63d28bb51fd7c5e4779341a3c5d01012 IntJouMol_a2020m11v21n13p9051.pdf 28bb7c9468a116493afce601b89e488619daed9b IntJouMol_a2020m11v21n13p9051.pdf d8185a53183c60776b4a5d33fe9dc9475fc700b566cc0530eb44562132c1a4e6 IntJouMol_a2020m11v21n13p9051.pdf Title: Kisspeptin Influences the Reproductive Axis and Circulating Levels of microRNAs in Senegalese Sole Subject: Kisspeptin regulates puberty and reproduction onset, acting upstream of the brain–pituitary–gonad (HPG) axis. This study aimed to test a kisspeptin-based hormonal therapy on cultured Senegalese sole (G1) breeders, known to have reproductive dysfunctions. A single intramuscular injection of KISS2-10 decapeptide (250 g/kg) was tested in females and males during the reproductive season, and gonad maturation, sperm motility, plasma levels of gonadotropins (Fsh and Lh) and sex steroids (11-ketotestosterone, testosterone and estradiol), as well as changes in small non-coding RNAs (sncRNAs) in plasma, were investigated. Fsh, Lh, and testosterone levels increased after kisspeptin injection in both sexes, while sperm analysis did not show differences between groups. Let7e, miR-199a-3p and miR-100-5p were differentially expressed in females, while miR-1-3p miRNA was up-regulated in kisspeptin-treated males. In silico prediction of mRNAs targeted by miRNAs revealed that kisspeptin treatment might affect paracellular transporters, regulate structural and functional polarity of cells, neural networks and intracellular trafficking in Senegalese sole females; also, DNA methylation and sphingolipid metabolism might be altered in kisspeptin-treated males. Results demonstrated that kisspeptin stimulated gonadotropin and testosterone secretion in both sexes and induced an unanticipated alteration of plasma miRNAs, opening new research venues to understand how this neuropeptide impacts in fish HPG axis. Keywords: Solea senegalensis; G1 breeders; hormonal treatment; KISS2; gonadotropins; sex steroids Author: Catarina C. V. Oliveira, Elvira Fatsini, Ignacio Fernández, Catarina Anjos, François Chauvigné, Joan Cerdà, Robin Mjelle, Jorge M. O. Fernandes and Elsa Cabrita Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Sat Nov 28 10:11:31 2020 CET ModDate: Sat Nov 28 10:11:31 2020 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 21 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3109088 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- ANUMHB+URWPalladioL-Ital Type 1 Custom yes yes no 108 0 ZDLZNW+URWPalladioL-Bold Type 1 Custom yes yes no 109 0 QTLELQ+Pxbsy Type 1 Builtin yes yes no 110 0 NCRKTZ+VnURWPalladioL-Bold Type 1 Custom yes yes no 111 0 AUAWGZ+URWPalladioL-Roma Type 1 Custom yes yes no 112 0 ECBNSP+Rpxr Type 1 Builtin yes yes no 113 0 KSXHNW+VnURWPalladioL Type 1 Custom yes yes no 114 0 LCSSTQ+Pxsy Type 1 Builtin yes yes no 115 0 CAMXTK+EURM10 Type 1 Builtin yes yes no 116 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 121 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 122 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 141 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 142 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 143 0 WTSICF+Rpxi Type 1 Builtin yes yes no 238 0 FPJONU+PalatinoLinotype,Bold CID TrueType Identity-H yes yes yes 243 0 FPLQTT+PalatinoLinotype CID TrueType Identity-H yes yes yes 244 0 FPMFTG+TimesNewRoman CID TrueType Identity-H yes yes yes 245 0 FPJONU+PalatinoLinotype,Italic CID TrueType Identity-H yes yes yes 246 0 FPJONU+PalatinoLinotype,Bold CID TrueType Identity-H yes yes yes 288 0 FPLQTT+PalatinoLinotype CID TrueType Identity-H yes yes yes 289 0 FPMFTG+TimesNewRoman