189b194a223af02c178da32369133dad pmc_32346016.pdf 147cd2b379ef83bd0c316a3c9064b06b228258c5 pmc_32346016.pdf 0226539086d514e2a5c7213eb2f5671142b44e541c476b434c585b79c4f167d3 pmc_32346016.pdf Title: Chitinase 3-like 1 is neurotoxic in primary cultured neurons Subject: Scientific Reports, doi:10.1038/s41598-020-64093-2 Keywords: Creator: Springer Producer: iText® 5.3.5 ©2000-2012 1T3XT BVBA (SPRINGER SBM; licensed version) CreationDate: Mon Apr 20 21:45:50 2020 CEST ModDate: Wed Apr 22 09:34:54 2020 CEST Tagged: no UserProperties: no Suspects: no Form: AcroForm JavaScript: no Pages: 6 Encrypted: no Page size: 595.276 x 782.362 pts Page rot: 0 File size: 2158322 bytes Optimized: no PDF version: 1.4 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- FERCWO+Corbel-Bold CID TrueType Identity-H yes yes yes 52 0 RIBCIQ+ArialUnicodeMS CID TrueType Identity-H yes yes yes 215 0 MLLGQG+Corbel-BoldItalic Type 1C WinAnsi yes yes yes 216 0 MinionPro-Regular Type 1C Custom yes no yes 54 0 PTSLAF+Corbel-Bold2 Type 1C WinAnsi yes yes yes 55 0 MinionPro-It Type 1C Custom yes no yes 53 0 PXHPGK+Corbel2 Type 1C WinAnsi yes yes yes 58 0 NSTIEY+Corbel CID TrueType Identity-H yes yes yes 60 0 MyriadPro-It Type 1C WinAnsi yes no yes 61 0 PXHPGK+Corbel2 Type 1C WinAnsi yes yes yes 260 0 MinionPro-Bold Type 1C WinAnsi yes no yes 56 0 EuclidSymbol Type 1C Custom yes no yes 57 0 TCEEFM+STIXGeneral-Regular Type 1C Custom yes yes yes 59 0 NTCPZY+TimesNewRomanPSMT Type 1C WinAnsi yes yes yes 118 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-05-27 03:43:51 CEST RepresentationInformation: pmc_32346016.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-03-31 11:46:22 CEST Size: 2158322 Format: PDF Version: 1.4 Status: Well-Formed, but not valid SignatureMatches: PDF-hul ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_64093.indd:Figure 1. Dose-response study of CHI3L1 neurotoxic effect. Cortical neurons from E16 mice at 11DIV were treated with mouse recombinant CHI3L1 (100, 300 and 600⁜琀渀最⼀洀氀Ⰰ 最氀甀琀愀洀愀琀攀 ㈀　〠딀䴀 漀爀 洀攀搀椀甀洀 挀漀渀琀爀漀氀 昀漀爀 ㈀㐀 愀渀搀 㐀㠠栀漀甀爀猀⸀ 儀甀愀渀琀椀琀愀琀椀瘀攀 愀渀愀氀㨀㌀㐩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㐴㤮㈹㔠㐶㐮㈶㌠㐵㌮㘲㐠㐵㈮ㄲ㉝⽈⽎⽁值㰯丠㌰‰⁒㸾㸾੥湤潢樊ㄲ‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_64093.indd:Figure 2. Neurotoxic effect of CHI3L1. Cortical neurons from E16 mice at 11DIV were treated with PBS (vehicle), mouse recombinant CHI3L1 (300⁜琀渀最⼀洀氀Ⰰ 最氀甀琀愀洀愀琀攀 ㈀　〠딀䴀 漀爀 洀攀搀椀甀洀 挀漀渀琀爀漀氀 昀漀爀 ㈀㐀 愀渀搀 㐀㠠栀漀甀爀猀⸀ ＀䇾＀ 刀攀瀀爀攀猀攀渀琀愀琀椀瘀攀 椀洀愀最攀猀 漀昀 渀攀甀爀㨀㌀㔩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㈴㐮㜷㐠㐲㐮㈶㌠㈶㈮㘹㈠㐱㈮ㄲ㉝⽈⽎⽁值㰯丠㌱‰⁒㸾㸾੥湤潢樊ㄳ‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_64093.indd:Figure 2. Neurotoxic effect of CHI3L1. Cortical neurons from E16 mice at 11DIV were treated with PBS (vehicle), mouse recombinant CHI3L1 (300⁜琀渀最⼀洀氀Ⰰ 