Sonic Hedgehog Is a Chemoattractant for Midbrain Dopaminergic Axons
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{"title"=>"Sonic Hedgehog is a chemoattractant for midbrain dopaminergic axons", "type"=>"journal", "authors"=>[{"first_name"=>"Rachel", "last_name"=>"Hammond", "scopus_author_id"=>"16063713000"}, {"first_name"=>"Sandra", "last_name"=>"Blaess", "scopus_author_id"=>"6506426311"}, {"first_name"=>"Asa", "last_name"=>"Abeliovich", "scopus_author_id"=>"7005330930"}], "year"=>2009, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-70349631211", "pui"=>"355364860", "doi"=>"10.1371/journal.pone.0007007", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "sgr"=>"70349631211", "pmid"=>"19774071"}, "id"=>"bc73de46-9650-359e-bbfe-6f200693bb1f", "abstract"=>"Midbrain dopaminergic axons project from the substantia nigra (SN) and the ventral tegmental area (VTA) to rostral target tissues, including the striatum, pallidum, and hypothalamus. The axons from the medially located VTA project primarily to more medial target tissues in the forebrain, whereas the more lateral SN axons project to lateral targets including the dorsolateral striatum. This structural diversity underlies the distinct functions of these pathways. Although a number of guidance cues have been implicated in the formation of the distinct axonal projections of the SN and VTA, the molecular basis of their diversity remains unclear. Here we investigate the molecular basis of structural diversity in mDN axonal projections. We find that Sonic Hedgehog (Shh) is expressed at a choice point in the course of the rostral dopaminergic projections. Furthermore, in midbrain explants, dopaminergic projections are attracted to a Shh source. Finally, in mice in which Shh signaling is inactivated during late neuronal development, the most medial dopaminergic projections are deficient. In addition to the role of Shh in the induction of mDN precursors, Shh plays an important role in dopaminergic axon pathfinding to rostral target tissues. Furthermore, Shh signaling is involved in determining the structural diversity of these dopaminergic projections.", "link"=>"http://www.mendeley.com/research/sonic-hedgehog-chemoattractant-midbrain-dopaminergic-axons", "reader_count"=>34, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>4, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>2, "Student > Master"=>2, "Student > Bachelor"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>4, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>2, "Student > Master"=>2, "Student > Bachelor"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>23, "Medicine and Dentistry"=>3, "Neuroscience"=>4}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Neuroscience"=>{"Neuroscience"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>23}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}}, "reader_count_by_country"=>{"China"=>1, "Australia"=>1}, "group_count"=>5}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/882910"], "description"=>"<p>(A) Hematoxylin and eosin staining on sagittal sections of <i>Nestin-Smo</i> cko mice (<i>Nestin-Cre; Smo <sup>flox</sup>/<sup>rec</sup></i>) mutant mice and their control (<i>Smo <sup>flox</sup>/<sup>rec</sup></i>) littermates at E12.5 and E15.5. The histology of the conditional mutants closely resembles that of their <i>smo<sup>flox</sup>/smo<sup>rec</sup></i> littermates. HB – hindbrain, MB – midbrain, FB – forebrain; A – anterior, P – posterior, D – dorsal, V – ventral. (B) Schematics illustrating the axonal projections of the midbrain dopaminergic neurons (red), which project rostrally away from the midbrain-hindbrain boundary (MHB). The majority of these neurons project towards the lateral ganglionic eminence (LGE), the striatal precursor, but a subset constitutes the extra-striatal projection and courses more ventrally. The regions imaged in panels C and D of this figure are schematized by grey boxes in the first schematic, and their medio-lateral position in the second. (C) The dopaminergic (TH positive) projections to the LGE are comparable between <i>Nestin-Smo</i> cko mice and <i>control</i> mice at E13.5, which is confirmed by pixel counting across lateral sections (n = 4 mice in each, data not shown). (D) In control mice the extra-striatal dopaminergic projections course ventrally, but in <i>Nestin-Smo</i> cko mice these projections are much reduced, and some axons appear to misdirected. Asterisk indicates the ‘choice point’ where axons either project rostrally towards the LGE, or project ventrally to form the extra-striatal projection (indicated by red arrows). (E) Quantification of the reduction in extra-striatal projection, pixels counted across 6 medial most sections in n = 4 animals for each condition. Statistical significance assessed using 2-tailed Student T-test (p<0.01). Scale bars: (A) 500 µm, (B+C) 100 µm.