f3bcbb741aaf0dd1ffe412a88d4c832b mol_a2019v24n13p2493.pdf ecca68f53ff1e300a880380500aa917915ba3177 mol_a2019v24n13p2493.pdf 54cce93be1c3c1cf593d27c190dec17543df08f52eda108fc99902c12cf44b03 mol_a2019v24n13p2493.pdf Title: Interactome Analysis and Docking Sites of MutS Homologs Reveal New Physiological Roles in Arabidopsis thaliana Subject: Due to their sedentary lifestyle, plants are constantly exposed to different stress stimuli. Stress comes in variety of forms where factors like radiation, free radicals, “replication errors, polymerase slippage”, and chemical mutagens result in genotoxic or cytotoxic damage. In order to face “the base oxidation or DNA replication stress”, plants have developed many sophisticated mechanisms. One of them is the DNA mismatch repair (MMR) pathway. The main part of the MMR is the MutS homologue (MSH) protein family. The genome of Arabidopsis thaliana encodes at least seven homologues of the MSH family: AtMSH1, AtMSH2, AtMSH3, AtMSH4, AtMSH5, AtMSH6, and AtMSH7. Despite their importance, the functions of AtMSH homologs have not been investigated. In this work, bioinformatics tools were used to obtain a better understanding of MSH-mediated DNA repair mechanisms in Arabidopsis thaliana and to understand the additional biological roles of AtMSH family members. In silico analysis, including phylogeny tracking, prediction of 3D structure, interactome analysis, and docking site prediction, suggested interactions with proteins were important for physiological development of A. thaliana. The MSH homologs extensively interacted with both TIL1 and TIL2 (DNA polymerase epsilon catalytic subunit), proteins involved in cell fate determination during plant embryogenesis and involved in flowering time repression. Additionally, interactions with the RECQ protein family (helicase enzymes) and proteins of nucleotide excision repair pathway were detected. Taken together, the results presented here confirm the important role of AtMSH proteins in mismatch repair and suggest important new physiological roles. Keywords: DNA mismatch repair; MSH; docking site; interactome Author: Mohamed Ragab AbdelGawwad, Aida Marić, Abdullah Ahmed Al-Ghamdi and Ashraf A. Hatamleh Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Mon Jul 8 10:03:10 2019 CEST ModDate: Fri Feb 7 16:51:54 2020 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 19 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2632593 bytes Optimized: yes PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- IDOLTJ+URWPalladioL-Ital Type 1 Custom yes yes no 642 0 EYVRLQ+URWPalladioL-Bold Type 1 Custom yes yes no 645 0 WSATAY+URWPalladioL-BoldItal Type 1 Custom yes yes no 648 0 NGUSYV+URWPalladioL-Roma Type 1 Custom yes yes no 651 0 FESXTA+Rpxr Type 1 Builtin yes yes no 654 0 PUSVWS+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 658 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 667 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 670 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 673 0 GBFCNM+TimesNewRoman TrueType WinAnsi yes yes no 139 0 GBFBNK+PalatinoLinotype TrueType WinAnsi yes yes no 141 0 GBFCBL+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 143 0 GBFCCM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 145 0 GBFCNM+TimesNewRoman TrueType WinAnsi yes yes no 155 0 GBFGAJ+Arial TrueType WinAnsi yes yes no 157 0 GBFBNK+PalatinoLinotype TrueType WinAnsi yes yes no 159 0 GBFCBL+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 