DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 8.470,300 B2 Clark Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 8.470,300 B2 Clark Et Al USOO8470300B2 (12) United States Patent (10) Patent No.: US 8.470,300 B2 Clark et al. (45) Date of Patent: Jun. 25, 2013 (54) COATED SENSORS AND METHODS FOREIGN PATENT DOCUMENTS RELATED THERETO WO WO 2008/O16646 2, 2008 WO WO-2008/O16646 * 2/2008 (75) Inventors: Heather A. Clark, Lexington, MA (US); WO WO 2008/063151 5, 2008 Karen K. Gleason, Cambridge, MA WO WO 2008,153930 12/2008 (US); Salmaan Baxamusa, Cambridge, WO WO 2009/051703 4/2009 MA (US); John M. Dubach, Somerville, MA (US) OTHER PUBLICATIONS Dubach, J. M. et al., “Fluorescent Ion-Selective Nanosensors for (73) Assignees: The Charles Stark Draper Laboratory, Intracellular Analysis with Improved Lifetime and Size” Nano Let Inc., Cambridge, MA (US); ters, 7(6):1827-1831 (2007). Massachusetts Institute of Technology, PCT/US2009/005065 International Search Report dated Feb. 15, Cambridge, MA (US) 2010. Xu, C et al., “Multicolour Quantum Dot Encoding for Polymeric (*) Notice: Subject to any disclaimer, the term of this Particle-Based Optical Ion Sensors'. Analytical Chemistry, patent is extended or adjusted under 35 79(10):3716-23 (2007). U.S.C. 154(b) by 568 days. * cited by examiner (21) Appl. No.: 12/584,528 (22) Filed: Sep. 8, 2009 Primary Examiner — Michael G. Hartley Assistant Examiner — Jagadishwar Samala (65) Prior Publication Data (74) Attorney, Agent, or Firm — Foley & Lardner LLP US 2010/0221 188A1 Sep. 2, 2010 (57) ABSTRACT Related U.S. Application Data The invention provides coated sensors for detecting the pres (60) Provisional application No. 61/191,467, filed on Sep. ence of analytes. The sensor comprises one or more fluores 8, 2008. cent sources, such as one or more quantum dots or one or more fluorescent dyes, a polymeric matrix, a Surface coating, (51) Int. Cl. and one or more analyte sensing components. The Surface A6 IK 49/00 (2006.01) coating may be a conformal polymeric film, permeable to the CI2O I/02 (2006.01) analyte, which may be deposited via a solventless process (52) U.S. Cl. Such as initiated chemical vapor deposition or photoinitiated USPC ............................. 424/9.6; 424/417; 424/489 chemical vapor deposition. The Surface coating may increase (58) Field of Classification Search the biocompatibility of the sensor, reduce nonspecific protein USPC ................. 424/9.6, 417,489: 562/14, 31, 35, adsorption, and/or sequester functional sensor components 562/43, 44; 435/14, 29, 288.7 within the sensor. The invention also provides methods for See application file for complete search history. detecting the presence of an analyte with coated sensors of the invention. (56) References Cited U.S. PATENT DOCUMENTS 19 Claims, 15 Drawing Sheets 2006/0083688 A1* 4/2006 Singaram et al. .............. 424, 9.6 (7 of 15 Drawing Sheet(s) Filed in Color) U.S. Patent Jun. 25, 2013 Sheet 1 of 15 US 8,470,300 B2 o 134 - 130 111 AGENT EXCITATION ANALYSS INTRODUCTION CONTROL MODULE MODULE MODULE - 108 106 Figure 1 U.S. Patent Jun. 25, 2013 Sheet 2 of 15 US 8,470,300 B2 coating. 