</p>", "links"=>[], "tags"=>["conditional", "mutant", "mice", "aberrant", "mdn", "axonal"], "article_id"=>553360, "categories"=>["Developmental Biology", "Neuroscience", "Cell Biology"], "users"=>["Rachel Hammond", "Sandra Blaess", "Asa Abeliovich"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007007.g003", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Smoothened_conditional_mutant_mice_display_aberrant_mDN_axonal_projections_/553360", "title"=>"Smoothened conditional mutant mice display aberrant mDN axonal projections.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-09-23 00:56:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/437795", "https://ndownloader.figshare.com/files/437806", "https://ndownloader.figshare.com/files/437824"], "description"=>"<div><p>Midbrain dopaminergic axons project from the substantia nigra (SN) and the ventral tegmental area (VTA) to rostral target tissues, including the striatum, pallidum, and hypothalamus. The axons from the medially located VTA project primarily to more medial target tissues in the forebrain, whereas the more lateral SN axons project to lateral targets including the dorsolateral striatum. This structural diversity underlies the distinct functions of these pathways. Although a number of guidance cues have been implicated in the formation of the distinct axonal projections of the SN and VTA, the molecular basis of their diversity remains unclear. Here we investigate the molecular basis of structural diversity in mDN axonal projections. We find that Sonic Hedgehog (Shh) is expressed at a choice point in the course of the rostral dopaminergic projections. Furthermore, in midbrain explants, dopaminergic projections are attracted to a Shh source. Finally, in mice in which Shh signaling is inactivated during late neuronal development, the most medial dopaminergic projections are deficient.</p><p>In addition to the role of Shh in the induction of mDN precursors, Shh plays an important role in dopaminergic axon pathfinding to rostral target tissues. Furthermore, Shh signaling is involved in determining the structural diversity of these dopaminergic projections.</p></div>", "links"=>[], "tags"=>["sonic", "hedgehog", "chemoattractant", "midbrain", "dopaminergic", "axons"], "article_id"=>146306, "categories"=>["Developmental Biology", "Neuroscience", "Cell Biology"], "users"=>["Rachel Hammond", "Sandra Blaess", "Asa Abeliovich"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007007.s001", "https://dx.doi.org/10.1371/journal.pone.0007007.s002", "https://dx.doi.org/10.1371/journal.pone.0007007.s003"], "stats"=>{"downloads"=>3, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Sonic_Hedgehog_Is_a_Chemoattractant_for_Midbrain_Dopaminergic_Axons/146306", "title"=>"Sonic Hedgehog Is a Chemoattractant for Midbrain Dopaminergic Axons", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-09-23 01:45:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/883209"], "description"=>"<p>(A) Medial midbrain dopaminergic explants demonstrated increased TH-positive axonal outgrowth from the rostral side (facing the explant) in the presence of a Shh source; in contrast, lateral explants did not appear to be attracted to the Shh source (n>15 explants for each group). The effects of Shh were significant when tested using the two-tailed Student T-test (p<0.05). Scale bar: 100 µm.</p>", "links"=>[], "tags"=>["mdn", "axonal", "dissection", "signaling"], "article_id"=>553667, "categories"=>["Developmental Biology", "Neuroscience", "Cell Biology"], "users"=>["Rachel Hammond", "Sandra Blaess", "Asa Abeliovich"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007007.g005", "stats"=>{"downloads"=>1, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Shh_regulation_of_mDN_axonal_projections_dissection_of_signaling_interactions_/553667", "title"=>"Shh regulation of mDN axonal projections: dissection of signaling interactions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-09-23 01:01:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/883069"], "description"=>"<p>(A) At the choice point for rostrally coursing mDN axonal projections (as in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007007#pone-0007007-g003\" target=\"_blank\">Figure 3</a>) the most medial fibers course ventrally (arrowheads in lower left panel) to the embryonic pallidum, subthalamus, and hypothalamus, as indicated by immunostaining with an antibody specific for Nkx2.1. These fibers are deficient in the <i>Nestin-Smo</i> cko mice at E12.5 (arrowheads in upper left panel). (B) Analysis of gene expression by in situ hybridization in the midbrain and target tissues of wild-type and <i>Nestin-Smo</i> cko mice