161 0 GBFCCM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 163 0 GBFCNM+TimesNewRoman TrueType WinAnsi yes yes no 170 0 GBFGAJ+Arial TrueType WinAnsi yes yes no 172 0 GBFBNK+PalatinoLinotype TrueType WinAnsi yes yes no 174 0 GBFCBL+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 176 0 GBFCCM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 178 0 RWCTBB+Pxsy Type 1 Builtin yes yes no 363 0 NJTDWR+EURM10 Type 1 Builtin yes yes no 365 0 VSHNAE+Rpcxr Type 1 Builtin yes yes no 367 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2020-02-08 05:38:54 CET RepresentationInformation: mol_a2019v24n13p2493.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2020-02-07 17:45:33 CET Size: 2632593 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf Profile: Linearized PDF PDFMetadata: Objects: 0 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Item: Title: Results Children: Item: Title: Multiple Sequence Alignment Item: Title: Phylogenetic Profile Rendering Item: Title: Protein 3D Structure Prediction and Refinement Item: Title: Protein 3D Structure Validation Item: Title: Protein Domain Identification Item: Title: Interactome Analysis Item: Title: Protein Subcellular Localization Item: Title: Docking Site Prediction Item: Title: Discussion Item: Title: Materials and Methods Children: Item: Title: Sequences Retrieving and Multiple Sequence Alignment MSA Item: Title: Phylogenetic Profile Rendering Item: Title: Protein 3D Structure Prediction and Refinement Item: Title: Protein 3D Structure Validation Item: Title: Protein Domain Identification Item: Title: Interactome Analysis Item: Title: Protein Localization Item: Title: Docking Site Prediction Item: Title: References Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: IDOLTJ+URWPalladioL-Ital FontSubset: true FirstChar: 2 LastChar: 122 FontDescriptor: FontName: IDOLTJ+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: EYVRLQ+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 180 FontDescriptor: FontName: EYVRLQ+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: WSATAY+URWPalladioL-BoldItal FontSubset: true FirstChar: 65 LastChar: 116 FontDescriptor: FontName: WSATAY+URWPalladioL-BoldItal Flags: Symbolic FontBBox: -170, -300, 1073, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: NGUSYV+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: NGUSYV+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: RWCTBB+Pxsy FontSubset: true FirstChar: 0 LastChar: 48 FontDescriptor: FontName: RWCTBB+Pxsy Flags: Symbolic FontBBox: -21, -994, 1292, 912 FontFile: true Font: BaseFont: NJTDWR+EURM10 FontSubset: true FirstChar: 11 LastChar: 39 FontDescriptor: FontName: NJTDWR+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: FESXTA+Rpxr FontSubset: true FirstChar: 11 LastChar: 62 FontDescriptor: FontName: FESXTA+Rpxr Flags: Symbolic FontBBox: -40, -283, 904, 728 FontFile: true Font: BaseFont: VSHNAE+Rpcxr FontSubset: true FirstChar: 169 LastChar: 169 FontDescriptor: FontName: VSHNAE+Rpcxr Flags: Symbolic FontBBox: -212, -286, 1344, 973 FontFile: true XMP: application/pdf Mohamed Ragab AbdelGawwad, Aida Marić, Abdullah Ahmed Al-Ghamdi and Ashraf A. Hatamleh Due to their sedentary lifestyle, plants are constantly exposed to different stress stimuli. Stress comes in variety of forms where factors like radiation, free radicals, “replication errors, polymerase slippage”, and chemical mutagens result in genotoxic or cytotoxic damage. In