Beta Cell Adaptation to Pregnancy Requires Prolactin Action on Both
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Transcriptomic Analysis of Human Brain Microvascular Endothelial
www.nature.com/scientificreports OPEN Transcriptomic analysis of human brain microvascular endothelial cells exposed to laminin binding protein (adhesion lipoprotein) and Streptococcus pneumoniae Irene Jiménez‑Munguía1, Zuzana Tomečková1, Evelína Mochnáčová1, Katarína Bhide1, Petra Majerová2 & Mangesh Bhide1,2* Streptococcus pneumoniae invades the CNS and triggers a strong cellular response. To date, signaling events that occur in the human brain microvascular endothelial cells (hBMECs), in response to pneumococci or its surface adhesins are not mapped comprehensively. We evaluated the response of hBMECs to the adhesion lipoprotein (a laminin binding protein—Lbp) or live pneumococci. Lbp is a surface adhesin recently identifed as a potential ligand, which binds to the hBMECs. Transcriptomic analysis was performed by RNA‑seq of three independent biological replicates and validated with qRT‑PCR using 11 genes. In total 350 diferentially expressed genes (DEGs) were identifed after infection with S. pneumoniae, whereas 443 DEGs when challenged with Lbp. Total 231 DEGs were common in both treatments. Integrative functional analysis revealed participation of DEGs in cytokine, chemokine, TNF signaling pathways and phagosome formation. Moreover, Lbp induced cell senescence and breakdown, and remodeling of ECM. This is the frst report which maps complete picture of cell signaling events in the hBMECs triggered against S. pneumoniae and Lbp. The data obtained here could contribute in a better understanding of the invasion of pneumococci across BBB and underscores role of Lbp adhesin in evoking the gene expression in neurovascular unit. Streptococcus pneumoniae (also known as pneumococcus) is a life-threatening pathogen responsible for high morbidity and mortality rates worldwide1. It can cross the blood–brain barrier (BBB) and cause meningitis, commonly known as pneumococcal meningitis, a rare but life-threatening medical emergency. -
The Rise and Fall of the Bovine Corpus Luteum
University of Nebraska Medical Center DigitalCommons@UNMC Theses & Dissertations Graduate Studies Spring 5-6-2017 The Rise and Fall of the Bovine Corpus Luteum Heather Talbott University of Nebraska Medical Center Follow this and additional works at: https://digitalcommons.unmc.edu/etd Part of the Biochemistry Commons, Molecular Biology Commons, and the Obstetrics and Gynecology Commons Recommended Citation Talbott, Heather, "The Rise and Fall of the Bovine Corpus Luteum" (2017). Theses & Dissertations. 207. https://digitalcommons.unmc.edu/etd/207 This Dissertation is brought to you for free and open access by the Graduate Studies at DigitalCommons@UNMC. It has been accepted for inclusion in Theses & Dissertations by an authorized administrator of DigitalCommons@UNMC. For more information, please contact [email protected]. THE RISE AND FALL OF THE BOVINE CORPUS LUTEUM by Heather Talbott A DISSERTATION Presented to the Faculty of the University of Nebraska Graduate College in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Biochemistry and Molecular Biology Graduate Program Under the Supervision of Professor John S. Davis University of Nebraska Medical Center Omaha, Nebraska May, 2017 Supervisory Committee: Carol A. Casey, Ph.D. Andrea S. Cupp, Ph.D. Parmender P. Mehta, Ph.D. Justin L. Mott, Ph.D. i ACKNOWLEDGEMENTS This dissertation was supported by the Agriculture and Food Research Initiative from the USDA National Institute of Food and Agriculture (NIFA) Pre-doctoral award; University of Nebraska Medical Center Graduate Student Assistantship; University of Nebraska Medical Center Exceptional Incoming Graduate Student Award; the VA Nebraska-Western Iowa Health Care System Department of Veterans Affairs; and The Olson Center for Women’s Health, Department of Obstetrics and Gynecology, Nebraska Medical Center. -