28 (a) (b) coating, 28 (a) (b) coating, 28 (b) Figure 4 U.S. Patent Jun. 25, 2013 Sheet 3 of 15 US 8,470,300 B2 U.S. Patent Jun. 25, 2013 Sheet 4 of 15 US 8,470,300 B2 Figure 6. FLUORESCENT RESPONSE OF SOD TO Na r 0.0 |-- W ----------- O.O 0.5 10 1.5 2.O 2.5 3.0 log on mM U.S. Patent Jun. 25, 2013 Sheet 5 Of 15 US 8,470,300 B2 > I - - - - - OO nM Na f 6OOO - - - - - - 1 O in V. Na 2 - - - - - - - - - - 1 mM Na 4000 - - - - - - O Na CO S 2000 O - - O W ------ W-M ----& 550 600 650 700 (a) 4 Lo 3 st 2 2 1 W (b) -6 -5 -4 -3 -2 - 1 O log Na M Figure 8. CHANGING ABSORBANCE OF CHROMOIONOPHORE WITH CONCENTRATIONCANGING ON ESGN For O - - C N if 0.8 & v - --. -" M W -...-e-- ^ aD 0.6 N. .- . " 3. I N is 0.4 st O C. 35 -------e. : 0.2 & N < O ---to- ------...--—- --- ----- --- - - - - - - - 5OO 550 6OO 650 700 WAVELENGTH, nm Figure 9. U.S. Patent Jun. 25, 2013 Sheet 6 of 15 US 8,470,300 B2 4. 24 ORS 48 ORS 72 HOURS O. 22NT TROL ATEX Figure 10. No.z?? Figure 12. U.S. Patent Jun. 25, 2013 Sheet 7 Of 15 US 8,470,300 B2 (a) - SODIUMNANO-SPHERES IN CLAYCOMB HL-1 CELLS FIELDSTIMULATED AT 1.0Hz 6113/06 3. 2O 2 - (b) o 0.5 O 5 20 2.5 3.0 vvvvv-u-v-m TIME (SEC) U.S. Patent Jun. 25, 2013 Sheet 8 of 15 US 8,470,300 B2 polymer matrix, 20 r coating, 28 G9 ionic analyte, 21 ionophore, 22 (a proton, 23 67) chromoionophore, 24 photons, 25 quantum dot, wavelength 1, 26 Osun dot, wavelength 2, 27 Figure 14. U.S. Patent Jun. 25, 2013 Sheet 9 Of 15 US 8,470,300 B2 polymer matrix, 20 r G ionic analyte, 28 ionophore, 22 K proton, 23 4) chromoionophore, 24 photons, 25 quantum dot, wavelength 1, 26 quantum dot, wavelength 2, 27 Figure 15. Figure 16. U.S. Patent Jun. 25, 2013 Sheet 10 of 15 US 8,470,300 B2 JiN LO AAR OERA FORSCENCE ASEANC FORSCENCE ESSION (VARIABLE WRT ISSION ,8 (CONSTANT) GLUCOSE RO , i GOOSE , AERO GCOSE a 42 5 4 3 25 WAVELENGTH, nM (a) (b) Figure 19. U.S. Patent Jun. 25, 2013 Sheet 11 of 15 US 8,470,300 B2 105 --- &W xSS8 w xx ------ .. - - - - - - - CONTROL . onese sees FRUCOSE ---e GCOSE 3. s O f TIME (MINUTES) Figure 20. 1 Warp Pressure 3 in age controls s Quartz Top Correer Throttling Butterfly Recirculating Wale cosia rter er a Figure 21. U.S. Patent Jun. 25, 2013 Sheet 12 of 15 US 8,470,300 B2 OOO 35 3 OO 25 O 2OOO SOO OOC Waven unber (cm) Figure 22. Figure 23. U.S. Patent Jun. 25, 2013 Sheet 13 of 15 US 8,470,300 B2 s 5 O 3 3. on 29 5 2 25 3. 35 40 (a) Residence time sec) s 50 5 40 3 5 3 2 5 2O O 0.2 0.4 0.6 .8 1 (b) Fractional saturation, PP" Figure 24. O 2 e O 0.2 O4 O. 6 0.8 t Fractional saturation, PP" Figure 25. U.S. Patent Jun. 25, 2013 Sheet 14 of 15 US 8,470,300 B2 Bare S i icon pHEMA Figure 26. Time ( Figure 27. ure 28. U.S. Patent Jun. 25, 2013 Sheet 15 of 15 US 8,470,300 B2 Figure 29. US 8,470,300 B2 1. 2 COATED SENSORS AND METHODS and/or fluorescent dye or dyes, a pH-sensitive dye, and RELATED THERETO optionally an ion-selective component Such as an ionophore. These elements may, for example, be disposed in a polymer CROSS-REFERENCE TO RELATED CASES matrix and/or in the Surface coating. In certain embodiments, the sensors may detectionic analytes by selective ion extrac This application claims the benefit of U.S. Provisional tion by the polymer matrix and/or coating, thereby inducing a Patent Application No. 61/191,467, entitled “Coated Sensors pH change within the sensor which in turn changes the absor and Methods Related Thereto' filed on Sep. 8, 2008, the bance of the pH-sensitive dye. The change of absorbance may entire disclosure of which is hereby incorporated by reference in turn attenuate the intensity of detectable emissions, e.g., as if set forth herein in its entirety. 