CID TrueType Identity-H yes yes yes 290 0 FPJONU+PalatinoLinotype,Italic CID TrueType Identity-H yes yes yes 291 0 FPJONU+PalatinoLinotype,Bold CID TrueType Identity-H yes yes yes 319 0 FPLQTT+PalatinoLinotype CID TrueType Identity-H yes yes yes 320 0 FPMFTG+TimesNewRoman CID TrueType Identity-H yes yes yes 321 0 FPJONU+PalatinoLinotype,Italic CID TrueType Identity-H yes yes yes 322 0 FPJONU+PalatinoLinotype,Bold CID TrueType Identity-H yes yes yes 360 0 FPLQTT+PalatinoLinotype CID TrueType Identity-H yes yes yes 361 0 FPMFTG+TimesNewRoman CID TrueType Identity-H yes yes yes 362 0 FPJONU+PalatinoLinotype,Italic CID TrueType Identity-H yes yes yes 363 0 FPJONU+PalatinoLinotype,Bold CID TrueType Identity-H yes yes yes 393 0 FPLQTT+PalatinoLinotype CID TrueType Identity-H yes yes yes 394 0 FPMFTG+TimesNewRoman CID TrueType Identity-H yes yes yes 395 0 FPJONU+PalatinoLinotype,Italic CID TrueType Identity-H yes yes yes 396 0 FPJONU+PalatinoLinotype,Bold CID TrueType Identity-H yes yes yes 435 0 FPLQTT+PalatinoLinotype CID TrueType Identity-H yes yes yes 436 0 FPMFTG+TimesNewRoman CID TrueType Identity-H yes yes yes 437 0 FPJONU+PalatinoLinotype,Italic CID TrueType Identity-H yes yes yes 438 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes no 478 0 FPJONU+PalatinoLinotype,Bold CID TrueType Identity-H yes yes yes 488 0 FPLQTT+PalatinoLinotype CID TrueType Identity-H yes yes yes 489 0 FPMFTG+TimesNewRoman CID TrueType Identity-H yes yes yes 490 0 FPJONU+PalatinoLinotype,Italic CID TrueType Identity-H yes yes yes 491 0 FPJONU+PalatinoLinotype,Bold CID TrueType Identity-H yes yes yes 524 0 FPLQTT+PalatinoLinotype CID TrueType Identity-H yes yes yes 525 0 FPMFTG+TimesNewRoman CID TrueType Identity-H yes yes yes 526 0 FPJONU+PalatinoLinotype,Italic CID TrueType Identity-H yes yes yes 527 0 YNURIB+Rpxmi Type 1 Builtin yes yes no 587 0 VSHNAE+Rpcxr Type 1 Builtin yes yes no 860 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2021-02-17 02:19:43 CET RepresentationInformation: IntJouMol_a2020m11v21n13p9051.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2021-02-16 17:49:24 CET Size: 3109088 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/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: ぉのぴひはつふっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸲ Item: Title: げづびふぬぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮ㄩ‾㸊⡜㌷㙜㌷㝜〰かどびびばづばぴどのぜ〴ぜ〰ごひづちぴねづのぴぜ〴ぜ〰ぁててづっぴびぜ〴ぜ〰ぴとづぜ〴ぜ〰げづばひはつふっぴどぶづぜ〴ぜ〰ちへどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰ぃどひっふぬちぴどのでぜ〴ぜ〰びのっげぎぁぜ〴ぜ〰ぐひはてどぬづびぜ〴ぜ〰どのぜ〴ぜ〰ぐぬちびねちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰あどはどのてはひねちぴどっぜ〴ぜ〰ぐひづつどっぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ねげぎぁびぜ〴ぜ〰ごちひでづぴびぜ〴ぜ〰ぢべぜ〴ぜ〰いどててづひづのぴどちぬぬべぜ〴ぜ〰ぅへばひづびびづつぜ〴ぜ〰ぜ〵ぜ〰いぅぜ〵ㅜ〰ぜ〴ぜ〰ねどげぎぁびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Children: Item: Title: かどびびばづばぴどのぜ〴ぜ〰ごひづちぴねづのぴぜ〴ぜ〰ぁててづっぴびぜ〴ぜ〰ぴとづぜ〴ぜ〰げづばひはつふっぴどぶづぜ〴ぜ〰ちへどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰ぃどひっふぬちぴどのでぜ〴ぜ〰びのっげぎぁぜ〴ぜ〰ぐひはてどぬづびぜ〴ぜ〰どのぜ〴ぜ〰ぐぬちびねちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰あどはどのてはひねちぴどっぜ〴ぜ〰ぐひづつどっぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ねげぎぁびぜ〴ぜ〰ごちひでづぴびぜ〴ぜ〰ぢべぜ〴ぜ〰いどててづひづのぴどちぬぬべぜ〴ぜ〰ぅへばひづびびづつぜ〴ぜ〰ぜ〵ぜ〰いぅぜ〵ㅜ〰ぜ〴ぜ〰ねどげぎぁびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ぃどひっふぬちぴどのでぜ〴ぜ〰びのっげぎぁぜ〴ぜ〰ぐひはてどぬづびぜ〴ぜ〰どのぜ〴ぜ〰ぐぬちびねちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰あどはどのてはひねちぴどっぜ〴ぜ〰ぐひづつどっぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ねげぎぁびぜ〴ぜ〰ごちひでづぴびぜ〴ぜ〰ぢべぜ〴ぜ〰いどててづひづのぴどちぬぬべぜ〴ぜ〰ぅへばひづびびづつぜ〴ぜ〰ぜ〵ぜ〰いぅぜ〵ㅜ〰ぜ〴ぜ〰ねどげぎぁびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: あどはどのてはひねちぴどっぜ〴ぜ〰ぐひづつどっぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ねげぎぁびぜ〴ぜ〰ごちひでづぴびぜ〴ぜ〰ぢべぜ〴ぜ〰いどててづひづのぴどちぬぬべぜ〴ぜ〰ぅへばひづびびづつぜ〴ぜ〰ぜ〵ぜ〰いぅぜ〵ㅜ〰ぜ〴ぜ〰ねどげぎぁびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: いどびっふびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: きちぴづひどちぬびぜ〴ぜ〰ちのつぜ〴ぜ〰きづぴとはつびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮ㄩ‾㸊⡜㌷㙜㌷㝜〰ぁのどねちぬびぜ〴ぜ〰ちのつぜ〴ぜ〰えはふびどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㈩‾㸊⡜㌷㙜㌷㝜〰ぅへばづひどねづのぴちぬぜ〴ぜ〰いづびどでのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㌩‾㸊⡜㌷㙜㌷㝜〰こばづひねぜ〴ぜ〰けふちぬどぴべぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㐩‾㸊⡜㌷㙜㌷㝜〰ぁのちぬべびどびぜ〴ぜ〰はてぜ〴ぜ〰えはひねはのづびぜ〴ぜ〰どのぜ〴ぜ〰あぬははつぜ〴ぜ〰ぐぬちびねちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㔩‾㸊⡜㌷㙜㌷㝜〰ねどっひはげぎぁびぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸴⸵⸱ Children: Item: Title: ぁのどねちぬびぜ〴ぜ〰ちのつぜ〴ぜ〰えはふびどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㈩‾㸊⡜㌷㙜㌷㝜〰ぅへばづひどねづのぴちぬぜ〴ぜ〰いづびどでのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㌩‾㸊⡜㌷㙜㌷㝜〰こばづひねぜ〴ぜ〰けふちぬどぴべぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㐩‾㸊⡜㌷㙜㌷㝜〰ぁのちぬべびどびぜ〴ぜ〰はてぜ〴ぜ〰えはひねはのづびぜ〴ぜ〰どのぜ〴ぜ〰あぬははつぜ〴ぜ〰ぐぬちびねちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㔩‾㸊⡜㌷㙜㌷㝜〰ねどっひはげぎぁびぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸴⸵⸱ Item: Title: ぅへばづひどねづのぴちぬぜ〴ぜ〰いづびどでのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㌩‾㸊⡜㌷㙜㌷㝜〰こばづひねぜ〴ぜ〰けふちぬどぴべぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㐩‾㸊⡜㌷㙜㌷㝜〰ぁのちぬべびどびぜ〴ぜ〰はてぜ〴ぜ〰えはひねはのづびぜ〴ぜ〰どのぜ〴ぜ〰あぬははつぜ〴ぜ〰ぐぬちびねちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㔩‾㸊⡜㌷㙜㌷㝜〰ねどっひはげぎぁびぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸴⸵⸱ Item: Title: こばづひねぜ〴ぜ〰けふちぬどぴべぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㐩‾㸊⡜㌷㙜㌷㝜〰ぁのちぬべびどびぜ〴ぜ〰はてぜ〴ぜ〰えはひねはのづびぜ〴ぜ〰どのぜ〴ぜ〰あぬははつぜ〴ぜ〰ぐぬちびねちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㔩‾㸊⡜㌷㙜㌷㝜〰ねどっひはげぎぁびぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸴⸵⸱ Item: Title: ぁのちぬべびどびぜ〴ぜ〰はてぜ〴ぜ〰えはひねはのづびぜ〴ぜ〰どのぜ〴ぜ〰あぬははつぜ〴ぜ〰ぐぬちびねちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㔩‾㸊⡜㌷㙜㌷㝜〰ねどっひはげぎぁびぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸴⸵⸱ Item: Title: ねどっひはげぎぁびぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸴⸵⸱ Children: Item: Title: ぉびはぬちぴどはの〬ぜ〴ぜ〰がどぢひちひどづびぜ〴ぜ〰ぐひづばちひちぴどはの〬ぜ〴ぜ〰ちのつぜ〴ぜ〰こづぱふづのっどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸴⸵⸲ Item: Title: いちぴちぜ〴ぜ〰ぐひはっづびびどのでぜ〴ぜ〰ちのつぜ〴ぜ〰ぁののはぴちぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸴⸵⸳ Item: Title: ねげぎぁぜ〴ぜ〰ごちひでづぴぜ〴ぜ〰ぐひづつどっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㘩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: ぃはのっぬふびどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: げづてづひづのっづび Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: YNURIB+Rpxmi FontSubset: true FirstChar: 12 LastChar: 12 FontDescriptor: FontName: YNURIB+Rpxmi Flags: Symbolic FontBBox: -70, -289, 949, 802 FontFile: true Font: BaseFont: ANUMHB+URWPalladioL-Ital FontSubset: true FirstChar: 2 LastChar: 150 FontDescriptor: FontName: ANUMHB+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: ZDLZNW+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 231 FontDescriptor: FontName: ZDLZNW+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: QTLELQ+Pxbsy FontSubset: true FirstChar: 121 LastChar: 121 FontDescriptor: FontName: QTLELQ+Pxbsy Flags: Symbolic FontBBox: 5, -978, 1382, 913 FontFile: true Font: BaseFont: WTSICF+Rpxi FontSubset: true FirstChar: 11 LastChar: 14 FontDescriptor: FontName: WTSICF+Rpxi Flags: Symbolic FontBBox: -162, -280, 856, 733 FontFile: true Font: BaseFont: NCRKTZ+VnURWPalladioL-Bold FontSubset: true FirstChar: 160 LastChar: 178 FontDescriptor: FontName: NCRKTZ+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: AUAWGZ+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: AUAWGZ+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: ECBNSP+Rpxr FontSubset: true FirstChar: 11 LastChar: 61 FontDescriptor: FontName: ECBNSP+Rpxr Flags: Symbolic FontBBox: -40, -283, 904, 728 FontFile: true Font: BaseFont: KSXHNW+VnURWPalladioL FontSubset: true FirstChar: 129 LastChar: 226 FontDescriptor: FontName: KSXHNW+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: LCSSTQ+Pxsy FontSubset: true FirstChar: 0 LastChar: 121 FontDescriptor: FontName: LCSSTQ+Pxsy Flags: Symbolic FontBBox: -21, -994, 1292, 912 FontFile: true Font: BaseFont: CAMXTK+EURM10 FontSubset: true FirstChar: 12 LastChar: 22 FontDescriptor: FontName: CAMXTK+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 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 Font: BaseFont: WBVKDJ+URWPalladioL-BoldItal FontSubset: true FirstChar: 112 LastChar: 112 FontDescriptor: FontName: WBVKDJ+URWPalladioL-BoldItal Flags: Symbolic FontBBox: -170, -300, 1073, 935 FontFile: true EncodingDictionary: Differences: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 75, 757, 221, 793 Annotation: Subtype: Link Rect: 474, 757, 519, 793 Annotation: Subtype: Link Rect: 198, 660, 209, 674 Annotation: Subtype: Link Rect: 286, 660, 297, 674 Annotation: Subtype: Link Rect: 391, 660, 402, 674 Annotation: Subtype: Link Rect: 234, 647, 245, 660 Annotation: Subtype: Link Rect: 429, 647, 440, 660 Annotation: Subtype: Link Rect: 466, 482, 518, 501 Annotation: Subtype: Link Rect: 261, 131, 268, 141 ActionDest: 732 Annotation: Subtype: Link Rect: 268, 131, 275, 141 ActionDest: 732 Annotation: Subtype: Link Rect: 146, 104, 153, 114 ActionDest: 732 Annotation: Subtype: Link Rect: 478, 104, 485, 114 ActionDest: 758 Annotation: Subtype: Link Rect: 435, 77, 442, 87 ActionDest: 758 Annotation: Subtype: Link Rect: 193, 38, 270, 50 Annotation: Subtype: Link Rect: 416, 38, 519, 50 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 498, 729, 505, 738 ActionDest: 758 Annotation: Subtype: Link Rect: 508, 729, 515, 738 ActionDest: 758 Annotation: Subtype: Link Rect: 341, 702, 348, 711 ActionDest: 758 Annotation: Subtype: Link Rect: 281, 688, 288, 698 ActionDest: 758 Annotation: Subtype: Link Rect: 288, 688, 300, 698 ActionDest: 758 Annotation: Subtype: Link Rect: 247, 661, 254, 671 ActionDest: 758 Annotation: Subtype: Link Rect: 393, 648, 400, 657 ActionDest: 758 Annotation: Subtype: Link Rect: 132, 594, 144, 603 ActionDest: 758 Annotation: Subtype: Link Rect: 338, 580, 350, 590 ActionDest: 758 Annotation: Subtype: Link Rect: 350, 580, 362, 590 ActionDest: 758 Annotation: Subtype: Link Rect: 118, 553, 130, 562 ActionDest: 758 Annotation: Subtype: Link Rect: 266, 553, 278, 562 ActionDest: 758 Annotation: Subtype: Link Rect: 434, 553, 446, 562 ActionDest: 758 Annotation: Subtype: Link Rect: 339, 526, 351, 535 ActionDest: 758 Annotation: Subtype: Link Rect: 352, 526, 364, 535 ActionDest: 758 Annotation: Subtype: Link Rect: 503, 526, 515, 535 ActionDest: 758 Annotation: Subtype: Link Rect: 454, 513, 466, 522 ActionDest: 758 Annotation: Subtype: Link Rect: 316, 486, 328, 495 ActionDest: 758 Annotation: Subtype: Link Rect: 328, 486, 340, 495 ActionDest: 758 Annotation: Subtype: Link Rect: 173, 472, 185, 481 ActionDest: 783 Annotation: Subtype: Link Rect: 392, 472, 404, 481 ActionDest: 783 Annotation: Subtype: Link Rect: 405, 472, 417, 481 ActionDest: 783 Annotation: Subtype: Link Rect: 358, 405, 370, 414 ActionDest: 783 Annotation: Subtype: Link Rect: 303, 351, 315, 360 ActionDest: 783 Annotation: Subtype: Link Rect: 441, 324, 453, 333 ActionDest: 783 Annotation: Subtype: Link Rect: 433, 310, 445, 319 ActionDest: 