KLF2 Induced
UvA-DARE (Digital Academic Repository) The transcription factor KLF2 in vascular biology Boon, R.A. Publication date 2008 Link to publication Citation for published version (APA): Boon, R. A. (2008). The transcription factor KLF2 in vascular biology. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:23 Sep 2021 Supplementary data: Genes induced by KLF2 Dekker et al. LocusLink Accession Gene Sequence Description Fold p-value ID number symbol change (FDR) 6654 AK022099 SOS1 cDNA FLJ12037 fis, clone HEMBB1001921. 100.00 5.9E-09 56999 AF086069 ADAMTS9 full length insert cDNA clone YZ35C05. 100.00 1.2E-09 6672 AF085934 SP100 full length insert cDNA clone YR57D07. 100.00 6.7E-13 9031 AF132602 BAZ1B Williams Syndrome critical region WS25 mRNA, partial sequence. -
Roles and Regulation of Transcription Factor Mafa in Islet Β-Cells
Endocr. J./ S. ARAMATA et al.: INSULIN TRANSCRIPTION AND MafA doi: 10.1507/endocrj.KR-101 REVIEW Roles and Regulation of Transcription Factor MafA in Islet β-cells * SHINSAKU ARAMATA, SONG-IEE HAN AND KOHSUKE KATAOKA Graduate School of Biological Science, Nara Institute of Science and Technology, 8916-5 Takayama-cho, Ikoma, Nara 630-0192, Japan *Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan. Released online August 30, 2007 Correspondence to: Kohsuke KATAOKA, Graduate School of Biological Science, Nara Institute of Science and Technology, 8916-5 Takayama-cho, Ikoma, Nara 630-0192, Japan Abstract. Insulin is a critical hormone in the regulation of blood glucose levels. It is produced exclusively by pancreatic islet β-cells. β-cell-enriched transcription factors, such as Pdx1 and Beta2, have dual roles in the activation of the insulin gene promoter establishing β-cell-specific insulin expression, and in the regulation of β-cell differentiation. It was shown that MafA, a β-cell-specific member of the Maf family of transcription factors, binds to the conserved C1/RIPE3b element of the insulin promoter. The Maf family proteins regulate tissue-specific gene expression and cell differentiation in a wide variety of tissues. MafA acts synergistically with Pdx1 and Beta2 to activate the insulin gene promoter, and mice with a targeted deletion of mafA develop age-dependent diabetes. MafA also regulates genes involved in β-cell function such as Glucose transporter 2, Glucagons-like peptide 1 receptor, and Prohormone convertase 1/3. The abundance of MafA in β-cells is regulated at both the transcriptional and post-translational levels by glucose and oxidative stress. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Steroid-Dependent Regulation of the Oviduct: a Cross-Species Transcriptomal Analysis
University of Kentucky UKnowledge Theses and Dissertations--Animal and Food Sciences Animal and Food Sciences 2015 Steroid-dependent regulation of the oviduct: A cross-species transcriptomal analysis Katheryn L. Cerny University of Kentucky, [email protected] Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Cerny, Katheryn L., "Steroid-dependent regulation of the oviduct: A cross-species transcriptomal analysis" (2015). Theses and Dissertations--Animal and Food Sciences. 