10 fluorescence, from the one or more quantum dots and/or fluorescent dye or dyes by directly absorbing their fluores BACKGROUND OF THE INVENTION cence emissions. In other embodiments, the Subject sensors include coated Biological sensors are very useful for monitoring and sensors and sensor particles that may detect the presence of a understanding biological mechanisms, both within individual 15 chelatable analyte. Such as glucose, comprising a quantum cells and in more general biological environments such as the dot and/or a fluorescent dye or dyes, a polymer matrix com human body: For example, intra-cellular sensors offer a pow prising a polymer including moieties that bind the chelatable erful tool for understanding the mechanisms within a cell. analyte, a chromophore associated with the polymer matrix Such sensors can detect the presence or concentration of an that binds to the moieties in the absence of the chelatable analyte within the cell, and when multiple sensors are distrib analyte, and a surface coating. In some embodiments, pho uted within the interior of the cell, the presence of analytes in tons emitted by the quantum dot in an excited State are relation to different cellular organelles and the cell membrane absorbed by the chromophore in an unbound state but not by can be better understood. the chromophore in a bound state. The moieties may bind the An important consideration for sensors deployed for bio chelatable analyte and chromophore reversibly and competi logical applications is compatibility with the physiological 25 tively. In certain embodiments, the moieties are boronic acids environment. Sensors in the physiological environment are or boronic esters. In some embodiments, one or more com extremely Susceptible to nonspecific adsorption of biological ponents of the sensor. Such as the moieties and/or chro materials such as proteins. This nonspecific adsorption may mophore, are covalently bound to or associated with the poly degrade sensor performance as well as cause inflammation mer matrix. and thrombosis. Therefore, methods or compositions that 30 In certain aspects, the invention comprises methods for reduce nonspecific adsorption to biological sensors would be detecting the presence of an analyte in a medium using the highly desirable.
Load more

Recommended publications
  • Transcriptomic Analysis of Native Versus Cultured Human and Mouse Dorsal Root Ganglia Focused on Pharmacological Targets Short
    bioRxiv preprint doi: https://doi.org/10.1101/766865; this version posted September 12, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. Transcriptomic analysis of native versus cultured human and mouse dorsal root ganglia focused on pharmacological targets Short title: Comparative transcriptomics of acutely dissected versus cultured DRGs Andi Wangzhou1, Lisa A. McIlvried2, Candler Paige1, Paulino Barragan-Iglesias1, Carolyn A. Guzman1, Gregory Dussor1, Pradipta R. Ray1,#, Robert W. Gereau IV2, # and Theodore J. Price1, # 1The University of Texas at Dallas, School of Behavioral and Brain Sciences and Center for Advanced Pain Studies, 800 W Campbell Rd. Richardson, TX, 75080, USA 2Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine # corresponding authors [email protected], [email protected] and [email protected] Funding: NIH grants T32DA007261 (LM); NS065926 and NS102161 (TJP); NS106953 and NS042595 (RWG). The authors declare no conflicts of interest Author Contributions Conceived of the Project: PRR, RWG IV and TJP Performed Experiments: AW, LAM, CP, PB-I Supervised Experiments: GD, RWG IV, TJP Analyzed Data: AW, LAM, CP, CAG, PRR Supervised Bioinformatics Analysis: PRR Drew Figures: AW, PRR Wrote and Edited Manuscript: AW, LAM, CP, GD, PRR, RWG IV, TJP All authors approved the final version of the manuscript. 1 bioRxiv preprint doi: https://doi.org/10.1101/766865; this version posted September 12, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
