Lessons from “Lower” Organisms: What Worms, Flies, and Zebrafish Can Teach Us about Human Energy Metabolism
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{"title"=>"Lessons from \"lower\" organisms: What worms, flies, and zebrafish can teach US about human energy metabolism", "type"=>"generic", "authors"=>[{"first_name"=>"Amnon", "last_name"=>"Schlegel", "scopus_author_id"=>"7006453333"}, {"first_name"=>"Didier Y.R.", "last_name"=>"Stainier", "scopus_author_id"=>"7005076881"}], "year"=>2007, "source"=>"PLoS Genetics", "identifiers"=>{"scopus"=>"2-s2.0-37348999201", "sgr"=>"37348999201", "issn"=>"15537390", "doi"=>"10.1371/journal.pgen.0030199", "pmid"=>"18081423", "isbn"=>"1553-7404", "pui"=>"350291567"}, "id"=>"b25bfa7d-ab82-3017-ab03-359aaae6a334", "abstract"=>"A pandemic of metabolic diseases (atherosclerosis, diabetes mellitus, and obesity), unleashed by multiple social and economic factors beyond the control of most individuals, threatens to diminish human life span for the first time in the modern era. Given the redundancy and inherent complexity of processes regulating the uptake, transport, catabolism, and synthesis of nutrients, magic bullets to target these diseases will be hard to find. Recent studies using the worm Caenorhabditis elegans, the fly Drosophila melanogaster, and the zebrafish Danio rerio indicate that these \"lower\" metazoans possess unique attributes that should help in identifying, investigating, and even validating new pharmaceutical targets for these diseases. We summarize findings in these organisms that shed light on highly conserved pathways of energy homeostasis.", "link"=>"http://www.mendeley.com/research/lessons-lower-organisms-worms-flies-zebrafish-teach-about-human-energy-metabolism", "reader_count"=>148, "reader_count_by_academic_status"=>{"Unspecified"=>6, "Professor > Associate Professor"=>10, "Librarian"=>1, "Researcher"=>33, "Student > Doctoral Student"=>7, "Student > Ph. D. Student"=>50, "Student > Postgraduate"=>5, "Student > Master"=>12, "Other"=>2, "Student > Bachelor"=>15, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>5}, "reader_count_by_user_role"=>{"Unspecified"=>6, "Professor > Associate Professor"=>10, "Librarian"=>1, "Researcher"=>33, "Student > Doctoral Student"=>7, "Student > Ph. D. Student"=>50, "Student > Postgraduate"=>5, "Student > Master"=>12, "Other"=>2, "Student > Bachelor"=>15, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>5}, "reader_count_by_subject_area"=>{"Unspecified"=>9, "Agricultural and Biological Sciences"=>96, "Philosophy"=>2, "Chemical Engineering"=>1, "Chemistry"=>1, "Computer Science"=>1, "Economics, Econometrics and Finance"=>1, "Engineering"=>6, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>17, "Medicine and Dentistry"=>10, "Neuroscience"=>1, "Psychology"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>10}, "Psychology"=>{"Psychology"=>1}, "Unspecified"=>{"Unspecified"=>9}, "Environmental Science"=>{"Environmental Science"=>1}, "Chemical Engineering"=>{"Chemical Engineering"=>1}, "Engineering"=>{"Engineering"=>6}, "Chemistry"=>{"Chemistry"=>1}, "Neuroscience"=>{"Neuroscience"=>1}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>96}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>17}, "Philosophy"=>{"Philosophy"=>2}}, "reader_count_by_country"=>{"United States"=>3, "Japan"=>2, "Sudan"=>1, "United Kingdom"=>1, "Malaysia"=>1, "Switzerland"=>1, "Portugal"=>1, "Spain"=>3, "India"=>1, "Czech Republic"=>1, "Sweden"=>1, "Belgium"=>1, "France"=>1, "Germany"=>2}, "group_count"=>6}

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  • {"files"=>["https://ndownloader.figshare.com/files/941064"], "description"=>"<p>Lipid transport in the liver and intestine involves similar cellular machinery, although the direction of traffic of nutrients and wastes is directed differentially. In the intestine, TAG, cholesterol esters (CE), and phospholipids (not shown) are hydrolyzed into FA and cholesterol by lipases (red) and cholesteryl esterases (not shown) in the intestinal lumen. FAs are transported across the apical membrane of the enterocyte by FA transport proteins (FATP, purple) and then activated with coenzyme A by acyl coenzyme A (AcSCoA) synthase (pink). AcSCoAs are used by various acyl transferases (not shown) to build TAG and CE. In the lumen of the endoplasmic reticulum (ER), microsomal triacylglycerol transfer protein (MTP) and its obligate binding partner protein disulfide isomerase (Pdi) combine neutral lipids with ApoB to make chylomicrons (blue). Chylomicrons are secreted across the basolateral membrane. Orlistat inhibits TAG hydrolysis [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0030199#pgen-0030199-b085\" target=\"_blank\">85</a>] and ezetimibe blocks cholesterol uptake (red arrows) [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0030199#pgen-0030199-b086\" target=\"_blank\">86</a>]. Alpha lipoproteins (high density lipoprotein particles, HDL) are also secreted by the intestine in small amounts, but the major site of synthesis is the liver. The liver retrieves free FAs from the circulation through basolateral FA transport proteins on the surface of hepatocytes; beta lipoprotein particles are retrieved by receptor mediated endocytosis on this surface as well by the low density lipoprotein particle receptor (LDL-R). Retrieved FAs are either subjected to beta oxidation in mitochondria, or reincorporation in TAG. Either cholesterol is esterified to FAs, repackaged into nascent VLDL, or subjected to hydroxylation and subsequent secretion into the bile. De novo synthesis of cholesterol and FAs also occurs in the hepatocyte, a process regulated by sterol regulatory element binding proteins and various nuclear receptors (not shown). Familial hypercholesterolemia is due to defects in LDL-R. Abetalipoproteinemia is due to mutations in MTP. Hypobetalipoproteinemia is due to mutations in Apob.