ABE 1 Yafeng Wang 1 Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical Study Design A AB 1 Ailan Huang University, Nanning, Guangxi, P.R. China Data Collection B 2 Department of Gynecology, People’s Hospital of Guangxi Zhuang Autonomous Statistical Analysis C BEF 1 Lixia Gan Region, The First Affiliated Hospital of Guangxi Medical University, Nanning, Data Interpretation D BCF 1 Yanli Bao Guangxi, P.R. China Manuscript Preparation E BDF 1 Weilin Zhu 3 Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical Literature Search F University, Nanning, Guangxi, P.R. China Funds Collection G EF 1 Yanyan Hu AE 1 Li Ma CF 2 Shiyang Wei DE 3 Yuyan Lan Corresponding Author: Yafeng Wang, e-mail: [email protected] Source of support: Departmental sources Background: The aim of this study was to explore the potential genes and transcription factors involved in postoperative cognitive dysfunction (POCD) via bioinformatics analysis. Material/Methods: GSE95070 miRNA expression profiles were downloaded from Gene Expression Omnibus database, which in- cluded five hippocampal tissues from POCD mice and controls. Moreover, the differentially expressed miRNAs (DEMs) between the two groups were identified. In addition, the target genes of DEMs were predicted using Targetscan 7.1, followed by protein-protein interaction (PPI) network construction, functional enrichment anal- ysis, pathway analysis, and prediction of transcription factors (TFs) targeting the potential targets. -
Mitoxplorer, a Visual Data Mining Platform To
mitoXplorer, a visual data mining platform to systematically analyze and visualize mitochondrial expression dynamics and mutations Annie Yim, Prasanna Koti, Adrien Bonnard, Fabio Marchiano, Milena Dürrbaum, Cecilia Garcia-Perez, José Villaveces, Salma Gamal, Giovanni Cardone, Fabiana Perocchi, et al. To cite this version: Annie Yim, Prasanna Koti, Adrien Bonnard, Fabio Marchiano, Milena Dürrbaum, et al.. mitoXplorer, a visual data mining platform to systematically analyze and visualize mitochondrial expression dy- namics and mutations. Nucleic Acids Research, Oxford University Press, 2020, 10.1093/nar/gkz1128. hal-02394433 HAL Id: hal-02394433 https://hal-amu.archives-ouvertes.fr/hal-02394433 Submitted on 4 Dec 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License Nucleic Acids Research, 2019 1 doi: 10.1093/nar/gkz1128 Downloaded from https://academic.oup.com/nar/advance-article-abstract/doi/10.1093/nar/gkz1128/5651332 by Bibliothèque de l'université la Méditerranée user on 04 December 2019 mitoXplorer, a visual data mining platform to systematically analyze and visualize mitochondrial expression dynamics and mutations Annie Yim1,†, Prasanna Koti1,†, Adrien Bonnard2, Fabio Marchiano3, Milena Durrbaum¨ 1, Cecilia Garcia-Perez4, Jose Villaveces1, Salma Gamal1, Giovanni Cardone1, Fabiana Perocchi4, Zuzana Storchova1,5 and Bianca H. -
Transcriptome Analysis of Human Diabetic Kidney Disease
ORIGINAL ARTICLE Transcriptome Analysis of Human Diabetic Kidney Disease Karolina I. Woroniecka,1 Ae Seo Deok Park,1 Davoud Mohtat,2 David B. Thomas,3 James M. Pullman,4 and Katalin Susztak1,5 OBJECTIVE—Diabetic kidney disease (DKD) is the single cases, mild and then moderate mesangial expansion can be leading cause of kidney failure in the U.S., for which a cure has observed. In general, diabetic kidney disease (DKD) is not yet been found. The aim of our study was to provide an considered a nonimmune-mediated degenerative disease unbiased catalog of gene-expression changes in human diabetic of the glomerulus; however, it has long been noted that kidney biopsy samples. complement and immunoglobulins sometimes can be de- — tected in diseased glomeruli, although their role and sig- RESEARCH DESIGN AND METHODS Affymetrix expression fi arrays were used to identify differentially regulated transcripts in ni cance is not clear (4). 44 microdissected human kidney samples. The DKD samples were The understanding of DKD has been challenged by multi- significant for their racial diversity and decreased glomerular ple issues. First, the diagnosis of DKD usually is made using filtration rate (~20–30 mL/min). Stringent statistical analysis, using clinical criteria, and kidney biopsy often is not performed. the Benjamini-Hochberg corrected two-tailed t test, was used to According to current clinical practice, the development of identify differentially expressed transcripts in control and diseased albuminuria in patients with diabetes is sufficient to make the glomeruli and tubuli. Two different Web-based algorithms were fi diagnosis of DKD (5). We do not understand the correlation used to de ne differentially regulated pathways. -