    [Show full text]
  • Cldn19 Clic2 Clmp Cln3
    NewbornDx™ Advanced Sequencing Evaluation When time to diagnosis matters, the NewbornDx™ Advanced Sequencing Evaluation from Athena Diagnostics delivers rapid, 5- to 7-day results on a targeted 1,722-genes. A2ML1 ALAD ATM CAV1 CLDN19 CTNS DOCK7 ETFB FOXC2 GLUL HOXC13 JAK3 AAAS ALAS2 ATP1A2 CBL CLIC2 CTRC DOCK8 ETFDH FOXE1 GLYCTK HOXD13 JUP AARS2 ALDH18A1 ATP1A3 CBS CLMP CTSA DOK7 ETHE1 FOXE3 GM2A HPD KANK1 AASS ALDH1A2 ATP2B3 CC2D2A CLN3 CTSD DOLK EVC FOXF1 GMPPA HPGD K ANSL1 ABAT ALDH3A2 ATP5A1 CCDC103 CLN5 CTSK DPAGT1 EVC2 FOXG1 GMPPB HPRT1 KAT6B ABCA12 ALDH4A1 ATP5E CCDC114 CLN6 CUBN DPM1 EXOC4 FOXH1 GNA11 HPSE2 KCNA2 ABCA3 ALDH5A1 ATP6AP2 CCDC151 CLN8 CUL4B DPM2 EXOSC3 FOXI1 GNAI3 HRAS KCNB1 ABCA4 ALDH7A1 ATP6V0A2 CCDC22 CLP1 CUL7 DPM3 EXPH5 FOXL2 GNAO1 HSD17B10 KCND2 ABCB11 ALDOA ATP6V1B1 CCDC39 CLPB CXCR4 DPP6 EYA1 FOXP1 GNAS HSD17B4 KCNE1 ABCB4 ALDOB ATP7A CCDC40 CLPP CYB5R3 DPYD EZH2 FOXP2 GNE HSD3B2 KCNE2 ABCB6 ALG1 ATP8A2 CCDC65 CNNM2 CYC1 DPYS F10 FOXP3 GNMT HSD3B7 KCNH2 ABCB7 ALG11 ATP8B1 CCDC78 CNTN1 CYP11B1 DRC1 F11 FOXRED1 GNPAT HSPD1 KCNH5 ABCC2 ALG12 ATPAF2 CCDC8 CNTNAP1 CYP11B2 DSC2 F13A1 FRAS1 GNPTAB HSPG2 KCNJ10 ABCC8 ALG13 ATR CCDC88C CNTNAP2 CYP17A1 DSG1 F13B FREM1 GNPTG HUWE1 KCNJ11 ABCC9 ALG14 ATRX CCND2 COA5 CYP1B1 DSP F2 FREM2 GNS HYDIN KCNJ13 ABCD3 ALG2 AUH CCNO COG1 CYP24A1 DST F5 FRMD7 GORAB HYLS1 KCNJ2 ABCD4 ALG3 B3GALNT2 CCS COG4 CYP26C1 DSTYK F7 FTCD GP1BA IBA57 KCNJ5 ABHD5 ALG6 B3GAT3 CCT5 COG5 CYP27A1 DTNA F8 FTO GP1BB ICK KCNJ8 ACAD8 ALG8 B3GLCT CD151 COG6 CYP27B1 DUOX2 F9 FUCA1 GP6 ICOS KCNK3 ACAD9 ALG9
    [Show full text]
  • GJB4 (NM 153212) Human Tagged ORF Clone Product Data
    OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for RC204406 GJB4 (NM_153212) Human Tagged ORF Clone Product data: Product Type: Expression Plasmids Product Name: GJB4 (NM_153212) Human Tagged ORF Clone Tag: Myc-DDK Symbol: GJB4 Synonyms: CX30.3; EKV; EKVP2 Vector: pCMV6-Entry (PS100001) E. coli Selection: Kanamycin (25 ug/mL) Cell Selection: Neomycin ORF Nucleotide >RC204406 ORF sequence Sequence: Red=Cloning site Blue=ORF Green=Tags(s) TTTTGTAATACGACTCACTATAGGGCGGCCGGGAATTCGTCGACTGGATCCGGTACCGAGGAGATCTGCC GCCGCGATCGCC ATGAACTGGGCATTTCTGCAGGGCCTGCTGAGTGGCGTGAACAAGTACTCCACAGTGCTGAGCCGCATCT GGCTGTCTGTGGTGTTCATCTTTCGTGTGCTGGTGTACGTGGTGGCAGCGGAGGAGGTGTGGGACGATGA GCAGAAGGACTTTGTCTGCAACACCAAGCAGCCCGGCTGCCCCAACGTCTGCTATGACGAGTTCTTCCCC GTGTCCCACGTGCGCCTCTGGGCCCTACAGCTCATCCTGGTCACGTGCCCCTCACTGCTCGTGGTCATGC ACGTGGCCTACCGCGAGGAACGCGAGCGCAAGCACCACCTGAAACACGGGCCCAATGCCCCGTCCCTGTA CGACAACCTGAGCAAGAAGCGGGGCGGACTGTGGTGGACGTACTTGCTGAGCCTCATCTTCAAGGCCGCC GTGGATGCTGGCTTCCTCTATATCTTCCACCGCCTCTACAAGGATTATGACATGCCCCGCGTGGTGGCCT GCTCCGTGGAGCCTTGCCCCCACACTGTGGACTGTTACATCTCCCGGCCCACGGAGAAGAAGGTCTTCAC CTACTTCATGGTGACCACAGCTGCCATCTGCATCCTGCTCAACCTCAGTGAAGTCTTCTACCTGGTGGGC AAGAGGTGCATGGAGATCTTCGGCCCCAGGCACCGGCGGCCTCGGTGCCGGGAATGCCTACCCGATACGT GCCCACCATATGTCCTCTCCCAGGGAGGGCACCCTGAGGATGGGAACTCTGTCCTAATGAAGGCTGGGTC GGCCCCAGTGGATGCAGGTGGGTATCCA ACGCGTACGCGGCCGCTCGAGCAGAAACTCATCTCAGAAGAGGATCTGGCAGCAAATGATATCCTGGATT
    [Show full text]
