Oxidative Stress Induced Age Dependent Meibomian Gland Dysfunction in Cu, Zn-Superoxide Dismutase-1 (Sod1) Knockout Mice
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{"title"=>"Oxidative stress induced age dependent meibomian gland dysfunction in Cu, Zn-superoxide dismutase-1 (Sod1) knockout mice", "type"=>"journal", "authors"=>[{"first_name"=>"Osama M.A.", "last_name"=>"Ibrahim", "scopus_author_id"=>"24470826900"}, {"first_name"=>"Murat", "last_name"=>"Dogru", "scopus_author_id"=>"7006540932"}, {"first_name"=>"Yukihiro", "last_name"=>"Matsumoto", "scopus_author_id"=>"7404546633"}, {"first_name"=>"Ayako", "last_name"=>"Igarashi", "scopus_author_id"=>"9433955100"}, {"first_name"=>"Takashi", "last_name"=>"Kojima", "scopus_author_id"=>"56359083100"}, {"first_name"=>"Tais Hitomi", "last_name"=>"Wakamatsu", "scopus_author_id"=>"14424611200"}, {"first_name"=>"Takaaki", "last_name"=>"Inaba", "scopus_author_id"=>"55143818900"}, {"first_name"=>"Takahiko", "last_name"=>"Shimizu", "scopus_author_id"=>"7408147386"}, {"first_name"=>"Jun", "last_name"=>"Shimazaki", "scopus_author_id"=>"56489943800"}, {"first_name"=>"Kazuo", "last_name"=>"Tsubota", "scopus_author_id"=>"36044308900"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"25036096", "sgr"=>"84904512205", "doi"=>"10.1371/journal.pone.0099328", "scopus"=>"2-s2.0-84904512205", "pui"=>"373567617", "isbn"=>"1932-6203", "issn"=>"19326203"}, "id"=>"aa9afbc7-b8ed-3a09-9a70-6123b20d89b6", "abstract"=>"PURPOSE: The purpose of our study was to investigate alterations in the meibomian gland (MG) in Cu, Zn-Superoxide Dismutase-1 knockout (Sod1-/-) mouse. METHODS: Tear function tests [Break up time (BUT) and cotton thread] and ocular vital staining test were performed on Sod1-/- male mice (n = 24) aged 10 and 50 weeks, and age and sex matched wild-type (+/+) mice (n = 25). Tear and serum samples were collected at sacrifice for inflammatory cytokine assays. MG specimens underwent Hematoxylin and Eosin staining, Mallory staining for fibrosis, Oil Red O lipid staining, TUNEL staining, immunohistochemistry stainings for 4HNE, 8-OHdG and CD45. Transmission electron microscopic examination (TEM) was also performed. RESULTS: Corneal vital staining scores in the Sod1-/- mice were significantly higher compared with the wild type mice throughout the follow-up. Tear and serum IL-6 and TNF-alpha levels also showed significant elevations in the 10 to 50 week Sod1-/- mice. Oil Red O staining showed an accumulation of large lipid droplets in the Sod1-/- mice at 50 weeks. Immunohistochemistry revealed both increased TUNEL and oxidative stress marker stainings of the MG acinar epithelium in the Sod1-/- mice compared to the wild type mice. Immunohistochemistry staining for CD45 showed increasing inflammatory cell infiltrates from 10 to 50 weeks in the Sod1-/- mice compared to the wild type mice. TEM revealed prominent mitochondrial changes in 50 week Sod1-/- mice. CONCLUSIONS: Our results suggest that reactive oxygen species might play a vital role in the pathogensis of meibomian gland dysfunction. The Sod1-/- mouse appears to be a promising model for the study of reactive oxygen species associated MG alterations.", "link"=>"http://www.mendeley.com/research/oxidative-stress-induced-age-dependent-meibomian-gland-dysfunction-cu-znsuperoxide-dismutase1-sod1-k", "reader_count"=>15, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Postgraduate"=>1, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Postgraduate"=>1, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>9, "Medicine and Dentistry"=>5, "Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1600409"], "description"=>"<p>A, Representative images for meibomian glands from the 10 and 50 week Cu, Zn-Superoxide Dismutase-1 knockout (<i>Sod1</i><sup>−/−</sup>) and wild type (WT) mice show normal meibomian gland acinar units morphology. Note the extensive periglandular inflammatory infiltration, and meibomian gland changes in the <i>Sod1</i><sup>−/−</sup> mice at 50 weeks. Bar = 50 micrometer. B, Mallory stainings show increased fibrosis (dark blue stained areas) from 10 to 50 weeks in the <i>Sod1</i><sup>−/−</sup> mice. Similar changes