at E12.5. Expression of the target tissue markers <i>Hnf3β</i> (<i>Foxa2</i>; i–ii), <i>Shh</i> (iii–iv), and <i>Islet-1</i> ( Isl1;v–vi) appear unaltered in the mutant mice, as determined in horizontal sections. Plane of section is indicated in D. (C) Analysis of <i>Netrin1</i> gene expression by in situ hybridization in the hypothalmus of wild-type and <i>Nestin-Smo</i> cko mice at E12.5. Expression of the chemoattractant Netrin-1 is unaltered in the mutant mice. Arrows indicate ventral midline/floor plate region where Netrin expression is maximal. Arrowheads indicate weak Netrin expression in the thalamus. Plane of section is indicated in D. (D) Schematic of sagittal section of midbrain at E12.5. Scale bars: (A) 100 µm, (B+C) 200 µm.</p>", "links"=>[], "tags"=>["alterations", "smoothened", "conditional", "mutant", "mice"], "article_id"=>553524, "categories"=>["Developmental Biology", "Neuroscience", "Cell Biology"], "users"=>["Rachel Hammond", "Sandra Blaess", "Asa Abeliovich"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007007.g004", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dopaminergic_projection_alterations_in_Smoothened_conditional_mutant_mice_do_not_appear_to_be_a_consequence_of_target_tissue_defects_/553524", "title"=>"Dopaminergic projection alterations in Smoothened conditional mutant mice do not appear to be a consequence of target tissue defects.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-09-23 00:58:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/882794"], "description"=>"<p>(A) Schematic of explant dissection. The ventral third of the midbrain neuroepithelium, including the floor plate, of E11.5 mouse was dissected and placed in an ‘open-book’ preparation in apposition to transfected HEK293T cells or appropriate tissue as indicated. HB – hindbrain, MB – midbrain, FB – forebrain. (B) E11.5 bilateral ventral midbrain explants cultures (FP – floor plate) in apposition to mock-transfected or Shh transfected HEK293T cells (delineated by white dotted lines). Explants and cell clusters were cocultured for 3 days, fixed, and immunostained for TH. Explants demonstrated increased TH-positive axonal outgrowth in the rostral quadrant (facing the explant – quadrants delineated by yellow dotted lines) in the presence of a Shh source. This effect was diminished by the addition of cyclopamine (Cyc) at 10 nM to the culture medium. The axonal extension from the rostral side was quantified using pixel counting software (see Materials and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007007#s4\" target=\"_blank\">Methods</a>) and expressed as a percentage of total rostral and caudal outgrowth. The effect of Shh was significant when tested using the two-tailed Student T-test (p<0.05), n>25 explants in each condition. Total (non-directional) outgrowth from the lateral and caudal sides remained unaffected by the presence of Shh. (C) The effects of Shh transfected HEK293T cells can be mimicked by the presence of rostro-ventral neuroepithelium known to express Shh (excluding the zona limitans intrathalamica; ZLI), and this effect can be reduced by the addition of cyclopamine to the medium. This effect is significant (p<0.05) by the two-tailed Student T-test, n>25 explants in each condition. Total axonal outgrowth from the caudal and lateral sides of the explants appears unaffected by the presence of dorsal or ventral tissue pieces. However dorsal tissue, which lacks Shh expression, does appear to have a positive effect on dopaminergic axonal outgrowth from the rostral side of ventral midbrain explants, an effect that is not blocked by cyclopamine implicating a Shh/Smo independent mechanism. Scale bar: (B+C) 100 µm.</p>", "links"=>[], "tags"=>["chemoattractant", "mdn", "explant"], "article_id"=>553253, "categories"=>["Developmental Biology", "Neuroscience", "Cell Biology"], "users"=>["Rachel Hammond", "Sandra Blaess", "Asa Abeliovich"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007007.g002", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Shh_as_a_chemoattractant_in_mDN_explant_cultures_/553253", "title"=>"Shh as a chemoattractant in mDN explant cultures.