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{"title"=>"Polymorphisms in the Human Tropoelastin Gene Modify In Vitro Self-Assembly and Mechanical Properties of Elastin-Like Polypeptides", "type"=>"journal", "authors"=>[{"first_name"=>"David", "last_name"=>"He", "scopus_author_id"=>"36850269400"}, {"first_name"=>"Ming", "last_name"=>"Miao", "scopus_author_id"=>"35332313200"}, {"first_name"=>"Eva E.", "last_name"=>"Sitarz", "scopus_author_id"=>"6603159101"}, {"first_name"=>"Lisa D.", "last_name"=>"Muiznieks", "scopus_author_id"=>"8388063400"}, {"first_name"=>"Sean", "last_name"=>"Reichheld", "scopus_author_id"=>"14046009600"}, {"first_name"=>"Richard J.", "last_name"=>"Stahl", "scopus_author_id"=>"7101622478"}, {"first_name"=>"Fred W.", "last_name"=>"Keeley", "scopus_author_id"=>"7004980739"}, {"first_name"=>"John", "last_name"=>"Parkinson", "scopus_author_id"=>"18335998200"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84866651409", "doi"=>"10.1371/journal.pone.0046130", "pui"=>"365720827", "pmid"=>"23049958", "scopus"=>"2-s2.0-84866651409", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"9e663918-0eef-3995-b08d-dd6ddf1334af", "abstract"=>"Elastin is a major structural component of elastic fibres that provide properties of stretch and recoil to tissues such as arteries, lung and skin. Remarkably, after initial deposition of elastin there is normally no subsequent turnover of this protein over the course of a lifetime. Consequently, elastic fibres must be extremely durable, able to withstand, for example in the human thoracic aorta, billions of cycles of stretch and recoil without mechanical failure. Major defects in the elastin gene (ELN) are associated with a number of disorders including Supravalvular aortic stenosis (SVAS), Williams-Beuren syndrome (WBS) and autosomal dominant cutis laxa (ADCL). Given the low turnover of elastin and the requirement for the long term durability of elastic fibres, we examined the possibility for more subtle polymorphisms in the human elastin gene to impact the assembly and long-term durability of the elastic matrix. Surveys of genetic variation resources identified 118 mutations in human ELN, 17 being non-synonymous. Introduction of two of these variants, G422S and K463R, in elastin-like polypeptides as well as full-length tropoelastin, resulted in changes in both their assembly and mechanical properties. Most notably G422S, which occurs in up to 40% of European populations, was found to enhance some elastomeric properties. These studies reveal that even apparently minor polymorphisms in human ELN can impact the assembly and mechanical properties of the elastic matrix, effects that over the course of a lifetime could result in altered susceptibility to cardiovascular disease.", "link"=>"http://www.mendeley.com/research/polymorphisms-human-tropoelastin-gene-modify-vitro-selfassembly-mechanical-properties-elastinlike-po", "reader_count"=>22, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Student > Doctoral Student"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>4, "Student > Master"=>4, "Other"=>4, "Student > Bachelor"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Student > Doctoral Student"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>4, "Student > Master"=>4, "Other"=>4, "Student > Bachelor"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>5, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>9, "Medicine and Dentistry"=>3, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"United Kingdom"=>1}, "group_count"=>1}

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• http://doi.org/10.1021/acsami.5b11076
• http://doi.org/10.1002/bip.23007
• http://doi.org/10.1126/sciadv.1501145
• http://doi.org/10.1111/ics.12372
• http://doi.org/10.1021/bi400760f
• http://doi.org/10.1080/00207454.2016.1212027
• http://doi.org/10.1021/acsbiomaterials.6b00469
• http://doi.org/10.1146/annurev-bioeng-071516-044555
• http://doi.org/10.1111/febs.14929
• http://doi.org/10.1016/j.actbio.2013.08.003
• http://doi.org/10.1002/psc.2866
• http://doi.org/10.1002/bip.23414
• http://doi.org/10.1016/j.matbio.2019.06.010