order to face “the base oxidation or DNA replication stress”, plants have developed many sophisticated mechanisms. One of them is the DNA mismatch repair (MMR) pathway. The main part of the MMR is the MutS homologue (MSH) protein family. The genome of Arabidopsis thaliana encodes at least seven homologues of the MSH family: AtMSH1, AtMSH2, AtMSH3, AtMSH4, AtMSH5, AtMSH6, and AtMSH7. Despite their importance, the functions of AtMSH homologs have not been investigated. In this work, bioinformatics tools were used to obtain a better understanding of MSH-mediated DNA repair mechanisms in Arabidopsis thaliana and to understand the additional biological roles of AtMSH family members. In silico analysis, including phylogeny tracking, prediction of 3D structure, interactome analysis, and docking site prediction, suggested interactions with proteins were important for physiological development of A. thaliana. The MSH homologs extensively interacted with both TIL1 and TIL2 (DNA polymerase epsilon catalytic subunit), proteins involved in cell fate determination during plant embryogenesis and involved in flowering time repression. Additionally, interactions with the RECQ protein family (helicase enzymes) and proteins of nucleotide excision repair pathway were detected. Taken together, the results presented here confirm the important role of AtMSH proteins in mismatch repair and suggest important new physiological roles. Interactome Analysis and Docking Sites of MutS Homologs Reveal New Physiological Roles in Arabidopsis thaliana 2019-07-08T16:03:10+08:00 LaTeX with hyperref package 2020-02-07T16:51:54+01:00 2020-02-07T16:51:54+01:00 DNA mismatch repair; MSH; docking site; interactome pdfTeX-1.40.18 False This is pdfTeX, Version 3.14159265-2.6-1.40.18 (TeX Live 2017/W32TeX) kpathsea version 6.2.3 uuid:1400fca3-571c-40c1-86d9-add8f1a059ba uuid:de1351b7-09e4-4b89-87a9-ce984f459ca0 Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 75, 757, 219, 793 Annotation: Subtype: Link Rect: 474, 757, 519, 793 Annotation: Subtype: Link Rect: 466, 524, 518, 543 Annotation: Subtype: Link Rect: 410, 145, 417, 154 ActionDest: 78 Annotation: Subtype: Link Rect: 219, 118, 226, 127 ActionDest: 78 Annotation: Subtype: Link Rect: 229, 118, 236, 127 ActionDest: 78 Annotation: Subtype: Link Rect: 175, 38, 272, 50 Annotation: Subtype: Link Rect: 395, 38, 519, 50 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 290, 688, 297, 698 ActionDest: 78 Annotation: Subtype: Link Rect: 173, 661, 180, 671 ActionDest: 78 Annotation: Subtype: Link Rect: 374, 648, 386, 657 ActionDest: 81 Annotation: Subtype: Link Rect: 191, 526, 203, 535 ActionDest: 81 Annotation: Subtype: Link Rect: 204, 526, 216, 535 ActionDest: 81 Annotation: Subtype: Link Rect: 291, 513, 303, 522 ActionDest: 81 Annotation: Subtype: Link Rect: 304, 513, 316, 522 ActionDest: 81 Annotation: Subtype: Link Rect: 399, 499, 411, 508 ActionDest: 81 Annotation: Subtype: Link Rect: 120, 432, 132, 441 ActionDest: 81 Annotation: Subtype: Link Rect: 326, 405, 338, 414 ActionDest: 81 Annotation: Subtype: Link Rect: 339, 405, 351, 414 ActionDest: 81 Annotation: Subtype: Link Rect: 274, 378, 286, 387 ActionDest: 81 Annotation: Subtype: Link Rect: 205, 364, 217, 373 ActionDest: 81 Annotation: Subtype: Link Rect: 179, 337, 191, 346 ActionDest: 81 Annotation: Subtype: Link Rect: 503, 310, 515, 319 ActionDest: 81 Annotation: Subtype: Link Rect: 124, 270, 136, 279 ActionDest: 81 Annotation: Subtype: Link Rect: 137, 