  • Ion Channels
    UC Davis UC Davis Previously Published Works Title THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels. Permalink https://escholarship.org/uc/item/1442g5hg Journal British journal of pharmacology, 176 Suppl 1(S1) ISSN 0007-1188 Authors Alexander, Stephen PH Mathie, Alistair Peters, John A et al. Publication Date 2019-12-01 DOI 10.1111/bph.14749 License https://creativecommons.org/licenses/by/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Ion channels. British Journal of Pharmacology (2019) 176, S142–S228 THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels Stephen PH Alexander1 , Alistair Mathie2 ,JohnAPeters3 , Emma L Veale2 , Jörg Striessnig4 , Eamonn Kelly5, Jane F Armstrong6 , Elena Faccenda6 ,SimonDHarding6 ,AdamJPawson6 , Joanna L Sharman6 , Christopher Southan6 , Jamie A Davies6 and CGTP Collaborators 1School of Life Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK 2Medway School of Pharmacy, The Universities of Greenwich and Kent at Medway, Anson Building, Central Avenue, Chatham Maritime, Chatham, Kent, ME4 4TB, UK 3Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK 4Pharmacology and Toxicology, Institute of Pharmacy, University of Innsbruck, A-6020 Innsbruck, Austria 5School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK 6Centre for Discovery Brain Science, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties.
    [Show full text]
  • Altered Physiological Functions and Ion Currents in Atrial Fibroblasts From
    Physiological Reports ISSN 2051-817X ORIGINAL RESEARCH Altered physiological functions and ion currents in atrial fibroblasts from patients with chronic atrial fibrillation Claire Poulet1, Stephan Kunzel€ 1, Edgar Buttner€ 1, Diana Lindner2, Dirk Westermann2 & Ursula Ravens1 1 Department of Pharmacology and Toxicology, Medical Faculty Carl-Gustav-Carus, TU Dresden, Dresden, Germany 2 Department of General and Interventional Cardiology, University Heart Center Hamburg Eppendorf, Hamburg, Germany Keywords Abstract Atrial fibrillation, electrophysiology, fibroblasts. The contribution of human atrial fibroblasts to cardiac physiology and patho- physiology is poorly understood. Fibroblasts may contribute to arrhythmogen- Correspondence esis through fibrosis, or by directly altering electrical activity in Claire Poulet, Imperial College London, Imperial cardiomyocytes. The objective of our study was to uncover phenotypic differ- Centre for Translational and Experimental ences between cells from patients in sinus rhythm (SR) and chronic atrial fib- Medicine, Hammersmith Campus, Du Cane rillation (AF), with special emphasis on electrophysiological properties. We Road, London W12 0NN, UK isolated fibroblasts from human right atrial tissue for patch-clamp experi- Tel: +44 207 594 2738 Fax: +44 207 594 3653 ments, proliferation, migration, and differentiation assays, and gene expression E-mail: [email protected] profiling. In culture, proliferation and migration of AF fibroblasts were strongly impaired but differentiation into myofibroblasts was increased. This Present Addresses was associated with a higher number of AF fibroblasts expressing functional Claire Poulet, Imperial College London, Nav1.5 channels. Strikingly Na+ currents were considerably larger in AF cells. National Heart and Lung Institute, London, UK Blocking Na+ channels in culture with tetrodotoxin did not affect prolifera- tion, migration, or differentiation in neither SR nor AF cells.