最氀甀琀愀洀愀琀攀 ㈀　〠딀䴀 漀爀 洀攀搀椀甀洀 挀漀渀琀爀漀氀 昀漀爀 ㈀㐀 愀渀搀 㐀㠠栀漀甀爀猀⸀ ＀䇾＀ 刀攀瀀爀攀猀攀渀琀愀琀椀瘀攀 椀洀愀最攀猀 漀昀 渀攀甀㨀㌀㘩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㐹㔮㌷㤠㐱㐮㈶㌠㔱㌮㈵㌠㐰㈮ㄲ㉝⽈⽎⽁值㰯丠㌲‰⁒㸾㸾੥湤潢樊ㄴ‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_64093.indd:Figure 2. Neurotoxic effect of CHI3L1. Cortical neurons from E16 mice at 11DIV were treated with PBS (vehicle), mouse recombinant CHI3L1 (300⁜琀渀最⼀洀氀Ⰰ 最氀甀琀愀洀愀琀攀 ㈀　〠딀䴀 漀爀 洀攀搀椀甀洀 挀漀渀琀爀漀氀 昀漀爀 ㈀㐀 愀渀搀 㐀㠠栀漀甀爀猀⸀ ＀䇾＀ 刀攀瀀爀攀猀攀渀琀愀琀椀瘀攀 椀洀愀最攀猀 漀昀 渀攀㨀㌀㜩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㌸㤮㔰㌠㌸㐮㈶㌠㐰㠮〷㤠㌷㈮ㄲ㉝⽈⽎⽁值㰯丠㌳‰⁒㸾㸾੥湤潢樊ㄵ‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_64093.indd:Figure 2. Neurotoxic effect of CHI3L1. Cortical neurons from E16 mice at 11DIV were treated with PBS (vehicle), mouse recombinant CHI3L1 (300⁜琀渀最⼀洀氀Ⰰ 最氀甀琀愀洀愀琀攀 ㈀　〠딀䴀 漀爀 洀攀搀椀甀洀 挀漀渀琀爀漀氀 昀漀爀 ㈀㐀 愀渀搀 㐀㠠栀漀甀爀猀⸀ ＀䇾＀ 刀攀瀀爀攀猀攀渀琀愀琀椀瘀攀 椀洀愀最攀猀 漀昀 渀㨀㌀㠩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛ㄷ㐮〵㐠㌴㐮㈶㌠ㄹ㐮㠶㈠㌳㈮ㄲ㉝⽈⽎⽁值㰯丠㌴‰⁒㸾㸾੥湤潢樊ㄶ‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_64093.indd:Figure 3. CHI3L1 effect on immune and CNS cells. Splenocytes,astrocytes and microglia from mixed glial cultures were treated with PBS (vehicle), mouse recombinant CHI3L1 (50, 100, 300 and 600⁜琀渀最⼀洀氀 漀爀 洀攀搀椀甀洀 挀漀渀琀爀漀氀 昀漀爀 㘀Ⰰ ㈀㐀 愀渀搀 㐀㠠栀漀甀爀猀⸀ ＀㨀㌀㤩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㌵㠮〹㠠㈸㈮㌸″㘲⸴㌴′㜰⸱㈲崯䠯丯䅐㰼⽎″㔠〠刾㸾㸊敮摯扪਱㜠〠潢樊㰼⽆‴⽔祰支䅮湯琯䑥獴⣾＀匀瀀爀椀渀最攀爀一愀琀甀爀攀开匀挀椀刀攀瀀开㘀㐀　㤀㌀⸀椀渀搀搀㫾＀￾＀㔀⻾￾＀￾￾￾￾＀刀攀渀欀攀洀愀Ⰰ 䜀⸀ 䠀⸀⃾＀攀琀 愀泾＀⸀ 䌀栀椀琀漀琀爀椀漀猀椀搀愀猀攀Ⰰ 愀 挀栀椀琀椀渀愀猀攀Ⰰ 愀渀搀 琀栀攀 ㌀㤀ⴀ欀䐀愀 栀甀洀愀渀 挀愀爀琀椀氀愀最攀 最氀礀挀漀瀀爀漀琀攀椀渀Ⰰ 愀 挀栀椀琀椀渀ⴀ戀椀渀搀椀渀最 氀攀挀琀椀渀Ⰰ 愀爀攀 栀漀洀漀氀漀最甀攀猀 漀昀 昀愀洀椀氀礀 ㄀㠀 最氀礀挀漀猀礀氀 栀礀搀爀漀氀愀猀攀猀 猀攀挀爀攀琀攀搀 戀礀 栀甀洀愀渀 洀愀挀爀漀瀀栀愀最攀猀⸀⃾＀䔀甀爀 䨀 䈀椀漀挀栀攀洀⻾＀⃾＀㈀㔀ㇾ＀Ⰰ 㔀　㐠ጀ㔀　㤀 ㄀㤀㤀㠀㨀㐀〩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㈴㈮㔹㠠㈳〮㈶㌠㈴㔮㐵㠠㈱㠮ㄲ㉝⽈⽎⽁值㰯丠㌶‰⁒㸾㸾੥湤潢樊ㄸ‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_64093.indd: 2. Canto, E. et al. Chitinase 3-like 1: prognostic biomarker in clinically isolated syndromes. Brain 138, 918–931 (2015). :41' cannot be found Offset: 1598367 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_64093.indd:Figure 2. Neurotoxic effect of CHI3L1. Cortical neurons from E16 mice at 11DIV were treated with PBS (vehicle), mouse recombinant CHI3L1 (300⁜琀渀最⼀洀氀Ⰰ 最氀甀琀愀洀愀琀攀 ㈀　〠딀䴀 漀爀 洀攀搀椀甀洀 挀漀渀琀爀漀氀 昀漀爀 ㈀㐀 愀渀搀 㐀㠠栀漀甀爀猀⸀ ＀䇾＀ 刀攀瀀爀攀猀攀渀琀愀琀椀瘀攀 椀洀愀最攀猀 漀昀 渀攀甀爀㨀㌀㔩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㈴㐮㜷㐠㐲㐮㈶㌠㈶㈮㘹㈠㐱㈮ㄲ㉝⽈⽎⽁值㰯丠㌱‰⁒㸾㸾੥湤潢樊ㄳ‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_64093.indd:Figure 2. Neurotoxic effect of CHI3L1. Cortical neurons from E16 mice at 11DIV were treated with PBS (vehicle), mouse recombinant CHI3L1 (300⁜琀渀最⼀洀氀Ⰰ 最氀甀琀愀洀愀琀攀 ㈀　〠딀䴀 漀爀 洀攀搀椀甀洀 挀漀渀琀爀漀氀 昀漀爀 ㈀㐀 愀渀搀 㐀㠠栀漀甀爀猀⸀ ＀䇾＀ 刀攀瀀爀攀猀攀渀琀愀琀椀瘀攀 椀洀愀最攀猀 漀昀 渀攀甀㨀㌀㘩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㐹㔮㌷㤠㐱㐮㈶㌠㔱㌮㈵㌠㐰㈮ㄲ㉝⽈⽎⽁值㰯丠㌲‰⁒㸾㸾੥湤潢樊ㄴ‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_64093.indd:Figure 