783 Annotation: Subtype: Link Rect: 416, 297, 427, 306 ActionDest: 783 Annotation: Subtype: Link Rect: 428, 297, 440, 306 ActionDest: 783 Annotation: Subtype: Link Rect: 393, 283, 404, 292 ActionDest: 783 Annotation: Subtype: Link Rect: 405, 283, 417, 292 ActionDest: 783 Annotation: Subtype: Link Rect: 443, 270, 454, 279 ActionDest: 758 Annotation: Subtype: Link Rect: 455, 270, 467, 279 ActionDest: 783 Annotation: Subtype: Link Rect: 123, 242, 135, 252 ActionDest: 783 Annotation: Subtype: Link Rect: 264, 229, 276, 238 ActionDest: 783 Annotation: Subtype: Link Rect: 341, 215, 353, 225 ActionDest: 783 Annotation: Subtype: Link Rect: 206, 175, 217, 184 ActionDest: 758 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 237, 643, 244, 655 ActionDest: 235 Annotation: Subtype: Link Rect: 422, 306, 429, 318 ActionDest: 282 Annotation: Subtype: Link Rect: 187, 265, 194, 277 ActionDest: 282 Annotation: Subtype: Link Rect: 189, 238, 196, 250 ActionDest: 282 Annotation: Subtype: Link Rect: 317, 225, 325, 237 ActionDest: 282 Annotation: Subtype: Link Rect: 105, 184, 112, 196 ActionDest: 282 Annotation: Subtype: Link Rect: 138, 157, 145, 169 ActionDest: 282 Annotation: Subtype: Link Rect: 109, 130, 116, 142 ActionDest: 282 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 319, 261, 326, 273 ActionDest: 354 Annotation: Subtype: Link Rect: 458, 234, 465, 246 ActionDest: 354 Annotation: Subtype: Link Rect: 337, 207, 344, 219 ActionDest: 354 Annotation: Subtype: Link Rect: 324, 194, 331, 206 ActionDest: 354 Annotation: Subtype: Link Rect: 500, 167, 507, 179 ActionDest: 354 Annotation: Subtype: Link Rect: 242, 126, 249, 138 ActionDest: 354 Annotation: Subtype: Link Rect: 426, 113, 432, 125 ActionDest: 429 Annotation: Subtype: Link Rect: 239, 72, 246, 84 ActionDest: 429 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 109, 726, 116, 738 ActionDest: 429 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 429, 438, 436, 450 ActionDest: 482 Annotation: Subtype: Link Rect: 196, 303, 203, 315 ActionDest: 482 Annotation: Subtype: Link Rect: 444, 262, 451, 274 ActionDest: 482 Annotation: Subtype: Link Rect: 400, 249, 407, 261 ActionDest: 482 Annotation: Subtype: Link Rect: 166, 222, 173, 234 ActionDest: 482 Annotation: Subtype: Link Rect: 387, 181, 394, 193 ActionDest: 475 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 206, 504, 213, 516 ActionDest: 518 Annotation: Subtype: Link Rect: 314, 450, 321, 461 ActionDest: 518 Annotation: Subtype: Link Rect: 405, 423, 412, 434 ActionDest: 518 Annotation: Subtype: Link Rect: 166, 382, 173, 394 ActionDest: 518 Annotation: Subtype: Link Rect: 205, 342, 212, 353 ActionDest: 518 Annotation: Subtype: Link Rect: 217, 328, 224, 340 ActionDest: 518 Page: Sequence: 8 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 107, 234, 119, 243 ActionDest: 758 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 114, 729, 126, 738 ActionDest: 783 Annotation: Subtype: Link Rect: 503, 675, 515, 684 ActionDest: 783 Annotation: Subtype: Link Rect: 370, 661, 377, 671 ActionDest: 732 Annotation: Subtype: Link Rect: 377, 661, 384, 671 ActionDest: 758 Annotation: Subtype: Link Rect: 217, 621, 224, 630 ActionDest: 758 Annotation: Subtype: Link Rect: 444, 594, 456, 603 ActionDest: 783 Annotation: Subtype: Link Rect: 124, 553, 135, 562 ActionDest: 783 Annotation: Subtype: Link Rect: 340, 526, 347, 535 ActionDest: 758 Annotation: Subtype: Link Rect: 347, 526, 354, 535 ActionDest: 758 Annotation: Subtype: Link Rect: 355, 526, 367, 535 ActionDest: 783 Annotation: Subtype: Link Rect: 367, 526, 379, 535 ActionDest: 812 Annotation: Subtype: Link Rect: 503, 486, 