    [Show full text]
  • Download (PDF)
    Supplemental Information Biological and Pharmaceutical Bulletin Promoter Methylation Profiles between Human Lung Adenocarcinoma Multidrug Resistant A549/Cisplatin (A549/DDP) Cells and Its Progenitor A549 Cells Ruiling Guo, Guoming Wu, Haidong Li, Pin Qian, Juan Han, Feng Pan, Wenbi Li, Jin Li, and Fuyun Ji © 2013 The Pharmaceutical Society of Japan Table S1. Gene categories involved in biological functions with hypomethylated promoter identified by MeDIP-ChIP analysis in lung adenocarcinoma MDR A549/DDP cells compared with its progenitor A549 cells Different biological Genes functions transcription factor MYOD1, CDX2, HMX1, THRB, ARNT2, ZNF639, HOXD13, RORA, FOXO3, HOXD10, CITED1, GATA1, activity HOXC6, ZGPAT, HOXC8, ATOH1, FLI1, GATA5, HOXC4, HOXC5, PHTF1, RARB, MYST2, RARG, SIX3, FOXN1, ZHX3, HMG20A, SIX4, NR0B1, SIX6, TRERF1, DDIT3, ASCL1, MSX1, HIF1A, BAZ1B, MLLT10, FOXG1, DPRX, SHOX, ST18, CCRN4L, TFE3, ZNF131, SOX5, TFEB, MYEF2, VENTX, MYBL2, SOX8, ARNT, VDR, DBX2, FOXQ1, MEIS3, HOXA6, LHX2, NKX2-1, TFDP3, LHX6, EWSR1, KLF5, SMAD7, MAFB, SMAD5, NEUROG1, NR4A1, NEUROG3, GSC2, EN2, ESX1, SMAD1, KLF15, ZSCAN1, VAV1, GAS7, USF2, MSL3, SHOX2, DLX2, ZNF215, HOXB2, LASS3, HOXB5, ETS2, LASS2, DLX5, TCF12, BACH2, ZNF18, TBX21, E2F8, PRRX1, ZNF154, CTCF, PAX3, PRRX2, CBFA2T2, FEV, FOS, BARX1, PCGF2, SOX15, NFIL3, RBPJL, FOSL1, ALX1, EGR3, SOX14, FOXJ1, ZNF92, OTX1, ESR1, ZNF142, FOSB, MIXL1, PURA, ZFP37, ZBTB25, ZNF135, HOXC13, KCNH8, ZNF483, IRX4, ZNF367, NFIX, NFYB, ZBTB16, TCF7L1, HIC1, TSC22D1, TSC22D2, REXO4, POU3F2, MYOG, NFATC2, ENO1,
    [Show full text]
  • Download Positional Information of Genomic Sequence (Refseq Gene: Hg38) and Common Snps (Snp147common: Hg38) in the Region of Interest
    Abstracts medgen 2017 · 29:86–192 DOI 10.1007/s11825-017-0126-6 Topics Online publiziert: 23. Februar 2017 © Springer-Verlag Berlin Heidelberg 2017 Keynote Lecture Workshops (W1-9) WS1 Monogenic Disease WS2 Cancer Genetics I Plenary Sessions (PLEN) WS3 Enhancers, Modifiers and Rare Variants Plen 1 WS4 Intellectual Disability Plen 2 WS5 Technology WS6 Complex Genetics WS7 Clinical Genetics Symposia (S1-6) WS8 Cancer Genetics II WS9 Basic Mechanisms and Epigenetics S1 Studying Genetic Diseases with iPSCs and Organoids S2 Intracellular Organelles and their Diseases S3 Huntington Disease Poster (P-) S4 Consequences of Human Germline Variations S6 The Genetic and Epigenetic Basis of Obesity P-BasEpi 001–029 P-Basic Mechanisms and Epigenetic S6 Genomics of Immune Mechanisms P-CancG 030–049 P-Cancer Genetics P-ClinG 050–115 P-Clinical Genetics, Genetic Counselling and Prenatal Diagnosis Selected Presentations (SEL1-4) P-Compl 116–126 P-Complex Diseases, Population & Evolutionary Genetics and Genetic Epidemiology P-CytoG 127–135 P-Cytogenetics and CNVs Sessions P-MonoG 136–169 P-Monogenic Diseases – Educational Session 1 from Gene Identification to Molecular Educational Session 2 Mechanisms Pro & Contra I P-Techno 170–180 P-Technology and Bioinformatics Pro & Contra II P-Therap 181–184 P-Therapy for Genetic Diseases Talk nach 12 DFG-Workshop Oral History Projekt Qualitätsmanagement-Workshop SHG-Session 86 medizinische genetik 1 · 2017 Vorträge Plenary Sessions Keynote Lecture Plen 1 X chromosome structure and regulation Human Olfactory Receptors: Their role in odor perception and as C. M. Disteche new targets for diagnosis and therapy Departments of Pathology and Medicine (Medical Genetics) University of Washington Seattle WA98195, USA H.