2. Neurotoxic effect of CHI3L1. Cortical neurons from E16 mice at 11DIV were treated with PBS (vehicle), mouse recombinant CHI3L1 (300⁜琀渀最⼀洀氀Ⰰ 最氀甀琀愀洀愀琀攀 ㈀　〠딀䴀 漀爀 洀攀搀椀甀洀 挀漀渀琀爀漀氀 昀漀爀 ㈀㐀 愀渀搀 㐀㠠栀漀甀爀猀⸀ ＀䇾＀ 刀攀瀀爀攀猀攀渀琀愀琀椀瘀攀 椀洀愀最攀猀 漀昀 渀攀㨀㌀㜩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㌸㤮㔰㌠㌸㐮㈶㌠㐰㠮〷㤠㌷㈮ㄲ㉝⽈⽎⽁值㰯丠㌳‰⁒㸾㸾੥湤潢樊ㄵ‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_64093.indd:Figure 2. Neurotoxic effect of CHI3L1. Cortical neurons from E16 mice at 11DIV were treated with PBS (vehicle), mouse recombinant CHI3L1 (300⁜琀渀最⼀洀氀Ⰰ 最氀甀琀愀洀愀琀攀 ㈀　〠딀䴀 漀爀 洀攀搀椀甀洀 挀漀渀琀爀漀氀 昀漀爀 ㈀㐀 愀渀搀 㐀㠠栀漀甀爀猀⸀ ＀䇾＀ 刀攀瀀爀攀猀攀渀琀愀琀椀瘀攀 椀洀愀最攀猀 漀昀 渀㨀㌀㠩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛ㄷ㐮〵㐠㌴㐮㈶㌠ㄹ㐮㠶㈠㌳㈮ㄲ㉝⽈⽎⽁值㰯丠㌴‰⁒㸾㸾੥湤潢樊ㄶ‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_64093.indd:Figure 3. CHI3L1 effect on immune and CNS cells. Splenocytes,astrocytes and microglia from mixed glial cultures were treated with PBS (vehicle), mouse recombinant CHI3L1 (50, 100, 300 and 600⁜琀渀最⼀洀氀 漀爀 洀攀搀椀甀洀 挀漀渀琀爀漀氀 昀漀爀 㘀Ⰰ ㈀㐀 愀渀搀 㐀㠠栀漀甀爀猀⸀ ＀㨀㌀㤩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㌵㠮〹㠠㈸㈮㌸″㘲⸴㌴′㜰⸱㈲崯䠯丯䅐㰼⽎″㔠〠刾㸾㸊敮摯扪਱㜠〠潢樊㰼⽆‴⽔祰支䅮湯琯䑥獴⣾＀匀瀀爀椀渀最攀爀一愀琀甀爀攀开匀挀椀刀攀瀀开㘀㐀　㤀㌀⸀椀渀搀搀㫾＀￾＀㔀⻾￾＀￾￾￾￾＀刀攀渀欀攀洀愀Ⰰ 䜀⸀ 䠀⸀⃾＀攀琀 愀泾＀⸀ 䌀栀椀琀漀琀爀椀漀猀椀搀愀猀攀Ⰰ 愀 挀栀椀琀椀渀愀猀攀Ⰰ 愀渀搀 琀栀攀 ㌀㤀ⴀ欀䐀愀 栀甀洀愀渀 挀愀爀琀椀氀愀最攀 最氀礀挀漀瀀爀漀琀攀椀渀Ⰰ 愀 挀栀椀琀椀渀ⴀ戀椀渀搀椀渀最 氀攀挀琀椀渀Ⰰ 愀爀攀 栀漀洀漀氀漀最甀攀猀 漀昀 昀愀洀椀氀礀 ㄀㠀 最氀礀挀漀猀礀氀 栀礀搀爀漀氀愀猀攀猀 猀攀挀爀攀琀攀搀 戀礀 栀甀洀愀渀 洀愀挀爀漀瀀栀愀最攀猀⸀⃾＀䔀甀爀 䨀 䈀椀漀挀栀攀洀⻾＀⃾＀㈀㔀ㇾ＀Ⰰ 㔀　㐠ጀ㔀　㤀 ㄀㤀㤀㠀㨀㐀〩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㈴㈮㔹㠠㈳〮㈶㌠㈴㔮㐵㠠㈱㠮ㄲ㉝⽈⽎⽁值㰯丠㌶‰⁒㸾㸾੥湤潢樊ㄸ‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_64093.indd: 2. Canto, E. et al. Chitinase 3-like 1: prognostic biomarker in clinically isolated syndromes. Brain 138, 918–931 (2015). :41' cannot be found Offset: 1598367 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_64093.indd:Figure 2. Neurotoxic effect of CHI3L1. Cortical neurons from E16 mice at 11DIV were treated with PBS (vehicle), mouse recombinant CHI3L1 (300⁜琀渀最⼀洀氀Ⰰ 最氀甀琀愀洀愀琀攀 ㈀　〠딀䴀 漀爀 洀攀搀椀甀洀 挀漀渀琀爀漀氀 昀漀爀 ㈀㐀 愀渀搀 㐀㠠栀漀甀爀猀⸀ ＀䇾＀ 刀攀瀀爀攀猀攀渀琀愀琀椀瘀攀 椀洀愀最攀猀 漀昀 渀攀甀㨀㌀㘩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㐹㔮㌷㤠㐱㐮㈶㌠㔱㌮㈵㌠㐰㈮ㄲ㉝⽈⽎⽁值㰯丠㌲‰⁒㸾㸾੥湤潢樊ㄴ‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_64093.indd:Figure 2. Neurotoxic effect of CHI3L1. Cortical neurons from E16 mice at 11DIV were treated with PBS (vehicle), mouse recombinant CHI3L1 (300⁜琀渀最⼀洀氀Ⰰ 最氀甀琀愀洀愀琀攀 ㈀　〠딀䴀 漀爀 洀攀搀椀甀洀 挀漀渀琀爀漀氀 昀漀爀 ㈀㐀 愀渀搀 㐀㠠栀漀甀爀猀⸀ ＀䇾＀ 刀攀瀀爀攀猀攀渀琀愀琀椀瘀攀 椀洀愀最攀猀 漀昀 渀攀㨀㌀㜩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㌸㤮㔰㌠㌸㐮㈶㌠㐰㠮〷㤠㌷㈮ㄲ㉝⽈⽎⽁值㰯丠㌳‰⁒㸾㸾੥湤潢樊ㄵ‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_64093.indd:Figure 2. Neurotoxic effect of CHI3L1. Cortical neurons from E16 mice at 11DIV were treated with PBS (vehicle), mouse recombinant CHI3L1 (300⁜琀渀最⼀洀氀Ⰰ 最氀甀琀愀洀愀琀攀 ㈀　〠딀䴀 漀爀 洀攀搀椀甀洀 