49. https://uknowledge.uky.edu/animalsci_etds/49 This Doctoral Dissertation is brought to you for free and open access by the Animal and Food Sciences at UKnowledge. It has been accepted for inclusion in Theses and Dissertations--Animal and Food Sciences by an authorized administrator of UKnowledge. For more information, please contact [email protected]. STUDENT AGREEMENT: I represent that my thesis or dissertation and abstract are my original work. Proper attribution has been given to all outside sources. I understand that I am solely responsible for obtaining any needed copyright permissions. I have obtained needed written permission statement(s) from the owner(s) of each third-party copyrighted matter to be included in my work, allowing electronic distribution (if such use is not permitted by the fair use doctrine) which will be submitted to UKnowledge as Additional File. I hereby grant to The University of Kentucky and its agents the irrevocable, non-exclusive, and royalty-free license to archive and make accessible my work in whole or in part in all forms of media, now or hereafter known. -
1 Metabolic Dysfunction Is Restricted to the Sciatic Nerve in Experimental
Page 1 of 255 Diabetes Metabolic dysfunction is restricted to the sciatic nerve in experimental diabetic neuropathy Oliver J. Freeman1,2, Richard D. Unwin2,3, Andrew W. Dowsey2,3, Paul Begley2,3, Sumia Ali1, Katherine A. Hollywood2,3, Nitin Rustogi2,3, Rasmus S. Petersen1, Warwick B. Dunn2,3†, Garth J.S. Cooper2,3,4,5* & Natalie J. Gardiner1* 1 Faculty of Life Sciences, University of Manchester, UK 2 Centre for Advanced Discovery and Experimental Therapeutics (CADET), Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, UK 3 Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, UK 4 School of Biological Sciences, University of Auckland, New Zealand 5 Department of Pharmacology, Medical Sciences Division, University of Oxford, UK † Present address: School of Biosciences, University of Birmingham, UK *Joint corresponding authors: Natalie J. Gardiner and Garth J.S. Cooper Email: [email protected]; [email protected] Address: University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, United Kingdom Telephone: +44 161 275 5768; +44 161 701 0240 Word count: 4,490 Number of tables: 1, Number of figures: 6 Running title: Metabolic dysfunction in diabetic neuropathy 1 Diabetes Publish Ahead of Print, published online October 15, 2015 Diabetes Page 2 of 255 Abstract High glucose levels in the peripheral nervous system (PNS) have been implicated in the pathogenesis of diabetic neuropathy (DN). However our understanding of the molecular mechanisms which cause the marked distal pathology is incomplete. Here we performed a comprehensive, system-wide analysis of the PNS of a rodent model of DN. -
Rb and P53 Execute Distinct Roles in the Development of Pancreatic Neuroendocrine Tumors
Author Manuscript Published OnlineFirst on June 26, 2020; DOI: 10.1158/0008-5472.CAN-19-2232 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. 1 Title: Rb and p53 execute distinct roles in the development of pancreatic neuroendocrine tumors 2 Running Title: Roles of Rb and p53 in pancreatic neuroendocrine tumors 3 4 1Yuki Yamauchi, 1,2Yuzo Kodama, 1Masahiro Shiokawa, 1Nobuyuki Kakiuchi, 1Saiko Marui, 5 1Takeshi Kuwada, 1Yuko Sogabe, 1Teruko Tomono, 1Atsushi Mima, 1Toshihiro Morita, 1Tomoaki 6 Matsumori, 1Tatsuki Ueda, 1Motoyuki Tsuda, 1Yoshihiro Nishikawa, 1Katsutoshi Kuriyama, 7 1Yojiro Sakuma, 1Yuji Ota, 1Takahisa Maruno, 1Norimitsu Uza, 2Atsuhiro Masuda, 3Hisato 8 Tatsuoka, 3Daisuke Yabe, 4Sachiko Minamiguchi, 5Toshihiko Masui, 3Nobuya Inagaki, 5Shinji 9 Uemoto, 1,6Tsutomu Chiba, and 1Hiroshi Seno 10 11 1Department of Gastroenterology and Hepatology, Kyoto University Graduate School of 12 Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. 13 2Department of Gastroenterology, Kobe University Graduate School of Medicine, 7-5-1 14 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan. 15 3Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of 16 Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. 17 4Department of Diagnostic Pathology, Kyoto University Graduate School of Medicine, 54 18 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. 1 Downloaded from cancerres.aacrjournals.org on September 28, 2021. © 2020 American Association for Cancer Research. Author Manuscript Published OnlineFirst on June 26, 2020; DOI: 10.1158/0008-5472.CAN-19-2232 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. -