    [Show full text]
  • 1 1 2 3 Cell Type-Specific Transcriptomics of Hypothalamic
    1 2 3 4 Cell type-specific transcriptomics of hypothalamic energy-sensing neuron responses to 5 weight-loss 6 7 Fredrick E. Henry1,†, Ken Sugino1,†, Adam Tozer2, Tiago Branco2, Scott M. Sternson1,* 8 9 1Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 10 20147, USA. 11 2Division of Neurobiology, Medical Research Council Laboratory of Molecular Biology, 12 Cambridge CB2 0QH, UK 13 14 †Co-first author 15 *Correspondence to: [email protected] 16 Phone: 571-209-4103 17 18 Authors have no competing interests 19 1 20 Abstract 21 Molecular and cellular processes in neurons are critical for sensing and responding to energy 22 deficit states, such as during weight-loss. AGRP neurons are a key hypothalamic population 23 that is activated during energy deficit and increases appetite and weight-gain. Cell type-specific 24 transcriptomics can be used to identify pathways that counteract weight-loss, and here we 25 report high-quality gene expression profiles of AGRP neurons from well-fed and food-deprived 26 young adult mice. For comparison, we also analyzed POMC neurons, an intermingled 27 population that suppresses appetite and body weight. We find that AGRP neurons are 28 considerably more sensitive to energy deficit than POMC neurons. Furthermore, we identify cell 29 type-specific pathways involving endoplasmic reticulum-stress, circadian signaling, ion 30 channels, neuropeptides, and receptors. Combined with methods to validate and manipulate 31 these pathways, this resource greatly expands molecular insight into neuronal regulation of 32 body weight, and may be useful for devising therapeutic strategies for obesity and eating 33 disorders.
    [Show full text]
  • Gene % HDV Positive Cells % Infection Compared to Sictrl P-Value FDR
    % HDV % infection Gene positive compared to p-value FDR Toxicity cells siCtrl A2M 9,45 63,81 0,0001 0,0002 0,11 A4GALT 17,61 118,94 0,0887 0,1607 -0,13 A4GNT 16,11 108,83 0,0939 0,1683 0,20 AACS 15,76 106,48 0,5123 0,5979 0,00 AADAC 14,41 97,34 0,5533 0,6323 -0,03 AADACL1 14,44 97,53 0,2998 0,3678 0,14 AADAT 13,36 90,26 0,1557 0,2308 0,17 AAK1 18,00 121,58 0,0007 0,0028 0,04 AANAT 12,21 82,46 0,0004 0,0012 0,09 AARS 17,17 115,94 0,0671 0,1111 -0,13 AARSD1 14,78 99,83 0,8307 0,8622 -0,09 AASDH 18,69 126,24 0,0054 0,0129 -0,04 AASDHPPT 16,84 113,73 0,2685 0,3738 -0,05 AASS 16,33 110,31 0,0531 0,0836 -0,05 AATF 18,57 125,42 0,0111 0,0254 0,07 AATK 14,80 99,98 0,6699 0,7166 0,18 ABAT 16,31 110,16 0,0725 0,1215 0,34 ABCA1 14,86 100,36 0,9669 0,9774 0,18 ABCA10 13,09 88,44 0,3205 0,4130 0,09 ABCA12 17,44 117,81 < 0.0001 < 0.0001 -0,03 ABCA13 14,77 99,76 0,9409 0,9609 -0,04 ABCA2 10,93 73,82 0,0001 0,0003 0,19 ABCA3 10,03 67,74 0,0913 0,1645 0,23 ABCA4 12,89 87,10 0,2968 0,3890 -0,08 ABCA5 17,00 114,80 0,0598 0,1252 0,04 ABCA6 15,58 105,20 0,2367 0,3178 0,13 ABCA7 11,40 77,03 < 0.0001 < 0.0001 0,35 ABCA8 15,88 107,30 0,0001 0,0005 0,06 ABCA9 11,86 80,11 < 0.0001 < 0.0001 0,29 ABCB1 12,79 86,41 0,2516 0,3539 0,09 ABCB10 13,81 93,28 0,4109 0,4855 0,12 ABCB11 19,08 128,88 0,0079 0,0194 0,00 ABCB4 14,67 99,12 0,9630 0,9736 0,10 ABCB5 15,34 103,59 0,4524 0,5677 -0,02 ABCB6 11,31 76,40 < 0.0001 < 0.0001 0,19 ABCB7 10,89 73,56 0,0285 0,0575 0,04 ABCB8 13,69 92,50 0,0355 0,0652 0,16 ABCB9 14,27 96,37 0,8926 0,9239 0,05 ABCC1 15,92 107,56 0,2517 0,3138
    [Show full text]
  • An Investigation of the Properties and Functions of Connexins in the Mammalian Inner Ear
    An Investigation of the Properties and Functions of Connexins in the Mammalian Inner Ear John Joseph Kelly Ear Institute University College London A thesis submitted for the degree of Doctor of Philosophy September 2011 Declaration I, John Kelly, confirm that the work presented in this thesis is my own. Where information or assistance has been derived from other sources, I confirm that this has been indicated in the thesis. 