挀漀渀琀爀漀氀 昀漀爀 ㈀㐀 愀渀搀 㐀㠠栀漀甀爀猀⸀ ＀䇾＀ 刀攀瀀爀攀猀攀渀琀愀琀椀瘀攀 椀洀愀最攀猀 漀昀 渀㨀㌀㠩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛ㄷ㐮〵㐠㌴㐮㈶㌠ㄹ㐮㠶㈠㌳㈮ㄲ㉝⽈⽎⽁值㰯丠㌴‰⁒㸾㸾੥湤潢樊ㄶ‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_64093.indd:Figure 3. CHI3L1 effect on immune and CNS cells. Splenocytes,astrocytes and microglia from mixed glial cultures were treated with PBS (vehicle), mouse recombinant CHI3L1 (50, 100, 300 and 600⁜琀渀最⼀洀氀 漀爀 洀攀搀椀甀洀 挀漀渀琀爀漀氀 昀漀爀 㘀Ⰰ ㈀㐀 愀渀搀 㐀㠠栀漀甀爀猀⸀ ＀㨀㌀㤩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㌵㠮〹㠠㈸㈮㌸″㘲⸴㌴′㜰⸱㈲崯䠯丯䅐㰼⽎″㔠〠刾㸾㸊敮摯扪਱㜠〠潢樊㰼⽆‴⽔祰支䅮湯琯䑥獴⣾＀匀瀀爀椀渀最攀爀一愀琀甀爀攀开匀挀椀刀攀瀀开㘀㐀　㤀㌀⸀椀渀搀搀㫾＀￾＀㔀⻾￾＀￾￾￾￾＀刀攀渀欀攀洀愀Ⰰ 䜀⸀ 䠀⸀⃾＀攀琀 愀泾＀⸀ 䌀栀椀琀漀琀爀椀漀猀椀搀愀猀攀Ⰰ 愀 挀栀椀琀椀渀愀猀攀Ⰰ 愀渀搀 琀栀攀 ㌀㤀ⴀ欀䐀愀 栀甀洀愀渀 挀愀爀琀椀氀愀最攀 最氀礀挀漀瀀爀漀琀攀椀渀Ⰰ 愀 挀栀椀琀椀渀ⴀ戀椀渀搀椀渀最 氀攀挀琀椀渀Ⰰ 愀爀攀 栀漀洀漀氀漀最甀攀猀 漀昀 昀愀洀椀氀礀 ㄀㠀 最氀礀挀漀猀礀氀 栀礀搀爀漀氀愀猀攀猀 猀攀挀爀攀琀攀搀 戀礀 栀甀洀愀渀 洀愀挀爀漀瀀栀愀最攀猀⸀⃾＀䔀甀爀 䨀 䈀椀漀挀栀攀洀⻾＀⃾＀㈀㔀ㇾ＀Ⰰ 㔀　㐠ጀ㔀　㤀 ㄀㤀㤀㠀㨀㐀〩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㈴㈮㔹㠠㈳〮㈶㌠㈴㔮㐵㠠㈱㠮ㄲ㉝⽈⽎⽁值㰯丠㌶‰⁒㸾㸾੥湤潢樊ㄸ‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_64093.indd: 2. Canto, E. et al. Chitinase 3-like 1: prognostic biomarker in clinically isolated syndromes. Brain 138, 918–931 (2015). :41' cannot be found Offset: 1598367 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_64093.indd:Figure 2. Neurotoxic effect of CHI3L1. Cortical neurons from E16 mice at 11DIV were treated with PBS (vehicle), mouse recombinant CHI3L1 (300⁜琀渀最⼀洀氀Ⰰ 最氀甀琀愀洀愀琀攀 ㈀　〠딀䴀 漀爀 洀攀搀椀甀洀 挀漀渀琀爀漀氀 昀漀爀 ㈀㐀 愀渀搀 㐀㠠栀漀甀爀猀⸀ ＀䇾＀ 刀攀瀀爀攀猀攀渀琀愀琀椀瘀攀 椀洀愀最攀猀 漀昀 渀攀㨀㌀㜩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㌸㤮㔰㌠㌸㐮㈶㌠㐰㠮〷㤠㌷㈮ㄲ㉝⽈⽎⽁值㰯丠㌳‰⁒㸾㸾੥湤潢樊ㄵ‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_64093.indd:Figure 2. Neurotoxic effect of CHI3L1. Cortical neurons from E16 mice at 11DIV were treated with PBS (vehicle), mouse recombinant CHI3L1 (300⁜琀渀最⼀洀氀Ⰰ 最氀甀琀愀洀愀琀攀 ㈀　〠딀䴀 漀爀 洀攀搀椀甀洀 挀漀渀琀爀漀氀 昀漀爀 ㈀㐀 愀渀搀 㐀㠠栀漀甀爀猀⸀ ＀䇾＀ 刀攀瀀爀攀猀攀渀琀愀琀椀瘀攀 椀洀愀最攀猀 漀昀 渀㨀㌀㠩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛ㄷ㐮〵㐠㌴㐮㈶㌠ㄹ㐮㠶㈠㌳㈮ㄲ㉝⽈⽎⽁值㰯丠㌴‰⁒㸾㸾੥湤潢樊ㄶ‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_64093.indd:Figure 3. CHI3L1 effect on immune and CNS cells. Splenocytes,astrocytes and microglia from mixed glial cultures were treated with PBS (vehicle), mouse recombinant CHI3L1 (50, 100, 300 and 600⁜琀渀最⼀洀氀 漀爀 洀攀搀椀甀洀 挀漀渀琀爀漀氀 昀漀爀 㘀Ⰰ ㈀㐀 愀渀搀 㐀㠠栀漀甀爀猀⸀ ＀㨀㌀㤩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㌵㠮〹㠠㈸㈮㌸″㘲⸴㌴′㜰⸱㈲崯䠯丯䅐㰼⽎″㔠〠刾㸾㸊敮摯扪਱㜠〠潢樊㰼⽆‴⽔祰支䅮湯琯䑥獴⣾＀匀瀀爀椀渀最攀爀一愀琀甀爀攀开匀挀椀刀攀瀀开㘀㐀　㤀㌀⸀椀渀搀搀㫾＀￾＀㔀⻾￾＀￾￾￾￾＀刀攀渀欀攀洀愀Ⰰ 䜀⸀ 䠀⸀⃾＀攀琀 愀泾＀⸀ 䌀栀椀琀漀琀爀椀漀猀椀搀愀猀攀Ⰰ 愀 挀栀椀琀椀渀愀猀攀Ⰰ 愀渀搀 琀栀攀 ㌀㤀ⴀ欀䐀愀 栀甀洀愀渀 挀愀爀琀椀氀愀最攀 最氀礀挀漀瀀爀漀琀攀椀渀Ⰰ 愀 挀栀椀琀椀渀ⴀ戀椀渀搀椀渀最 氀攀挀琀椀渀Ⰰ 愀爀攀 栀漀洀漀氀漀最甀攀猀 漀昀 昀愀洀椀氀礀 ㄀㠀 最氀礀挀漀猀礀氀 栀礀搀爀漀氀愀猀攀猀 猀攀挀爀攀琀攀搀 戀礀 栀甀洀愀渀 洀愀挀爀漀瀀栀愀最攀猀⸀⃾＀䔀甀爀 䨀 䈀椀漀挀栀攀洀⻾＀⃾＀㈀㔀ㇾ＀Ⰰ 㔀　㐠ጀ㔀　㤀 ㄀㤀㤀㠀㨀㐀〩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㈴㈮㔹㠠㈳〮㈶㌠㈴㔮㐵㠠㈱㠮ㄲ㉝⽈⽎⽁值㰯丠㌶‰⁒㸾㸾੥湤潢樊ㄸ‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_64093.indd: 