Insulin/Glucose-Responsive Cells Derived from Induced Pluripotent Stem Cells: Disease Modeling and Treatment of Diabetes
Insulin/Glucose-Responsive Cells Derived from Induced Pluripotent Stem Cells: Disease Modeling and Treatment of Diabetes Sevda Gheibi *, Tania Singh, Joao Paulo M.C.M. da Cunha, Malin Fex and Hindrik Mulder * Unit of Molecular Metabolism, Lund University Diabetes Centre, Jan Waldenströms gata 35; Box 50332, SE-202 13 Malmö, Sweden; [email protected] (T.S.); [email protected] (J.P.M.C.M.d.C.); [email protected] (M.F.) * Correspondence: [email protected] (S.G.); [email protected] (H.M.) Supplementary Table 1. Transcription factors associated with development of the pancreas. Developmental Gene Aliases Function Ref. Stage SRY-Box Transcription Factor Directs the primitive endoderm SOX17 DE, PFE, PSE [1] 17 specification. Establishes lineage-specific transcriptional programs which leads DE, PFE, PSE, Forkhead Box A2; Hepatocyte to proper differentiation of stem cells FOXA2 PMPs, EPs, [2] Nuclear Factor 3-β into pancreatic progenitors. Regulates Mature β-cells expression of PDX1 gene and aids in maturation of β-cells A pleiotropic developmental gene which regulates growth, and Sonic Hedgehog Signaling differentiation of several organs. SHH DE [3] Molecule Repression of SHH expression is vital for pancreas differentiation and development Promotes cell differentiation, proliferation, and survival. Controls C-X-C Motif Chemokine the spatiotemporal migration of the Receptor 4; Stromal Cell- CXCR4 DE angioblasts towards pre-pancreatic [4] Derived Factor 1 Receptor; endodermal region which aids the Neuropeptide Y3 Receptor induction of PDX1 expression giving rise to common pancreatic progenitors Crucial for generation of pancreatic HNF1 Homeobox B HNF1B PFE, PSE, PMPs multipotent progenitor cells and [5] Hepatocyte Nuclear Factor 1-β NGN3+ endocrine progenitors Master regulator of pancreatic organogenesis. -
Angiogenic Patterning by STEEL, an Endothelial-Enriched Long
Angiogenic patterning by STEEL, an endothelial- enriched long noncoding RNA H. S. Jeffrey Mana,b, Aravin N. Sukumara,b, Gabrielle C. Lamc,d, Paul J. Turgeonb,e, Matthew S. Yanb,f, Kyung Ha Kub,e, Michelle K. Dubinskya,b, J. J. David Hob,f, Jenny Jing Wangb,e, Sunit Dasg,h, Nora Mitchelli, Peter Oettgeni, Michael V. Seftonc,d,j, and Philip A. Marsdena,b,e,f,1 aInstitute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; bKeenan Research Centre for Biomedical Science in the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, University of Toronto, Toronto, ON M5B 1T8, Canada; cDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E2, Canada; dInstitute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada; eDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada; fDepartment of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada; gArthur and Sonia Labatt Brain Tumour Research Institute, Hospital for SickKids, University of Toronto, Toronto, ON M5G 1X8, Canada; hDivision of Neurosurgery and Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, University of Toronto, Toronto, ON M5B 1W8, Canada; iDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115; and jDepartment of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, Canada Edited by Napoleone Ferrara, University of California, San Diego, La Jolla, CA, and approved January 24, 2018 (received for review August 28, 2017) Endothelial cell (EC)-enriched protein coding genes, such as endothelial formation in vitro and blood vessel formation in vivo. -