2 Acknowledgements First and foremost, I would like to thank my supervisors: Dr. Dan Jagger for your continued support, advice and patience throughout my Ph.D., and Prof. Andy Forge for all your help and guidance along the way. It’s been a privilege to have you both as my mentors. I’d also like to thank other members of the group: Regina, for your expertise and friendship and for helping me integrate into the lab with ease; Ruth, for your help and advice over the years; Graham for your expertise and recommendations of areas to explore in the UK (one day….), and Nicole, for your company both inside and outside of the lab, and for the fond memories of our road trip around southern California with Cassy. Lisa, I’ve had the pleasure of working with you in two different labs. Thank you for all your help and advice and for your infectious positivity! I would like to thank Dr. Sally Dawson for introducing me to the world of molecular biology and to both Sally and Dr. Jonathan Gale for the advice you have both given me. Emily, you’ve been a fantastic lab, desk and tea-break buddy.
    [Show full text]
  • Ion Channels: Function Unravelled by Dysfunction
    REVIEW ocus Ion channels: Function unravelled by dysfunction Thomas J. Jentsch, Christian A. Hübner and Jens C. Fuhrmann Ion channels allow the passage of specific ions and electrical charge. Plasma membrane channels are, for example, important for electrical excitability and transepithelial transport, whereas intracellular channels have roles in acidifying endosomes or in releasing Ca2+ from stores. The function of several channels emerged from mutations in humans or mice. The resulting phenotypes include kidney stones resulting from impaired endocytosis, hypertension, defective insulin secretion, cardiac arrhythmias, neurological diseases like epilepsy or deafness and even ‘developmental’ defects such as osteopetrosis. Ion channels are integral membrane proteins that form a pore to allow the of the selective expression of ion channels and transporters in apical passage of specific ions by passive diffusion. Most, if not all, ion channels or basolateral membranes. Typically, the ion is transported across one undergo conformational changes from closed to open states, and once of these membrane domains in an active transport process: primary open, channels allow the passage of thousands of ions. This distinguishes active transport occurs through transport ATPases (for example, the them from transporters and pumps, which can also transport ions but (Na+ + K+)ATPase), and secondary active transport couples trans- only one (or a few) at a time. The opening and closing of channels can be membrane ion gradients established by primary active transport (for controlled by various means, including voltage, the binding of ligands such example, the Na+ gradient) to the transport of another ion (for example, as intracellular Ca2+ or extracellular neurotransmitters, and post-transla- Cl– in Na–Cl cotransporters).
    [Show full text]
  • Connexins and Disease
    Downloaded from http://cshperspectives.cshlp.org/ on October 1, 2021 - Published by Cold Spring Harbor Laboratory Press Connexins and Disease Mario Delmar,1 Dale W. Laird,2 Christian C. Naus,3 Morten S. Nielsen,4 Vytautas K. Verselis,5 and Thomas W. White6 1The Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, New York 10016 2Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario N6A5C1, Canada 3Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada 4Department of Biological Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark 5Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, New York 10461 6Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York 11790 Correspondence: [email protected] Inherited or acquired alterations in the structure and function of connexin proteins have long been associated with disease. In the present work, we review current knowledge on the role of connexins in diseases associated with the heart, nervous system, cochlea, and skin, as well as cancer and pleiotropic syndromes such as oculodentodigital dysplasia (ODDD). Although incomplete by virtue of space and the extent of the topic, this review emphasizes the fact that connexin function is not only associated with gap junction channel formation. As such, both canonical and noncanonical functions of connexins are fundamental components in the pathophysiology of multiple connexin related disorders, many of them highly debilitating and life threatening. Improved understanding of connexin biology has the potential to advance our understanding of mechanisms, diagnosis, and treatment of disease.
    [Show full text]