Clues to Neuro-Degeneration in Niemann-Pick Type C Disease from Global Gene Expression Profiling
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{"title"=>"Clues to neuro-degeneration in Niemann-Pick type C disease from global gene expression profiling", "type"=>"journal", "authors"=>[{"first_name"=>"Jonathan V.", "last_name"=>"Reddy", "scopus_author_id"=>"23028813800"}, {"first_name"=>"Ian G.", "last_name"=>"Ganley", "scopus_author_id"=>"6507268479"}, {"first_name"=>"Suzanne R.", "last_name"=>"Pfeffer", "scopus_author_id"=>"7006744040"}], "year"=>2006, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"352589017", "sgr"=>"34250324909", "issn"=>"19326203", "pmid"=>"17183645", "scopus"=>"2-s2.0-34250324909", "doi"=>"10.1371/journal.pone.0000019", "isbn"=>"1932-6203"}, "id"=>"2b936ec9-1e81-332e-b6cd-e9189b784b82", "abstract"=>"BACKGROUND: Niemann-Pick Type C (NPC) disease is a neurodegenerative disease that is characterized by the accumulation of cholesterol and glycosphingolipids in the late endocytic pathway. The majority of NPC cases are due to mutations in the NPC1 gene. The precise function of this gene is not yet known.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: Using cDNA microarrays, we analyzed the genome-wide expression patterns of human fibroblasts homozygous for the I1061T NPC1 mutation that is characterized by a severe defect in the intracellular processing of low density lipoprotein-derived cholesterol. A distinct gene expression profile was identified in NPC fibroblasts from different individuals when compared with fibroblasts isolated from normal subjects. As expected, NPC1 mutant cells displayed an inappropriate homeostatic response to accumulated intracellular cholesterol. In addition, a number of striking parallels were observed between NPC disease and Alzheimer's disease.\\n\\nCONCLUSIONS/SIGNIFICANCE: Many genes involved in the trafficking and processing of amyloid precursor protein and the microtubule binding protein, tau, were more highly expressed. Numerous genes important for membrane traffic and the cellular regulation of calcium, metals and other ions were upregulated. Finally, NPC fibroblasts exhibited a gene expression profile indicative of oxidative stress. These changes are likely contributors to the pathophysiology of Niemann-Pick Type C disease.", "link"=>"http://www.mendeley.com/research/clues-neurodegeneration-niemannpick-type-c-disease-global-gene-expression-profiling-1", "reader_count"=>34, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>11, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>13, "Student > Master"=>1, "Other"=>1, "Student > Bachelor"=>2, "Lecturer"=>1, "Student > Postgraduate"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>11, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>13, "Student > Master"=>1, "Other"=>1, "Student > Bachelor"=>2, "Lecturer"=>1, "Student > Postgraduate"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>17, "Medicine and Dentistry"=>6, "Neuroscience"=>2, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Chemistry"=>2, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Neuroscience"=>{"Neuroscience"=>2}, "Chemistry"=>{"Chemistry"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>17}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United States"=>2, "Japan"=>1, "Chile"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/470102", "https://ndownloader.figshare.com/files/470146", "https://ndownloader.figshare.com/files/470177", "https://ndownloader.figshare.com/files/470204"], "description"=>"<div><h3>Background</h3><p>Niemann-Pick Type C (NPC) disease is a neurodegenerative disease that is characterized by the accumulation of cholesterol and glycosphingolipids in the late endocytic pathway. The majority of NPC cases are due to mutations in the NPC1 gene. The precise function of this gene is not yet known.