270, 149, 279 ActionDest: 81 Annotation: Subtype: Link Rect: 112, 79, 119, 91 ActionDest: 4 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 411, 743, 423, 752 ActionDest: 81 Annotation: Subtype: Link Rect: 508, 519, 515, 531 ActionDest: 4 Annotation: Subtype: Link Rect: 422, 495, 433, 504 ActionDest: 81 Annotation: Subtype: Link Rect: 250, 265, 257, 277 ActionDest: 32 Annotation: Subtype: Link Rect: 372, 182, 378, 194 ActionDest: 32 Annotation: Subtype: Link Rect: 305, 131, 317, 140 ActionDest: 81 Annotation: Subtype: Link Rect: 177, 117, 184, 127 ActionDest: 51 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 140, 693, 147, 705 ActionDest: 51 Annotation: Subtype: Link Rect: 324, 696, 336, 705 ActionDest: 81 Annotation: Subtype: Link Rect: 237, 683, 249, 692 ActionDest: 81 Page: Sequence: 5 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 503, 338, 515, 347 ActionDest: 81 Annotation: Subtype: Link Rect: 153, 311, 165, 320 ActionDest: 81 Annotation: Subtype: Link Rect: 208, 257, 220, 266 ActionDest: 81 Annotation: Subtype: Link Rect: 503, 257, 515, 266 ActionDest: 84 Annotation: Subtype: Link Rect: 478, 189, 490, 198 ActionDest: 84 Annotation: Subtype: Link Rect: 298, 90, 305, 102 ActionDest: 63 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 295, 702, 307, 711 ActionDest: 84 Annotation: Subtype: Link Rect: 221, 551, 233, 560 ActionDest: 84 Annotation: Subtype: Link Rect: 457, 548, 464, 560 ActionDest: 66 Page: Sequence: 8 Page: Sequence: 9 Page: Sequence: 10 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 276, 509, 386, 521 Annotation: Subtype: Link Rect: 351, 199, 363, 208 ActionDest: 84 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 184, 661, 196, 671 ActionDest: 84 Annotation: Subtype: Link Rect: 386, 607, 398, 617 ActionDest: 84 Annotation: Subtype: Link Rect: 248, 580, 260, 590 ActionDest: 84 Annotation: Subtype: Link Rect: 261, 580, 273, 590 ActionDest: 84 Annotation: Subtype: Link Rect: 197, 513, 209, 522 ActionDest: 84 Annotation: Subtype: Link Rect: 118, 486, 130, 495 ActionDest: 84 Annotation: Subtype: Link Rect: 352, 405, 364, 414 ActionDest: 84 Annotation: Subtype: Link Rect: 367, 405, 379, 414 ActionDest: 84 Annotation: Subtype: Link Rect: 279, 297, 291, 306 ActionDest: 84 Annotation: Subtype: Link Rect: 220, 256, 232, 265 ActionDest: 84 Annotation: Subtype: Link Rect: 233, 256, 245, 265 ActionDest: 84 Annotation: Subtype: Link Rect: 460, 215, 472, 225 ActionDest: 84 Annotation: Subtype: Link Rect: 435, 175, 447, 184 ActionDest: 84 Annotation: Subtype: Link Rect: 238, 81, 250, 90 ActionDest: 84 Annotation: Subtype: Link Rect: 251, 80, 263, 90 ActionDest: 84 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 420, 702, 432, 711 ActionDest: 84 Annotation: Subtype: Link Rect: 386, 621, 398, 630 ActionDest: 84 Annotation: Subtype: Link Rect: 462, 607, 474, 617 ActionDest: 81 Annotation: Subtype: Link Rect: 254, 406, 266, 416 ActionDest: 84 Annotation: Subtype: Link Rect: 504, 406, 516, 416 ActionDest: 87 Annotation: Subtype: Link Rect: 104, 390, 111, 402 ActionDest: 72 Annotation: Subtype: Link Rect: 403, 393, 415, 402 ActionDest: 87 Annotation: Subtype: Link Rect: 418, 393, 430, 402 ActionDest: 87 Annotation: Subtype: Link Rect: 148, 159, 160, 168 ActionDest: 87 Annotation: Subtype: Link Rect: 161, 159, 173, 168 ActionDest: 87 Annotation: Subtype: Link Rect: 108, 76, 120, 85 ActionDest: 87 Page: Sequence: 14 Annotations: Annotation: Subtype: Link Rect: 385, 742, 397, 752 