2. Canto, E. et al. Chitinase 3-like 1: prognostic biomarker in clinically isolated syndromes. Brain 138, 918–931 (2015). :41' cannot be found Offset: 1598367 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_64093.indd:Figure 2. Neurotoxic effect of CHI3L1. Cortical neurons from E16 mice at 11DIV were treated with PBS (vehicle), mouse recombinant CHI3L1 (300⁜琀渀最⼀洀氀Ⰰ 最氀甀琀愀洀愀琀攀 ㈀　〠딀䴀 漀爀 洀攀搀椀甀洀 挀漀渀琀爀漀氀 昀漀爀 ㈀㐀 愀渀搀 㐀㠠栀漀甀爀猀⸀ ＀䇾＀ 刀攀瀀爀攀猀攀渀琀愀琀椀瘀攀 椀洀愀最攀猀 漀昀 渀㨀㌀㠩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛ㄷ㐮〵㐠㌴㐮㈶㌠ㄹ㐮㠶㈠㌳㈮ㄲ㉝⽈⽎⽁值㰯丠㌴‰⁒㸾㸾੥湤潢樊ㄶ‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_64093.indd:Figure 3. CHI3L1 effect on immune and CNS cells. Splenocytes,astrocytes and microglia from mixed glial cultures were treated with PBS (vehicle), mouse recombinant CHI3L1 (50, 100, 300 and 600⁜琀渀最⼀洀氀 漀爀 洀攀搀椀甀洀 挀漀渀琀爀漀氀 昀漀爀 㘀Ⰰ ㈀㐀 愀渀搀 㐀㠠栀漀甀爀猀⸀ ＀㨀㌀㤩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㌵㠮〹㠠㈸㈮㌸″㘲⸴㌴′㜰⸱㈲崯䠯丯䅐㰼⽎″㔠〠刾㸾㸊敮摯扪਱㜠〠潢樊㰼⽆‴⽔祰支䅮湯琯䑥獴⣾＀匀瀀爀椀渀最攀爀一愀琀甀爀攀开匀挀椀刀攀瀀开㘀㐀　㤀㌀⸀椀渀搀搀㫾＀￾＀㔀⻾￾＀￾￾￾￾＀刀攀渀欀攀洀愀Ⰰ 䜀⸀ 䠀⸀⃾＀攀琀 愀泾＀⸀ 䌀栀椀琀漀琀爀椀漀猀椀搀愀猀攀Ⰰ 愀 挀栀椀琀椀渀愀猀攀Ⰰ 愀渀搀 琀栀攀 ㌀㤀ⴀ欀䐀愀 栀甀洀愀渀 挀愀爀琀椀氀愀最攀 最氀礀挀漀瀀爀漀琀攀椀渀Ⰰ 愀 挀栀椀琀椀渀ⴀ戀椀渀搀椀渀最 氀攀挀琀椀渀Ⰰ 愀爀攀 栀漀洀漀氀漀最甀攀猀 漀昀 昀愀洀椀氀礀 ㄀㠀 最氀礀挀漀猀礀氀 栀礀搀爀漀氀愀猀攀猀 猀攀挀爀攀琀攀搀 戀礀 栀甀洀愀渀 洀愀挀爀漀瀀栀愀最攀猀⸀⃾＀䔀甀爀 䨀 䈀椀漀挀栀攀洀⻾＀⃾＀㈀㔀ㇾ＀Ⰰ 㔀　㐠ጀ㔀　㤀 ㄀㤀㤀㠀㨀㐀〩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㈴㈮㔹㠠㈳〮㈶㌠㈴㔮㐵㠠㈱㠮ㄲ㉝⽈⽎⽁值㰯丠㌶‰⁒㸾㸾੥湤潢樊ㄸ‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_64093.indd: 2. Canto, E. et al. Chitinase 3-like 1: prognostic biomarker in clinically isolated syndromes. Brain 138, 918–931 (2015). :41' cannot be found Offset: 1598367 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_64093.indd:Figure 3. CHI3L1 effect on immune and CNS cells. Splenocytes,astrocytes and microglia from mixed glial cultures were treated with PBS (vehicle), mouse recombinant CHI3L1 (50, 100, 300 and 600⁜琀渀最⼀洀氀 漀爀 洀攀搀椀甀洀 挀漀渀琀爀漀氀 昀漀爀 㘀Ⰰ ㈀㐀 愀渀搀 㐀㠠栀漀甀爀猀⸀ ＀㨀㌀㤩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㌵㠮〹㠠㈸㈮㌸″㘲⸴㌴′㜰⸱㈲崯䠯丯䅐㰼⽎″㔠〠刾㸾㸊敮摯扪਱㜠〠潢樊㰼⽆‴⽔祰支䅮湯琯䑥獴⣾＀匀瀀爀椀渀最攀爀一愀琀甀爀攀开匀挀椀刀攀瀀开㘀㐀　㤀㌀⸀椀渀搀搀㫾＀￾＀㔀⻾￾＀￾￾￾￾＀刀攀渀欀攀洀愀Ⰰ 䜀⸀ 䠀⸀⃾＀攀琀 愀泾＀⸀ 䌀栀椀琀漀琀爀椀漀猀椀搀愀猀攀Ⰰ 愀 挀栀椀琀椀渀愀猀攀Ⰰ 愀渀搀 琀栀攀 ㌀㤀ⴀ欀䐀愀 栀甀洀愀渀 挀愀爀琀椀氀愀最攀 最氀礀挀漀瀀爀漀琀攀椀渀Ⰰ 愀 挀栀椀琀椀渀ⴀ戀椀渀搀椀渀最 氀攀挀琀椀渀Ⰰ 愀爀攀 栀漀洀漀氀漀最甀攀猀 漀昀 昀愀洀椀氀礀 ㄀㠀 最氀礀挀漀猀礀氀 栀礀搀爀漀氀愀猀攀猀 猀攀挀爀攀琀攀搀 戀礀 栀甀洀愀渀 洀愀挀爀漀瀀栀愀最攀猀⸀⃾＀䔀甀爀 䨀 䈀椀漀挀栀攀洀⻾＀⃾＀㈀㔀ㇾ＀Ⰰ 㔀　㐠ጀ㔀　㤀 ㄀㤀㤀㠀㨀㐀〩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㈴㈮㔹㠠㈳〮㈶㌠㈴㔮㐵㠠㈱㠮ㄲ㉝⽈⽎⽁值㰯丠㌶‰⁒㸾㸾੥湤潢樊ㄸ‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_64093.indd: 2. Canto, E. et al. Chitinase 3-like 1: prognostic biomarker in clinically isolated syndromes. Brain 138, 918–931 (2015). :41' cannot be found Offset: 1598367 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_64093.indd: 2. Canto, E. et al. Chitinase 3-like 1: prognostic biomarker in clinically isolated syndromes. Brain 138, 918–931 (2015). :41' cannot be found