515, 495 ActionDest: 812 Annotation: Subtype: Link Rect: 402, 405, 414, 414 ActionDest: 812 Annotation: Subtype: Link Rect: 197, 378, 209, 387 ActionDest: 812 Annotation: Subtype: Link Rect: 336, 364, 343, 373 ActionDest: 758 Annotation: Subtype: Link Rect: 122, 324, 133, 333 ActionDest: 812 Annotation: Subtype: Link Rect: 137, 324, 148, 333 ActionDest: 812 Annotation: Subtype: Link Rect: 107, 283, 119, 292 ActionDest: 812 Annotation: Subtype: Link Rect: 407, 270, 419, 279 ActionDest: 812 Annotation: Subtype: Link Rect: 214, 215, 226, 225 ActionDest: 812 Annotation: Subtype: Link Rect: 363, 215, 375, 225 ActionDest: 812 Annotation: Subtype: Link Rect: 114, 202, 126, 211 ActionDest: 812 Annotation: Subtype: Link Rect: 503, 202, 515, 211 ActionDest: 812 Annotation: Subtype: Link Rect: 144, 175, 156, 184 ActionDest: 758 Annotation: Subtype: Link Rect: 246, 148, 258, 157 ActionDest: 812 Annotation: Subtype: Link Rect: 452, 134, 464, 144 ActionDest: 812 Annotation: Subtype: Link Rect: 337, 121, 349, 130 ActionDest: 812 Annotation: Subtype: Link Rect: 466, 94, 478, 103 ActionDest: 812 Annotation: Subtype: Link Rect: 122, 80, 134, 90 ActionDest: 812 Annotation: Subtype: Link Rect: 470, 80, 482, 90 ActionDest: 812 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 425, 742, 437, 752 ActionDest: 812 Annotation: Subtype: Link Rect: 450, 648, 461, 657 ActionDest: 812 Annotation: Subtype: Link Rect: 472, 634, 484, 644 ActionDest: 812 Annotation: Subtype: Link Rect: 484, 634, 496, 644 ActionDest: 812 Annotation: Subtype: Link Rect: 484, 621, 496, 630 ActionDest: 812 Annotation: Subtype: Link Rect: 131, 580, 143, 590 ActionDest: 812 Annotation: Subtype: Link Rect: 441, 553, 453, 562 ActionDest: 842 Annotation: Subtype: Link Rect: 503, 526, 515, 535 ActionDest: 842 Annotation: Subtype: Link Rect: 228, 486, 240, 495 ActionDest: 842 Annotation: Subtype: Link Rect: 202, 472, 214, 481 ActionDest: 842 Annotation: Subtype: Link Rect: 171, 459, 183, 468 ActionDest: 842 Annotation: Subtype: Link Rect: 186, 432, 198, 441 ActionDest: 758 Annotation: Subtype: Link Rect: 313, 405, 325, 414 ActionDest: 842 Annotation: Subtype: Link Rect: 434, 391, 446, 400 ActionDest: 812 Annotation: Subtype: Link Rect: 144, 297, 156, 306 ActionDest: 842 Annotation: Subtype: Link Rect: 167, 283, 179, 292 ActionDest: 842 Annotation: Subtype: Link Rect: 180, 283, 192, 292 ActionDest: 842 Annotation: Subtype: Link Rect: 449, 270, 461, 279 ActionDest: 842 Annotation: Subtype: Link Rect: 344, 229, 355, 238 ActionDest: 842 Annotation: Subtype: Link Rect: 208, 161, 220, 171 ActionDest: 842 Annotation: Subtype: Link Rect: 435, 148, 447, 157 ActionDest: 842 Annotation: Subtype: Link Rect: 378, 94, 390, 103 ActionDest: 842 Annotation: Subtype: Link Rect: 161, 80, 173, 90 ActionDest: 842 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 166, 743, 178, 752 ActionDest: 842 Annotation: Subtype: Link Rect: 348, 742, 360, 752 ActionDest: 842 Annotation: Subtype: Link Rect: 98, 715, 110, 725 ActionDest: 842 Annotation: Subtype: Link Rect: 328, 661, 340, 671 ActionDest: 842 Annotation: Subtype: Link Rect: 394, 648, 406, 657 ActionDest: 842 Annotation: Subtype: Link Rect: 449, 634, 461, 644 ActionDest: 842 Annotation: Subtype: Link Rect: 317, 594, 329, 603 ActionDest: 842 Annotation: Subtype: Link Rect: 484, 346, 496, 356 ActionDest: 758 Annotation: Subtype: Link Rect: 323, 74, 335, 83 ActionDest: 783 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 314, 648, 326, 657 ActionDest: 857 Annotation: Subtype: Link Rect: 198, 634, 210, 644 ActionDest: 758 Annotation: Subtype: Link Rect: 509, 553, 516, 562 ActionDest: 758 Annotation: Subtype: Link Rect: 193, 540, 205, 549 ActionDest: 783 Annotation: Subtype: Link Rect: 246, 472, 258, 481 ActionDest: 758 Annotation: Subtype: Link Rect: 235, 321, 247, 331 ActionDest: 758 Page: Sequence: 14 Annotations: Annotation: Subtype: Link Rect: 344, 696, 356, 705 ActionDest: 758 Annotation: Subtype: Link Rect: 356, 696, 368, 705 ActionDest: 758 Annotation: Subtype: Link Rect: 369, 696, 380, 705 ActionDest: 758 Annotation: Subtype: Link Rect: 406, 655, 418, 665 ActionDest: 758 Annotation: Subtype: Link Rect: 419, 655, 431, 665 ActionDest: 857 Annotation: Subtype: Link Rect: 198, 615, 210, 624 ActionDest: 758 Annotation: Subtype: Link Rect: 462, 519, 469, 531 ActionDest: 715 Annotation: Subtype: Link Rect: 356, 465, 363, 477 ActionDest: 715 Page: Sequence: 15 Annotations: Annotation: Subtype: Link Rect: 392, 527, 403, 537 ActionDest: 857 Annotation: Subtype: Link Rect: 256, 484, 364, 496 Annotation: Subtype: Link Rect: 153, 473, 165, 483 ActionDest: 857 Annotation: Subtype: Link Rect: 371, 457, 519, 469 Annotation: Subtype: Link Rect: 75, 444, 312, 456 Annotation: Subtype: Link Rect: 418, 403, 515, 415 Annotation: Subtype: Link Rect: 78, 363, 415, 375 Annotation: Subtype: Link Rect: 465, 266, 519, 278 Annotation: Subtype: Link Rect: 75, 253, 339, 264 Annotation: Subtype: Link Rect: 411, 228, 423, 237 ActionDest: 857 Annotation: Subtype: Link Rect: 136, 188, 148, 197 ActionDest: 857 Annotation: Subtype: Link Rect: 149, 188, 161, 197 ActionDest: 857 Annotation: Subtype: Link Rect: 134, 158, 257, 170 Annotation: Subtype: Link Rect: 75, 144, 203, 156 Annotation: Subtype: Link Rect: 310, 77, 322, 87 ActionDest: 857 Page: Sequence: 16 Annotations: Annotation: Subtype: Link Rect: 359, 486, 519, 497 Annotation: Subtype: Link Rect: 75, 476, 106, 487 Annotation: Subtype: Link Rect: 289, 131, 326, 141 Annotation: Subtype: Link Rect: 100, 93, 137, 103 Page: Sequence: 17 Annotations: Annotation: Subtype: Link Rect: 412, 714, 450, 725 Annotation: Subtype: Link Rect: 456, 714, 492, 725 Annotation: Subtype: Link Rect: 100, 663, 137, 673 Annotation: Subtype: Link Rect: 143, 663, 179, 673 Annotation: Subtype: Link Rect: 395, 637, 433, 648 Annotation: Subtype: Link Rect: 371, 598, 408, 609 Annotation: Subtype: Link Rect: 200, 559, 238, 570 Annotation: Subtype: Link Rect: 300, 533, 337, 544 Annotation: Subtype: Link Rect: 376, 496, 414, 506 Annotation: Subtype: Link Rect: 356, 469, 393, 480 Annotation: Subtype: Link Rect: 373, 430, 411, 441 Annotation: Subtype: Link Rect: 154, 392, 191, 402 Annotation: Subtype: Link Rect: 198, 392, 234, 402 Annotation: Subtype: Link Rect: 428, 353, 466, 364 Annotation: Subtype: Link Rect: 440, 327, 478, 338 Annotation: Subtype: Link Rect: 366, 288, 404, 299 Annotation: Subtype: Link Rect: 100, 250, 137, 260 Annotation: Subtype: Link Rect: 277, 211, 314, 222 Annotation: Subtype: Link Rect: 261, 172, 299, 183 Annotation: Subtype: Link Rect: 419, 146, 457, 157 Annotation: Subtype: Link Rect: 474, 107, 511, 118 Annotation: Subtype: Link Rect: 392, 69, 430, 80 Page: Sequence: 18 Annotations: Annotation: Subtype: Link Rect: 418, 714, 456, 725 Annotation: Subtype: Link Rect: 176, 676, 214, 686 Annotation: Subtype: Link Rect: 321, 637, 359, 648 Annotation: Subtype: Link Rect: 444, 598, 481, 609 Annotation: Subtype: Link Rect: 306, 559, 343, 570 Annotation: Subtype: Link Rect: 298, 508, 335, 519 Annotation: Subtype: Link Rect: 149, 483, 187, 493 Annotation: Subtype: Link Rect: 215, 457, 252, 467 Annotation: Subtype: Link Rect: 364, 431, 402, 441 Annotation: Subtype: Link Rect: 291, 404, 329, 415 Annotation: Subtype: Link Rect: 127, 366, 165, 376 Annotation: Subtype: Link Rect: 159, 341, 196, 351 Annotation: Subtype: Link Rect: 228, 314, 265, 325 Annotation: Subtype: Link Rect: 172, 276, 210, 286 Annotation: Subtype: Link Rect: 296, 236, 334, 247 Annotation: Subtype: Link Rect: 217, 198, 255, 209 Annotation: Subtype: Link Rect: 412, 159, 449, 170 Annotation: Subtype: Link Rect: 359, 120, 396, 131 Annotation: Subtype: Link Rect: 270, 82, 308, 92 Page: Sequence: 19 Annotations: Annotation: Subtype: Link Rect: 478, 727, 516, 738 Annotation: Subtype: Link Rect: 100, 715, 136, 725 Annotation: Subtype: Link Rect: 345, 688, 383, 699 Annotation: Subtype: Link Rect: 453, 663, 490, 673 Annotation: Subtype: Link Rect: 177, 625, 214, 635 Annotation: Subtype: Link Rect: 243, 598, 281, 609 Annotation: Subtype: Link Rect: 336, 559, 374, 570 Annotation: Subtype: Link Rect: 263, 521, 301, 531 Annotation: Subtype: Link Rect: 393, 495, 431, 506 Annotation: Subtype: Link Rect: 450, 469, 487, 480 Annotation: Subtype: Link Rect: 100, 431, 137, 441 Annotation: Subtype: Link Rect: 264, 391, 302, 402 Annotation: Subtype: Link Rect: 308, 391, 344, 402 Annotation: Subtype: Link Rect: 243, 353, 280, 364 Annotation: Subtype: Link Rect: 423, 327, 460, 338 Annotation: Subtype: Link Rect: 466, 327, 502, 338 Annotation: Subtype: Link Rect: 405, 288, 443, 299 Annotation: Subtype: Link Rect: 449, 288, 485, 299 Annotation: Subtype: Link Rect: 306, 249, 343, 260 Annotation: Subtype: Link Rect: 100, 224, 137, 234 Annotation: Subtype: Link Rect: 143, 224, 179, 234 Annotation: Subtype: Link Rect: 100, 186, 137, 196 Annotation: Subtype: Link Rect: 405, 160, 442, 170 Annotation: Subtype: Link Rect: 298, 133, 335, 144 Annotation: Subtype: Link Rect: 462, 120, 500, 131 Page: Sequence: 20 Annotations: Annotation: Subtype: Link Rect: 417, 727, 454, 738 Annotation: Subtype: Link Rect: 168, 689, 205, 699 Annotation: Subtype: Link Rect: 211, 651, 249, 661 Annotation: Subtype: Link Rect: 218, 612, 256, 622 Annotation: Subtype: Link Rect: 419, 572, 457, 583 Annotation: Subtype: Link Rect: 207, 533, 244, 544 Annotation: Subtype: Link Rect: 464, 521, 501, 531 Annotation: Subtype: Link Rect: 441, 495, 479, 506 Annotation: Subtype: Link Rect: 419, 469, 456, 480 Annotation: Subtype: Link Rect: 100, 431, 137, 441 Annotation: Subtype: Link Rect: 279, 404, 316, 415 Annotation: Subtype: Link Rect: 199, 379, 237, 389 Annotation: Subtype: Link Rect: 362, 353, 400, 364 Annotation: Subtype: Link Rect: 456, 327, 494, 338 Annotation: Subtype: Link Rect: 158, 289, 196, 299 Annotation: Subtype: Link Rect: 202, 289, 238, 299 Annotation: Subtype: Link Rect: 429, 249, 467, 260 Annotation: Subtype: Link Rect: 473, 249, 509, 260 Annotation: Subtype: Link Rect: 257, 211, 295, 222 Annotation: Subtype: Link Rect: 136, 186, 174, 196 Annotation: Subtype: Link Rect: 131, 134, 169, 144 Annotation: Subtype: Link Rect: 365, 107, 402, 118 Annotation: Subtype: Link Rect: 376, 82, 413, 92 Annotation: Subtype: Link Rect: 419, 82, 456, 92 Page: Sequence: 21 Annotations: Annotation: Subtype: Link Rect: 398, 714, 436, 725 Annotation: Subtype: Link Rect: 260, 675, 297, 686 Annotation: Subtype: Link Rect: 304, 675, 340, 686 Annotation: Subtype: Link Rect: 122, 651, 160, 661 Annotation: Subtype: Link Rect: 100, 625, 137, 635 Annotation: Subtype: Link Rect: 208, 599, 246, 609 Annotation: Subtype: Link Rect: 464, 572, 502, 583 Annotation: Subtype: Link Rect: 300, 546, 338, 557 Annotation: Subtype: Link Rect: 76, 461, 166, 493 Annotation: Subtype: Link Rect: 234, 456, 407, 467 Checksum: ef5b6283 Type: CRC32 Checksum: 63d28bb51fd7c5e4779341a3c5d01012 Type: MD5 Checksum: 28bb7c9468a116493afce601b89e488619daed9b Type: SHA-1