were observed in the WT mice but not to the extent observed in the <i>Sod1</i><sup>−/−</sup> mice. Bar = 50 micrometer. C, Meibomian gland acinar unit density significantly decreased from 10 to 50 weeks in both <i>Sod1</i><sup>−/−</sup> mice and the WT mice (<i>p</i> = 0.0007 and <i>p</i> = 0.0175, respectively). Meibomian gland acinar unit density was also significantly lower in the <i>Sod1</i><sup>−/−</sup> mice compared to the WT mice at 50 weeks (<i>p</i> = 0.0003). Five tissue sections of each mouse eye were analyzed to produce the meibomian gland acinar unit density values. Data represent the mean ± standard deviation for at least 7 mice from the <i>Sod1</i><sup>−/−</sup> groups and 10 mice from the WT groups, at 10 and 50 weeks. Five tissues sections from each eye of 7 animals (5 images per animal's eye) for each group were analyzed to produce the representative Mallory staining images.</p>", "links"=>[], "tags"=>["developmental biology", "Organism development", "aging", "Veterinary science", "Veterinary medicine", "Veterinary ophthalmology", "ophthalmology", "Geriatric ophthalmology", "Pathology and laboratory medicine", "Animal studies", "Animal models of disease", "Model organisms", "Animal models", "Mouse models", "gland", "histopathological", "alterations", "fibrosis"], "article_id"=>1110246, "categories"=>["Biological Sciences"], "users"=>["Osama M. A. Ibrahim", "Murat Dogru", "Yukihiro Matsumoto", "Ayako Igarashi", "Takashi Kojima", "Tais Hitomi Wakamatsu", "Takaaki Inaba", "Takahiko Shimizu", "Jun Shimazaki", "Kazuo Tsubota"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0099328.g002", "stats"=>{"downloads"=>3, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Meibomian_gland_histopathological_alterations_and_tissue_fibrosis_in_the_Sod1_8722_8722_and_wild_type_mice_/1110246", "title"=>"Meibomian gland histopathological alterations and tissue fibrosis in the <i>Sod1</i><sup>−/−</sup> and wild type mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-18 02:46:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1600433"], "description"=>"<p>Oil Red O staining showed an accumulation of large lipid droplets in the Cu, Zn-Superoxide Dismutase-1 knockout (<i>Sod1</i><sup>−/−</sup>) mice from 10 to 50 weeks. Note the diffusely uniform staining pattern in the wild type (WT) mice at 10 weeks and some accumulation of large lipid droplets in the WT mice at 50 weeks, but not to the extent observed in the same age <i>Sod1</i><sup>−/−</sup> mice. Bar = 100 micrometer. Five tissues sections from each eye of the 7 animals in each mice group were analyzed to produce the representative images.</p>", "links"=>[], "tags"=>["developmental biology", "Organism development", "aging", "Veterinary science", "Veterinary medicine", "Veterinary ophthalmology", "ophthalmology", "Geriatric ophthalmology", "Pathology and laboratory medicine", "Animal studies", "Animal models of disease", "Model organisms", "Animal models", "Mouse models", "alterations", "meibomian", "gland", "lipid"], "article_id"=>1110260, "categories"=>["Biological Sciences"], "users"=>["Osama M. A. Ibrahim", "Murat Dogru", "Yukihiro Matsumoto", "Ayako Igarashi", "Takashi Kojima", "Tais Hitomi Wakamatsu", "Takaaki Inaba", "Takahiko Shimizu", "Jun Shimazaki", "Kazuo Tsubota"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0099328.g005", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Timewise_alterations_in_meibomian_gland_lipid_staining_/1110260", "title"=>"Timewise alterations in meibomian gland lipid staining.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-18 02:46:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1600405"], "description"=>"<p>A, The weight adjusted tear quantity decreased significantly from 10 to 50 weeks in the Cu, Zn-Superoxide Dismutase-1 knockout (<i>Sod1</i><sup>−/−</sup>) mice (<i>p</i> = 0.0012). The tear quantity was also significantly lower in the <i>Sod1</i><sup>−/−</sup> mice compared to the age matched wild type (WT) mice at 10 and 50 weeks (<i>p</i> = 0.0079 and <i>p</i><0.0001, respectively). B, The mean tear break-up time values decreased significantly from 10 to 50 weeks in the <i>Sod1</i><sup>−/−</sup> mice (<i>p</i> = 0.0330). The tear stability was significantly worse in the <i>Sod1</i><sup>−/−</sup> mice compared to WT mice at 50 weeks (<i>p</i> = 0.0004). C, Fluorescein staining scores were significantly higher in the <i>Sod1</i><sup>−/−</sup> mice compared to the WT mice both at 10 (<i>p</i> = 0.0005) and 50 (<i>p</i> = 0.0006) weeks. Fluorescein staining also increased significantly from 10 to 50 weeks in both the <i>Sod1</i><sup>−/−</sup> and WT mice (<i>p</i> = 0.0113 and <i>p</i> = 0.0032, respectively). Data represent the mean ± standard deviation of 9 mice from the <i>Sod1</i><sup>−/−</sup> groups and 10 mice from the WT groups, at 10 and 50 weeks.</p>", "links"=>[], "tags"=>["developmental biology", "Organism development", "aging", "Veterinary science", "Veterinary medicine", "Veterinary ophthalmology", "ophthalmology", "Geriatric ophthalmology", "Pathology and laboratory medicine", "Animal studies", "Animal models of disease", "Model organisms", "Animal models", "Mouse models", "ocular", "epithelial"], "article_id"=>1110242, "categories"=>["Biological Sciences"], "users"=>["Osama M. A. Ibrahim", "Murat Dogru", "Yukihiro Matsumoto", "Ayako Igarashi", "Takashi Kojima", "Tais Hitomi Wakamatsu", "Takaaki Inaba", "Takahiko Shimizu", "Jun Shimazaki", "Kazuo Tsubota"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0099328.g001", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Aqueous_tear_production_tear_stability_and_ocular_surface_epithelial_cell_damage_assessment_/1110242", "title"=>"Aqueous tear production, tear stability and ocular surface epithelial cell damage assessment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-18 02:46:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1600414"], "description"=>"<p>A, Late phase lipid peroxidation marker 4-HNE stainings show dense staining in the 50 week old Cu, Zn-Superoxide Dismutase-1 knockout (<i>Sod1</i><sup>−/−</sup>) mice. Wild type (WT) mice specimens also had some staining but not to the extent observed in the same age <i>Sod1</i><sup>−/−</sup> mice. Bar = 50 micrometer. B, The extent of cellular staining with 4-HNE was significantly higher in the <i>Sod1</i><sup>−/−</sup> than the WT mice at 50 weeks (<i>p</i> = 0.0022). Note the significant timewise elevation in the anti-4-HNE staining from 10 to 50 weeks in the <i>Sod1</i><sup>−/−</sup> mice. C, Staining with 8-OHdG antibodies in <i>Sod1</i><sup>−/−</sup> and WT mice samples at 10 and 50 weeks. Meibomian gland acinar cell nuclei showed scant staining in 10 week <i>Sod1</i><sup>−/−</sup> and WT mice. Bar = 100 micrometer. There was a marked increase in nuclear staining from 10 to 50 weeks, especially in <i>Sod1</i><sup>−/−</sup> mice. Relatively more acinar nuclei were stained with anti-8-OHdG antibodies in the <i>Sod1</i><sup>−/−</sup> mice at 50 weeks compared to meibomian gland specimens from the same age WT mice. D, Quantitative assessment for the cellular staining of anti-8-OHdG antibodies showed a statistically significant timewise increase from 10 to 50 weeks in <i>Sod1</i><sup>−/−</sup> and WT mice (<i>p</i> = 0.0003, <i>p</i> = 0.0011, respectively). A significant timewise elevation in staining was observed in the <i>Sod1</i><sup>−/−</sup> and WT mice at 50 weeks (<i>p</i> = 0.0133). Five tissue sections of each animal's eye were analyzed to produce the figure. Data represent the mean ± standard deviation for 7 mice from the <i>Sod1</i><sup>−/−</sup> group and 6 mice from the wild type group at 10 and 50 weeks.</p>", "links"=>[], "tags"=>["developmental biology", "Organism development", "aging", "Veterinary science", "Veterinary medicine", "Veterinary ophthalmology", "ophthalmology", "Geriatric ophthalmology", "Pathology and laboratory medicine", "Animal studies", "Animal models of disease", "Model organisms", "Animal models", "Mouse models", "lipid", "dna", "meibomian"], "article_id"=>1110251, "categories"=>["Biological Sciences"], "users"=>["Osama M. A. Ibrahim", "Murat Dogru", "Yukihiro Matsumoto", "Ayako Igarashi", "Takashi Kojima", "Tais Hitomi Wakamatsu", "Takaaki Inaba", "Takahiko Shimizu", "Jun Shimazaki", "Kazuo Tsubota"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0099328.g004", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Oxidative_lipid_and_DNA_changes_in_the_meibomian_glands_/1110251", "title"=>"Oxidative lipid and DNA changes in the meibomian glands.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-18 02:46:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1600438"], "description"=>"<p>A, Meibomian gland samples from Cu, Zn-Superoxide Dismutase-1 knockout (<i>Sod1</i><sup>−/−</sup>) and wild type (WT) mice at 10 and 50 weeks stained with TUNEL (red) and DAPI (blue). There was marked positive staining with TUNEL for apoptotic cells in the 50 week <i>Sod1</i><sup>−/−</sup> mice in comparison to specimens from <i>Sod1</i><sup>−/−</sup> mice at 10 weeks and WT mice at 50 weeks. Yellow arrows indicate cells positively stained with TUNEL. A timewise increase in positively stained cells was also observed in WT mice meibomian gland specimens from 10 weeks to 50 weeks. Bar = 100 micrometer. B, There was a statistically significant difference between the number of positively stained cell densities of the <i>Sod1</i><sup>−/−</sup> and WT mice at 10 weeks (<i>p</i> = 0.0006). A significant timewise increase in the number of positively stained cell densities from 10 to 50 weeks was observed in both <i>Sod1</i><sup>−/−</sup> and WT mice (<i>p</i><0.0001). The density of positively stained cells in the meibomian gland specimens of the <i>Sod1</i><sup>−/−</sup> mice at 50 weeks was significantly higher than for those observed in the 50 week WT mice (<i>p</i><0.0001). The images represent at least five independent samples of mouse eye per group. Data represent the mean ± standard deviation for 7 mice from the <i>Sod1</i><sup>−/−</sup> groups and 6 mice from the WT groups at 10 and 50 weeks.</p>", "links"=>[], "tags"=>["developmental biology", "Organism development", "aging", "Veterinary science", "Veterinary medicine", "Veterinary ophthalmology", "ophthalmology", "Geriatric ophthalmology", "Pathology and laboratory medicine", "Animal studies", "Animal models of disease", "Model organisms", "Animal models", "Mouse models", "quantitative", "timewise", "apoptotic", "meibomian"], "article_id"=>1110265, "categories"=>["Biological Sciences"], "users"=>["Osama M. A. Ibrahim", "Murat Dogru", "Yukihiro Matsumoto", "Ayako Igarashi", "Takashi Kojima", "Tais Hitomi Wakamatsu", "Takaaki Inaba", "Takahiko Shimizu", "Jun Shimazaki", "Kazuo Tsubota"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0099328.g006", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immunohistochemical_and_quantitative_evaluation_of_the_timewise_apoptotic_changes_in_meibomian_glands_/1110265", "title"=>"Immunohistochemical and quantitative evaluation of the timewise apoptotic changes in meibomian glands.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-18 02:46:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1600413"], "description"=>"<p>A, Specimens stained with CD45 from 10 and 50 weeks Cu, Zn-Superoxide Dismutase-1 knockout (<i>Sod1</i><sup>−/−</sup>) and wild type (WT) mice. Note the timewise increase in inflammatory cell staining from 10 to 50 weeks in the <i>Sod1</i><sup>−/−</sup> mice. Wild type mice specimens showed scant inflammatory cell staining, which increased significantly in the 50 week WT mice but not to the extent observed in the <i>Sod1</i><sup>−/−</sup> mice at 50 weeks. Bar = 50 micrometer. B, A significant timewise increase in the mean inflammatory cell densities from 10 to 50 weeks was observed in both the <i>Sod1</i><sup>−/−</sup> and WT mice (<i>p</i> = 0.0143 and <i>p</i> = 0.0286, respectively). Note the significantly higher inflammatory cell density in the <i>Sod1</i><sup>−/−</sup> mice at 50 weeks compared to the age matched WT mice (<i>p</i> = 0.0317). Five tissue sections of each eye of 6 animals (5 per mouse eye) were analyzed to produce the figure. Data represent the mean ± standard deviation for 6 mice from the <i>Sod1</i><sup>−/−</sup> groups and 6 mice from the WT groups at 10 and 50 weeks. C, The mean serum IL-6 concentration increased significantly from 10 to 50 weeks in both the <i>Sod1</i><sup>−/−</sup> (<i>p</i> = 0.0195) and WT mice (<i>p</i> = 