</p><h3>Methodology/Principal Findings</h3><p>Using cDNA microarrays, we analyzed the genome-wide expression patterns of human fibroblasts homozygous for the I1061T NPC1 mutation that is characterized by a severe defect in the intracellular processing of low density lipoprotein-derived cholesterol. A distinct gene expression profile was identified in NPC fibroblasts from different individuals when compared with fibroblasts isolated from normal subjects. As expected, NPC1 mutant cells displayed an inappropriate homeostatic response to accumulated intracellular cholesterol. In addition, a number of striking parallels were observed between NPC disease and Alzheimer's disease.</p><h3>Conclusions/Significance</h3><p>Many genes involved in the trafficking and processing of amyloid precursor protein and the microtubule binding protein, tau, were more highly expressed. Numerous genes important for membrane traffic and the cellular regulation of calcium, metals and other ions were upregulated. Finally, NPC fibroblasts exhibited a gene expression profile indicative of oxidative stress. These changes are likely contributors to the pathophysiology of Niemann-Pick Type C disease.</p></div>", "links"=>[], "tags"=>["clues", "neuro-degeneration", "niemann-pick", "profiling"], "article_id"=>152648, "categories"=>["Neuroscience", "Biochemistry", "Cell Biology", "Genetics"], "users"=>["Jonathan V. Reddy", "Ian G. Ganley", "Suzanne R. Pfeffer"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0000019.s001", "https://dx.doi.org/10.1371/journal.pone.0000019.s002", "https://dx.doi.org/10.1371/journal.pone.0000019.s003", "https://dx.doi.org/10.1371/journal.pone.0000019.s004"], "stats"=>{"downloads"=>14, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Clues_to_Neuro_Degeneration_in_Niemann_Pick_Type_C_Disease_from_Global_Gene_Expression_Profiling/152648", "title"=>"Clues to Neuro-Degeneration in Niemann-Pick Type C Disease from Global Gene Expression Profiling", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2006-12-20 00:44:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/954897"], "description"=>"<p>Protein levels in control and NPC-1 fibroblasts, determined by immunoblot (panel A), are quantified in B (dark shaded bars); mRNA levels from microarray data are shown in light shaded bars for comparison.</p>", "links"=>[], "tags"=>["mrna", "npc"], "article_id"=>625192, "categories"=>["Neuroscience", "Biochemistry", "Cell Biology", "Genetics"], "users"=>["Jonathan V. Reddy", "Ian G. Ganley", "Suzanne R. Pfeffer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0000019.g002", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Links_to_Alzheimer_s_disease_at_the_mRNA_and_protein_levels_in_NPC_Cells_/625192", "title"=>"Links to Alzheimer's disease at the mRNA and protein levels in NPC Cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:01:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/954834"], "description"=>"<div><p>(A) Supervised hierarchical clustering of the top 200 genes after SAM analysis.</p>\n<p>The dendrogram at the top shows clustering of NPC and control fibroblasts into distinct groups.</p>\n<p>Genes with higher expression are shown in red; genes with lower expression are shown in green.</p>\n<p>Gray bars indicate missing data.</p>\n<p>Cell lines clustered in the following order (left to right): control lines AG10803, GM05659, GM09503, GM03726; NPC-1 lines GM017909, 59413, 83.16, and GM18453.</p>\n<p>(B) Significance Analysis of Microarrays <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000019#pone.0000019-Tusher1\" target=\"_blank\">[12]</a> was used to identify genes that varied in expression between NPC fibroblasts and control fibroblasts from healthy patients.</p>\n<p>The plot of the data from 43,000 elements reveals approximately 3600 significant genes that have increased expression in NPC fibroblasts (shown in red).</p></div>", "links"=>[], "tags"=>["altered", "npc1"], "article_id"=>625129, "categories"=>["Neuroscience", "Biochemistry", "Cell Biology", "Genetics"], "users"=>["Jonathan V. Reddy", "Ian G. Ganley", "Suzanne R. Pfeffer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0000019.g001", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gene_expression_is_significantly_altered_in_NPC1_fibroblasts_/625129", "title"=>"Gene expression is significantly altered in NPC1 fibroblasts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:01:29"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"15", "full-text"=>"18", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"14", "full-text"=>"14", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"8", "full-text"=>"11", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}

