Functional Characterization of BC039389-GATM and KLK4
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Laboratory Diagnosis of Creatine Deficiency Syndromes: a Technical Standard and Guideline of the American College of Medical Genetics and Genomics
ACMG STaNDaRDs aND GUIDELINEs © American College of Medical Genetics and Genomics Laboratory diagnosis of creatine deficiency syndromes: a technical standard and guideline of the American College of Medical Genetics and Genomics J. Daniel Sharer, PhD1, Olaf Bodamer, MD, PhD2, Nicola Longo, MD, PhD3, Silvia Tortorelli, MD, PhD4,5, Mirjam M.C. Wamelink, PhD6 and Sarah Young, PhD7; a Workgroup of the ACMG Laboratory Quality Assurance Committee Disclaimer: These ACMG Standards and Guidelines are intended as an educational resource for clinical laboratory geneticists to help them provide quality clinical laboratory genetic services. Adherence to these standards and guidelines is voluntary and does not necessarily assure a successful medical outcome. These Standards and Guidelines should not be considered inclusive of all proper procedures and tests or exclusive of others that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, clinical laboratory geneticists should apply their professional judgment to the specific circumstances presented by the patient or specimen. Clinical laboratory geneticists are encouraged to document in the patient’s record the rationale for the use of a particular procedure or test, whether or not it is in conformance with these Standards and Guidelines. They also are advised to take notice of the date any particular guideline was adopted, and to consider other relevant medical and scientific information that becomes available after that date. It also would be prudent to consider whether intellectual property interests may restrict the performance of certain tests and other procedures. Cerebral creatine deficiency syndromes are neurometabolic condi- the diagnosis of creatine deficiency syndromes. -
Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’S Biological Network Based on Systematic Pharmacology
ORIGINAL RESEARCH published: 25 June 2021 doi: 10.3389/fphar.2021.601846 Exploring the Regulatory Mechanism of Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’s Biological Network Based on Systematic Pharmacology Kailin Yang 1†, Liuting Zeng 1†, Anqi Ge 2†, Yi Chen 1†, Shanshan Wang 1†, Xiaofei Zhu 1,3† and Jinwen Ge 1,4* Edited by: 1 Takashi Sato, Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of 2 Tokyo University of Pharmacy and Life Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China, Galactophore Department, The First 3 Sciences, Japan Hospital of Hunan University of Chinese Medicine, Changsha, China, School of Graduate, Central South University, Changsha, China, 4Shaoyang University, Shaoyang, China Reviewed by: Hui Zhao, Capital Medical University, China Background: Clinical research found that Hedysarum Multijugum Maxim.-Chuanxiong Maria Luisa Del Moral, fi University of Jaén, Spain Rhizoma Compound (HCC) has de nite curative effect on cerebral ischemic diseases, *Correspondence: such as ischemic stroke and cerebral ischemia-reperfusion injury (CIR). However, its Jinwen Ge mechanism for treating cerebral ischemia is still not fully explained. [email protected] †These authors share first authorship Methods: The traditional Chinese medicine related database were utilized to obtain the components of HCC. The Pharmmapper were used to predict HCC’s potential targets. Specialty section: The CIR genes were obtained from Genecards and OMIM and the protein-protein This article was submitted to interaction (PPI) data of HCC’s targets and IS genes were obtained from String Ethnopharmacology, a section of the journal database. -
Inherited Renal Tubulopathies—Challenges and Controversies