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-09-23 00:54:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/882677"], "description"=>"<p>(A, B) Immunohistochemical analysis of Sonic Hedgehog (Shh) and Smoothened (Smo) expression in relation to the tyrosine hydroxylase (TH)- positive midbrain dopaminergic neurons (mDN) in E12.5 mouse embryos. (A) Shh expression in the ventral midline of the midbrain (mb) ventricular zone (indicated by arrowhead in left panel) lies dorsal to differentiated mDN (TH+). Shh expression in the hypothalamus (hyp) lies ventral and rostral to the dopaminergic cell bodies (indicated by arrow in left panel). Note that TH+ mDN axonal projections are found in the Shh expressing region in the hypothalamus (arrows in right panel). The right panel, a higher magnification of the boxed area in the merged image, is a maximum intensity projection of a Z-stack acquired with the Zeiss ApoTome system. Asterisks in merged image indicate background staining of blood vessels. Aqueduct is outlined. Immunostaining was performed on coronal sections. The plane of section is indicated in schematic in D. (B) Smo expression co-localizes with the midbrain dopaminergic population. Immunostaining was performed on sagittal sections. The area shown is indicated in the schematic in D. (C) Mid-sagittal sections of E12.5 embryonic brain. Arrows indicate location of dopaminergic neurons. The area shown is indicated in the schematic in D. TH/Hoechst: Immunostaining for TH and Hoechst showing the location of dopaminergic neurons (arrow) in relation to the aqueduct (aq) and 3<sup>rd</sup> ventricle (vt) (outlined) and the mid/hindbrain boundary (MHB). Ptc: Analysis of <i>Ptc-lacZ </i><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007007#pone.0007007-Goodrich1\" target=\"_blank\">[18]</a> mice by X-gal staining for β-galactosidase activity shows expression of Patched in the ventral midbrain. Blue staining indicates Ptc-lacZ expression, pink staining is a nuclear stain (nuclear fast red). Smo: In situ hybridization for Smo shows expression of Smo in the ventral midbrain. Shh: In situ hybridization for Shh shows expression dorsal (in mb) and rostral (in hyp) to the mDN cell population. (D) Schematic of sagittal (left panel) and transverse sections (right panels) of midbrain at E12.5. Lateral SN neuronal projections that course to the dorsolateral striatum precursor are in green. Medial ventral projections from the VTA, which project to the nucleus accumbens precursor, are in red. Additional medial fibers project ventrally to the pallidum. Pink line depicts the floor plate and ventral midline. Sagittal schematic: Brown line displays the midbrain-hindbrain junction. Dashed line corresponds to the orientation of the transverse section in A. Black box depicts the sagittal sections in B. Dashed box depict sagittal sections in C. Transverse schematic: Green and red circles in midbrain depict mDN cell bodies, small green and red circles in hypothalamus depict mDN axonal projections. Scale bars: (A) 100 µm (merge) and 20 µm (high mag); (B) 50 µm; (C) 200 µm.</p>", "links"=>[], "tags"=>["hedgehog", "signaling"], "article_id"=>553135, "categories"=>["Developmental Biology", "Neuroscience", "Cell Biology"], "users"=>["Rachel Hammond", "Sandra Blaess", "Asa Abeliovich"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007007.g001", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sonic_Hedgehog_signaling_is_a_candidate_guidance_cue_for_mDNs_/553135", "title"=>"Sonic Hedgehog signaling is a candidate guidance cue for mDNs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-09-23 00:52:15"}

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  • {"unique-ip"=>"13", "full-text"=>"8", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2014", "month"=>"9"}
  • {"unique-ip"=>"12", "full-text"=>"6", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2014", "month"=>"10"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"8", "full-text"=>"10", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"3", "cited-by"=>"1", "year"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
  • {"unique-ip"=>"9", "full-text"=>"7", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"1"}
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  • {"unique-ip"=>"2", "full-text"=>"1", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"8", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"1", "full-text"=>"0", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
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  • {"unique-ip"=>"2", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
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  • {"unique-ip"=>"7", "full-text"=>"4", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"1", "year"=>"2017", "month"=>"9"}
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  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
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  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
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  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"4", "full-text"=>"2", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"6", "full-text"=>"8", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
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Relative Metric

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