Relative Metric

{"start_date"=>"2006-01-01T00:00:00Z", "end_date"=>"2006-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[297, 950, 1258, 1471, 1611, 1717, 1818, 1905, 1988, 2074, 2148, 2220, 2272, 2329, 2392, 2437, 2475, 2527, 2606, 2656, 2729, 2792, 2864, 2922, 2984, 3036, 3093, 3147, 3215, 3295, 3385, 3458, 3534, 3586, 3651, 3691, 3739, 3774, 3838, 3892, 3953, 4006, 4091, 4153, 4218, 4284, 4348, 4394, 4439, 4497, 4540, 4599, 4643, 4697, 4742, 4798, 4847, 4887, 4933, 4983, 5015, 5043, 5088, 5131, 5194, 5251, 5314, 5377, 5424, 5478, 5550, 5625, 5702, 5758, 5841, 5921, 6038, 6102, 6190, 6288, 6368, 6475, 6557, 6601, 6685, 6762, 6861, 6903, 7017, 7075, 7132, 7198, 7314, 7361, 7426, 7532, 7554]}, {"subject_area"=>"/Biology and life sciences/Anatomy and physiology", "average_usage"=>[299, 882, 1102, 1256, 1370, 1487, 1570, 1636, 1705, 1787, 1892, 1975, 2072, 2120, 2169, 2211, 2244, 2293, 2359, 2410, 2449, 2508, 2554, 2600, 2632, 2711, 2754, 2816, 2902, 3009, 3057, 3109, 3174, 3228, 3267, 3313, 3345, 3389, 3455, 3511, 3550, 3582, 3614, 3684, 3744, 3837, 3896, 3935, 3975, 4036, 4076, 4153, 4184, 4246, 4281, 4320, 4372, 4415, 4459, 4488, 4534, 4568, 4613, 4641, 4670, 4701, 4753, 4769, 4806, 4829, 4880, 4968, 5050, 5109, 5238, 5363, 5473, 5549, 5574, 5614, 5684, 5821, 5913, 5945]}, {"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[260, 840, 1139, 1300, 1416, 1539, 1668, 1748, 1842, 1919, 1990, 2048, 2104, 2160, 2240, 2292, 2350, 2403, 2452, 2498, 2544, 2592, 2652, 2706, 2764, 2823, 2885, 2946, 2991, 3034, 3093, 3171, 3245, 3305, 3390, 3444, 3496, 3541, 3587, 3634, 3686, 3732, 3795, 3855, 3902, 3970, 4020, 4073, 4134, 4187, 4244, 4301, 4346, 4415, 4473, 4511, 4552, 4608, 4646, 4690, 4730, 4772, 4820, 4862, 4946, 5004, 5062, 5144, 5201, 5260, 5315, 5378, 5458, 5541, 5589, 5677, 5739, 5809, 5865, 5918, 5968, 6015, 6149, 6226, 6291, 6363, 6443, 6503, 6576, 6660, 6712, 6778, 6824, 6904, 6939, 6984, 7048]}, {"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[226, 741, 959, 1170, 1290, 1381, 1458, 1540, 1602, 1672, 1741, 1791, 1844, 1890, 1948, 2012, 2062, 2096, 2146, 2199, 2246, 2290, 2339, 2396, 2460, 2497, 2551, 2624, 2690, 2769, 2823, 2867, 2896, 2950, 3001, 3036, 3078, 3121, 3166, 3225, 3282, 3327, 3377, 3420, 3501, 3569, 3611, 3659, 3705, 3749, 3798, 3881, 3922, 3952, 4000, 4070, 4098, 4128, 4157, 4200, 4264, 4307, 4340, 4369, 4406, 4438, 4457, 4498, 4546, 4610, 4665, 4703, 4756, 4806, 4859, 4993, 5103, 5179, 5229, 5302, 5384, 5452, 5546, 5619, 5675, 5772, 5891, 6000, 6069, 6127, 6162, 6219, 6256, 6338, 6416, 6525, 6643]}, {"subject_area"=>"/Medicine and health sciences/Anatomy and physiology", "average_usage"=>[272, 843, 1058, 1195, 1304, 1387, 1511, 1569, 1643, 1741, 1791, 1847, 1897, 1935, 1990, 2044, 2092, 2155, 2186, 2256, 2276, 2307, 2370, 2453, 2527, 2618, 2679, 2736, 2784, 2853, 2888, 2918, 2985, 3029, 3123, 3182, 3248, 3305, 3369, 3427, 3474, 3536, 3602, 3654, 3722, 3764, 3809, 3856, 3899, 3961, 4022, 4059, 4108, 4139, 4176, 4221, 4273, 4329, 4388, 4417, 4467, 4506, 4552, 4589, 4629, 4696, 4762, 4845, 4917, 4965, 5029, 5079, 5139, 5181, 5211, 5256, 5371, 5438, 5480, 5543, 5685, 5727, 5775, 5826]}]}
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Net::HTTPBadRequest

Source
CrossRef
Time
2019-04-17 04:18:26 UTC
Target URL
http://doi.crossref.org/servlet/getForwardLinks?usr=plos&pwd=plos1&doi=10.1371%2Fjournal.pone.0000019
Trace

/app/models/concerns/networkable.rb:21:in `get_result'
/app/models/source.rb:165:in `get_data'
/app/models/retrieval_status.rb:47:in `perform_get_data'
/app/jobs/source_job.rb:52:in `block (2 levels) in perform'
/app/jobs/source_job.rb:51:in `block in perform'
/app/jobs/source_job.rb:35:in `each'
/app/jobs/source_job.rb:35:in `perform'