G C A T T A C G G C A T genes Review Inherited Renal Tubulopathies—Challenges and Controversies Daniela Iancu 1,* and Emma Ashton 2 1 UCL-Centre for Nephrology, Royal Free Campus, University College London, Rowland Hill Street, London NW3 2PF, UK 2 Rare & Inherited Disease Laboratory, London North Genomic Laboratory Hub, Great Ormond Street Hospital for Children National Health Service Foundation Trust, Levels 4-6 Barclay House 37, Queen Square, London WC1N 3BH, UK; [email protected] * Correspondence: [email protected]; Tel.: +44-2381204172; Fax: +44-020-74726476 Received: 11 February 2020; Accepted: 29 February 2020; Published: 5 March 2020 Abstract: Electrolyte homeostasis is maintained by the kidney through a complex transport function mostly performed by specialized proteins distributed along the renal tubules. Pathogenic variants in the genes encoding these proteins impair this function and have consequences on the whole organism. Establishing a genetic diagnosis in patients with renal tubular dysfunction is a challenging task given the genetic and phenotypic heterogeneity, functional characteristics of the genes involved and the number of yet unknown causes. Part of these difficulties can be overcome by gathering large patient cohorts and applying high-throughput sequencing techniques combined with experimental work to prove functional impact. This approach has led to the identification of a number of genes but also generated controversies about proper interpretation of variants. In this article, we will highlight these challenges and controversies. Keywords: inherited tubulopathies; next generation sequencing; genetic heterogeneity; variant classification. 1. Introduction Mutations in genes that encode transporter proteins in the renal tubule alter kidney capacity to maintain homeostasis and cause diseases recognized under the generic name of inherited tubulopathies. -
New Insights Into the Functional Mechanisms and Clinical Applications of the Kallikrein-Related Peptidase Family
MOLECULAR ONCOLOGY 1 (2007) 269–287 available at www.sciencedirect.com www.elsevier.com/locate/molonc Review New insights into the functional mechanisms and clinical applications of the kallikrein-related peptidase family Nashmil Emamia,b, Eleftherios P. Diamandisa,b,* aDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 1L5, Canada bDepartment of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada ABSTRACT ARTICLE INFO Article history: The Kallikrein-related peptidase (KLK) family consists of fifteen conserved serine proteases Received 13 July 2007 that form the largest contiguous cluster of proteases in the human genome. While primar- Received in revised form ily recognized for their clinical utilities as potential disease biomarkers, new compelling 4 September 2007 evidence suggests that this family plays a significant role in various physiological pro- Accepted 7 September 2007 cesses, including skin desquamation, semen liquefaction, neural plasticity, and body fluid Available online 15 September 2007 homeostasis. KLK activation is believed to be mediated through highly organized proteo- lytic cascades, regulated through a series of feedback loops, inhibitors, auto-degradation Keywords: and internal cleavages. Gene expression is mainly hormone-dependent, even though tran- Kallikrein-related peptidases scriptional epigenetic regulation has also been reported. These regulatory mechanisms are PSA integrated with various signaling pathways to mediate multiple functions. Dysregulation of Proteolytic cascades these pathways has been implicated in a large number of neoplastic and non-neoplastic Skin desquamation pathological conditions. This review highlights our current knowledge of structural/ * Corresponding author. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada. -
Table of Contents
Table of Contents Preface V List of contributing authors VII Table of Contents XI Introduction to Volume 1: Kallikrein-related Peptidases. Characterization, Regulation, and Interactions Within the Protease Web 1 Bibliography 3 1 Genomic Structure of the KLK Locus 5 1.1 Introduction 5 1.2 Kallikreins in rodents 6 1.2.1 The mouse kallikrein gene family 7 1.2.2 The rat kallikrein gene family 8 1.3 Characterization and sequence analysis of the human KLK gene locus 9 1.3.1 Locus overview 9 1.3.2 Repeat elements and pleomorphism 11 1.4 Structural features of the human KLK genes and proteins 12 1.4.1 Common structural features 12 1.5 Sequence variations of human KLK genes 13 1.6 Regulation of KLK activity 14 1.6.1 At the mRNA level 14 1.6.2 Locus control of KLK expression 15 1.6.3 Epigenetic regulation of KLK gene expression 17 1.7 Isoforms and splice variants of human KLKs 18 1.8 Evolution of KLKs 21 Bibliography 22 2 Single Nucleotide Polymorphisms in the Human KLK Locus and Their Implication in Various Diseases 31 2.1 Introduction 31 2.2 KLK SNPs – data-mining from SNPdb and 1000 Genomes 32 2.3 Functional annotations using web-based prediction tools 34 2.4 Experimentally validated functional KLK SNPs 35 2.5 KLK SNP haplotypes and tagging 36 2.6 Malignant and non-malignant diseases and association with KLK SNPs 38 2.6.1 Association studies on high-risk variants in KLK genes 39 XII Table of Contents 2.6.2 Association studies on low-risk variants in KLK genes 39 2.7 Conclusions 71 Bibliography 71 3 Evolution of Kallikrein-related Peptidases 79 -