</p>", "links"=>[], "tags"=>["vertebrate", "intestinal", "hepatic", "lipid"], "article_id"=>611484, "categories"=>["Chemistry", "Genetics", "Developmental Biology"], "users"=>["Amnon Schlegel", "Didier Y. R Stainier"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.0030199.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Machinery_of_Vertebrate_Intestinal_and_Hepatic_Lipid_Transport_/611484", "title"=>"Machinery of Vertebrate Intestinal and Hepatic Lipid Transport", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 11:26:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/941147"], "description"=>"<div><p>(A) C. elegans lipid stores are found in gut granules, intestinal cell lysosomes that can be visualized with polarized microscopy, and labeled for neutral lipids with fluorescent dyes like nile red (red circles). Following feeding, greater lipid mass can be appreciated by the increased number and size of lipid-laden gut granules. To identify proteins involved in regulating the amount of lipids stored in gut granules, a reverse genetic screen can be performed. Depletion of individual proteins using an RNAi library may cause increases or decreases in lipid mass.</p><p>(B) Higher magnification view of the boxed region in (A) (bottom) showing the proteins involved in gut granule biogenesis and lipid accumulation. Acidification of nascent gut granules by the proton pump PGP-2 (dark blue) precedes lipid accumulation. Intracellular trafficking of nascent gut granules is governed by the GTPase encoded by <i>glo-1</i> (black) and its guanine nucleotide exchange factor, encoded by <i>glo-4</i> (light blue). The <i>lpd-3</i> gene may regulate biogenesis (dashed circle) of gut granules, be required for the accumulation of lipids nascent gut granules, or it may contribute to both processes.</p></div>", "links"=>[], "tags"=>["lipid"], "article_id"=>611580, "categories"=>["Chemistry", "Genetics", "Developmental Biology"], "users"=>["Amnon Schlegel", "Didier Y. R Stainier"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.0030199.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_C_elegans_Lipid_Storage_/611580", "title"=>"C. elegans Lipid Storage", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 11:26:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/941208"], "description"=>"<div><p>In the fed state, IPCs release insulin. In the fat body, insulin promotes nutrient storage. In the fasted state, AKH is released from the CC cells. AKH promotes release of FAs from the fat body. FAs are retrieved by oenocytes in the fasted state where they are stored as triacylglycerol in lipid droplets (red circles) and metabolized to generate ketone bodies. These metabolites are then released into the circulation for use as fuel until the next feeding. The parallel cells and tissues in vertebrates are shown in parentheses, although their physical arrangement is different (e.g., vertebrate α and β cells reside in pancreatic islet of Langerhans). Also, AKH and glucagon show no structural similarity, despite their related function.</p><p>(B) During flight, <i>Drosophila</i> neutral lipid stored as TAG is partially hydrolyzed into DAG in a process regulated by adipokinetic hormone (not shown). This lipid mobilization may involve lipid storage droplet proteins (LSD), the Brummer lipase (Bmm), and microsomal triglyceride transfer protein (Mtp). Liberated DAGs combine with high density lipophorin particles (HDLp), which have the coat proteins apolipophorins I and II (stylized as a black curve on the surface of the blue sphere), to make low density lipophorin particles (LDLp) when combined with apolipophorin III (green). This LDLp particle delivers DAGs to active skeletal muscles, which extract DAG from LDLp. Myocytes hydrolyze the delivered DAG molecules into FAs. Beta oxidation generates the energy required to sustain flight [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0030199#pgen-0030199-b087\" target=\"_blank\">87</a>]. Also, lipids are delivered to insect fat body cells by HDLp, which is bound to an insect lipophorin receptor (iLR) that is internalized [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0030199#pgen-0030199-b088\" target=\"_blank\">88</a>], but unlike endocytosed vertebrate LDL, insect HDLp is not degraded. Rather, HDLp is recycled to the hemolymph after lipids are extracted from the lipoprotein particle [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0030199#pgen-0030199-b089\" target=\"_blank\">89</a>].