Homeobox Transcription Factor Prox1 in Sympathetic Ganglia of Vertebrate Embryos: Correlation with Human Stage 4S Neuroblastoma
0031-3998/10/6802-0112 Vol. 68, No. 2, 2010 PEDIATRIC RESEARCH Printed in U.S.A. Copyright © 2010 International Pediatric Research Foundation, Inc. Homeobox Transcription Factor Prox1 in Sympathetic Ganglia of Vertebrate Embryos: Correlation With Human Stage 4s Neuroblastoma JU¨ RGEN BECKER, BAIGANG WANG, HELENA PAVLAKOVIC, KERSTIN BUTTLER, AND JO¨ RG WILTING Department of Anatomy and Cell Biology, University Medicine Goettingen, 37075 Goettingen, Germany ABSTRACT: Previously, we observed expression of the homeobox progression of tumors derived from these tissues has not been transcription factor Prox1 in neuroectodermal embryonic tissues. investigated. We have studied Prox1 expression in the sym- Besides essential functions during embryonic development, Prox1 pathetic nervous system of avian and murine embryos, and in has been implicated in both progression and suppression of malig- childhood tumors derived from this tissue: neuroblastoma nancies. Here, we show that Prox1 is expressed in embryonic sym- (NB). We show that Prox1 is expressed in sympathetic neu- pathetic trunk ganglia of avian and murine embryos. Prox1 protein is rons during early stages of development at similar levels as in localized in the nucleus of neurofilament-positive sympathetic neu- rons. Sympathetic progenitors represent the cell of origin of neuro- lymphatic endothelial cells (LECs), but at greatly reduced blastoma (NB), the most frequent solid extracranial malignancy of levels in human NB cell lines. Studies of primary NB of all children. NB may progress to life-threatening stage 4, or regress stages (stages 1–4s) show significantly higher amounts of spontaneously in the special stage 4s. By qRT-PCR, we show that Prox1 mRNA in stage 4s. -
Genome-Wide DNA Methylation Analysis of KRAS Mutant Cell Lines Ben Yi Tew1,5, Joel K
www.nature.com/scientificreports OPEN Genome-wide DNA methylation analysis of KRAS mutant cell lines Ben Yi Tew1,5, Joel K. Durand2,5, Kirsten L. Bryant2, Tikvah K. Hayes2, Sen Peng3, Nhan L. Tran4, Gerald C. Gooden1, David N. Buckley1, Channing J. Der2, Albert S. Baldwin2 ✉ & Bodour Salhia1 ✉ Oncogenic RAS mutations are associated with DNA methylation changes that alter gene expression to drive cancer. Recent studies suggest that DNA methylation changes may be stochastic in nature, while other groups propose distinct signaling pathways responsible for aberrant methylation. Better understanding of DNA methylation events associated with oncogenic KRAS expression could enhance therapeutic approaches. Here we analyzed the basal CpG methylation of 11 KRAS-mutant and dependent pancreatic cancer cell lines and observed strikingly similar methylation patterns. KRAS knockdown resulted in unique methylation changes with limited overlap between each cell line. In KRAS-mutant Pa16C pancreatic cancer cells, while KRAS knockdown resulted in over 8,000 diferentially methylated (DM) CpGs, treatment with the ERK1/2-selective inhibitor SCH772984 showed less than 40 DM CpGs, suggesting that ERK is not a broadly active driver of KRAS-associated DNA methylation. KRAS G12V overexpression in an isogenic lung model reveals >50,600 DM CpGs compared to non-transformed controls. In lung and pancreatic cells, gene ontology analyses of DM promoters show an enrichment for genes involved in diferentiation and development. Taken all together, KRAS-mediated DNA methylation are stochastic and independent of canonical downstream efector signaling. These epigenetically altered genes associated with KRAS expression could represent potential therapeutic targets in KRAS-driven cancer. Activating KRAS mutations can be found in nearly 25 percent of all cancers1.