Development and Validation of a Protein-Based Risk Score for Cardiovascular Outcomes Among Patients with Stable Coronary Heart Disease
Supplementary Online Content Ganz P, Heidecker B, Hveem K, et al. Development and validation of a protein-based risk score for cardiovascular outcomes among patients with stable coronary heart disease. JAMA. doi: 10.1001/jama.2016.5951 eTable 1. List of 1130 Proteins Measured by Somalogic’s Modified Aptamer-Based Proteomic Assay eTable 2. Coefficients for Weibull Recalibration Model Applied to 9-Protein Model eFigure 1. Median Protein Levels in Derivation and Validation Cohort eTable 3. Coefficients for the Recalibration Model Applied to Refit Framingham eFigure 2. Calibration Plots for the Refit Framingham Model eTable 4. List of 200 Proteins Associated With the Risk of MI, Stroke, Heart Failure, and Death eFigure 3. Hazard Ratios of Lasso Selected Proteins for Primary End Point of MI, Stroke, Heart Failure, and Death eFigure 4. 9-Protein Prognostic Model Hazard Ratios Adjusted for Framingham Variables eFigure 5. 9-Protein Risk Scores by Event Type This supplementary material has been provided by the authors to give readers additional information about their work. Downloaded From: https://jamanetwork.com/ on 10/02/2021 Supplemental Material Table of Contents 1 Study Design and Data Processing ......................................................................................................... 3 2 Table of 1130 Proteins Measured .......................................................................................................... 4 3 Variable Selection and Statistical Modeling ........................................................................................ -
Potential Role of Genomic Imprinted Genes and Brain Developmental
Li et al. BMC Medical Genomics (2020) 13:54 https://doi.org/10.1186/s12920-020-0693-2 RESEARCH ARTICLE Open Access Potential role of genomic imprinted genes and brain developmental related genes in autism Jian Li1*† , Xue Lin2†, Mingya Wang1†,YunyunHu1, Kaiyu Xue1,ShuanglinGu1,LiLv1, Saijun Huang3 and Wei Xie1* Abstract Background: Autism is a complex disease involving both environmental and genetic factors. Recent efforts have implicated the correlation of genomic imprinting and brain development in autism, however the pathogenesis of autism is not completely clear. Here, we used bioinformatic tools to provide a comprehensive analysis of the autism-related genes, genomic imprinted genes and the spatially and temporally differentially expressed genes of human brain, aiming to explore the relationship between autism, brain development and genomic imprinting. Methods: This study analyzed the distribution correlation between autism-related genes and imprinted genes on chromosomes using sliding windows and statistical methods. The normal brains’ gene expression microarray data were reanalyzed to construct a spatio-temporal coordinate system of gene expression during brain development. Finally, we intersected the autism-related genes, imprinted genes and brain spatio-temporally differentially expressed genes for further analysis to find the major biological processes that these genes involved. Results: We found a positive correlation between the autism-related genes’ and imprinted genes’ distribution on chromosomes. Through the analysis of the normal brain microarray data, we constructed a spatio-temporal coordinate system of gene expression during human brain development, and obtained 13 genes that are differentially expressed in the process of brain development, which are both autism-related genes and imprinted genes. -
Original Article KLK4 Is Synchronically Expressed to CTSC in Ameloblasts During Amelogenesis Molars
Int J Clin Exp Pathol 2017;10(5):5751-5757 www.ijcep.com /ISSN:1936-2625/IJCEP0047909 Original Article KLK4 is synchronically expressed to CTSC in ameloblasts during amelogenesis molars Lijie Wang1,2*, Xiaohua Xie1*, Yunduan Sun3, Jingyu Wang1, Yan Wang1, Xiumei Wang1 1Department of Stomatology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China; 2Department of Stomatology, General Hospital of Daqing Oil Field, Daqing, Heilongjiang Prov- ince, China; 3The 1st Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China. *Equal contributors. Received January 2, 2017; Accepted January 27, 2017; Epub May 1, 2017; Published May 15, 2017 Abstract: The aim of this study was to provide the evidence that the CTSC product, DPPI is the activator of KLK4 dur- ing amelogenesis by examining the expression pattern of KLK4 and CTSC in developing teeth. The 1st mandibular molars from E16.5 embryos and postnatal mice, and incisor from P5 mandibles were selected for the immunohisto- chemistry with antibodies against KLK4 and DPPI. The expression of KLK4 and CTSC were initiated from postnatal day 1 (P1) expressed in molar ameloblasts. From P5 on, KLK4 was distributed not only in ameloblasts, but also in the degenerating satellite reticulum of molar enamel organ. However, DPPI distribution is always restricted to the molar ameloblasts. In the P5 incisor, the distribution of KLK4 and DPPI were spatiotemporally consistent in the ameloblasts. The coincidence of KLK4 and DPPI distribution in ameloblasts strongly suggested that DPPI activated KLK4. The distribution of KLK4 in satellite reticulum suggested that KLK4 most likely plays a proteolytic role in degeneration of enamel organ. -
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Florida State University Libraries Faculty Publications The Department of Biomedical Sciences 2010 Functional Intersection of the Kallikrein- Related Peptidases (KLKs) and Thrombostasis Axis Michael Blaber, Hyesook Yoon, Maria Juliano, Isobel Scarisbrick, and Sachiko Blaber Follow this and additional works at the FSU Digital Library. For more information, please contact [email protected] Article in press - uncorrected proof Biol. Chem., Vol. 391, pp. 311–320, April 2010 • Copyright ᮊ by Walter de Gruyter • Berlin • New York. DOI 10.1515/BC.2010.024 Review Functional intersection of the kallikrein-related peptidases (KLKs) and thrombostasis axis Michael Blaber1,*, Hyesook Yoon1, Maria A. locus (Gan et al., 2000; Harvey et al., 2000; Yousef et al., Juliano2, Isobel A. Scarisbrick3 and Sachiko I. 2000), as well as the adoption of a commonly accepted Blaber1 nomenclature (Lundwall et al., 2006), resolved these two fundamental issues. The vast body of work has associated 1 Department of Biomedical Sciences, Florida State several cancer pathologies with differential regulation or University, Tallahassee, FL 32306-4300, USA expression of individual members of the KLK family, and 2 Department of Biophysics, Escola Paulista de Medicina, has served to elevate the importance of the KLKs in serious Universidade Federal de Sao Paulo, Rua Tres de Maio 100, human disease and their diagnosis (Diamandis et al., 2000; 04044-20 Sao Paulo, Brazil Diamandis and Yousef, 2001; Yousef and Diamandis, 2001, 3 Program for Molecular Neuroscience and Departments of 2003; -
Figure S1. Reverse Transcription‑Quantitative PCR Analysis of ETV5 Mrna Expression Levels in Parental and ETV5 Stable Transfectants
Figure S1. Reverse transcription‑quantitative PCR analysis of ETV5 mRNA expression levels in parental and ETV5 stable transfectants. (A) Hec1a and Hec1a‑ETV5 EC cell lines; (B) Ishikawa and Ishikawa‑ETV5 EC cell lines. **P<0.005, unpaired Student's t‑test. EC, endometrial cancer; ETV5, ETS variant transcription factor 5. Figure S2. Survival analysis of sample clusters 1‑4. Kaplan Meier graphs for (A) recurrence‑free and (B) overall survival. Survival curves were constructed using the Kaplan‑Meier method, and differences between sample cluster curves were analyzed by log‑rank test. Figure S3. ROC analysis of hub genes. For each gene, ROC curve (left) and mRNA expression levels (right) in control (n=35) and tumor (n=545) samples from The Cancer Genome Atlas Uterine Corpus Endometrioid Cancer cohort are shown. mRNA levels are expressed as Log2(x+1), where ‘x’ is the RSEM normalized expression value. ROC, receiver operating characteristic. Table SI. Clinicopathological characteristics of the GSE17025 dataset. Characteristic n % Atrophic endometrium 12 (postmenopausal) (Control group) Tumor stage I 91 100 Histology Endometrioid adenocarcinoma 79 86.81 Papillary serous 12 13.19 Histological grade Grade 1 30 32.97 Grade 2 36 39.56 Grade 3 25 27.47 Myometrial invasiona Superficial (<50%) 67 74.44 Deep (>50%) 23 25.56 aMyometrial invasion information was available for 90 of 91 tumor samples. Table SII. Clinicopathological characteristics of The Cancer Genome Atlas Uterine Corpus Endometrioid Cancer dataset. Characteristic n % Solid tissue normal 16 Tumor samples Stagea I 226 68.278 II 19 5.740 III 70 21.148 IV 16 4.834 Histology Endometrioid 271 81.381 Mixed 10 3.003 Serous 52 15.616 Histological grade Grade 1 78 23.423 Grade 2 91 27.327 Grade 3 164 49.249 Molecular subtypeb POLE 17 7.328 MSI 65 28.017 CN Low 90 38.793 CN High 60 25.862 CN, copy number; MSI, microsatellite instability; POLE, DNA polymerase ε. -
