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Lacritin Rescues Stressed Epithelia Via Rapid Forkhead Box O3
THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 288, NO. 25, pp. 18146–18161, June 21, 2013 © 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A. Lacritin Rescues Stressed Epithelia via Rapid Forkhead Box O3 (FOXO3)-associated Autophagy That Restores Metabolism*□S Received for publication, November 14, 2012, and in revised form, May 1, 2013 Published, JBC Papers in Press, May 2, 2013, DOI 10.1074/jbc.M112.436584 Ningning Wang‡, Keith Zimmerman‡, Ronald W. Raab§, Robert L. McKown§, Cindy M. L. Hutnik¶, Venu Talla‡, Milton F. Tyler, IV‡, Jae K. Leeʈ**, and Gordon W. Laurie‡ ‡‡1 From the Departments of ‡Cell Biology, ʈPublic Health Sciences, **Systems and Information Engineering, and ‡‡Ophthalmology, University of Virginia, Charlottesville, Virginia 22908, §Department of Integrated Science and Technology, James Madison University, Harrisonburg, Virginia 22807, and ¶Department of Ophthalmology, University of Western Ontario, London, Ontario N6A 4V2, Canada Background: Homeostatic regulation of epithelia influences disease acquisition and aging. Results: Prosecretory mitogen lacritin stimulates FOXO3-ATG101 and FOXO1-ATG7 autophagic coupling and restores met- abolic homeostasis. Conclusion: Lacritin is a homeostatic regulator. Significance: Exogenous lacritin restores prohomeostatic activity to tears from dry eye individuals. Homeostasis is essential for cell survival. However, homeo- trol can trigger developmental abnormalities, disease, or death static regulation of surface epithelia is poorly understood. The (3). How homeostasis is controlled is an investigative area with eye surface, lacking the cornified barrier of skin, provides an wide biological significance. excellent model. Tears cover the surface of the eye and are defi- Macroautophagy (hereafter referred to as autophagy) con- cient in dry eye, the most common eye disease affecting at least tributes to the regulation of homeostasis. -
Biosynthesized Multivalent Lacritin Peptides Stimulate Exosome Production in Human Corneal Epithelium
International Journal of Molecular Sciences Article Biosynthesized Multivalent Lacritin Peptides Stimulate Exosome Production in Human Corneal Epithelium Changrim Lee 1, Maria C. Edman 2 , Gordon W. Laurie 3 , Sarah F. Hamm-Alvarez 1,2,* and J. Andrew MacKay 1,2,4,* 1 Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90033, USA; [email protected] 2 Department of Ophthalmology, USC Roski Eye Institute and Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; [email protected] 3 Department of Cell Biology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA; [email protected] 4 Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089, USA * Correspondence: [email protected] (S.F.H.-A.); [email protected] (J.A.M.) Received: 30 July 2020; Accepted: 24 August 2020; Published: 26 August 2020 Abstract: Lacripep is a therapeutic peptide derived from the human tear protein, Lacritin. Lacripep interacts with syndecan-1 and induces mitogenesis upon the removal of heparan sulfates (HS) that are attached at the extracellular domain of syndecan-1. The presence of HS is a prerequisite for the syndecan-1 clustering that stimulates exosome biogenesis and release. Therefore, syndecan-1- mediated mitogenesis versus HS-mediated exosome biogenesis are assumed to be mutually exclusive. This study introduces a biosynthesized fusion between Lacripep and an elastin-like polypeptide named LP-A96, and evaluates its activity on cell motility enhancement versus exosome biogenesis. LP-A96 activates both downstream pathways in a dose-dependent manner. -
Clinical Study of Canine Tear Lacritin As a Treatment for Dry Eye Katherine E
James Madison University JMU Scholarly Commons Senior Honors Projects, 2010-current Honors College Spring 2016 Clinical study of canine tear lacritin as a treatment for dry eye Katherine E. Kelly James Madison University Follow this and additional works at: https://commons.lib.jmu.edu/honors201019 Part of the Amino Acids, Peptides, and Proteins Commons, Biotechnology Commons, and the Small or Companion Animal Medicine Commons Recommended Citation Kelly, Katherine E., "Clinical study of canine tear lacritin as a treatment for dry eye" (2016). Senior Honors Projects, 2010-current. 169. https://commons.lib.jmu.edu/honors201019/169 This Thesis is brought to you for free and open access by the Honors College at JMU Scholarly Commons. It has been accepted for inclusion in Senior Honors Projects, 2010-current by an authorized administrator of JMU Scholarly Commons. For more information, please contact [email protected]. Clinical Study of Canine Tear Lacritin as a Treatment for Dry Eye _______________________ An Honors Program Project Presented to the Faculty of the Undergraduate College of Integrated Science and Engineering James Madison University _______________________ by Katherine Elizabeth Kelly May 2016 Accepted by the faculty of the Department of ISAT, James Madison University, in partial fulfillment of the requirements for the Honors Program. FACULTY COMMITTEE: HONORS PROGRAM APPROVAL: Project Advisor: Robert McKown, Ph. D. Bradley R. Newcomer, Ph.D., Professor, ISAT Director, Honors Program Reader: Ronald Raab, Ph. D. Professor, ISAT Reader: Stephanie Stockwell, Ph. D. Assistant Professor, ISAT PUBLIC PRESENTATION This work is accepted for presentation, in part or in full, at [venue] The ISAT Senior Capstone Symposium on [date] April 15th, 2016 . -
Tear Proteomics Study of Dry Eye Disease: Which Eye Do You Adopt As the Representative Eye for the Study?
International Journal of Molecular Sciences Article Tear Proteomics Study of Dry Eye Disease: Which Eye Do You Adopt as the Representative Eye for the Study? Ming-Tse Kuo 1,* , Po-Chiung Fang 1, Shu-Fang Kuo 2,3 , Alexander Chen 1 and Yu-Ting Huang 1 1 Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; [email protected] (P.-C.F.); [email protected] (A.C.); [email protected] (Y.-T.H.) 2 Department of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; [email protected] 3 Department of Medical Biotechnology and Laboratory Sciences, College of and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan * Correspondence: [email protected]; Tel.: +886-7731-7123 (ext. 2801) Abstract: Most studies about dry eye disease (DED) chose unilateral eye for investigation and drew conclusions based on monocular results, whereas most studies involving tear proteomics were based on the results of pooling tears from a group of DED patients. Patients with DED were consecutively enrolled for binocular clinical tests, tear biochemical markers of DED, and tear proteome. We found that bilateral eyes of DED patients may have similar but different ocular surface performance and tear proteome. Most ocular surface homeostatic markers and tear biomarkers were not significantly different in the bilateral eyes of DED subjects, and most clinical parameters and tear biomarkers were correlated significantly between bilateral eyes. However, discrepant binocular presentation in the markers of ocular surface homeostasis and the associations with tear proteins suggested that one eye’s performance cannot represent that of the other eye or both eyes. -
Cellular and Molecular Signatures in the Disease Tissue of Early
Cellular and Molecular Signatures in the Disease Tissue of Early Rheumatoid Arthritis Stratify Clinical Response to csDMARD-Therapy and Predict Radiographic Progression Frances Humby1,* Myles Lewis1,* Nandhini Ramamoorthi2, Jason Hackney3, Michael Barnes1, Michele Bombardieri1, Francesca Setiadi2, Stephen Kelly1, Fabiola Bene1, Maria di Cicco1, Sudeh Riahi1, Vidalba Rocher-Ros1, Nora Ng1, Ilias Lazorou1, Rebecca E. Hands1, Desiree van der Heijde4, Robert Landewé5, Annette van der Helm-van Mil4, Alberto Cauli6, Iain B. McInnes7, Christopher D. Buckley8, Ernest Choy9, Peter Taylor10, Michael J. Townsend2 & Costantino Pitzalis1 1Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. Departments of 2Biomarker Discovery OMNI, 3Bioinformatics and Computational Biology, Genentech Research and Early Development, South San Francisco, California 94080 USA 4Department of Rheumatology, Leiden University Medical Center, The Netherlands 5Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology & Immunology Center, Amsterdam, The Netherlands 6Rheumatology Unit, Department of Medical Sciences, Policlinico of the University of Cagliari, Cagliari, Italy 7Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK 8Rheumatology Research Group, Institute of Inflammation and Ageing (IIA), University of Birmingham, Birmingham B15 2WB, UK 9Institute of -
Cdna and Genomic Cloning of Lacritin, a Novel Secretion Enhancing Factor from the Human Lacrimal Gland
doi:10.1006/jmbi.2001.4748 available online at http://www.idealibrary.com on J. Mol. Biol. (2001) 310, 127±139 cDNA and Genomic Cloning of Lacritin, a Novel Secretion Enhancing Factor from the Human Lacrimal Gland Sandhya Sanghi1, Rajesh Kumar1, Angela Lumsden1 Douglas Dickinson2, Veronica Klepeis3, Vickery Trinkaus-Randall3 Henry F. Frierson Jr4 and Gordon W. Laurie1* 1Department of Cell Biology Multiple extracellular factors are hypothesized to promote the differen- University of Virginia tiation of unstimulated and/or stimulated secretory pathways in exocrine Charlottesville, VA 22908 USA secretory cells, but the identity of differentiation factors, particularly those organ-speci®c, remain largely unknown. Here, we report on the 2Department of Oral Biology identi®cation of a novel secreted glycoprotein, lacritin, that enhances exo- Medical College of Georgia crine secretion in overnight cultures of lacrimal acinar cells which other- Augusta, GA 30912 USA wise display loss of secretory function. Lacritin mRNA and protein are 3Department of Biochemistry highly expressed in human lacrimal gland, moderately in major and Boston University, Boston, MA minor salivary glands and slightly in thyroid. No lacritin message or pro- 02118 USA tein is detected elsewhere among more than 50 human tissues examined. 4 Lacritin displays partial similarity to the glycosaminoglycan-binding Department of Pathology region of brain-speci®c neuroglycan C (32 % identity over 102 amino University of Virginia acid residues) and to the possibly mucin-like amino globular region of Charlottesville, VA 22908 ®bulin-2 (30 % identity over 81 amino acid residues), and localizes pri- USA marily to secretory granules and secretory ¯uid. The lacritin gene consists of ®ve exons, displays no alternative splicing and maps to 12q13. -
Levels of Human Tear Lacritin Isoforms in Healthy Adults Brooke Justis
James Madison University JMU Scholarly Commons Senior Honors Projects, 2010-current Honors College Spring 2019 Levels of human tear lacritin isoforms in healthy adults Brooke Justis Follow this and additional works at: https://commons.lib.jmu.edu/honors201019 Part of the Ophthalmology Commons Recommended Citation Justis, Brooke, "Levels of human tear lacritin isoforms in healthy adults" (2019). Senior Honors Projects, 2010-current. 687. https://commons.lib.jmu.edu/honors201019/687 This Thesis is brought to you for free and open access by the Honors College at JMU Scholarly Commons. It has been accepted for inclusion in Senior Honors Projects, 2010-current by an authorized administrator of JMU Scholarly Commons. For more information, please contact [email protected]. Levels of Human Tear Lacritin Isoforms in Healthy Adults _______________________ An Honors College Project Presented to the Faculty of the Undergraduate College of Science and Mathematics James Madison University _______________________ by Brooke Madison Justis April 9th 2019 Accepted by the faculty of the Department of ISAT, James Madison University, in partial fulfillment of the requirements for the Honors College. FACULTY COMMITTEE: HONORS COLLEGE APPROVAL: Project Advisor: Robert McKown, Ph.D. Bradley R. Newcomer, Ph.D., Professor, ISAT Dean, Honors College Reader: Ronald Raab, Ph.D. Professor, ISAT Reader: Louise Temple, Ph.D. Professor, ISAT PUBLIC PRESENTATION This work is accepted for presentation at the ISAT Senior Capstone Symposium on April 12th, 2019. TABLE OF CONTENTS Acknowledgements 3 Abstract 4 Introduction 4 Materials and Methods 7 Results 10 Discussion 18 References 21 Appendix A: Bicinchoninic Assay Data 23 Appendix B: Quantitated Western Blot Data 28 LIST OF FIGURES Figure 1. -