Proximity Proteomics Identifies PAK4 As a Component of Afadin–Nectin
ARTICLE https://doi.org/10.1038/s41467-021-25011-w OPEN Proximity proteomics identifies PAK4 as a component of Afadin–Nectin junctions Yohendran Baskaran 1,5, Felicia Pei-Ling Tay2,5, Elsa Yuen Wai Ng1, Claire Lee Foon Swa 3, Sheena Wee 3, ✉ Jayantha Gunaratne3 & Edward Manser 1,4 Human PAK4 is an ubiquitously expressed p21-activated kinase which acts downstream of Cdc42. Since PAK4 is enriched in cell-cell junctions, we probed the local protein environment 1234567890():,; around the kinase with a view to understanding its location and substrates. We report that U2OS cells expressing PAK4-BirA-GFP identify a subset of 27 PAK4-proximal proteins that are primarily cell-cell junction components. Afadin/AF6 showed the highest relative biotin labelling and links to the nectin family of homophilic junctional proteins. Reciprocally >50% of the PAK4-proximal proteins were identified by Afadin BioID. Co-precipitation experiments failed to identify junctional proteins, emphasizing the advantage of the BioID method. Mechanistically PAK4 depended on Afadin for its junctional localization, which is similar to the situation in Drosophila. A highly ranked PAK4-proximal protein LZTS2 was immuno- localized with Afadin at cell-cell junctions. Though PAK4 and Cdc42 are junctional, BioID analysis did not yield conventional cadherins, indicating their spatial segregation. To identify cellular PAK4 substrates we then assessed rapid changes (12’) in phospho-proteome after treatment with two PAK inhibitors. Among the PAK4-proximal junctional proteins seventeen PAK4 sites were identified. We anticipate mammalian group II PAKs are selective for the Afadin/nectin sub-compartment, with a demonstrably distinct localization from tight and cadherin junctions. -
PAK4 Signaling in Health and Disease
Won et al. Experimental & Molecular Medicine (2019) 51:11 https://doi.org/10.1038/s12276-018-0204-0 Experimental & Molecular Medicine REVIEW ARTICLE Open Access PAK4signalinginhealthanddisease: defining the PAK4–CREB axis So-Yoon Won1,Jung-JinPark1,Eun-YoungShin1 and Eung-Gook Kim1 Abstract p21-Activated kinase 4 (PAK4), a member of the PAK family, regulates a wide range of cellular functions, including cell adhesion, migration, proliferation, and survival. Dysregulation of its expression and activity thus contributes to the development of diverse pathological conditions. PAK4 plays a pivotal role in cancer progression by accelerating the epithelial–mesenchymal transition, invasion, and metastasis. Therefore, PAK4 is regarded as an attractive therapeutic target in diverse types of cancers, prompting the development of PAK4-specific inhibitors as anticancer drugs; however, these drugs have not yet been successful. PAK4 is essential for embryonic brain development and has a neuroprotective function. A long list of PAK4 effectors has been reported. Recently, the transcription factor CREB has emerged as a novel effector of PAK4. This finding has broad implications for the role of PAK4 in health and disease because CREB-mediated transcriptional reprogramming involves a wide range of genes. In this article, we review the PAK4 signaling pathways involved in prostate cancer, Parkinson’s disease, and melanogenesis, focusing in particular on the PAK4-CREB axis. 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; Introduction kinase domain of all PAK family members is located at the p21-Activated kinase (PAK) was initially identified as an C-terminus. In the inactive state, group I PAKs are effector of Rho GTPases that play a central role in reor- homodimers, and group II PAKs are monomers. -
Identification of Key Genes and Pathways for Alzheimer's Disease