Functional and Structural Insights Into Astacin Metallopeptidases
Biol. Chem., Vol. 393, pp. 1027–1041, October 2012 • Copyright © by Walter de Gruyter • Berlin • Boston. DOI 10.1515/hsz-2012-0149 Review Functional and structural insights into astacin metallopeptidases F. Xavier Gomis-R ü th 1, *, Sergio Trillo-Muyo 1 Keywords: bone morphogenetic protein; catalytic domain; and Walter St ö cker 2, * meprin; metzincin; tolloid; zinc metallopeptidase. 1 Proteolysis Lab , Molecular Biology Institute of Barcelona, CSIC, Barcelona Science Park, Helix Building, c/Baldiri Reixac, 15-21, E-08028 Barcelona , Spain Introduction: a short historical background 2 Institute of Zoology , Cell and Matrix Biology, Johannes Gutenberg University, Johannes-von-M ü ller-Weg 6, The fi rst report on the digestive protease astacin from the D-55128 Mainz , Germany European freshwater crayfi sh, Astacus astacus L. – then termed ‘ crayfi sh small-molecule protease ’ or ‘ Astacus pro- * Corresponding authors tease ’ – dates back to the late 1960s (Sonneborn et al. , 1969 ). e-mail: [email protected]; [email protected] Protein sequencing by Zwilling and co-workers in the 1980s did not reveal homology to any other protein (Titani et al. , Abstract 1987 ). Shortly after, the enzyme was identifi ed as a zinc met- allopeptidase (St ö cker et al., 1988 ), and other family mem- The astacins are a family of multi-domain metallopepti- bers emerged. The fi rst of these was bone morphogenetic β dases with manifold functions in metabolism. They are protein 1 (BMP1), a protease co-purifi ed with TGF -like either secreted or membrane-anchored and are regulated growth factors termed bone morphogenetic proteins due by being synthesized as inactive zymogens and also by co- to their capacity to induce ectopic bone formation in mice localizing protein inhibitors. -
Clinical Significance of Kallikrein-Related Peptidase-4 in Oral Cancer
ANTICANCER RESEARCH 35: 1861-1866 (2015) Clinical Significance of Kallikrein-related Peptidase-4 in Oral Cancer PETROS PAPAGERAKIS1,2, GIUSEPPE PANNONE3, LI ZHENG1,4, MARIA ATHANASSIOU-PAPAEFTHYMIOU1,4, YASHUO YAMAKOSHI5, HOWARD STAN MCGUFF6, OMAR SHKEIR4, KONSTANTINOS GHIRTIS1,4 and SILVANA PAPAGERAKIS4 Departments of 1Pediatric Dentistry and Orthodontics and 5Biomaterials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI, U.S.A.; Departments of 2Computational Medicine and Bioinformatics and 4Otolaryngology-Head & Neck Surgery, Medical School, University of Michigan, Ann Arbor, MI, U.S.A.; 3Department of Clinical and Experimental Medicine, Section of Anatomic Pathology, University of Foggia, Foggia, Italy; 6Department of Pathology, School of Medicine, University of Texas Health Science Center, San Antonio, TX, U.S.A. Abstract. Kallikrein-related-peptidase-4 (KLK4), a serine zymograms. Inhibition of KLK4 expression results in protease originally discovered in developing tooth with broad diminished invasive potential in OSCC cell lines. Consistently, target sequence specificity, serves vital functions in dental KLK4 expression is stronger in primary tumors that later enamel formation. KLK4 is involved in degradation of extra - either recurred or developed metastases, suggesting that its cellular matrix proteins and it is thought that this proteolytic preferential expression in OSCC might contribute to activity could also promote tumor invasion and metastasis. individual tumor biology. Therefore, this study provides Recent studies have associated KLK4 expression with tumor supportive evidence in favor of a prognostic value for KLK4 progression and clinical outcome, particularly in prostate and in OSCC and suggests that KLK4 could serve as a potential ovarian cancer. Very little is known in regard KLK4 therapeutic target in patients with oral cancer.