</p></div>", "links"=>[], "tags"=>["metabolic", "lipoprotein"], "article_id"=>611635, "categories"=>["Chemistry", "Genetics", "Developmental Biology"], "users"=>["Amnon Schlegel", "Didier Y. R Stainier"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.0030199.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Drosophila_Metabolic_Integration_and_Lipoprotein_Transport_/611635", "title"=>"<i>Drosophila</i> Metabolic Integration and Lipoprotein Transport", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 11:26:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/941297"], "description"=>"<div><p>(A) Zebrafish embryos and larvae subsist on yolk lipids for the first 4 d of life.</p><p>(B) By 7 d post-fertilization, only the surfactant-filled swim bladder (lavender) stains faintly with Oil Red O. The liver, pancreas (green), intestine, and heart are visible through the skin at this stage of development. The skeletal muscles (chevron-shaped somites) occupy the posterior of the animal.</p><p>(C) Mutations causing inappropriate lipid accumulation in the liver (upper), skeletal and cardiac muscles (middle), and vasculature (bottom) can be easily visualized.</p></div>", "links"=>[], "tags"=>["larval", "anatomy", "detection", "mutations", "lipid"], "article_id"=>611718, "categories"=>["Chemistry", "Genetics", "Developmental Biology"], "users"=>["Amnon Schlegel", "Didier Y. R Stainier"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.0030199.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Zebrafish_Larval_Anatomy_and_Detection_of_Mutations_in_Lipid_Homeostasis_/611718", "title"=>"Zebrafish Larval Anatomy and Detection of Mutations in Lipid Homeostasis", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 11:27:26"}

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  • {"unique-ip"=>"19", "full-text"=>"15", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"4"}
  • {"unique-ip"=>"16", "full-text"=>"13", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
  • {"unique-ip"=>"27", "full-text"=>"23", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"8"}
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  • {"unique-ip"=>"28", "full-text"=>"29", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"10"}
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  • {"unique-ip"=>"16", "full-text"=>"16", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
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  • {"unique-ip"=>"22", "full-text"=>"22", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
  • {"unique-ip"=>"27", "full-text"=>"30", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"25", "full-text"=>"31", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"14", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"32", "full-text"=>"34", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"19", "full-text"=>"22", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"35", "full-text"=>"39", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"31", "full-text"=>"33", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"3", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"25", "full-text"=>"21", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
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  • {"unique-ip"=>"28", "full-text"=>"25", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
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  • {"unique-ip"=>"20", "full-text"=>"24", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"15", "full-text"=>"14", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"18", "full-text"=>"24", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"22", "full-text"=>"29", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"16", "full-text"=>"16", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"17", "full-text"=>"20", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"22", "full-text"=>"25", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"16", "full-text"=>"17", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"18", "full-text"=>"16", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"21", "full-text"=>"25", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
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  • {"unique-ip"=>"18", "full-text"=>"18", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"39", "full-text"=>"43", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"19", "full-text"=>"20", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
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  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"54", "full-text"=>"57", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"30", "full-text"=>"32", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"31", "full-text"=>"37", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"43", "full-text"=>"50", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"2"}
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Relative Metric

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