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• {"files"=>["https://ndownloader.figshare.com/files/571414"], "description"=>"<p>Tropoelastin protein sequence corresponds to RefSeq, variant 1 (NM_000501). This variant does not include exons 22 or 26a (an extension of exon 26). Exons are boxed, with exon numbers above. The positions of mutations and substituted amino acids are indicated within the shaded boxes, minor allele is indicated second.</p>", "links"=>[], "tags"=>["nucleotide", "polymorphisms", "causing", "non-synonymous", "changes"], "article_id"=>241885, "categories"=>["Biochemistry", "Genetics", "Biophysics"], "users"=>["David He", "Ming Miao", "Eva E. Sitarz", "Lisa D. Muiznieks", "Sean Reichheld", "Richard J. Stahl", "Fred W. Keeley", "John Parkinson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0046130.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Single_nucleotide_polymorphisms_causing_non_synonymous_changes_in_tropoelastin_/241885", "title"=>"Single nucleotide polymorphisms causing non-synonymous changes in tropoelastin.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 22:51:47"}
• {"files"=>["https://ndownloader.figshare.com/files/571558"], "description"=>"<p>(A) CD spectra comparing reference ELP, EP20–24–24, with ELPs containing single and triple G to S substitutions. (B) CD spectra comparing reference ELP, EP20–24–24, with ELPs containing single and double K to R substitutions. Compared to the reference polypeptide, the introduction of the substitutions does not appear to result in any major changes in conformation of these ELPs.</p>", "links"=>[], "tags"=>["introducing", "amino", "substitutions", "elastin-like", "peptides"], "article_id"=>242046, "categories"=>["Biochemistry", "Genetics", "Biophysics"], "users"=>["David He", "Ming Miao", "Eva E. Sitarz", "Lisa D. Muiznieks", "Sean Reichheld", "Richard J. Stahl", "Fred W. Keeley", "John Parkinson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0046130.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_introducing_select_amino_acid_substitutions_on_the_secondary_structure_of_elastin_like_peptides_ELPs_/242046", "title"=>"Effect of introducing select amino acid substitutions on the secondary structure of elastin-like peptides (ELPs).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 22:52:40"}
• {"files"=>["https://ndownloader.figshare.com/files/571664"], "description"=>"<p>(A) Coacervation (temperature-induce phase separation) of reference ELP, EP20–24–24, and ELPs containing single and triple G to S substitutions. Time 0 corresponds to 20°C, and temperature was raised at a rate of 1°C/min. (B) Coacervation of reference ELP, EP20–24–24, and ELPs containing single and double K to R substitutions. Time 0 corresponds to 15°C, and temperature was raised at a rate of 1°C/min. Coacervation was followed by turbidity as measured by absorbance at 440 nm. Curves represent means for three replicate experiments. Note the curves for the K to R substitutions are shifted to the left indicating that coacervation is initiated at a lower temperature.</p>", "links"=>[], "tags"=>["characteristics", "elastin-like", "peptides"], "article_id"=>242153, "categories"=>["Biochemistry", "Genetics", "Biophysics"], "users"=>["David He", "Ming Miao", "Eva E. Sitarz", "Lisa D. Muiznieks", "Sean Reichheld", "Richard J. Stahl", "Fred W. Keeley", "John Parkinson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0046130.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Coacervation_characteristics_of_select_elastin_like_peptides_ELPs_/242153", "title"=>"Coacervation characteristics of select elastin-like peptides (ELPs).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 22:53:16"}
• {"files"=>["https://ndownloader.figshare.com/files/571779"], "description"=>"<p>The four bar graphs indicate the means and standard errors for tensile mechanical properties of sheets of materials constructed with reference ELP, EP20–24–24, and ELPs containing the double K to R substitution. The number of replicates for each experiment (n) is indicated. *** indicates a significant difference between the two materials (ANOVA with Bonferoni correction, p<0.005).</p>", "links"=>[], "tags"=>["properties", "elastin-like", "peptides", "containing"], "article_id"=>242270, "categories"=>["Biochemistry", "Genetics", "Biophysics"], "users"=>["David He", "Ming Miao", "Eva E. Sitarz", "Lisa D. Muiznieks", "Sean Reichheld", "Richard J. Stahl", "Fred W. Keeley", "John Parkinson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0046130.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mechanical_properties_of_elastin_like_peptides_ELPs_containing_K_to_R_substitutions_/242270", "title"=>"Mechanical properties of elastin-like peptides (ELPs) containing K to R substitutions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 22:53:55"}
• {"files"=>["https://ndownloader.figshare.com/files/571892"], "description"=>"<p>The four bar graphs indicate the means and standard errors for tensile mechanical properties of sheets of materials constructed with reference ELP, EP20–24–24, and ELPs containing the single G to S substitution. Materials constructed from ELPs containing the triple G to S substitution were too fragile to generate meaningful values. The number of replicates for each experiment (n) is indicated. ** indicates a significant difference between the two materials (ANOVA with Bonferoni correction, p<0.01).</p>", "links"=>[], "tags"=>["properties", "elastin-like", "peptides", "containing"], "article_id"=>242378, "categories"=>["Biochemistry", "Genetics", "Biophysics"], "users"=>["David He", "Ming Miao", "Eva E. Sitarz", "Lisa D. Muiznieks", "Sean Reichheld", "Richard J. Stahl", "Fred W. Keeley", "John Parkinson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0046130.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mechanical_properties_of_elastin_like_peptides_ELPs_containing_G_to_S_substitutions_/242378", "title"=>"Mechanical properties of elastin-like peptides (ELPs) containing G to S substitutions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 22:54:33"}