Offset: 1598367 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_64093.indd: 2. Canto, E. et al. Chitinase 3-like 1: prognostic biomarker in clinically isolated syndromes. Brain 138, 918–931 (2015). :44' cannot be found Offset: 1598367 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_64093.indd: 2. Canto, E. et al. Chitinase 3-like 1: prognostic biomarker in clinically isolated syndromes. Brain 138, 918–931 (2015). :45' cannot be found Offset: 1598367 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_64093.indd: 2. Canto, E. et al. Chitinase 3-like 1: prognostic biomarker in clinically isolated syndromes. Brain 138, 918–931 (2015). :46' cannot be found Offset: 1598367 MIMEtype: application/pdf PDFMetadata: Objects: 302 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: false CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseOutlines Language: EN Outlines: Item: Title: Chitinase 3-like 1 is neurotoxic in primary cultured neurons Children: Item: Title: Results Children: Item: Title: CHI3L1 impairs neuronal functionality and survival. Item: Title: CHI3L1 does not impair survival of immune cells and other central nervous system (CNS) cells. Item: Title: Discussion Item: Title: Methods Children: Item: Title: Animals. Item: Title: Primary neuronal cultures. Item: Title: Primary splenocyte cultures. Item: Title: Primary astrocyte cultures. Item: Title: Primary mixed glial cultures. Item: Title: Immunofluorescence. Item: Title: Cell death and neurite tracing. Item: Title: FACS analysis. Item: Title: Statistical analysis. Item: Title: Acknowledgements Item: Title: Figure 1 Dose-response study of CHI3L1 neurotoxic effect. Item: Title: Figure 2 Neurotoxic effect of CHI3L1. Item: Title: Figure 3 CHI3L1 effect on immune and CNS cells. 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Note: Publication name can be used to differentiate between a print magazine and the online version if the names are different such as “magazine” and “magazine.com.” publicationName Text external This element provides the url for an article or unit of content. The attribute platform is optionally allowed for situations in which multiple URLs must be specified. PRISM recommends that a subset of the PCV platform values, namely “mobile” and “web”, be used in conjunction with this element. NOTE: PRISM recommends against the use of the #other value allowed in the PRISM Platform controlled vocabulary. In lieu of using #other please reach out to the PRISM group at prism-wg@yahoogroups.com to request addition of your term to the Platform Controlled Vocabulary. url Text http://www.niso.org/schemas/jav/1.0/ jav NISO external Values for Journal Article Version are one of the following: AO = Author’s Original SMUR = Submitted Manuscript Under