0.0001). Serum IL-6 concentration was significantly higher in the 50 week <i>Sod1</i><sup>−/−</sup> compared to 50 week WT mice (<i>p</i> = 0.0100). Serum TNF-α levels were also significantly higher (<i>p</i> = 0.0011) in the 50 week <i>Sod1</i><sup>−/−</sup> mice compared to the age matched WT mice. The mean serum TNF-α concentration significantly increased from 10 to 50 weeks in the <i>Sod1</i><sup>−/−</sup> mice (<i>p</i> = 0.0457). Data represent the mean ± standard deviation for 14 and 8 <i>Sod1</i><sup>−/−</sup> mice at 10 and 50 weeks as well as 11 and 9 wild type mice at 10 and 50 weeks, respectively. D, There was also a significant (<i>p</i> = 0.0148) timewise increase in the mean tear IL-6 concentration in the <i>Sod1</i><sup>−/−</sup> mice from 10 to 50 weeks. Note the significantly higher IL-6 concentration in the <i>Sod1</i><sup>−/−</sup> mice at 10 (<i>p</i> = 0.0414) and 50 weeks (<i>p</i> = 0.0022) compared to the age matched WT mice. Tear TNF-α concentrations increased significantly from 10 to 50 weeks in the <i>Sod1</i><sup>−/−</sup> (<i>p</i> = 0.0115). Also note the significantly higher TNF-α concentration in the <i>Sod1</i><sup>−/−</sup> mice compared to the WT mice at 50 weeks (<i>p</i> = 0.0087). Data represent the mean ± standard deviation for 7 mice from the <i>Sod1</i><sup>−/−</sup> groups and 9 mice from the WT groups at 10 and 50 weeks.</p>", "links"=>[], "tags"=>["developmental biology", "Organism development", "aging", "Veterinary science", "Veterinary medicine", "Veterinary ophthalmology", "ophthalmology", "Geriatric ophthalmology", "Pathology and laboratory medicine", "Animal studies", "Animal models of disease", "Model organisms", "Animal models", "Mouse models", "meibomian", "serum", "tears"], "article_id"=>1110250, "categories"=>["Biological Sciences"], "users"=>["Osama M. A. Ibrahim", "Murat Dogru", "Yukihiro Matsumoto", "Ayako Igarashi", "Takashi Kojima", "Tais Hitomi Wakamatsu", "Takaaki Inaba", "Takahiko Shimizu", "Jun Shimazaki", "Kazuo Tsubota"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0099328.g003", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inflammatory_changes_in_the_meibomian_glands_serum_and_tears_of_the_Sod1_8722_8722_and_wild_type_mice_/1110250", "title"=>"Inflammatory changes in the meibomian glands, serum and tears of the <i>Sod1</i><sup>−/−</sup> and wild type mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-18 02:46:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1600444"], "description"=>"<p>Marked ultrastructural changes in the mitochondria including swelling, disorientation, shortening, and disorganization of cristae were noted at 50 weeks in the Cu, Zn-Superoxide Dismutase-1 knockout (<i>Sod1</i><sup>−/−</sup>) mice. We observed abnormalities in 40 percent of the 50 week wild type (WT) mice and 80 percent in the age matched <i>Sod1</i><sup>−/−</sup> mice. No such phenotypic alterations were observed in the mitochondria of the 10 to 50 week WT mice. Bar = 1 micrometer. Five tissues sections from each eye of the 6 animals in each mice group were analyzed to produce the representative images.</p>", "links"=>[], "tags"=>["developmental biology", "Organism development", "aging", "Veterinary science", "Veterinary medicine", "Veterinary ophthalmology", "ophthalmology", "Geriatric ophthalmology", "Pathology and laboratory medicine", "Animal studies", "Animal models of disease", "Model organisms", "Animal models", "Mouse models", "electron", "microscopic", "mitochondrial"], "article_id"=>1110271, "categories"=>["Biological Sciences"], "users"=>["Osama M. A. Ibrahim", "Murat Dogru", "Yukihiro Matsumoto", "Ayako Igarashi", "Takashi Kojima", "Tais Hitomi Wakamatsu", "Takaaki Inaba", "Takahiko Shimizu", "Jun Shimazaki", "Kazuo Tsubota"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0099328.g007", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Transmission_electron_microscopic_examination_of_the_mitochondrial_alterations_/1110271", "title"=>"Transmission electron microscopic examination of the mitochondrial alterations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-18 02:46:35"}

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