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{"title"=>"Inhibition of TDP-43 Aggregation by Nucleic Acid Binding", "type"=>"journal", "authors"=>[{"first_name"=>"Yi Chen", "last_name"=>"Huang", "scopus_author_id"=>"57100265400"}, {"first_name"=>"Ku Feng", "last_name"=>"Lin", "scopus_author_id"=>"57198848810"}, {"first_name"=>"Ruei Yu", "last_name"=>"He", "scopus_author_id"=>"55989120700"}, {"first_name"=>"Pang Hsien", "last_name"=>"Tu", "scopus_author_id"=>"7005250380"}, {"first_name"=>"Jiri", "last_name"=>"Koubek", "scopus_author_id"=>"54986066000"}, {"first_name"=>"Yin Chih", "last_name"=>"Hsu", "scopus_author_id"=>"55327344600"}, {"first_name"=>"Joseph Jen Tse", "last_name"=>"Huang", "scopus_author_id"=>"35195919500"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84878476630", "sgr"=>"84878476630", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0064002", "pmid"=>"23737961", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pui"=>"369039433"}, "id"=>"403230ae-bfbb-3a1c-bbc2-4e0866f79dd6", "abstract"=>"The aggregation of TAR DNA-binding protein (TDP-43) has been shown as a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) since 2006. While evidence has suggested that mutation or truncation in TDP-43 influences its aggregation process, nevertheless, the correlation between the TDP-43 aggregation propensity and its binding substrates has not been fully established in TDP-43 proteinopathy. To address this question, we have established a platform based on the in vitro protein expression system to evaluate the solubility change of TDP-43 in response to factors such as nucleotide binding and temperature. Our results suggest that the solubility of TDP-43 is largely influenced by its cognate single-strand DNA (ssDNA) or RNA (ssRNA) rather than hnRNP, which is known to associate with TDP-43 C-terminus. The direct interaction between the refolded TDP-43, purified from E.coli, and ssDNA were further characterized by Circular Dichroism (CD) as well as turbidity and filter binding assay. In addition, ssDNA or ssRNA failed to prevent the aggregation of the F147L/F149L double mutant or truncated TDP-43 (TDP208-414). Consistently, these two mutants form aggregates, in contrast with the wild-type TDP-43, when expressed in Neuro2a cells. Our results demonstrate an intimate relationship between the solubility of TDP-43 and its DNA or RNA binding affinity, which may shed light on the role of TDP-43 in ALS and FTLD.", "link"=>"http://www.mendeley.com/research/inhibition-tdp43-aggregation-nucleic-acid-binding", "reader_count"=>70, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>7, "Researcher"=>13, "Student > Ph. D. Student"=>26, "Student > Postgraduate"=>2, "Student > Master"=>6, "Other"=>2, "Student > Bachelor"=>6, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>7, "Researcher"=>13, "Student > Ph. D. Student"=>26, "Student > Postgraduate"=>2, "Student > Master"=>6, "Other"=>2, "Student > Bachelor"=>6, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>10, "Agricultural and Biological Sciences"=>41, "Medicine and Dentistry"=>7, "Neuroscience"=>4, "Chemistry"=>5}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>7}, "Neuroscience"=>{"Neuroscience"=>4}, "Chemistry"=>{"Chemistry"=>5}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>41}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>10}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"Belgium"=>1, "United States"=>1, "Taiwan"=>1, "United Kingdom"=>1, "Spain"=>1}, "group_count"=>1}

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PMC Usage Stats | Further Information

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• {"unique-ip"=>"7", "full-text"=>"9", "pdf"=>"0", "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"=>"16", "full-text"=>"22", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2020", "month"=>"10"}
• {"unique-ip"=>"7", "full-text"=>"9", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"11"}
• {"unique-ip"=>"13", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2020", "month"=>"12"}

Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[266, 468, 593, 703, 804, 903, 993, 1084, 1171, 1256, 1339, 1422, 1492]}, {"subject_area"=>"/Biology and life sciences/Molecular biology", "average_usage"=>[272, 466, 589, 702, 806, 903, 995, 1086, 1176, 1258, 1347, 1422, 1493]}, {"subject_area"=>"/Physical sciences", "average_usage"=>[254, 431, 547, 651, 748, 842, 932, 1017, 1098, 1178, 1259, 1336, 1404]}, {"subject_area"=>"/Physical sciences/Materials science", "average_usage"=>[250, 417, 535, 649, 758, 857, 952, 1036, 1113, 1206, 1287, 1353, 1429]}, {"subject_area"=>"/Physical sciences/Physics", "average_usage"=>[254, 421, 527, 626, 720, 813, 900, 983, 1063, 1136, 1210, 1283, 1342]}]}

F1000Prime