Review AM = Accepted Manuscript P = Proof VoR = Version of Record CVoR = Corrected Version of Record EVoR = Enhanced Version of Record journal_article_version Closed Choice of Text Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 223, 25, 370, 16 Flags: Print AppearanceDictionary: true Annotation: Subtype: Link Rect: 339, 406, 342, 394 Flags: Print AppearanceDictionary: true Destination: 87 Annotation: Subtype: Link Rect: 343, 406, 346, 394 Flags: Print AppearanceDictionary: true Destination: 87 Annotation: Subtype: Link Rect: 478, 396, 481, 384 Flags: Print AppearanceDictionary: true Destination: 87 Annotation: Subtype: Link Rect: 515, 356, 518, 344 Flags: Print AppearanceDictionary: true Destination: 87 Annotation: Subtype: Link Rect: 240, 326, 243, 314 Flags: Print AppearanceDictionary: true Destination: 87 Annotation: Subtype: Link Rect: 403, 296, 406, 284 Flags: Print AppearanceDictionary: true Destination: 87 Annotation: Subtype: Link Rect: 315, 276, 317, 264 Flags: Print AppearanceDictionary: true Destination: 87 Annotation: Subtype: Link Rect: 174, 256, 177, 244 Flags: Print AppearanceDictionary: true Destination: 87 Annotation: Subtype: Link Rect: 294, 216, 297, 204 Flags: Print AppearanceDictionary: true Destination: 87 Annotation: Subtype: Link Rect: 298, 216, 301, 204 Flags: Print AppearanceDictionary: true Destination: 87 Annotation: Subtype: Link Rect: 501, 64, 554, 52 Flags: Print AppearanceDictionary: true Annotation: Subtype: Link Rect: 155, 53, 182, 43 Flags: Print AppearanceDictionary: true Annotation: Subtype: Link Rect: 186, 53, 286, 43 Flags: Print AppearanceDictionary: true Annotation: Subtype: Link Rect: 481, 655, 556, 637 Flags: Print AppearanceDictionary: true Thumb: true Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 223, 25, 370, 16 Flags: Print AppearanceDictionary: true Annotation: Subtype: Link Rect: 295, 474, 298, 462 Flags: Print AppearanceDictionary: true Destination: 87 Annotation: Subtype: Link Rect: 491, 230, 493, 218 Flags: Print AppearanceDictionary: true Destination: null Annotation: Subtype: Link Rect: 491, 230, 493, 218 Flags: Print AppearanceDictionary: true Destination: null Annotation: Subtype: Link Rect: 491, 230, 493, 218 Flags: Print AppearanceDictionary: true Destination: null Annotation: Subtype: Link Rect: 491, 230, 493, 218 Flags: Print AppearanceDictionary: true Destination: null Annotation: Subtype: Link Rect: 491, 230, 493, 218 Flags: Print AppearanceDictionary: true Destination: null Annotation: Subtype: Link Rect: 491, 230, 493, 218 Flags: Print AppearanceDictionary: true Destination: null Annotation: Subtype: Link Rect: 242, 230, 245, 218 Flags: Print AppearanceDictionary: true Destination: 87 Annotation: Subtype: Link Rect: 491, 230, 493, 218 Flags: Print