ActionDest: 87 Annotation: Subtype: Link Rect: 398, 742, 410, 752 ActionDest: 87 Annotation: Subtype: Link Rect: 264, 661, 276, 671 ActionDest: 87 Annotation: Subtype: Link Rect: 435, 648, 447, 657 ActionDest: 87 Annotation: Subtype: Link Rect: 117, 621, 129, 630 ActionDest: 87 Annotation: Subtype: Link Rect: 490, 565, 502, 574 ActionDest: 87 Annotation: Subtype: Link Rect: 428, 551, 440, 560 ActionDest: 87 Annotation: Subtype: Link Rect: 261, 481, 272, 491 ActionDest: 87 Annotation: Subtype: Link Rect: 273, 481, 285, 491 ActionDest: 87 Annotation: Subtype: Link Rect: 353, 398, 365, 407 ActionDest: 87 Annotation: Subtype: Link Rect: 238, 288, 250, 297 ActionDest: 87 Annotation: Subtype: Link Rect: 132, 234, 144, 243 ActionDest: 87 Annotation: Subtype: Link Rect: 247, 164, 259, 173 ActionDest: 87 Annotation: Subtype: Link Rect: 262, 164, 274, 173 ActionDest: 90 Annotation: Subtype: Link Rect: 269, 97, 281, 106 ActionDest: 90 Page: Sequence: 15 Annotations: Annotation: Subtype: Link Rect: 179, 743, 191, 752 ActionDest: 90 Annotation: Subtype: Link Rect: 218, 262, 255, 272 Annotation: Subtype: Link Rect: 261, 262, 297, 272 Annotation: Subtype: Link Rect: 311, 235, 348, 246 Annotation: Subtype: Link Rect: 355, 235, 391, 246 Annotation: Subtype: Link Rect: 418, 222, 456, 233 Annotation: Subtype: Link Rect: 462, 222, 498, 233 Annotation: Subtype: Link Rect: 100, 197, 137, 207 Annotation: Subtype: Link Rect: 143, 197, 179, 207 Annotation: Subtype: Link Rect: 100, 172, 137, 182 Annotation: Subtype: Link Rect: 334, 146, 372, 156 Annotation: Subtype: Link Rect: 378, 146, 414, 156 Annotation: Subtype: Link Rect: 168, 120, 205, 130 Annotation: Subtype: Link Rect: 464, 80, 502, 91 Page: Sequence: 16 Annotations: Annotation: Subtype: Link Rect: 136, 728, 174, 738 Annotation: Subtype: Link Rect: 478, 701, 516, 712 Annotation: Subtype: Link Rect: 100, 689, 136, 699 Annotation: Subtype: Link Rect: 337, 663, 373, 673 Annotation: Subtype: Link Rect: 363, 637, 399, 648 Annotation: Subtype: Link Rect: 193, 599, 229, 609 Annotation: Subtype: Link Rect: 148, 573, 186, 583 Annotation: Subtype: Link Rect: 223, 534, 260, 544 Annotation: Subtype: Link Rect: 266, 534, 302, 544 Annotation: Subtype: Link Rect: 269, 495, 307, 506 Annotation: Subtype: Link Rect: 313, 495, 349, 506 Annotation: Subtype: Link Rect: 478, 469, 516, 480 Annotation: Subtype: Link Rect: 100, 457, 136, 467 Annotation: Subtype: Link Rect: 304, 417, 342, 428 Annotation: Subtype: Link Rect: 460, 391, 498, 402 Annotation: Subtype: Link Rect: 158, 354, 196, 364 Annotation: Subtype: Link Rect: 202, 354, 238, 364 Annotation: Subtype: Link Rect: 141, 315, 178, 325 Annotation: Subtype: Link Rect: 185, 315, 221, 325 Annotation: Subtype: Link Rect: 369, 288, 406, 299 Annotation: Subtype: Link Rect: 412, 288, 449, 299 Annotation: Subtype: Link Rect: 100, 250, 137, 260 Annotation: Subtype: Link Rect: 143, 250, 179, 260 Annotation: Subtype: Link Rect: 236, 224, 274, 234 Annotation: Subtype: Link Rect: 468, 172, 506, 183 Annotation: Subtype: Link Rect: 332, 146, 370, 157 Annotation: Subtype: Link Rect: 441, 121, 478, 131 Annotation: Subtype: Link Rect: 198, 95, 236, 105 Page: Sequence: 17 Annotations: Annotation: Subtype: Link Rect: 180, 715, 217, 725 Annotation: Subtype: Link Rect: 223, 715, 259, 725 Annotation: Subtype: Link Rect: 383, 675, 421, 686 Annotation: Subtype: Link Rect: 427, 675, 463, 686 Annotation: Subtype: Link Rect: 370, 650, 407, 661 Annotation: Subtype: Link Rect: 414, 