The Network Organization of Cancer-Associated Protein
The Network Organization of Cancer-associated Protein Complexes in SUBJECT AREAS: PROTEOME Human Tissues INFORMATICS COMPUTATIONAL SCIENCE Jing Zhao1, Sang Hoon Lee2,3, Mikael Huss4,5 & Petter Holme2,6 ONCOGENESIS COMPLEX NETWORKS 1Department of Mathematics, Logistical Engineering University, Chongqing, China, 2IceLab, Department of Physics, Umea˚ University, Umea˚, Sweden, 3Oxford Centre for Industrial and Applied Mathematics, Mathematical Institute, University of Oxford, Oxford, United Kingdom, 4Science for Life Laboratory Stockholm, Solna, Sweden, 5Department of Biochemistry and Biophysics, Received Stockholm University, Stockholm, Sweden, 6Department of Energy Science, Sungkyunkwan University, Suwon, Korea. 24 October 2012 Accepted Differential gene expression profiles for detecting disease genes have been studied intensively in systems 7 March 2013 biology. However, it is known that various biological functions achieved by proteins follow from the ability of the protein to form complexes by physically binding to each other. In other words, the functional units are Published often protein complexes rather than individual proteins. Thus, we seek to replace the perspective of 9 April 2013 disease-related genes by disease-related complexes, exemplifying with data on 39 human solid tissue cancers and their original normal tissues. To obtain the differential abundance levels of protein complexes, we apply an optimization algorithm to genome-wide differential expression data. From the differential abundance of Correspondence and complexes, we extract tissue- and cancer-selective complexes, and investigate their relevance to cancer. The method is supported by a clustering tendency of bipartite cancer-complex relationships, as well as a more requests for materials concrete and realistic approach to disease-related proteomics. should be addressed to J.Z. -
Tear Biomarkers in Dry Eye Disease
Review Dry Eye Disease Tear Biomarkers in Dry Eye Disease Andreea Chiva Department of Clinical Chemistry, University Emergency Hospital, Bucharest, Romania DOI: https://doi.org/10.17925/EOR.2019.13.1.21 he diagnosis of dry eye disease (the early stages in particular) is important, but difficult, due to the lack of gold standards and poor correlation between tear biochemical changes and clinical signs. The current diagnostic tests (Schirmer’s tests, tear film break-up time, Tand vital staining of the ocular surface) are more sensitive for severe cases. As a proximal fluid of the ocular surface, tear film analysis could be a promising area in the diagnosis and monitoring of dry eye because of the non-invasive nature of tear sampling procedures and the significant correlation between tear biochemical changes and progression of the disease. This article provides an overview of the most important tear biomarkers for dry eye disease (markers for lacrimal gland dysfunction, contact lens intolerance, inflammation, and oxidative stress) and their correlation with disease subtype and severity. The role of SDS-agarose gel electrophoresis of tear proteins (Hyrys-Hydrasys System, Sebia, Evry, France) as a potential routine test in diagnosis and management of dry eye disease and high-risk groups (computer users, contact lens wearers, cataract surgery, and glaucoma) is also detailed. Keywords Dry eye disease (DED) is a common ocular condition with a high impact on visual function and Contact lens, dry eye, electrophoresis, glaucoma, quality of life.1 However, DED is one of the most misdiagnosed diseases because of a delay in inflammation, lactoferrin, lysozyme, oxidative symptoms and clinical signs, and the lack of unitary diagnostic criteria.2,3 Moreover, current stress, tear biomarkers, tear proteome diagnostic tests are useful only in severe cases.2 Thus, the identification of new tests for the diagnosis and management of DED is of great interest, and tear-biomarker assessment is a Disclosure: Andreea Chiva has nothing to declare in relation to this article. -
Molecular Markers of Diabetic Retinopathy: Potential Screening Tool of the Future?
REVIEW published: 01 June 2016 doi: 10.3389/fphys.2016.00200 Molecular Markers of Diabetic Retinopathy: Potential Screening Tool of the Future? Priyia Pusparajah 1*, Learn-Han Lee 2, 3* and Khalid Abdul Kadir 1 1 Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Malaysia, 2 School of Pharmacy, Monash University Malaysia, Bandar Sunway, Malaysia, 3 Center of Health Outcomes Research and Therapeutic Safety (Cohorts), School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand Diabetic retinopathy (DR) is among the leading causes of new onset blindness in adults. Effective treatment may delay the onset and progression of this disease provided it is diagnosed early. At present retinopathy can only be diagnosed via formal examination of the eye by a trained specialist, which limits the population that can be effectively screened. An easily accessible, reliable screening biomarker of diabetic retinopathy would be of tremendous benefit in detecting the population in need of further assessment and treatment. This review highlights specific biomarkers that show promise as screening markers to detect early diabetic retinopathy or even to detect patients at increased risk of DR at the time of diagnosis of diabetes. The pathobiology of DR is complex and Edited by: Gaetano Santulli, multifactorial giving rise to a wide array of potential biomarkers. This review provides an Columbia University, USA overview of these pathways and looks at older markers such as advanced glycation end Reviewed -
January 2019 Volume 66 · Issue 01
ISSN 0002-9920 (print) ISSN 1088-9477 (online) Notices ofof the American MathematicalMathematical Society January 2019 Volume 66, Number 1 The cover art is from the JMM Sampler, page 84. AT THE AMS BOOTH, JMM 2019 ISSN 0002-9920 (print) ISSN 1088-9477 (online) Notices of the American Mathematical Society January 2019 Volume 66, Number 1 © Pomona College © Pomona Talk to Erica about the AMS membership magazine, pick up a free Notices travel mug*, and enjoy a piece of cake. facebook.com/amermathsoc @amermathsoc A WORD FROM... Erica Flapan, Notices Editor in Chief I would like to introduce myself as the new Editor in Chief of the Notices and share my plans with readers. The Notices is an interesting and engaging magazine that is read by mathematicians all over the world. As members of the AMS, we should all be proud to have the Notices as our magazine of record. Personally, I have enjoyed reading the Notices for over 30 years, and I appreciate the opportunity that the AMS has given me to shape the magazine for the next three years. I hope that under my leadership even more people will look forward to reading it each month as much as I do. Above all, I would like the focus of the Notices to be on expository articles about pure and applied mathematics broadly defined. I would like the authors, topics, and writing styles of these articles to be diverse in every sense except for their desire to explain the mathematics that they love in a clear and engaging way. -
International Conference on Deep Brain Stimulation – 25 Years –
We thank all exhibitors and sponsors Programme for their generous support Special thanks to our platinum sponsors International Conference on Deep Brain Stimulation – 25 years – Special thanks to our gold sponsors Special thanks to our silver sponsors FHCNeural microTargeting™ Worldwide Exhibitors AbbVie Deutschland GmbH & Co. KG | Wiesbaden (D) ALPHA OMEGA GmbH | Ubstadt-Weihes (D) Boston Scientific Medizintechnik GmbH | Ratingen (D) Brainlab Sales GmbH | Feldkirchen (D) Cyberonics Europe Bvba | Zaventem (B) Elekta GmbH | Hamburg (D) FHC Inc. | Bowdoin, ME (USA) inomed Medizintechnik GmbH | Emmendingen (D) May 30th - May 31st, 2013 MEDA Pharma GmbH & Co. KG | Bad Homburg (D) Hyatt Regency Medtech S.A.S. | Montpellier (F) Düsseldorf | Germany Medtronic GmbH | Meerbusch (D) Renishaw GmbH | Pliezhausen (D) Synaptix N.V. | Niel (B) Chairmen: St. Jude Medical Coordination Center Bvba | Zaventem (B) Alfons Schnitzler, MD | Jan Vesper, MD TEVA Pharma GmbH | Berlin (D) Conference Secretary: Ziehm Imaging GmbH | Nürnberg (D) Martin Südmeyer, MD | Lars Wojtecki, MD University Hospital Düsseldorf 33 Moorenstraße 5 | D-40225 Düsseldorf | Germany Table of contents / Imprint Greetings by Dirk Elbers 5 Welcome address 7 Scientific programme Thursday May 30th, 2013 8 Scientific programme Friday May 31st, 2013 10 Abstracts: Oral presentations 13 Abstracts 18 General information 28 Floor plan of the exhibition 32 Exhibitors and sponsors 33 Editors Alfons Schnitzler, MD | Jan Vesper, MD University Hospital Düsseldorf Moorenstraße 5 | D-40225 Düsseldorf | Germany Organizer bsh medical communications GmbH Liebfrauenstraße 7 | D-40591 Düsseldorf Phone: +49 (0) 211 - 770 589 - 0 | Fax: - 29 [email protected] | www.medical-communications.de Cover picture Andrea Schaufler-Jurányi, Vienna (A) Graphic design ProScript Michael Hellmessen | www.proscript-mh.de The content and works provided in these booklet are governed by the copyright laws of Germany.