AppearanceDictionary: true Destination: null Annotation: Subtype: Link Rect: 495, 230, 498, 218 Flags: Print AppearanceDictionary: true Destination: 87 Annotation: Subtype: Link Rect: 198, 210, 201, 198 Flags: Print AppearanceDictionary: true Destination: 87 Annotation: Subtype: Link Rect: 341, 200, 344, 188 Flags: Print AppearanceDictionary: true Destination: null Annotation: Subtype: Link Rect: 495, 190, 498, 178 Flags: Print AppearanceDictionary: true Destination: null Annotation: Subtype: Link Rect: 423, 150, 426, 138 Flags: Print AppearanceDictionary: true Destination: null Annotation: Subtype: Link Rect: 421, 120, 424, 108 Flags: Print AppearanceDictionary: true Destination: 87 Annotation: Subtype: Link Rect: 359, 90, 362, 78 Flags: Print AppearanceDictionary: true Destination: 87 Annotation: Subtype: Link Rect: 363, 90, 366, 78 Flags: Print AppearanceDictionary: true Destination: 87 Thumb: true Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 223, 25, 370, 16 Flags: Print AppearanceDictionary: true Annotation: Subtype: Link Rect: 545, 293, 548, 281 Flags: Print AppearanceDictionary: true Destination: 87 Annotation: Subtype: Link Rect: 549, 293, 552, 281 Flags: Print AppearanceDictionary: true Destination: 87 Thumb: true Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 223, 25, 370, 16 Flags: Print AppearanceDictionary: true Thumb: true Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 223, 25, 370, 16 Flags: Print AppearanceDictionary: true Annotation: Subtype: Link Rect: 508, 636, 554, 624 Flags: Print AppearanceDictionary: true Annotation: Subtype: Link Rect: 155, 626, 245, 614 Flags: Print AppearanceDictionary: true Annotation: Subtype: Link Rect: 270, 578, 361, 566 Flags: Print AppearanceDictionary: true Annotation: Subtype: Link Rect: 449, 578, 554, 566 Flags: Print AppearanceDictionary: true Annotation: Subtype: Link Rect: 155, 568, 256, 556 Flags: Print AppearanceDictionary: true Annotation: Subtype: Link Rect: 259, 568, 264, 556 Flags: Print AppearanceDictionary: true Destination: 87 Annotation: Subtype: Link Rect: 458, 440, 554, 427 Flags: Print AppearanceDictionary: true Annotation: Subtype: Link Rect: 155, 430, 321, 417 Flags: Print AppearanceDictionary: true Annotation: Subtype: Link Rect: 271, 401, 368, 389 Flags: Print AppearanceDictionary: true Thumb: true Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 223, 25, 370, 16 Flags: Print AppearanceDictionary: true Annotation: Subtype: Link Rect: 349, 678, 441, 665 Flags: Print AppearanceDictionary: true Annotation: Subtype: Link Rect: 344, 568, 504, 556 Flags: Print AppearanceDictionary: true Thumb: true Checksum: 086d2824 Type: CRC32 Checksum: 189b194a223af02c178da32369133dad Type: MD5 Checksum: 147cd2b379ef83bd0c316a3c9064b06b228258c5 Type: SHA-1