650, 450, 661 Annotation: Subtype: Link Rect: 100, 625, 137, 635 Annotation: Subtype: Link Rect: 143, 625, 179, 635 Annotation: Subtype: Link Rect: 417, 598, 454, 609 Annotation: Subtype: Link Rect: 100, 573, 137, 583 Annotation: Subtype: Link Rect: 143, 573, 179, 583 Annotation: Subtype: Link Rect: 335, 534, 373, 544 Annotation: Subtype: Link Rect: 379, 534, 415, 544 Annotation: Subtype: Link Rect: 394, 508, 431, 519 Annotation: Subtype: Link Rect: 438, 508, 474, 519 Annotation: Subtype: Link Rect: 154, 418, 191, 428 Annotation: Subtype: Link Rect: 198, 418, 234, 428 Annotation: Subtype: Link Rect: 100, 366, 137, 376 Annotation: Subtype: Link Rect: 100, 328, 137, 338 Annotation: Subtype: Link Rect: 143, 328, 179, 338 Annotation: Subtype: Link Rect: 314, 288, 351, 299 Annotation: Subtype: Link Rect: 357, 288, 393, 299 Annotation: Subtype: Link Rect: 220, 250, 257, 260 Annotation: Subtype: Link Rect: 263, 250, 299, 260 Annotation: Subtype: Link Rect: 402, 211, 440, 222 Annotation: Subtype: Link Rect: 446, 211, 482, 222 Annotation: Subtype: Link Rect: 254, 185, 292, 196 Annotation: Subtype: Link Rect: 298, 185, 334, 196 Annotation: Subtype: Link Rect: 100, 160, 137, 170 Annotation: Subtype: Link Rect: 143, 160, 179, 170 Annotation: Subtype: Link Rect: 172, 95, 210, 105 Annotation: Subtype: Link Rect: 359, 82, 480, 92 Page: Sequence: 18 Annotations: Annotation: Subtype: Link Rect: 195, 715, 233, 725 Annotation: Subtype: Link Rect: 127, 676, 165, 686 Annotation: Subtype: Link Rect: 395, 650, 432, 661 Annotation: Subtype: Link Rect: 439, 650, 475, 661 Annotation: Subtype: Link Rect: 479, 624, 516, 635 Annotation: Subtype: Link Rect: 100, 612, 136, 622 Annotation: Subtype: Link Rect: 300, 559, 337, 570 Annotation: Subtype: Link Rect: 344, 559, 380, 570 Annotation: Subtype: Link Rect: 198, 521, 235, 531 Annotation: Subtype: Link Rect: 241, 521, 278, 531 Annotation: Subtype: Link Rect: 361, 495, 398, 506 Annotation: Subtype: Link Rect: 404, 495, 440, 506 Annotation: Subtype: Link Rect: 244, 470, 282, 480 Annotation: Subtype: Link Rect: 288, 470, 324, 480 Annotation: Subtype: Link Rect: 136, 431, 173, 441 Annotation: Subtype: Link Rect: 180, 431, 216, 441 Annotation: Subtype: Link Rect: 281, 391, 319, 402 Annotation: Subtype: Link Rect: 285, 378, 407, 389 Annotation: Subtype: Link Rect: 226, 341, 263, 351 Annotation: Subtype: Link Rect: 269, 314, 307, 325 Annotation: Subtype: Link Rect: 478, 288, 516, 299 Annotation: Subtype: Link Rect: 100, 276, 136, 286 Annotation: Subtype: Link Rect: 204, 250, 242, 260 Annotation: Subtype: Link Rect: 248, 250, 284, 260 Annotation: Subtype: Link Rect: 204, 212, 242, 222 Annotation: Subtype: Link Rect: 248, 212, 284, 222 Annotation: Subtype: Link Rect: 350, 186, 388, 196 Annotation: Subtype: Link Rect: 397, 159, 434, 170 Annotation: Subtype: Link Rect: 381, 133, 418, 144 Annotation: Subtype: Link Rect: 346, 107, 384, 118 Annotation: Subtype: Link Rect: 411, 82, 449, 92 Page: Sequence: 19 Annotations: Annotation: Subtype: Link Rect: 387, 727, 425, 738 Annotation: Subtype: Link Rect: 214, 701, 251, 712 Annotation: Subtype: Link Rect: 257, 701, 293, 712 Annotation: Subtype: Link Rect: 335, 675, 373, 686 Annotation: Subtype: Link Rect: 379, 675, 415, 686 Annotation: Subtype: Link Rect: 76, 611, 166, 642 Annotation: Subtype: Link Rect: 234, 606, 407, 617 Checksum: aa75670d Type: CRC32 Checksum: f3bcbb741aaf0dd1ffe412a88d4c832b Type: MD5 Checksum: ecca68f53ff1e300a880380500aa917915ba3177 Type: SHA-1