• {"files"=>["https://ndownloader.figshare.com/files/572018"], "description"=>"<p>The four bar graphs indicate the means and standard errors for tensile mechanical properties of sheets of materials constructed with full-length human tropoelastin (hTE) and hTE variants containing either a single or triple G to S substitution in domain 20. The number of replicates for each experiment (n) is indicated. *, ** and *** indicate a significant difference between hTE and hTE with the single G to S substitution (ANOVA with Bonferoni correction, p<0.05, p<0.01 and p<0.001 respectively). † and ††† indicate a significant difference between hTE with the single G to S substitution and hTE with the triple G to S substitution (ANOVA with Bonferoni correction, p<0.05, p<0.001 respectively).</p>", "links"=>[], "tags"=>["properties", "full-length", "tropoelastin", "containing"], "article_id"=>242499, "categories"=>["Biochemistry", "Genetics", "Biophysics"], "users"=>["David He", "Ming Miao", "Eva E. Sitarz", "Lisa D. Muiznieks", "Sean Reichheld", "Richard J. Stahl", "Fred W. Keeley", "John Parkinson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0046130.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mechanical_properties_of_full_length_human_tropoelastin_containing_G_to_S_substitutions_/242499", "title"=>"Mechanical properties of full-length human tropoelastin containing G to S substitutions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 22:55:16"}
• {"files"=>["https://ndownloader.figshare.com/files/572150"], "description"=>"<p>Mutated amino acids are indicated in bold</p>", "links"=>[], "tags"=>["sequences", "represented", "elastin-like"], "article_id"=>242635, "categories"=>["Biochemistry", "Genetics", "Biophysics"], "users"=>["David He", "Ming Miao", "Eva E. Sitarz", "Lisa D. Muiznieks", "Sean Reichheld", "Richard J. Stahl", "Fred W. Keeley", "John Parkinson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0046130.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Domain_Sequences_Represented_in_Elastin_Like_Polypeptides_/242635", "title"=>"Domain Sequences Represented in Elastin-Like Polypeptides.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 22:55:57"}
• {"files"=>["https://ndownloader.figshare.com/files/572184"], "description"=>"<p>1. See <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046130#pone-0046130-g001\" target=\"_blank\">Figure 1</a></p><p>2. See <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046130#pone-0046130-t002\" target=\"_blank\">Table 2</a></p><p>3. Coacervation conditions: 25 µM polypeptide, 1.5 M NaCl</p><p>4. p<0.01 vs. EP20–24–24 (n = 3)</p>", "links"=>[], "tags"=>["elastin-like"], "article_id"=>242677, "categories"=>["Biochemistry", "Genetics", "Biophysics"], "users"=>["David He", "Ming Miao", "Eva E. Sitarz", "Lisa D. Muiznieks", "Sean Reichheld", "Richard J. Stahl", "Fred W. Keeley", "John Parkinson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0046130.t003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characteristics_of_Elastin_Like_Polypeptide_/242677", "title"=>"Characteristics of Elastin-Like Polypeptide", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 22:56:09"}
• {"files"=>["https://ndownloader.figshare.com/files/572219"], "description"=>"<p>1. SNPs identified through dbSNP are indicated with an appropriate SNP reference. EST indicates that the polymorphism was identified through EST libraries.</p><p>2. Tropoelastin RefSeq variant 1 (NM_000501) was used for numbering mRNA and amino acid positions, counting from the initiator methionine. Exons 22 and 26a (an extension of exon 26) are not present in this variant and are not included in the position count.</p><p>3. T/C and Leu/Pro designate Major/Minor allele respectively e.g. from T to C or Leu to Pro, etc.</p><p>4. Minor allele amino acid is indicated in square brackets</p><p>5. For SNPs detected through ESTs, minor allele frequency (MAF) indicates the proportion of ESTs sequences coding the minor allele. For SNPs obtained from dbSNP, MAF indicates the range across populations provided through dbSNP.</p><p>6. Because of phase 1 intron/exon borders, although the mutation site is in the last base of exon 11 the mutated amino acid is the first amino acid coded by exon 12.</p>", "links"=>[], "tags"=>["nucleotide", "polymorphisms"], "article_id"=>242713, "categories"=>["Biochemistry", "Genetics", "Biophysics"], "users"=>["David He", "Ming Miao", "Eva E. Sitarz", "Lisa D. Muiznieks", "Sean Reichheld", "Richard J. Stahl", "Fred W. Keeley", "John Parkinson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0046130.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Single_nucleotide_polymorphisms_identified_in_human_tropelastin_/242713", "title"=>"Single nucleotide polymorphisms identified in human tropelastin.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 22:56:21"}

PMC Usage Stats | Further Information

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Relative Metric

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F1000Prime