Biophys Rep 2019, 5(2):98–109 https://doi.org/10.1007/s41048-019-0086-2 Biophysics Reports RESEARCH ARTICLE Identification of key genes and pathways for Alzheimer’s disease via combined analysis of genome-wide expression profiling in the hippocampus Mengsi Wu1,2, Kechi Fang1, Weixiao Wang1,2, Wei Lin1,2, Liyuan Guo1,2&, Jing Wang1,2& 1 CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China 2 Department of Psychology, University of Chinese Academy of Sciences, Beijing 10049, China Received: 8 August 2018 / Accepted: 17 January 2019 / Published online: 20 April 2019 Abstract In this study, combined analysis of expression profiling in the hippocampus of 76 patients with Alz- heimer’s disease (AD) and 40 healthy controls was performed. The effects of covariates (including age, gender, postmortem interval, and batch effect) were controlled, and differentially expressed genes (DEGs) were identified using a linear mixed-effects model. To explore the biological processes, func- tional pathway enrichment and protein–protein interaction (PPI) network analyses were performed on the DEGs. The extended genes with PPI to the DEGs were obtained. Finally, the DEGs and the extended genes were ranked using the convergent functional genomics method. Eighty DEGs with q \ 0.1, including 67 downregulated and 13 upregulated genes, were identified. In the pathway enrichment analysis, the 80 DEGs were significantly enriched in one Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, GABAergic synapses, and 22 Gene Ontology terms. These genes were mainly involved in neuron, synaptic signaling and transmission, and vesicle metabolism. These processes are all linked to the pathological features of AD, demonstrating that the GABAergic system, neurons, and synaptic function might be affected in AD. -
Diverse Gene Expression and DNA Methylation Profiles Correlate with Differential Adaptation of Breast Cancer Cells to the Antiestrogens Tamoxifen and Fulvestrant
Research Article Diverse Gene Expression and DNA Methylation Profiles Correlate with Differential Adaptation of Breast Cancer Cells to the Antiestrogens Tamoxifen and Fulvestrant Meiyun Fan,1 Pearlly S. Yan,2 Cori Hartman-Frey,1 Lei Chen,1 Henry Paik,1 Samuel L. Oyer,1 Jonathan D. Salisbury,1 Alfred S.L. Cheng,2 Lang Li,3 Phillip H. Abbosh,1 Tim H-M. Huang,2 and Kenneth P. Nephew1,4,5 1Medical Sciences, Indiana University School of Medicine, Bloomington, Indiana; 2Division of Human Cancer Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, Ohio; 3Division of Biostatistics, Department of Medicine and 4Department of Cellular and Integrative Physiology, Indiana University School of Medicine; and 5Indiana University Cancer Center, Indianapolis, Indiana Abstract Introduction The development of targeted therapies for antiestrogen- The steroid hormone estrogen is strongly implicated in the resistant breast cancer requires a detailed understanding development and progression of breast cancer (1). The primary of its molecular characteristics. To further elucidate the mediator of estrogen action in breast cancer cells is estrogen molecular events underlying acquired resistance to the receptor a (ERa), a ligand-activated transcription factor (1). antiestrogens tamoxifen and fulvestrant, we established Consequently, the leading drugs used for endocrine therapy of drug-resistant sublines from a single colony of hormone- breast cancer all block ERa activity, including antiestrogens (i.e., dependent breast cancer MCF7 cells. These model systems tamoxifen and fulvestrant) and aromatase inhibitors (2). Despite allowed us to examine the cellular and molecular changes the efficacy and favorable safety profile of these agents, the use of induced by antiestrogens in the context of a uniform clonal endocrine therapy is limited by the onset of drug resistance, in background. -
Mechanism of Yiqi Huoxue Compound for Treatment of Acute Myocardial Infarction Based on Network Pharmacology
Revista Argentina de Clínica Psicológica 2020, Vol. XXIX, N°4, 851-863 851 DOI: 10.24205/03276716.2020.892 Mechanism of Yiqi Huoxue Compound for Treatment of Acute Myocardial Infarction Based on Network Pharmacology ZhiXian Wanga,DiChi Jianga,XiaoJu Wangb, JinQian Wangc,GuoHeng Hud* ABSTRACT Objective: To explore the potential mechanism of Yiqi Huoxue Compound for the treatment of acute myocardial infarction (AMI) through network pharmacology. Methods: The main active compounds and related effect targets of Yiqi Huoxue Compound were searched and screened through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The standard names of effect targets were obtained using Uniprot database, the disease-related targets were obtained using GeneCards, Online Mendelian Inheritance in Man (OMIM) and A Database of Gene- Disease Associations (DisGeNET), and the protein interaction network of AMI-related core targets was constructed through STRING database and Cytoscape software. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for core targets using R language software. Results: Based on the screening conditions, 93 effective compounds, 140 drug targets of Yiqi Huoxue Compound and 71 potential therapeutic targets related to AMI were obtained. A total of 92 entries were excavated by GO enrichment analysis (P<0.05), and 42 pathways related to AMI were screened out by KEGG pathway enrichment analysis (P<0.05). Conclusion: Yiqi Huoxue Compound contains a variety of active compounds, which can exert its therapeutic effect through multiple targets and multiple signaling pathways. The research results can provide a modern theoretical basis for the clinical application and mechanism research of Yiqi Huoxue Compound. -
A High-Throughput Approach to Uncover Novel Roles of APOBEC2, a Functional Orphan of the AID/APOBEC Family
Rockefeller University Digital Commons @ RU Student Theses and Dissertations 2018 A High-Throughput Approach to Uncover Novel Roles of APOBEC2, a Functional Orphan of the AID/APOBEC Family Linda Molla Follow this and additional works at: https://digitalcommons.rockefeller.edu/ student_theses_and_dissertations Part of the Life Sciences Commons A HIGH-THROUGHPUT APPROACH TO UNCOVER NOVEL ROLES OF APOBEC2, A FUNCTIONAL ORPHAN OF THE AID/APOBEC FAMILY A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy by Linda Molla June 2018 © Copyright by Linda Molla 2018 A HIGH-THROUGHPUT APPROACH TO UNCOVER NOVEL ROLES OF APOBEC2, A FUNCTIONAL ORPHAN OF THE AID/APOBEC FAMILY Linda Molla, Ph.D. The Rockefeller University 2018 APOBEC2 is a member of the AID/APOBEC cytidine deaminase family of proteins. Unlike most of AID/APOBEC, however, APOBEC2’s function remains elusive. Previous research has implicated APOBEC2 in diverse organisms and cellular processes such as muscle biology (in Mus musculus), regeneration (in Danio rerio), and development (in Xenopus laevis). APOBEC2 has also been implicated in cancer. However the enzymatic activity, substrate or physiological target(s) of APOBEC2 are unknown. For this thesis, I have combined Next Generation Sequencing (NGS) techniques with state-of-the-art molecular biology to determine the physiological targets of APOBEC2. Using a cell culture muscle differentiation system, and RNA sequencing (RNA-Seq) by polyA capture, I demonstrated that unlike the AID/APOBEC family member APOBEC1, APOBEC2 is not an RNA editor. Using the same system combined with enhanced Reduced Representation Bisulfite Sequencing (eRRBS) analyses I showed that, unlike the AID/APOBEC family member AID, APOBEC2 does not act as a 5-methyl-C deaminase. -
A Systems-Genetics Analyses of Complex Phenotypes
A systems-genetics analyses of complex phenotypes A thesis submitted to the University of Manchester for the degree of Doctor of Philosophy in the Faculty of Life Sciences 2015 David Ashbrook Table of contents Table of contents Table of contents ............................................................................................... 1 Tables and figures ........................................................................................... 10 General abstract ............................................................................................... 14 Declaration ....................................................................................................... 15 Copyright statement ........................................................................................ 15 Acknowledgements.......................................................................................... 16 Chapter 1: General introduction ...................................................................... 17 1.1 Overview................................................................................................... 18 1.2 Linkage, association and gene annotations .............................................. 20 1.3 ‘Big data’ and ‘omics’ ................................................................................ 22 1.4 Systems-genetics ..................................................................................... 24 1.5 Recombinant inbred (RI) lines and the BXD .............................................. 25 Figure 1.1: