Result of the soil chemical analysis on the 11 locations in the Philippines.
\\n\\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
\n'}],latestNews:[{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"},{slug:"all-intechopen-books-available-on-perlego-20201215",title:"All IntechOpen Books Available on Perlego"},{slug:"oiv-awards-recognizes-intechopen-s-editors-20201127",title:"OIV Awards Recognizes IntechOpen's Editors"},{slug:"intechopen-joins-crossref-s-initiative-for-open-abstracts-i4oa-to-boost-the-discovery-of-research-20201005",title:"IntechOpen joins Crossref's Initiative for Open Abstracts (I4OA) to Boost the Discovery of Research"},{slug:"intechopen-hits-milestone-5-000-open-access-books-published-20200908",title:"IntechOpen hits milestone: 5,000 Open Access books published!"},{slug:"intechopen-books-hosted-on-the-mathworks-book-program-20200819",title:"IntechOpen Books Hosted on the MathWorks Book Program"},{slug:"intechopen-s-chapter-awarded-the-guenther-von-pannewitz-preis-2020-20200715",title:"IntechOpen's Chapter Awarded the Günther-von-Pannewitz-Preis 2020"},{slug:"suf-and-intechopen-announce-collaboration-20200331",title:"SUF and IntechOpen Announce Collaboration"}]},book:{item:{type:"book",id:"5085",leadTitle:null,fullTitle:"Telomere - A Complex End of a Chromosome",title:"Telomere",subtitle:"A Complex End of a Chromosome",reviewType:"peer-reviewed",abstract:'This book, Telomere - A Complex End of a Chromosome, is organized into nine chapters containing the latest aspects of the current knowledge about the structure of telomeres and the crucial role that telomerase plays not only in maintaining chromosomal stability but also in relation to cell immortality, cell instability, and cancer biology. We now appreciate that these unusual complexes of DNA and proteins we all know as "telomeres" are dynamic and key structures that depend on telomerase and other cellular factors for continuance. Regulation of telomere activity is a dynamic area of current research, and new insights into telomeres and their role in aging and cancer, among other biological functions and pathologies, appear regularly in the scientific world. However, one fact is more than understandable in this difficult biological conundrum: the end of the telomere story is far from being totally unraveled.',isbn:"978-953-51-2753-6",printIsbn:"978-953-51-2752-9",pdfIsbn:"978-953-51-4150-1",doi:"10.5772/60625",price:119,priceEur:129,priceUsd:155,slug:"telomere-a-complex-end-of-a-chromosome",numberOfPages:226,isOpenForSubmission:!1,isInWos:1,hash:"2a8f40859d7bc312dea327fd9b058a20",bookSignature:"Marcelo L. Larramendy",publishedDate:"November 23rd 2016",coverURL:"https://cdn.intechopen.com/books/images_new/5085.jpg",numberOfDownloads:10303,numberOfWosCitations:2,numberOfCrossrefCitations:2,numberOfDimensionsCitations:9,hasAltmetrics:1,numberOfTotalCitations:13,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 21st 2016",dateEndSecondStepPublish:"March 28th 2016",dateEndThirdStepPublish:"June 24th 2016",dateEndFourthStepPublish:"July 25th 2016",dateEndFifthStepPublish:"September 1st 2016",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,8,9",editedByType:"Edited by",kuFlag:!1,editors:[{id:"14764",title:"Dr.",name:"Marcelo L.",middleName:null,surname:"Larramendy",slug:"marcelo-l.-larramendy",fullName:"Marcelo L. Larramendy",profilePictureURL:"https://mts.intechopen.com/storage/users/14764/images/system/14764.jpeg",biography:"Marcelo L. Larramendy, Ph.D., serves as a Professor of Molecular Cell Biology at the School of Natural Sciences and Museum (National University of La Plata, Argentina). He was appointed as Senior Researcher of the National Scientific and Technological Research Council of Argentina. He is a former member of the Executive Committee of the Latin American Association of Environmental Mutagenesis, Teratogenesis, and Carcinogenesis. He is the author of more than 450 contributions, including scientific publications, research communications, and conferences worldwide. He is the recipient of several national and international awards. Prof. Larramendy is a regular lecturer at the international A. Hollaender courses organized by the IAEMS and a former guest scientist at NIH (USA) and the University of Helsinki, (Finland). He is an expert in genetic toxicology and is, or has been, a referee for more than 20 international scientific journals. He was a member of the International Panel of Experts at the International Agency for Research on Cancer (IARC, WHO, Lyon, France) in 2015 for the evaluation of DDT, 2,4-D, and Lindane. Presently, Prof. Dr. Larramendy is Head of the Laboratory of Molecular Cytogenetics and Genotoxicology at the UNLP.",institutionString:"National University of La Plata",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"17",institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"403",title:"Microbial Genetics",slug:"karyology-microbial-genetics"}],chapters:[{id:"49913",title:"Telomeres in Liver Transplantation Allografts",doi:"10.5772/62196",slug:"telomeres-in-liver-transplantation-allografts",totalDownloads:1057,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Tatsuaki Tsuruyama and Wulamujiang Aini",downloadPdfUrl:"/chapter/pdf-download/49913",previewPdfUrl:"/chapter/pdf-preview/49913",authors:[{id:"94907",title:"Prof.",name:"Tatsuaki",surname:"Tsuruyama",slug:"tatsuaki-tsuruyama",fullName:"Tatsuaki Tsuruyama"}],corrections:null},{id:"52668",title:"Telomere and Telomerase in Cancer",doi:"10.5772/64721",slug:"telomere-and-telomerase-in-cancer",totalDownloads:1403,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Angayarkanni Jayaraman, Kalarikkal Gopikrishnan Kiran and\nPalaniswamy Muthusamy",downloadPdfUrl:"/chapter/pdf-download/52668",previewPdfUrl:"/chapter/pdf-preview/52668",authors:[{id:"186991",title:"Dr.",name:"Angayarkanni",surname:"Jayaraman",slug:"angayarkanni-jayaraman",fullName:"Angayarkanni Jayaraman"},{id:"194080",title:"Dr.",name:"Kiran",surname:"Kalarikka",slug:"kiran-kalarikka",fullName:"Kiran Kalarikka"},{id:"194081",title:"Mr.",name:"K G",surname:"Kiran",slug:"k-g-kiran",fullName:"K G Kiran"},{id:"194082",title:"Dr.",name:"Muthusamy",surname:"Palaniswamy",slug:"muthusamy-palaniswamy",fullName:"Muthusamy Palaniswamy"}],corrections:null},{id:"49872",title:"Telomeres and Genomic Instability from Precancerous Lesions to Advanced Cancer – Understanding Through Ovarian Cancer",doi:"10.5772/62259",slug:"telomeres-and-genomic-instability-from-precancerous-lesions-to-advanced-cancer-understanding-through",totalDownloads:991,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Gautier Chene, Gery Lamblin, Karine Le Bail-Carval, Philippe\nChabert, Georges Mellier and Andrei Tchirkov",downloadPdfUrl:"/chapter/pdf-download/49872",previewPdfUrl:"/chapter/pdf-preview/49872",authors:[{id:"37320",title:"Prof.",name:"Gautier",surname:"Chene",slug:"gautier-chene",fullName:"Gautier Chene"},{id:"177707",title:"Dr.",name:"Karine",surname:"Le Bail-Carval",slug:"karine-le-bail-carval",fullName:"Karine Le Bail-Carval"},{id:"177708",title:"Dr.",name:"Gery",surname:"Lamblin",slug:"gery-lamblin",fullName:"Gery Lamblin"},{id:"177709",title:"Dr.",name:"Philippe",surname:"Chabert",slug:"philippe-chabert",fullName:"Philippe Chabert"},{id:"177710",title:"Prof.",name:"Georges",surname:"Mellier",slug:"georges-mellier",fullName:"Georges Mellier"},{id:"177711",title:"Prof.",name:"Andrei",surname:"Tchirkov",slug:"andrei-tchirkov",fullName:"Andrei Tchirkov"}],corrections:null},{id:"49834",title:"The Role of Telomeres and Telomere-associated Proteins as Components of Interactome in Cell-signaling Pathways",doi:"10.5772/62130",slug:"the-role-of-telomeres-and-telomere-associated-proteins-as-components-of-interactome-in-cell-signalin",totalDownloads:1171,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Ekta Khattar and Vinay Tergaonkar",downloadPdfUrl:"/chapter/pdf-download/49834",previewPdfUrl:"/chapter/pdf-preview/49834",authors:[{id:"118589",title:"Prof.",name:"Vinay",surname:"Tergaonkar",slug:"vinay-tergaonkar",fullName:"Vinay Tergaonkar"},{id:"176764",title:"Dr.",name:"Ekta",surname:"Khattar",slug:"ekta-khattar",fullName:"Ekta Khattar"}],corrections:null},{id:"52461",title:"Molecular Diagnosis and Precision Therapeutic Approaches for Telomere Biology Disorders",doi:"10.5772/65353",slug:"molecular-diagnosis-and-precision-therapeutic-approaches-for-telomere-biology-disorders",totalDownloads:1148,totalCrossrefCites:1,totalDimensionsCites:5,signatures:"Rosario Perona, Laura Iarriccio, Laura Pintado-Berninches, Javier\nRodriguez-Centeno, Cristina Manguan-Garcia, Elena Garcia, Blanca\nLopez-Ayllón and Leandro Sastre",downloadPdfUrl:"/chapter/pdf-download/52461",previewPdfUrl:"/chapter/pdf-preview/52461",authors:[{id:"179373",title:"Dr.",name:"Leandro",surname:"Sastre",slug:"leandro-sastre",fullName:"Leandro Sastre"},{id:"184869",title:"Dr.",name:"Rosario",surname:"Perona",slug:"rosario-perona",fullName:"Rosario Perona"},{id:"184870",title:"Dr.",name:"Laura",surname:"Iarriccio",slug:"laura-iarriccio",fullName:"Laura Iarriccio"},{id:"184871",title:"MSc.",name:"Laura",surname:"Pintado-Berninches",slug:"laura-pintado-berninches",fullName:"Laura Pintado-Berninches"},{id:"184872",title:"MSc.",name:"Javier",surname:"Rodriguez-Centeno",slug:"javier-rodriguez-centeno",fullName:"Javier Rodriguez-Centeno"},{id:"184873",title:"Ms.",name:"Cristina",surname:"Manguan-Garcia",slug:"cristina-manguan-garcia",fullName:"Cristina Manguan-Garcia"},{id:"184874",title:"Dr.",name:"Elena",surname:"Garcia",slug:"elena-garcia",fullName:"Elena Garcia"},{id:"184875",title:"Dr.",name:"Blanca",surname:"Lopez-Ayllon",slug:"blanca-lopez-ayllon",fullName:"Blanca Lopez-Ayllon"}],corrections:null},{id:"51801",title:"Telomere Instability Induced by Anticancer Drugs in Mammalian Cells",doi:"10.5772/64928",slug:"telomere-instability-induced-by-anticancer-drugs-in-mammalian-cells",totalDownloads:1110,totalCrossrefCites:0,totalDimensionsCites:1,signatures:"Alejandro D. Bolzán",downloadPdfUrl:"/chapter/pdf-download/51801",previewPdfUrl:"/chapter/pdf-preview/51801",authors:[{id:"186974",title:"Dr.",name:"Alejandro",surname:"Bolzan",slug:"alejandro-bolzan",fullName:"Alejandro Bolzan"}],corrections:null},{id:"51979",title:"Telomeres and Cellular Senescence in Metabolic and Endocrine Diseases",doi:"10.5772/64759",slug:"telomeres-and-cellular-senescence-in-metabolic-and-endocrine-diseases",totalDownloads:1134,totalCrossrefCites:0,totalDimensionsCites:1,signatures:"Ryusaku Matsumoto and Yutaka Takahashi",downloadPdfUrl:"/chapter/pdf-download/51979",previewPdfUrl:"/chapter/pdf-preview/51979",authors:[{id:"187040",title:"Dr.",name:"Yutaka",surname:"Takahashi",slug:"yutaka-takahashi",fullName:"Yutaka Takahashi"}],corrections:null},{id:"51978",title:"Telomere Length and Its Relation to Human Health",doi:"10.5772/64713",slug:"telomere-length-and-its-relation-to-human-health",totalDownloads:1149,totalCrossrefCites:1,totalDimensionsCites:1,signatures:"Vivian F. S. Kahl and Juliana da Silva",downloadPdfUrl:"/chapter/pdf-download/51978",previewPdfUrl:"/chapter/pdf-preview/51978",authors:[{id:"170193",title:"Dr.",name:"Juliana",surname:"Da Silva",slug:"juliana-da-silva",fullName:"Juliana Da Silva"},{id:"187307",title:"MSc.",name:"Vivian Francilia",surname:"Silva Kahl",slug:"vivian-francilia-silva-kahl",fullName:"Vivian Francilia Silva Kahl"}],corrections:null},{id:"52658",title:"On the Far Side of Telomeres: The Many Roles of Telomerase in the Acquisition and Retention of Cancer Stemness",doi:"10.5772/65762",slug:"on-the-far-side-of-telomeres-the-many-roles-of-telomerase-in-the-acquisition-and-retention-of-cancer",totalDownloads:1141,totalCrossrefCites:0,totalDimensionsCites:1,signatures:"Kerem Teralı and Açelya Yilmazer",downloadPdfUrl:"/chapter/pdf-download/52658",previewPdfUrl:"/chapter/pdf-preview/52658",authors:[{id:"187370",title:"Dr.",name:"Kerem",surname:"Teralı",slug:"kerem-terali",fullName:"Kerem Teralı"},{id:"187388",title:"Dr.",name:"Açelya",surname:"Yilmazer",slug:"acelya-yilmazer",fullName:"Açelya Yilmazer"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},relatedBooks:[{type:"book",id:"923",title:"Herbicides",subtitle:"Theory and Applications",isOpenForSubmission:!1,hash:"54a8eb808c05a5fe01c676e7047d4576",slug:"herbicides-theory-and-applications",bookSignature:"Sonia Soloneski and Marcelo L. Larramendy",coverURL:"https://cdn.intechopen.com/books/images_new/923.jpg",editedByType:"Edited by",editors:[{id:"14764",title:"Dr.",name:"Marcelo L.",surname:"Larramendy",slug:"marcelo-l.-larramendy",fullName:"Marcelo L. Larramendy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5179",title:"Organic Fertilizers",subtitle:"From Basic Concepts to Applied Outcomes",isOpenForSubmission:!1,hash:"93748f3bd6a9c0240d71ffd350d624b1",slug:"organic-fertilizers-from-basic-concepts-to-applied-outcomes",bookSignature:"Marcelo L. Larramendy and Sonia Soloneski",coverURL:"https://cdn.intechopen.com/books/images_new/5179.jpg",editedByType:"Edited by",editors:[{id:"14764",title:"Dr.",name:"Marcelo L.",surname:"Larramendy",slug:"marcelo-l.-larramendy",fullName:"Marcelo L. Larramendy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5170",title:"Green Nanotechnology",subtitle:"Overview and Further Prospects",isOpenForSubmission:!1,hash:"e2d4dc551be023ba3525e6126076af90",slug:"green-nanotechnology-overview-and-further-prospects",bookSignature:"Marcelo L. Larramendy and Sonia Soloneski",coverURL:"https://cdn.intechopen.com/books/images_new/5170.jpg",editedByType:"Edited by",editors:[{id:"14764",title:"Dr.",name:"Marcelo L.",surname:"Larramendy",slug:"marcelo-l.-larramendy",fullName:"Marcelo L. Larramendy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4637",title:"Toxicity and Hazard of Agrochemicals",subtitle:null,isOpenForSubmission:!1,hash:"6aff74df1ea32df7f1e20e29c8363ff5",slug:"toxicity-and-hazard-of-agrochemicals",bookSignature:"Marcelo L. Larramendy and Sonia Soloneski",coverURL:"https://cdn.intechopen.com/books/images_new/4637.jpg",editedByType:"Edited by",editors:[{id:"14764",title:"Dr.",name:"Marcelo L.",surname:"Larramendy",slug:"marcelo-l.-larramendy",fullName:"Marcelo L. Larramendy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5362",title:"Toxicology",subtitle:"New Aspects to This Scientific Conundrum",isOpenForSubmission:!1,hash:"2061f273c8b3134dffbcb5256969ecab",slug:"toxicology-new-aspects-to-this-scientific-conundrum",bookSignature:"Sonia Soloneski and Marcelo L. Larramendy",coverURL:"https://cdn.intechopen.com/books/images_new/5362.jpg",editedByType:"Edited by",editors:[{id:"14764",title:"Dr.",name:"Marcelo L.",surname:"Larramendy",slug:"marcelo-l.-larramendy",fullName:"Marcelo L. Larramendy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5184",title:"Environmental Health Risk",subtitle:"Hazardous Factors to Living Species",isOpenForSubmission:!1,hash:"aa20266ad595ce73a9396f4ab0f8112e",slug:"environmental-health-risk-hazardous-factors-to-living-species",bookSignature:"Marcelo L. Larramendy and Sonia Soloneski",coverURL:"https://cdn.intechopen.com/books/images_new/5184.jpg",editedByType:"Edited by",editors:[{id:"14764",title:"Dr.",name:"Marcelo L.",surname:"Larramendy",slug:"marcelo-l.-larramendy",fullName:"Marcelo L. Larramendy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5101",title:"Invertebrates",subtitle:"Experimental Models in Toxicity Screening",isOpenForSubmission:!1,hash:"ebef5298af7d87ad3c9c7f5fe808fa2c",slug:"invertebrates-experimental-models-in-toxicity-screening",bookSignature:"Marcelo L. Larramendy and Sonia Soloneski",coverURL:"https://cdn.intechopen.com/books/images_new/5101.jpg",editedByType:"Edited by",editors:[{id:"14764",title:"Dr.",name:"Marcelo L.",surname:"Larramendy",slug:"marcelo-l.-larramendy",fullName:"Marcelo L. Larramendy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4606",title:"Emerging Pollutants in the Environment",subtitle:"Current and Further Implications",isOpenForSubmission:!1,hash:"1502287827685f0b71235bd45fe35ae4",slug:"emerging-pollutants-in-the-environment-current-and-further-implications",bookSignature:"Marcelo L. Larramendy and Sonia Soloneski",coverURL:"https://cdn.intechopen.com/books/images_new/4606.jpg",editedByType:"Edited by",editors:[{id:"14764",title:"Dr.",name:"Marcelo L.",surname:"Larramendy",slug:"marcelo-l.-larramendy",fullName:"Marcelo L. Larramendy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4616",title:"Nanomaterials",subtitle:"Toxicity and Risk Assessment",isOpenForSubmission:!1,hash:"a96b5d34ca84aecacbab309ba1e7e563",slug:"nanomaterials-toxicity-and-risk-assessment",bookSignature:"Sonia Soloneski and Marcelo L. Larramendy",coverURL:"https://cdn.intechopen.com/books/images_new/4616.jpg",editedByType:"Edited by",editors:[{id:"14764",title:"Dr.",name:"Marcelo L.",surname:"Larramendy",slug:"marcelo-l.-larramendy",fullName:"Marcelo L. Larramendy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5358",title:"Soil Contamination",subtitle:"Current Consequences and Further Solutions",isOpenForSubmission:!1,hash:"e4d136df9f1658ae17f3ba7b3c992460",slug:"soil-contamination-current-consequences-and-further-solutions",bookSignature:"Marcelo L. Larramendy and Sonia Soloneski",coverURL:"https://cdn.intechopen.com/books/images_new/5358.jpg",editedByType:"Edited by",editors:[{id:"14764",title:"Dr.",name:"Marcelo L.",surname:"Larramendy",slug:"marcelo-l.-larramendy",fullName:"Marcelo L. Larramendy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],ofsBooks:[]},correction:{item:{id:"66301",slug:"corrigendum-to-denim-fabrics-woven-with-dual-core-spun-yarns",title:"Corrigendum to: Denim Fabrics Woven with Dual Core-Spun Yarns",doi:null,correctionPDFUrl:"https://cdn.intechopen.com/pdfs/66301.pdf",downloadPdfUrl:"/chapter/pdf-download/66301",previewPdfUrl:"/chapter/pdf-preview/66301",totalDownloads:null,totalCrossrefCites:null,bibtexUrl:"/chapter/bibtex/66301",risUrl:"/chapter/ris/66301",chapter:{id:"63209",slug:"denim-fabrics-woven-with-dual-core-spun-yarns",signatures:"Osman Babaarslan, Esin Sarioğlu, Halil İbrahim Çelik and Münevver\nArtek Avci",dateSubmitted:"February 5th 2018",dateReviewed:"July 12th 2018",datePrePublished:"November 5th 2018",datePublished:"February 13th 2019",book:{id:"7242",title:"Engineered Fabrics",subtitle:null,fullTitle:"Engineered Fabrics",slug:"engineered-fabrics",publishedDate:"February 13th 2019",bookSignature:"Mukesh Kumar Singh",coverURL:"https://cdn.intechopen.com/books/images_new/7242.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"36895",title:"Dr.",name:"Mukesh Kumar",middleName:null,surname:"Singh",slug:"mukesh-kumar-singh",fullName:"Mukesh Kumar Singh"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"119775",title:"Prof.",name:"Osman",middleName:null,surname:"Babaarslan",fullName:"Osman Babaarslan",slug:"osman-babaarslan",email:"teksob@cu.edu.tr",position:null,institution:{name:"Cukurova University",institutionURL:null,country:{name:"Turkey"}}},{id:"178353",title:"Dr.",name:"Halil",middleName:"İbrahim",surname:"Çelik",fullName:"Halil Çelik",slug:"halil-celik",email:"hcelik@gantep.edu.tr",position:null,institution:{name:"Gaziantep University",institutionURL:null,country:{name:"Turkey"}}},{id:"216179",title:"Dr.",name:"Esin",middleName:null,surname:"Sarıoğlu",fullName:"Esin Sarıoğlu",slug:"esin-sarioglu",email:"sarioglu@gantep.edu.tr",position:null,institution:{name:"Gaziantep University",institutionURL:null,country:{name:"Turkey"}}},{id:"245674",title:"Mrs.",name:"Münevver",middleName:null,surname:"Ertek Avci",fullName:"Münevver Ertek Avci",slug:"munevver-ertek-avci",email:"Munevver.ErtekAvci@calikdenim.com",position:null,institution:null}]}},chapter:{id:"63209",slug:"denim-fabrics-woven-with-dual-core-spun-yarns",signatures:"Osman Babaarslan, Esin Sarioğlu, Halil İbrahim Çelik and Münevver\nArtek Avci",dateSubmitted:"February 5th 2018",dateReviewed:"July 12th 2018",datePrePublished:"November 5th 2018",datePublished:"February 13th 2019",book:{id:"7242",title:"Engineered Fabrics",subtitle:null,fullTitle:"Engineered Fabrics",slug:"engineered-fabrics",publishedDate:"February 13th 2019",bookSignature:"Mukesh Kumar Singh",coverURL:"https://cdn.intechopen.com/books/images_new/7242.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"36895",title:"Dr.",name:"Mukesh Kumar",middleName:null,surname:"Singh",slug:"mukesh-kumar-singh",fullName:"Mukesh Kumar Singh"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"119775",title:"Prof.",name:"Osman",middleName:null,surname:"Babaarslan",fullName:"Osman Babaarslan",slug:"osman-babaarslan",email:"teksob@cu.edu.tr",position:null,institution:{name:"Cukurova University",institutionURL:null,country:{name:"Turkey"}}},{id:"178353",title:"Dr.",name:"Halil",middleName:"İbrahim",surname:"Çelik",fullName:"Halil Çelik",slug:"halil-celik",email:"hcelik@gantep.edu.tr",position:null,institution:{name:"Gaziantep University",institutionURL:null,country:{name:"Turkey"}}},{id:"216179",title:"Dr.",name:"Esin",middleName:null,surname:"Sarıoğlu",fullName:"Esin Sarıoğlu",slug:"esin-sarioglu",email:"sarioglu@gantep.edu.tr",position:null,institution:{name:"Gaziantep University",institutionURL:null,country:{name:"Turkey"}}},{id:"245674",title:"Mrs.",name:"Münevver",middleName:null,surname:"Ertek Avci",fullName:"Münevver Ertek Avci",slug:"munevver-ertek-avci",email:"Munevver.ErtekAvci@calikdenim.com",position:null,institution:null}]},book:{id:"7242",title:"Engineered Fabrics",subtitle:null,fullTitle:"Engineered Fabrics",slug:"engineered-fabrics",publishedDate:"February 13th 2019",bookSignature:"Mukesh Kumar Singh",coverURL:"https://cdn.intechopen.com/books/images_new/7242.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"36895",title:"Dr.",name:"Mukesh Kumar",middleName:null,surname:"Singh",slug:"mukesh-kumar-singh",fullName:"Mukesh Kumar Singh"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"8807",leadTitle:null,title:"Organic Synthesis",subtitle:null,reviewType:"peer-reviewed",abstract:"
\r\n\tOrganic synthesis has always been one of the central topics of research for the scientific community in the academic laboratories and industrial world. Many striking journal articles and remarkable reviews and books have been published in the past year describing the practicability and applications of the subject demonstrating the importance of organic synthesis. In the present book, we will be putting together the topics in organic synthesis which may include but not limited to, (1) the basic terms and concepts, (2) various organic reactions including reduction, oxidation, addition, elimination, rearrangements, and cycloadditions, (3) Total Synthesis of Natural products, (4) transition metal catalysts, organocatalysts, enzymes and biotransformations, (5) applications in medicinal chemistry and drug design and development, (6) purification methods and characterization techniques, etc. To set a limit and to increase the scope of the book, author(s) are encouraged to send the chapters that include selected examples with practical applications and good yielding reactions reported within the past decade. Older topics with significant findings or their essence to prepare the foundation may be included in the chapter are welcomed as well.
",isbn:null,printIsbn:"979-953-307-X-X",pdfIsbn:null,doi:null,price:0,priceEur:null,priceUsd:null,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"f3bbbd989d0896f142d317ccb8abcc35",bookSignature:"Dr. Prashant S Deore",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/8807.jpg",keywords:"Natural Product Synthesis, Organic Reaction Mechanism, Stereoselective synthesis, Chirality, C-H Functionalization, Cross-Coupling Reactions, Heterogeneous Catalysis, Homogeneous Catalysis, Green Synthesis, Green Solvents and Reagents, Bioorganic synthesis, Click Chemistry",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"December 10th 2018",dateEndSecondStepPublish:"January 14th 2019",dateEndThirdStepPublish:"March 15th 2019",dateEndFourthStepPublish:"May 20th 2019",dateEndFifthStepPublish:"July 19th 2019",remainingDaysToSecondStep:"2 years",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"251769",title:"Dr.",name:"Prashant",middleName:"S",surname:"Deore",slug:"prashant-deore",fullName:"Prashant Deore",profilePictureURL:"https://mts.intechopen.com/storage/users/251769/images/system/251769.png",biography:"Dr. Prashant S. Deore was born in India. He received a Master’s degree in organic chemistry from Pune University in 2007. In the same year, he qualified with the SET and CSIR-NET (JRF) and joined in the group of Prof. Narshinha P. Argade for the doctoral studies in National Chemical Laboratory, India. In 2014, he awarded with a Ph. D. in Chemistry and was a recipient of the 2nd prize in “2014 Eli Lilly and Company Asia Outstanding Thesis Awards”. In July 2014 he moved to Canada and joined as a postdoctoral researcher in the group of Prof. Richard Manderville at the University of Guelph, Canada. Presently, Dr. Deore is working on the collaborative project between the University of Guelph and Aterica health Inc., and providing consulting to the company. His research interest includes organic synthesis, fluorescent probes development, nucleic acid synthesis and modifications, and aptasensor development for proteins and food toxins.",institutionString:"University of Guelph",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"8",title:"Chemistry",slug:"chemistry"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"270935",firstName:"Rozmari",lastName:"Marijan",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/270935/images/7974_n.png",email:"rozmari@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3621",title:"Silver Nanoparticles",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"silver-nanoparticles",bookSignature:"David Pozo Perez",coverURL:"https://cdn.intechopen.com/books/images_new/3621.jpg",editedByType:"Edited by",editors:[{id:"6667",title:"Dr.",name:"David",surname:"Pozo",slug:"david-pozo",fullName:"David Pozo"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"71335",title:"Transcriptional and Epigenetic Regulation of Krüppel-Like Transcription Factors",doi:"10.5772/intechopen.91652",slug:"transcriptional-and-epigenetic-regulation-of-kr-ppel-like-transcription-factors",body:'\nThe specificity protein 1 (Sp1)/Krüppel-like factor (KLF) proteins are a family of highly conserved transcription factors that are characterized by the presence of three highly homologous Cys2/His2-type zinc fingers near the C-terminus that bind GC/CACCC box. Amino acid sequences in the transcription activation/repression domains are less conserved among family members; however, there are subfamilies based on sequence similarities within this group. These subfamilies tend to share co-activators or co-repressors to aid in how they regulate genes. So far, seven members in the specificity protein (Sp) subgroup and 18 members in the KLF subgroup have been identified in mammalian cells [1]. This family of transcription factors is able to function as both transcriptional activators and repressors based on the gene and cellular contexts. KLFs gained notoriety as Krüppel-like factor 4 (KLF4), Krüppel-like factor 2 (KLF2), and Krüppel-like factor 5 (KLF5) were suggested to be important for embryonic stem cells and stem cell reprogramming [2, 3, 4, 5, 6, 7] alongside Oct4, Sox2, and Nanog. However, we have only begun to touch the surface of the transcriptional control these factors exert during embryonic development, maintenance of normal function, and the breakdown of normal processes seen in many diseases.
\nThe goal of this chapter is to begin to describe our current knowledge of how the KLFs are regulated during development or disease. We seek to begin to understand the ways cells either promote or repress the presence of the KLFs through a variety of transcriptional and translational mechanisms.
\nKrüppel-like factor 1 (KLF1) or erythroid Krüppel-like factor is an essential transcription factor for erythroid development and was found to be key in the regulation of many facets of blood development. KLF1 is expressed in the developing blood as well as being weakly expressed in mast cells [1]. KLF1 is key to blood development as Klf1−/− mice die around E14 due to severe anemia [8]. Several studies also showed KLF1 is able to directly bind to the β-globin promoter to activate the gene’s transcription as part of fetal hematopoiesis in the liver [9, 10]. The null embryos provided a wealth of knowledge about KLF1 early on, suggesting that β-thalassemia could be linked with KLF1 deletions [11]. More recent studies have also shown that KLF1 is able to either directly or indirectly repress the transcription of the 𝛾-globin gene to promote the expression of β-globin during blood development [12].
\nIn humans, >140 KLF1 variants, causing different erythroid phenotypes, have been described. The KLF1 Nan variant, a single amino acid substitution (p.E339D) in the DNA-binding domain, causes hemolytic anemia and is dominant over wild-type KLF1 [13]. This variant in the developing liver demonstrates defects in erythroid maturation that resemble those seen with the KLF1−/−, again demonstrating the importance of KLF1 in blood development. Furthermore, recent studies suggest that there is an enhancer element in the KLF1 gene that is susceptible to methylation and that elevated levels of methylation in that region correlate with patients with juvenile myelomonocytic leukemia (JMML) [14]. KLF1 was also found to play a role in the inhibition of megakaryocytes while also stimulating erythroid lineages at the same time [15].
\nKrüppel-like factor 2 or lung Krüppel-like factor (LKLF) was isolated in humans in 1999 and found to be 85% similar in nucleotide identity and 90% similar in its amino acids to mouse and located on chromosome 19p13.1 [16]. Of special interest, a region of 75 nucleotides within its proximal promoter was found to be identical between human and mouse [16]. This identical region in the mouse and human promoters for KLF2 has been found to be critical for its regulation in lung, blood, endothelial cell, and T lymphocyte development [15, 16, 17, 18, 19, 20, 21, 22]. KLF2 was shown to be essential for normal development within mice, and knockout embryos were lethal around day 12.5 and lung function was also severely impaired in KLF2−/− chimeras [22]. KLF2 expression appears to also be important for the maintenance of normal lung function, as methylation of KLF2 was associated with metastasis and worsening prognosis in non-small-cell lung cancer [23].
\nKLF2 was also shown to be essential for early erythropoiesis and regulation of the β-globin gene, and klf2−/− mice also exhibited hemorrhage in developing blood cells [17]. In mature T cells, KLF2 is required for T-cell trafficking, and elimination of KLF2 in T cells affects the expression of sphingosine-1-phosphate receptor and CD2L and beta7 integrins, receptors all important in T-cell trafficking [18, 24]. ERK5 was also shown to be important in T-cell activation, and ERK5−/− cells were unable to activate genes for T-cell function [25, 26].
\nKLF2 is also an important regulator of heart and aorta development and normal maintenance of endothelial cells [27, 28, 29]. KLF2 has been shown to be activated by shear stress through the conserved 75-base pair region in the human and mouse promoters [30]. This region was shown to requite PI3K for activation and PCAF (p300/CAMP-response element-binding protein-associated factor) and heterogeneous nuclear riboprotein D to induce acetylation of H3 and H4 histones [31]. Additional riboproteins and acetyltransferases such as HnRNP-U, hnRNP-D, and p300 were also found to bind via this conserved region in the KLF2 promoter [32]. KLF2 was also found to be activated by nucleolin in endothelial cells following shear stress, and activation via nucleolin was also PI3K dependent [33].
\nIn terms of a negative regulation of KLF2 in endothelial cells, KLF2 was shown to be negatively regulated by p53, which bound to the KLF2 promoter to induce deacetylation of the KLF2 histone H3 [34]. Tumor necrosis factor alpha (TNF-α) was shown to activate NF-Кβ p65 to complex with histone deacetylase 4 to prevent MEF2 binding to the KLF2 promoter, demonstrating a possible additional mechanism of the downregulation of KLF2 in endothelial cells in response to injury. Finally, low-density lipoprotein (LDL) cholesterol was found to stimulate the methylation of both DNA and histones on the KLF2 promoter and to contribute to the downregulation of KLF2 in response to LDL cholesterol. These mechanisms suggest there are a number of complex pathways that control the expression of KLF2 in a number of different tissue types.
\nKrüppel-like factor 3 (KLF3) or basic Krüppel-like factor (BKLF) is widely expressed and abundant in erythroid cells. KLF3 is believed to regulate adipogenesis, erythropoiesis, and B-cell development [35, 36]. KLF3 is able to interact with the co-repressor CtBP to repress gene transcription much like Krüppel-like factor 8 (KLF8) and Krüppel-like factor 12 (KLF12), and the N-terminal repression domain is important for this interaction in KLF3 [37, 38, 39]. KLF3 has been found to be sumoylated and that this sumoylation also affects its interaction with CtBP [37]. KLF3 has been shown to have a role in adipogenesis as forced expression of KLF3 was shown to block adipocyte differentiation [40]. Recent methylation data from endothelial cells demonstrates that KLF3 is highly methylated in flow-dependent conditions but can be reversed with 5-aza-2′-deoxycytidine treatments [41]
\nKrüppel-like factor 4 or gut-enriched Krüppel-like factor (GKLF) or endothelial zinc finger (EZF) protein is most similar to KLF2 and functions in the regulation of the epithelial of the gut and skin, endothelial cells, smooth muscle cells in vascular disease, and induced pluripotent stem cells (iPSC) [1, 42]. KLF4−/− mice died shortly after birth due to epithelial barrier defects in skin and gut barriers [43]. KLF4 is regulated by AP-2alpha during early and mid-embryogenesis to help regulate proliferation [44].
\nKLF4 became well-known after the discovery that it was one of the regulating factors along with Oct4, Sox2, and Nanog of induced pluripotent stem cells [4, 5, 6, 7]. Oct4 was later found to regulate the expression of KLF2, while LIF/Stat3 was thought to regulate the activation of KLF4 in embryonic stem cells [45, 46]. Additional studies have suggested that posttranslational modifications increase or decrease the stability of KLF4 mRNA and these modifications control the exit from pluripotency [47]. Furthermore, these modifications mediate the ability of KLF4 to complex with other pluripotency transcription factors and bind DNA. Finally, Oct4 has been shown to contain a linker region that is important for loosening chromatin, complexing with Brg1, and allowing for KLF4 to bind during cellular reprogramming [2]. Clearly, the interactions and mechanisms of pluripotency factors in stem cells are complex and require further investigation.
\nKLF4 is required for normal functioning of the gut epithelial as deletion of KLF4 resulted in altered proliferation [48]. KLF4 and KLF5 are often found in the same types of tissues, bind to similar or identical DNA elements, and often exert opposing affects in different tissue types. KLF4 has been found to bind with p53 on the p21 genes in epithelial cells and in smooth muscle cells to inhibit proliferation [42, 49, 50].
\nIn the case of smooth muscle cell proliferation, sumoylation of KLF4 causes it to fall off the p21 promoter and decreases p21 transcription following PDGF-BB treatments [51]. Sumoylation is also believed to affect binding of KLF4 to smooth muscle marker genes in TGFβ treatment [52, 53]. In smooth muscle cells in vascular disease, KLf4 has been shown to be activated by Sp1 and Oct4 binding to the KLF4 promoter [54, 55]. Separately, in macrophages KLF4 sumoylation promotes an IL-4-induced macrophage polarization to an M2 state, suggesting KLF4 plays a role in inflammation and macrophage polarization states [56]. However, in endothelial cells KLF4 is important along with KLF2 for the maintenance of endothelial cell integrity and normal endothelial barrier function [29]. KLF4 function in vascular disease could fill chapters of books investigating its many roles and functions; however, our goal is to highlight some of the mechanisms of its regulation in these processes.
\nFinally, KLF4 is also regulated by DNA methylation in several different types of cancers. KLF4 was found to be hypermethylated in renal cell carcinomas [57] and endometrial cancers [58]. However, a surprising discovery was KLF4 can bind to methylated regions of chromatin to mediate activation of transcription without the need for demethylation of the DNA in some types of cancer cells [59, 60]. These studies demonstrate a new role for some transcription factors as methylation readers in the transcription process.
\nKrüppel-like factor 5 or intestinal-enriched Krüppel-like factor (IKLF) or basic transcription element-binding protein 2 (BTEB2) is located on chromosome 13q22.1 and is important in the expression of the gut epithelia, vascular smooth muscle cells, and white adipose tissues [1, 61]. KLF5 is important in epithelial cells as it is located in the base of the crypts where cells are proliferating toward the villi. In general, KLF4 and KLF5 have been shown to compete to the same sites on DNA [62] and have also been suggested to be involved in their own regulation [42]. KLF5 has been shown to be important in gastric tumor progression and initiation and often correlate with KRAS mutations [63, 64].
\nKLF5 has also demonstrated to be important in the development and maintenance of the heart, aorta, and lung systems [20, 65, 66, 67, 68, 69]. Following angiotensin II induction, KLF5 was shown to bind to PDGF-A and activate it. KLF5 was also shown to be activated by RARα binding site in the KLF5 promoter [65, 70]. KLF5 has been shown to be regulated by acetylation. When KLF5 is associated with p300, it is acetylated and able to activate gene expression. Conversely, when SET is bound to KLF5, it prevents acetylation of KLF5 and its transcriptional activity [71]. These studies suggest that KLF5 can be regulated directly by modifications to control its transcriptional activity.
\nExpression of KLF5 in breast cancers was found to be correlated with a negative prognosis and decreased survival [72], while in clear cell renal cell carcinoma, hypermethylation and decreased expression of KLF5 were associated with a poorer prognosis [73]. Hypermethylation of KLF5 in acute myeloid leukemia was also associated with a poorer prognosis [74]. These studies suggest that KLF5 function in cancer is cell and perhaps even cell lineage specific. Within various cancers, KLF5 has also been demonstrated to be regulated by micro-RNAs. In gastric cancer, miR-145-5p directly targets KLF5 and promotes the differentiation of gastric cancer via KLF5 downregulation [75]. Separately, in hepatocellular carcinoma miR-214-5p acted as a tumor suppressor that could directly target and promote the downregulation of KLF5 [76]. These data demonstrate complex regulatory pathways involved in KLF5 regulation in cancer progression.
\nKrüppel-like factor 6 (KLF6) or zinc finger transcription factor 9 (ZF9) has been shown to be important for endothelial biology, adipogenesis, and tumor suppression in a wide variety of cancers. During embryogenesis, it is expressed in a time-sensitive manner in the kidney, cornea, gut, and yolk sac [77, 78, 79, 80]. KLF6−/− mice are embryonic lethal due to yolk sac abnormalities [77, 78, 79, 80]. KLF6 has been suggested to have a role in endothelial vascular remodeling following injury as it binds and activated urokinase plasminogen activator 1, endoglin, and matrix metalloproteinase 9 [81]. Interestingly, KLF6 has an alternative form of regulation because the gene produces at least four different isoforms that are able to affect DNA binding and transcription [82]. The full-length isoform of KLF6 is believed to function as a tumor suppressor and can be regulated by loss of heterozygosity, mutation, or decreased expression in different cancer types. The full-length KLf6 was found to have one deleted allele in prostate cancer, and the leftover allele was mutated 71% of the time, preventing KLF6 from functioning to activate p21 [83]. Of the isoforms of KLF6, the Krüppel-like factor 6 splice variant 1 (KLF6-SV1) was found to be oncogenic and upregulated in prostate, lung, and breast cancers and inhibits the activity of the full-length KLF6 [82]. This is the first KLF to be regulated in part by alternative splicing and suggests that directed targeting of the splice variants of KLF6 could represent a potential target for elimination therapy.
\nKLF6 can be regulated by methylation both to downregulate its expression and to prevent its binding to certain sites in cancer. Studies have suggested a possible role for methylation of KLF6 in hepatocellular carcinoma and in colorectal cancer [84, 85]. Separately, KLF6 can be prevented from binding on the SIRT5 promoter by the presence of DNA methylation during adipocyte differentiation [86]. KLF6 also could not bind the tissue factor pathway inhibitor-2 promoter following hypermethylation of its promoter during adipocyte formation [87].
\nKrüppel-like factor 7 (KLF7) or ubiquitous Krüppel-like factor (UKLF) has high expression in the brain and spinal cord and is important in the developing brain and nervous system [88]. KLF7 was identified originally in 1998, located on chromosome 2, and was believed to share a strong similarity with KLF6 [89]. Studies by Laub et al. found that KLF7 was important for upregulation of p21, repression of cyclin D1, and growth arrest in neuronal cells, thereby helping to lead to their differentiation and maturation [88]. In separate but related studies, the same laboratory found that elimination of KLF7 leads to neonatal lethality and the elimination affected areas of the olfactory, visual system, cerebral cortex, and hippocampus [90]. They also further investigated the roles of p21 and p27 and found KLF7 affected their expression in these areas during development [90]. Additional studies suggest that KLF7 regulates a number of genes in olfactory neuron development and axonal growth [91, 92]. In corneal epithelial differentiation, KLF7 was found by ChIP-sequencing to inhibit the activity of KLF4 to promote a corneal “progenitor”-like state [93].
\nKLF7 has also been suggested to play a role in type 2 diabetes. Studies have suggested that there are single nucleotide polymorphisms (SNPs) in the KLF7 gene that are associated with increased type 2 diabetes in Asian populations [94]. The same group further investigated the role of KLF7 and found that overexpression of KLF7 impaired the insulin production system and secretion in pancreatic beta cells while also inhibiting insulin sensitivity in the peripheral tissues [95]. KLF7 was also found to activate the TLR4/NF-kB/IL-6 pathway in adipocytes [96]. Finally, KLF7 has recently been also been found to be elevated in gastric cancers in patient samples in some populations and has been suggested to be a possible biomarker for the disease [97].
\nKrüppel-like factor 8 is expressed at low level in most tissue types [1]. KLF8 is a member of the same subfamily of Krüppel-like factors that includes KLF3 and KLF12 as all three KLFs recruit CtBP to repress transcription [37, 38, 39, 98]. These data also demonstrated that KLF8 needs its own DNA-binding domain to bind DNA but needs its repression domain for interaction with CtBP. KLF8 has been shown to be upregulated and activated during several types of cancers including those from ovarian, breast, and renal carcinomas [99, 100, 101]. KLF8 was also shown to activate the FHL2 gene in pancreatic cancer cells and to promote metastasis and epithelial-to-mesenchymal (EMT) transitions in pancreatic tumor cells [100, 101]. Furthermore, KLF8 was shown in gastric cancer to induce HIF-1 expression and promote epithelial-to-mesenchymal transitions in gastric cancer [102]. Finally, KLF8 methylation levels were also tested in prostate cancer cell lines but did not prove to be causally related to the progression of prostate tumors [103].
\nKrüppel-like factor 9 (KLF9) or basic transcription element-binding protein (BTEB) is broadly expressed, but its expression is especially high in the developing brain and thymus and in the smooth muscle of the gut and bladder [1, 104]. Interestingly, it has been demonstrated that although the mRNA for KLF9 is transcribed in many areas, the brain is the main organ where it is translated into protein [105]. The zinc fingers of the KLF9 gene are commonly now thought to be very closely related to Sp1 as they have a high sequence similarity. However, beyond their DNA-binding domains, these proteins share little sequence similarity [105]. In the brain expression, there is a thyroid hormone response element in the promoter of the KLF9 gene that accounts for its transcription and expression in the postnatal brain [105, 106]. KLF9 was also found to bind to a number of proximal promoter regions on genes important for brain function to repress transcription in hippocampal neurons [106, 107].
\nKLF9 expression has been noted in cancers of the mammary glands and uterus because of its ability to interact with the progesterone response elements to stimulate progesterone response elements [108, 109]. KLF9 is also required for the development of fertility in females as KLF9−/− mice were subfertile and were unable to differentiate their reproductive tissue without KLF9 [109]. KLF9−/− mice also were found to have aberrant regulation of their intestinal crypt cell proliferation and villus migration [110]. These data suggest that KLF9 also regulates the smooth muscle and the turnover of intestinal cells.
\nFinally, in follicular lymphoma, KLF9 was found to be hypermethylated and silenced in tumors along with a number of polycomb genes [111]. Separately, in breast cancer hypermethylation of KLF9 was correlated with a favorable cancer prognosis [112].
\nKrüppel-like factor 10 (KLF10) or transforming growth factor-inducible early gene 1 (TIEG1) is known as a TGFβ-inducible gene as it is rapidly induced by TGFβ treatments and then quickly returns back to basal levels [113, 114]. KLF10 is induced by multiple members of the TGFβ superfamily and then goes on to suppress Smad7 and co-activate together with Smad2. It is believed that KLF10 plays a major role in the mediation of TGFβ inhibition of cell proliferation and inflammation and induction of apoptosis [113, 115]. The rapid induction and then degradation of KLF10 are believed to be accounted for by SIAH proteasomal degradation [113]. In these studies, KLF10 was found to interact directly with SIAH which then mediates its degradation [113]. These studies suggest a protein degradation method of regulation.
\nKLF10 has been cited to be important in bone development and osteoporosis, adipocyte development, and heart, lung, brain, and T-cell activation [1, 116]. In adipocyte differentiation, C/EBPβ was found to bind and activate the KLF10 promoter, while KLF10 bound to the C-EBPα promoter to inhibit its activation [117]. In bone development, SNP analysis revealed that variants in the KLF10 gene were associated with bone loss in older men [118]. Conversely, studies in KLF10 null mice suggest a gender-specific role of KLF10 in the maintenance of bone density [19]. KLF10 null osteoblasts were also found to be defective in mineralization and in osteoblast support of osteoclast differentiation [119]. Finally, KLF10 null mice had impaired tendon function as adults with corresponding difficulty in tendon function [120].
\nIn heart development, KLF10−/− mice developed cardiac hypertrophy and an increase in ventricle size and an increase in wall thickness, suggesting the importance of KLF10 to the maintenance of normal heart function [121]. KLF10 is also important in T-cell and Treg development along with TGFβ as deletion of KLF10 in T cells augmented atherosclerosis and led to impaired T-cell function [122].
\nKLF10 has been shown to be methylated in pancreatic cancers by DNMT1 with a correlation between methylation status and tumor grade [123]. The more the methylation and repression of the KLF10 promoter, the worse the tumor grade. These studies suggest that an important regulatory mechanism for KLF10 is also via methylation of its promoter.
\nKrüppel-like factor 11 (KLF11) or transforming growth factor-inducible early gene 2 (TIEG2) or FKLF is known to be expressed in the pancreas and in erythroid cells in the fetal liver. KLF11 is located in humans at chromosome 2p25 [1, 124, 125, 126]. KLF11 shares 91% homology with KLF10 in the zinc finger domain and 44% homology with the N-terminus of KLF10 [127]. These studies also demonstrated that overexpression of KLF11 inhibits cell proliferation [127] and is induced by TGFβ signaling pathways.
\nKLF11 contains three repression domains that are believed to be important for its repressor activities [128]. TGFβ signaling pathway induction means that KLF11 often cooperates with Smads to induce changes in transcription following TGFβ treatment. KLF11 later was found to be activated by several members of the TGFβ superfamily and not just by TGFβ treatment alone [114]. Studies have shown in neuronal cells that KLF11 regulates the transcription of the dopamine D2 receptor by complexing with p300, a histone acetylase, to promoter transcription [129]. KLF11 was also found to regulate collagen gene expression through the heterochromatin protein 1 gene-silencing pathway, as mutants defective for coupling to this epigenetic modifier lose the ability to repress COL1A2 and to prevent fibrosis in KLF11−/− mice [130]. As part of the TGFβ induction of KLF11, TGFβ induction allows KLF11 to interact with Smad3 and to repress certain promoters. In the case of pancreatic cancer, KLF11 was found to bind with Smad3 to the c-myc promoter following TFG-β treatment [131].
\nKLF11 is important not only for its TGFβ response but also for its associations with diabetes and obesity [132, 133]. A variant of KLF11 was found that could lead to type 2 diabetes and obesity [134]. Further studies revealed additional variants that may affect KLF11 regulation of the insulin promoter and type 2 diabetes [133]. KLF11 was also found to interact with p300 in maturity-onset diabetes of the young to induce transcriptional changes in the pancreas [135]. In converse, KLF11 can also interact with mSin3a in pancreatic cancer by repression of the Smad7 promoter [136]. Ectopic expression of KLF11 increased the sensitivity of cells to oxidative drugs [137]. Methylation of KLF11 has been suggested to be one mechanism of its downregulation in several types of cancers [138, 139].
\nKrüppel-like factor 12 or BETB1 was first identified in the regulation of the AP-2α gene and is located on chromosome 13q21-13q22 [140]. In the case of the AP-2α gene, KLF12 functions as a transcriptional activator and appears to relate back to KLF12’s function as a marker of tumor development [141, 142, 143]. KLF12 is a marker for gastric cancer progression, and overexpression of KLF12 promotes tumor cell invasion and progression [142]. However, in lung cancer cell lines, it was shown that KLF12 was important for the regulation of anoikis and the progression through the S phase of cell cycle [141]. These data suggest that KLF12 may have multiple different roles in cancer beyond what was previously identified. KLF12 is also one of the KLF factors to interact with the mSin3a repressor complex via an alpha-helical motif in a repression domain of the transcription factor [144].
\nKLF12 not only plays roles in tumor progression but is also believed to play a role in the developing kidney after birth. KLF12 was shown to be expressed in the collecting ducts of the kidney after birth and could directly regulate the UT-A1 but not the ENaC promoters, two genes important for the development of the collecting ducts [145]. A recent study suggests that KLF12 might in part be regulated in cancer by the methylation of miR-205 by long noncoding RNA ELF3-antisense RNA 1. These data suggest that miR-205 and RNA ELF3-antisense RNA 1 exist in a complex regulatory loop involving KLF12 [146].
\nKrüppel-like factor 13 (KLF13) or BTEB3, FKLF2, or RFLAT-1 was first discovered along with Krüppel-like factor 14 (KLF14) using an expressed sequence tag database to search for additional conserved KLF DNA-binding domains [129]. KLF13−/− mice are one of the few KLF mice that are viable and fertile; however, they display abnormal blood cell development [147, 148] suggesting that KLF13 is critical for both B- and T-cell developments [148, 149, 150]. One part of this developmental process is KLF13’s interaction with PPAR4 [151] to regulate CCL5. Not only is KLF13 important for blood cell development, it has also been shown to be important for the developing heart [104, 152]. To this end, KLF14 can also be linked to Holt-Oram syndrome, an inherited disorder characterized by abnormalities of the upper limbs and heart, via its interaction with the TBX5 promoter [153].
\nKLF13 has also recently been suggested to be a tumor suppressor in glioma cells [154]. These studies found that KLF13 was downregulated by hypomethylation across the gene to promote its silencing; however, decreases in DNMT1 expression or decreases in hypomethylation patterns of KLF13 decreased proliferation and migration of glioma cells [154]. Another example of KLF13 methylation is the methylation of the obesity-related variant of KLF13: cg07814318. The methylation of this particular SNP appears to be related to increased childhood obesity [155]. These studies suggest that methylation of promoters could be one possible mechanism of regulation of KLFs in development or disease.
\nAnother possible mechanism of regulation of KLF13 is through the co-repressor complex mSin3a [144]. In this instance, KLF13 was found to interact with the mSin3a repressor complex via an alpha-helical motif in a repression domain [144]. Additional studies from this group suggest that multiple KLF factors (BTEB1, BTEB3, BTEB4) could also contain this alpha-helical domain in their repression regions.
\nKrüppel-like factor 14 was first discovered using expressed sequence tag databases to search for the presence of additional conserved KLF DNA-binding domains [129]. KLF14 has 72% similarity with the human Sp2; however, the majority of its similarity exists within its DNA-binding domain [129]. Most reports suggest that its expression is ubiquitous [1]. Interestingly, KLF14 is intron-less and exists on chromosome 7q32. KLF14 is a mono-allelic expression pattern and shown to be hypomethylated in many tissues, further suggesting a pattern of ubiquitous expression [156]. Further evidence also suggests that KLF14 could be derived from a retro-transposed copy of Krüppel-like factor 16 (KLF16) [156] and could be an example of accelerated evolution. KLF14 deletion has recently been linked with centrosome amplification, aneuploidy, and spontaneous tumorigenesis because KLF14 functions as a repressor of polo-like kinase 4 (PLK4). Without the repressive activities of KLF14 on PLK-14, PLK-14 can cause chromosomal abnormalities and promote tumorigenesis in cancer cells. The KLF14 gene has been linked to genomic variants that are highly correlative with basal cell carcinoma [157].
\nGenome-wide association studies not only revealed that KLF14 was linked with basal cell carcinoma, it also has revealed that KLF14 is linked with cholesterol metabolism, metabolic disease, and coronary artery disease. These studies suggest that KLF14 might function as an imprinted master regulator of metabolic function and that mutation of certain SNPs within the KLF14 gene can lead to a large-scale deregulation of metabolic gene function [158]. KLF14 was also found to regulate levels of HDL-C and hepatic ApoA-I production [159]. Guo et al. were able to find evidence that perhexiline was able to activate KLF14 and to reduce lesions in ApoE−/− atherosclerotic mice [159]. Separate but related studies suggest that this activity is related to the phosphorylation of KLF14 by both p38 MAPK and ERK kinase [160]. However, KLF14 was found to be decreased in endothelial cells in atherosclerosis, and overexpression of KLF14 actually inhibited NF-KB signaling by suppressing p65 [161]. KLF14 has also been shown to interact with p300 to promote sphingosine kinase activation and to enhance sphingosine production [162]. These data suggest a complicated pattern of expression for a ubiquitous transcription factor that could produce paradoxical effects in inflammatory disease such as cardiovascular disease or cancer. Interestingly, there still appears to be less known about how KLF14 itself is regulated.
\nKLF15 or kidney-enriched Krüppel-like factor (KKLF) demonstrates low levels of cardiac-specific expression during development but then exhibits adult expression in the kidney, liver, pancreas, heart, skeletal muscle, lung, and ovary. KLF15 was originally thought to be important for the regulation of different cell types in the kidney and repressed genes such as CLC-K1 and CLC-K2 [163]. However, its regulatory effects can be seen in the heart, skeletal muscle, gluconeogenesis, and circadian rhythms. In terms of the heart, KLF15 was demonstrated to be an inhibitor of cardiac fibrosis by repression of connective tissue growth factor (CTGF) [164]. In this mechanism, KLF15 inhibits the recruitment of the co-activator P-CAF but does not prevent SMAD3 from binding to the promoter [164]. Additional studies by the same group demonstrated that KLF15 was a negative regulator of cardiac hypertrophy via inhibition of GATA4 and MEF2 functions [165]. Recent studies further suggest that KLF15 was identified as a putative upstream regulator of metabolic gene expression in the heart via RNA-Seq and methylation sequencing and that KLF15 was itself regulated by EZH2 in a SET domain-dependent manner [166]. KLF15 was demonstrated to be silenced via methylation in ischemic cardiomyopathy which in turn leads to the silencing of many cardiac-specific genes.
\nKLF15 has been shown to also be important for metabolism [167]. In terms of the skeletal muscle, overnight fasting and endurance exercise induce KLF15 expression, while knockout of KLF15 induces abnormal energy flux, excessive muscle fatigue, and impaired endurance capacity [168]. KLF15 was later shown to complex in the liver with liver X receptor (LXR) to inhibit SREBF1 during fasting by recruiting the co-repressor RIP140 [169]. Finally, KLF15 is also important for nitrogen homeostasis and the maintenance of circadian rhythm as KLF15 knockout mice had no amino acid rhythm and no rhythm of the production of urea from ammonia [170]. These studies suggest the importance of KLF15 and suggest that investigations into how it is regulated by chromatin readers and writers will become important to these metabolic diseases.
\nKrüppel-like factor 16 or dopamine receptor regulating factor (DRRF) was first discovered in its regulation of the dopamine receptors in the developing brain and eye [171]. It is now known that KLF16 is expressed not only in the developing brain but also in the thymus, intestine, kidney, liver, heart, and bladder. KLF16 has recently been shown to not only regulate the dopamine receptor but also to regulate the ephrin receptor A5 (EphA5), but this regulation was methylation specific as methylation of the EphA5 promoter prevented KLF16 from binding [171]. These data suggest that one possible epigenetic mechanism regulating KLF16 is methylation of regions near its binding site.
\nKLF16 was found by Daftary et al. to bind to all three types of KLF binding site, the GC, CA, and BTE boxes using electromobility shift assays but prefers binding to the BTE box in cells and to mediate its effects via mSin3a, a transcriptional co-repressor complex but suggests that this function is both promoter and cell context dependent [172]. To further study this interaction, site-directed mutagenesis was performed of all of the serine, threonine, and tyrosine residues believed to be possible targets for kinase phosphorylation signaling and found that mutation of tyrosine-10 altered the ability of KLF16 to interact with mSin3a [172]. Finally, KLF16 was also found to be regulated by nuclear localization and to be excluded from heterochromatin within the nucleus [172]. These studies suggest complex posttranslational regulatory mechanisms for KLF16 function in a cell- and promoter-dependent manner.
\nKrüppel-like factor 17 (KLF17) was first discovered in mouse as zinc finger protein 393 (ZFP393) or ZNF393 where it was shown to be expressed in the testis and ovaries, and the gene spans 8 kb in the distal portion of chromosome 4 in the mouse [173]. In humans KLF17 maps to chromosome 1p34.1. When it was discovered back in 2002, it was believed to be the first C2H2 germ cell-specific zinc finger protein. Identification of KLF17 in the human revealed that KLF17 was expressed not only in the testis but also in the brain and bone, albeit at relatively low amounts [174]. KLF17 also contains low sequence similarity between the human and mouse orthologues; however, a detailed transcriptional binding analysis by van Vliet et al. was able to demonstrate that KLF17 was a Krüppel-like transcription factor rather than being more closely linked to the specificity protein factor family (Sp family) [173].
\nKLF17 is hypothesized to be a tumor suppressor in multiple types of cancers, and a decrease in its expression has become correlated with a poor cancer prognosis [175]. KLF17 was demonstrated to be a tumor suppressor gene in metastatic breast cancer lines whose downregulation promotes the epithelial-to-mesenchymal transition in cancer cells [176]. These studies also suggested that KLF17 is a direct negative regulator of inhibitor of DNA binding 1 (ID1). Sadly, they do not offer a direct mechanism for the downregulation of KLF17 during breast cancer metastasis, but they do provide compelling data to suggest that KLF17 might have multiple functions in the male and female sex organs and that suppression of this factor could lead to increased tumorigenic potential [176].
\nFurther evidence in non-small-cell lung cancer also suggests that KLF17 could function as a tumor suppressor [177]. These studies suggested that p53 recruits p300 to the KLF17 promoter to acetylate and turn on transcription [177]. In addition, p53 also physically interacts with KLF17 and promotes binding of KLF17 to certain gene promoters and promotes transcription of p53, p21, and pRB [177]. These data suggest an intricate cross-talk between KLF17 and p53 in tumorigenesis. Another way KLF17 is believed to inhibit cancer progression is through inhibition of proliferation via repression of UPAI-1 [178], which Cai et al. proposed inhibited the invasive properties of small-cell lung cancer cells. KLF17 was also suggested to be a tumor suppressor through a TGFB-/SMAD-dependent mechanism where KLF17 physically interacts with SMAD3 to target genes to prevent metastases [179]. MiR-9, a micro-RNA important for tumor invasion and metastasis, has been shown to inhibit the activation of KLF17 by directly binding to the 3′-untranslated region (3′-UTR) [175]. These pathways suggest that KLF17 can be regulated both by direct promoter activation and by posttranscriptional modifications such as RNA degradation by micro-RNAs.
\nIn converse, in endometrial cancer KLF17 was found to be an inducer of epithelial-to-mesenchymal transition and resulted in activation of TWIST1 [180]. This finding demonstrated that KLF17 bound directly to the TWIST promoter to activate its transcription [180]. KLF17 was also shown to bind directly to estrogen receptor alpha (ERα) to prevent it from being able to bind directly to chromatin [181]. ERα then also contributed to the suppression of KLF17 using the co-repressor histone deacetylase 1 (HDAC1) to promote KLF17 deacetylation and chromatin condensation [181].
\nKrüppel-like factor 18 (KLF18) was identified in 2013 from sequence similarity searches and gene synteny analyses and was shown at that time to be highly related to KLF17 [182]. Like KLF17, it is believed to be expressed in the developing testis and restricted to that area. Little data currently exists examining its function; however, a detailed analysis of its structure and phylogenic tree in placental mammals has been investigated in detail by Pei et al. [182]. This group also suggested that KLF18 might be a pseudogene of KLF17 since its expression pattern is restricted and it is similar in sequence to KLF17. Despite this hypothesis, three genes in mouse and rat were identified that closely resemble KLF18: Zfp352, Zfp352-like, and Zfp353 [182]. The promoter and/or details into the transcriptional activation of this KLF are currently unknown. A more detailed analysis of the functions and regulations of KLF18 would provide more insight into this transcription factor’s function.
\nOver the past 20 years since the discovery of the first KLF transcription factor, there continues to be a growing body of evidence to suggest that KLFs are important to tumor progression, cardiovascular disease, metabolism, and even circadian rhythm [1]. While much of the work has focused on the functions of these factors and their roles in various disease processes, there still remains additional needed work to explain how the various KLFs become activated and/or repressed during diseased states. There is a growing body of evidence, which we have attempted to discuss in some detail in this chapter, in the more extensively studied KLFs such as KLF4, KLF5, and KLF2 that suggest that the KLFs are regulated extensively by posttranslational modifications such as phosphorylation, acetylation, ubiquitination, and sumoylation. These modifications appear to be critical for co-factor recruitment and determination of whether KLFs interact with either activators or repressors of transcription. It has been interesting to see the wealth of information that has developed over the past 20 years investigating the roles of these various factors in various diseases; however, relatively speaking, we still know little about how these factors are activated and/or repressed transcriptionally during diseased states.
\nSince the onset of the era of big data, more of the KLF field has come to focus on the roles of pathway analysis following genetic ablation of a KLF in a cell-specific manner. These studies have yielded enormous amounts of data that offer valuable insight into the overlap between various KLF factors in diseases [183]. It will be of interest in the future to see how the integration of single-cell genomics will come into play with various different roles of the same KLF in various cell types in diseased states [184]. For example, the integration of single-cell RNA-Seq [184] with Assay for Transposase-Accessible Chromatin using sequencing (ATAC-Seq) [185, 186] in cells where a single KLF bear separate functions could offer deeper insight of the role of the niche environment on KLF function and/or on the roles of KLFs in downstream activations of different types of pathways during disease. Cardiovascular diseases have recently begun to investigate single-cell sequencing with other factors, such as Tcf21, and were able to use these innovative studies to investigate the role of this factor in smooth muscle cell to fibroblast transitions during atherosclerosis [184]. It will be exciting to see how KLF biology will use this technology to further investigate how these transcription factors regulate disease.
\nNot only will the integration of single-cell studies with KLF function give us greater insight into KLF function in development and disease, but the study of the role of RNA posttranscriptional modifications will most likely play an emerging role in the KLF field in the near future [184]. Since the sequencing of the human genome and the growing realization of the stronger role of RNA in transcriptional and translational control, there has been a re-emergence of interest in the field of RNA posttranscriptional modifications [187]. There are over 100 different types of RNA modifications of which the N6-methyladenosine (m6A) modification is the most common [187]. Interestingly, m6A has recently been shown to be concentrated in the 3′-UTR of many messenger RNAs and that micro-RNAs are capable of mediating this modification via a sequence pairing mechanism to help promote stem cell pluripotency [187, 188, 189, 190, 191, 192]. This new role for RNA modification and stem cell maintenance has immense implications for KLFs involved in induced pluripotent stem maintenance like KLF4. Therefore, it will be of interest to determine whether RNA modifications affect other disease processes by similar sequence pairing mechanisms.
\nIn conclusion, the KLF field has offered many insights to different disease processes since the discovery of the first KLF over the past 20 years. New insights into the regulation of these factors will hopefully grant novel methods to directly and properly target these factors to inhibit diseased states that currently have no medical treatment therapy. Perhaps the newly emerging CRISP technology will be able to directly target KLFs in a cell-specific manner as many KLFs have opposing functions in many different cell types. In any case, this transcription factor family has offered much excitement since its discovery and hopefully will offer new insights as the field studies these factors in more depth in the future.
\nThis work was supported by the AHA Scientist Development Grant 14SDG18730000 (MS). The content is solely the responsibility of the authors and does not necessarily represent the views of the AHA.
\nThe authors declare no conflict of interest.
We thank Anthony Herring and Cindy Dodson for their knowledge and technical expertise.
\n\n DNA methyltransferase 1 Ephrin receptor A5 Epithelial-to-mesenchymal transition Estrogen receptor Histone deacetylase Inhibitor of DNA binding 1 Interleukin-4 Interleukin-6 Nuclear Factor kappa-light-chain-enhancer of activated B cells Krüppel-like factor N6-methyladenosine Co-repressor complex used for repression Histone acetylase TP53 or tumor protein Subunit of NF-KB Subunit of NF-KB signaling p21CIP1, cyclin-dependent protein inhibitor Platelet-derived growth factor BB Phosphorylated RB Smooth muscle cells Proteins transduce signals from transforming growth factor beta Smooth muscle alpha actin Specificity proteins Transforming growth factor beta Tumor necrosis factor alpha TWIST1-protein Zinc finger transcription factor Zinc finger protein
Soybean (Glycine max [L.]) is a leguminous plant that can form a symbiotic relationship with the nitrogen-fixing group of bacteria living in the rhizosphere, which are generally termed as rhizobia. In the Philippines, soybean production has been limited by the poor grain yield which leads to the importation of more than 90% of the country’s demand. Thus, it is essential to look for an alternative way to increase the volume of production per unit area.
The research about tropical bradyrhizobia indicated a high diversity of species and their distribution has been reported to be due to several abiotic and biotic factors such as soil acidity [1, 2, 3], alkalinity [3, 4], temperature [1, 5, 6, 7, 8, 9, 10, 11], climate [12, 13], soil water status [14, 15], soil type [2, 14, 16, 17, 18], and soil management or cultural practices [2, 14, 19, 20, 21, 22]. In case of the Philippines, the pioneer research that was able to identify the most dominant species of bradyrhizobia in the country reported that B. elkanii species was the most abundant, followed by the B. diazoefficiens, B. japonicum, and some yet unclassified Bradyrhizobium sp. [14]. In this later study, it was identified that the distribution of these indigenous species of bradyrhizobia were influenced mainly by the water status of the soil, followed by soil pH, nutrient content, and soil type.
Previous studies have reported that aside from the various agro-environmental factors, the competition with the native rhizobia is a hindrance for a successful inoculation [23, 24]. The utilization of inoculants for legumes had shown promising results for the increase in grain yield as evidenced by recent reports [25, 26]. The role of the biological nitrogen fixation (BNF) in providing the N requirement of the plant in a natural way has been deemed necessary especially these times that the soil has become more degraded due to over-fertilization. The indiscriminate use of NPK fertilizer could cause soil pollution and less crop production [27]. Therefore, it is essential to select and evaluate the symbiotic competitiveness of the indigenous strains which are native and existing in high density in the country. The use of different genetic markers to accurately identify the rhizobia for taxonomic purposes has been proposed [28] and so we have used three genetic markers such as the 16S rRNA gene, 16S-23S rRNA gene internal transcribed spacer (ITS) region, and the rpoB housekeeping gene.
Thus, this study was formulated with the aim to utilize the recently identified indigenous bradyrhizobia in the Philippines and characterize their symbiotic performance with the local soybean cultivars.
The soil samples were collected from 11 locations in the Philippines, where some basic information on the sites are listed in Table 1. The collection of soil was conducted by first removing the surface litters then, obtaining a bar of soil with a dimension of approximately 20 cm in depth and 3 cm in thickness that weighs about 1 kg. A total of 10 subsamples per location were obtained and were mixed thoroughly until a 1 kg of composite soil sample was taken. A 0.5 kg soil was air-dried for the chemical analyses while the remaining 0.5 kg of the fresh soil was used for the soybean cultivation.
Result of the soil chemical analysis on the 11 locations in the Philippines.
Mason et al., 2018
This study
The cultivation of soybean was performed using a 1-L capacity culture pots (n = 3). Each pot was filled with vermiculite and a N-free solution [29] was added at 40% (vol/vol) water content. The culture pots were sterilized by autoclaving for 20 min at 121°C. Meanwhile, the soybean seeds were surface-sterilized by soaking into a 70% EtOh for 30 s, then by a diluted sodium hypochlorite solution (0.25% available chlorine) for 3 min and followed by washing with sterile distilled water for about 6–8 times. Then, a 2–3 g of soil sample was placed on the vermiculite at a depth of about 2–3 cm, the seeds were sown on the soil and the pot was weighed and recorded. The plants were grown inside a growth chamber for 28 days at 28°C (8 h, night) and 33°C (16 h, day) then were supplied weekly with sterile distilled water until the initial weight of the pot was reached.
After 28 days, approximately 20 random nodules were collected from the roots of each soybean plants and were sterilized with 70% EtOh and sodium hypochlorite solution as previously described [29]. Each nodule was homogenized with sterile distilled water in a microtube and streaked on to a yeast-extract mannitol agar (YMA) plate [30]. The YMA plate was incubated in the dark at 28°C for about 1 week until a single colony was formed. After then, the single colony was streaked on to a YMA plate containing a 0.002% (wt/wt) bromothymol blue (BTB) [31] and was incubated as above. Repeated streaking was done until a pure single colony was obtained which was cultured for about 3–4 days in a HEPES-MES (HM) broth culture [32, 33] at 28°C in a shaker for 120 rpm. After then, the bacteria cells were collected by centrifugation at 9000×g and washed with sterile distilled water. The DNA was extracted by using BL buffer as described [34] from the method reported by Hiraishi et al. [35].
For the amplification of the 16S rRNA gene, the primer set: 16S-F: 5′ AGAG TTTGATCCTGGCTCAG-3′ and 16S-R2: 5′- CGGCTACCTTGTTACGACTT-3′ [36]. The PCR tubes were then placed in the PCR Thermal Cycler (TaKaRa Co. Ltd.) with the following conditions: pre-run at 94°C for 5 min; followed by 30 cycles of denaturation at 94°C for 1 min, annealing at 55°C for 1 min, and extension at 72°C for 1 min. Final extension was set at 72°C for 10 min and indefinite preservation at 4°C.
On the other hand, the PCR amplification of the ITS region was conducted using the following primer set: Bra-ITS-F: 5-GACTGGGGTGAAGTCGTAAC-3′ and Bra-ITS-R1: 5′-ACGTCCTTCATCGCC TC-3′ [6]. The PCR cycle for the ITS region was almost the same with the 16S rRNA gene except for a shorter denaturation and annealing periods which were conducted at 30 s for each step.
For the rpoB gene, simplification was done using the following primer sets: rpoB83F: 5′-CCTSATCGAGGTTCAC AGAAGGC-3′ and rpoB1540R: 5′-AGCTGCGAGGAACCGAAG-3′ [37]. The PCR cycle conditions were as follows: pre-run at 94°C for 5 min; followed by 30 cycles of denaturation at 94°C for 30 s, annealing at 60°C for 1 min, and extension at 72°C for 1 min. Final extension was set at 72°C for 5 min and indefinite preservation at 4°C.
The successfully amplified products were subjected to the RFLP treatment using four restriction enzymes which were HhaI, HaeIII, MspI, and XspI. For the rpoB gene, the enzymes that were used for RFLP are HaeIII, MspI, and AluI. The reference strains that were used in this study are the Bradyrhizobium USDA strains (B. japonicum USDA 4, 6T, 38, 62, 115, 122, 123, 124, 125, 127, 129, 135, B. diazoefficiens USDA 110T, B. elkanii 31, 46, 61, 76T, 94, 130, and B. liaoningense 3622T) which were previously described [38]. This was done in a 10-μL reaction mixture containing a 2.5-μL amplified PCR product and was incubated in a 37°C for 16 h. Afterward, a 3–4% agarose gel was used in a submerged gel electrophoresis for about 60 min, stained with ethidium bromide and the patterns were visualized using a Luminiscent Image Analyzer LAS-4000 (FUJIFILM Tokyo, Japan).
After the amplification and the RFLP treatment of the 16S rRNA gene, a single-strain inoculation test was conducted for all the amplified isolates that shared the same restriction enzymes’ fragment patterns with the USDA Bradyrhizobium reference strains. This was done to confirm the strain’s capability to nodulate soybean and was tested on two local varieties which are the PSB-SY2 and Collection 1 which are both commercially available across the country.
The cultivation of soybean was conducted as described above, but without soil. Each isolate was cultured in a YM broth (YMB) [30] at 28°C for about 1 week on a shaker. After then, the cultures were diluted with sterile distilled water at about 106 cells mL−1 and were inoculated on the cultivated soybean at a rate of 1.0 mL per seed. This was done with three replications. After inoculation, the weight of the pot was recorded and it was placed inside a growth chamber with a condition set to mimic the average temperature in the Philippines at 26°C (8 h, night) and 33°C (16 h, day). The same condition was used for the cultivation of an uninoculated control and a positive control pot that was inoculated with B. diazoefficiens USDA110. The pots were kept inside the growth chamber for 28 days and were supplied weekly with sterile distilled water until the initial weight of each pot was reached.
According to the similarities of the band patterns through the RFLP treatment, a representative of the most abundant isolates was chosen for each location. In total, there were 11 isolates that were selected to confirm the nucleotide sequence of the 16S rRNA gene and the ITS region. The sequence primers that were used were reported previously [22]. From the PCR amplified product, the samples were purified according to the protocol of the manufacturer (Nucleospin® Gel and PCR Clean-up; Macherey-Nagel, Germany). Then, the samples were sent to the company for the sequence analysis (Eurofins Genomics, Tokyo, Japan).
Then, the Basic Local Alignment Search Tool (BLAST) program in DNA Databank of Japan (DDBJ) was used to determine the nucleotide homology of the isolates. Only the sequences with a similarity of at least 99% for the 16S rRNA and 96% for the ITS region with our isolates were retrieved from the BLAST database. The alignment was performed using the ClustalW and Neighbor-Joining [21] method was used to construct the phylogenetic trees. The genetic distances were computed using the Kimura 2-parameter model [39] in the Molecular Evolutionary Genetic Analysis (MEGA v7) software [40]. Subsequently, the phylogenetic trees were bootstrapped with 1000 replications. All the nucleotide sequences determined in this study were deposited in DDBJ at
The soil samples that were used in this study were all slightly to moderately acidic (5.22–6.64) with non-saline condition (0.05–0.20 dS/m), low nutrient status as evidenced by low amounts of NPK and CEC (Table 1). These values are generally typical of agricultural soils that are used for crop production all throughout the year. These results showed that the soils used in this study have low fertility status that indicated the need for soil restoration strategies.
The growth morphologies of the pure single colony for each strain of bradyrhizobia were characterized and listed in Table 2. All the isolates were slow growers which were able to form single colonies measuring about 2 mm between 5 and 7 days upon streaking on YMA plates and incubation in a dark room. Based on the morphology, the isolates were grouped into three. Group I include the isolates IS-2, NE1–6, NR-2, and BO-4 which were translucent and the colonies are circular in shape with slightly convex elevation and an entire margin. When they were manipulated with a needle, the colony was liquid. Group II include the isolates BA-24, SO-1, LT-3, and SK-5 were translucent with circular colonies, convex elevation with entire margin. When manipulated with a needle, the colonies have mucoid viscosity. On the other hand, last group (III) are the isolates GI-4 and NE2-37 which have similar growth morphology with Group II except that their viscosity was intermediate between liquid and mucoid. All the isolates produced alkaline substances when grown on YMA plate with BTB which is an indication of the Bradyrhizobium genus.
Characterization of the morphology of the indigenous bradyrhizobia isolated from Philippines’ soil according to their growth on Yeast-Extract Mannitol Agar plate medium [30].
As seen in Figure 1, it is evident that the 11 most abundant indigenous soybean rhizobia in the Philippines are classified under the genus Bradyrhizobium, and are separated into its two species, B. japonicum and B. elkanii, according to the phylogenetic tree from the sequence analysis of the 16S rRNA gene. To further confirm the classification of the indigenous bradyrhizobia, the phylogenetic trees constructed from the ITS region and the rpoB gene are presented in Figures 2 and 3, respectively. For the ITS region and the rpoB gene, the isolates were distinctly grouped into three species, B. elkanii, B. japonicum, and B. diazoefficiens. Additionally, an independent cluster composed of the representative isolates GI-4 and NE2–37 that are seen in the ITS region and rpoB phylogenetic trees were treated as Bradyrhizobium sp. due to their nucleotide divergence with the known species from the BLAST engine.
Phylogenetic tree based on the sequence analysis of the 16S rRNA gene. The tree was constructed using the Neighbor-Joining method with the Kimura 2-parameter (K2P) distance correlation model and 1000 bootstrap replications in MEGA v.7 software. The accession numbers are indicated only for sequences obtained from BLAST. The isolates in this study are indicated with letters and number combinations, for example: BO-4–isolate no. 4 collected from Bohol.
Phylogenetic tree based on the sequence analysis of the 16S-23S rRNA internal transcribed spacer (ITS) region. The tree was constructed using the Neighbor-Joining method with the Kimura 2-parameter (K2P) distance correlation model and 1000 bootstrap replications in MEGA v.7 software. The accession numbers are indicated only for sequences obtained from BLAST. The isolates in this study are indicated with letters and number combinations, for example: BO-4–isolate no. 4 collected from Bohol.
Phylogenetic tree based on the sequence analysis of the rpoB housekeeping gene. The tree was constructed using the Neighbor-Joining method with the Kimura 2-parameter (K2P) distance correlation model and 1000 bootstrap replications in MEGA v.7 software. The accession numbers are indicated only for sequences obtained from BLAST. The isolates in this study are indicated with letters and number combinations, for example: BO-4–isolate no.4 collected from Bohol.
Meanwhile, the distribution of the most abundant soybean bradyrhizobia in the country is shown in Table 3, which was classified according to the results of the sequence analysis of the three genetic markers used in this study. From here, it can be seen that 4 of the 11 locations were dominated with B. elkanii species (37.74%), 3 locations were dominated by the isolates under the B. diazoefficiens (28.54%), whereas 2 locations each were dominated by the species of B. japonicum (16.98% and Bradyrhizobium sp. (16.74%). This indicated that in the Philippines, the species of B. elkanii is the most prevalent in terms of population and the most widespread in terms of location as its presence was detected even in minor populations on all the locations except for one, which was Sorsogon.
Percentage distribution of the dominant Bradyrhizobium species in the Philippines as identified from the sequence analysis of the 16S rRNA gene, 16S-23S internal transcribed spacer (ITS) region, and rpoB housekeeping gene.
Upon classification, it is important to determine the capability of the indigenous bradyrhizobia for their symbiotic performance and N-fixation ability. As can be seen in Figure 4A, although USDA110 strain has the highest N-fixation ability, it should be noted that the amount of N that was fixed by B. elkanii IS-2 is the highest among all the indigenous bradyrhizobia isolated from the Philippines’ soil on Rj4 plants. However, the N-fixation ability of IS-2 was comparably similar with other strains (GI-4, NE2–37, and SK-5) with the non-Rj plants. The lowest N-fixation ability was observed from the strain LT-3 which was classified under the B. diazoefficiens species. This suggested that the process of biological N-fixation is a mutual relationship that is influenced by both the plant and the rhizobia and that the plant-rhizobia compatibility should be taken into consideration for inoculation strategies.
Characterization of the dominant indigenous Bradyrhizobium strains isolated from the 11 locations in the Philippines based on the (A) amount of Nitrogen fixed (B) nodulation ability and (C) symbiotic efficiency as influenced by the single-strain inoculation test against the reference strain B. diazoefficiens USDA110 for the two soybean cultivars from the Philippines. Different letters indicate a significant difference by Tukey’s test at p > 0.05, n=3, bar=SE.
Presented in Figure 4B is the nodulation test performed on the strains and it can be seen for Rj4 plants, there was not much significant difference in the nodulation ability of the strains, except for the low nodulation ability that was observed for the BO-4. In contrast, a significant difference in the nodulation ability was detected on the strains upon inoculation on the non-Rj plants. Although all the strains were able to form nodules on both soybean cultivars, the strains GI-4, NR-2, and SK-5 obtained the highest number of nodules for the non-Rj plants.
On the other hand, the symbiotic efficiency of the strains used in this study is presented in Figure 4C. Similar with the N-fixation ability, the USDA110 still possesses the highest symbiotic efficiency. But among all the indigenous bradyrhizobia, the strain IS-2 obtained the highest efficiency regardless of the Rj genotype of the soybean plants. As with the N-fixation, LT-3 obtained the least efficiency for symbiosis. This result indicated that the symbiotic efficiency of the rhizobia might not be directly influenced by the Rj genotype of the plant.
The distribution of the most dominant and abundant species of soybean bradyrhizobia in the Philippines are reported in this study along with the characterization of their growth morphology. According to our earlier reports, we have elucidated that the Philippines was dominated by the soybean-nodulating bradyrhizobia that were classified under the B. elkanii species and the most important agro-environmental factors that affected their diversity and prevalence in the country was the similarity of soil pH, salinity, and temperature in the study locations [5, 14]. Our observation that there are abundant and high diversity of indigenous bradyrhizobia in the Philippines is similar with previous reports in other sub-tropical and tropical regions [12, 25, 41, 42, 43, 44]. The temperate regions of Japan and USA were studied in the past and were reported to be dominated by species of B. japonicum and B. diazoefficiens [6, 9, 10, 11, 13, 45]. Our report showed that the distribution of bradyrhizobia in a tropical region like the Philippines seemed to be different from those of temperate regions.
Meanwhile, it was included in a recent report that the distribution and abundance of B. diazoefficiens and B. japonicum at specific locations were due to the longer period of flooding conditions [14]. The effect of nutrient content and soil type were also correlated with the abundance of these two species. In a report by Shiina et al. [17], it was stated that the predominance of B. diazoefficiens was observed on more anaerobic condition; whereas, B. japonicum was predominant on aerobic soils which was supported by another study [18]. Additionally, it was reported that B. diazoefficiens becomes predominant with enhanced flooding condition [15]. These results confirmed that our observations for the abundant of B. diazoefficiens, followed by B. japonicum and Bradyrhizobium sp. on flooded areas in the country which were usually used for planting rice.
In this report, the symbiotic performance, N-fixation and nodulation ability of the indigenous soybean bradyrhizobia form the Philippines were evaluated against that of the B. diazoefficiens USDA110 strain. The USDA110 has been extensively used in the world as a model strain for soybean inoculation due to its high ability for N-fixation and symbiotic efficiency [25, 46, 47]. Additionally, its possession of a complete set of denitrification genes that allows the release of N2 back into the atmosphere makes it an ideal strain also for climate change mitigation studies [17, 48, 49, 50].
Therefore, we hypothesized that the indigenous isolates SO-1, LT-3, and SK-5, which were phylogenetically clustered under the USDA110 would also prove to be as effective N-fixer and efficient microsymbiont of soybean cultivars from the Philippines. However, our results indicated that the N-fixation ability and symbiotic efficiency of LT-3 and SO-1 were very low in comparison to the other indigenous isolates. For the low performance of these two isolates, it is hypothesized that the inherent ability of these strains to fix N and establish a symbiotic relationship with soybean is low. This could be explained by the fact that their nodulation ability was comparably similar with the other strains which possess higher N-fixation ability and symbiotic efficiency. In contrast, the isolate IS-2, which was clustered under the B. elkanii species, showed the highest symbiotic efficiency for both Rj-genotypes of the soybean cultivar used and the highest N-fixation ability for Rj4 plants. In a previous report, the Rj genes that could restrict the nodulation of soybean by some strains of bradyrhizobia was summarized [51] but in case of our present report, all the strains in this study were not restricted by the two Rj-plants that were used. This led us to consider that the low N-fixation and symbiotic performance of some strains were not due to the restrictions from the Rj-genotypes of the plants but could be attributed to the strains’ intrinsic capabilities. These observations might explain the reason for low yield of soybean in the Philippines. It was reported that many strains of B. elkanii were relatively inefficient microsymbionts of soybean and can induce chlorosis in soybean plants [52]. In a previous report [53], the high temperatures in tropical regions can limit the nodulation which could explain the low soybean yield.
It was expected that the strains which were classified as B. diazoefficiens could provide a better symbiotic performance than the other strains that were collected. However, the data showed that B. elkanii might establish a better symbiosis with local soybean cultivars in the Philippines. This result is crucial in order to devise strategies on how to increase the local production of soybean by inoculation with the indigenous strains.
Upon considering these results with the N-fixation and symbiotic performance ability of the strains, the number of nodules that can be formed from the single-strain inoculation does not seem to influence the amount of N that each strain can fix nor their symbiotic ability.
In this report, we have revealed that the distribution of tropical soybean bradyrhizobia seemed to be different than those of temperate bradyrhizobia in terms of population dominance of B. elkanii on higher temperature region like the Philippines. Additionally, it is proposed that for the Philippines, the most efficient N-fixer and symbiotically efficient species of bradyrhizobia would be B. elkanii. Yet, our results were made under the laboratory conditions only, so the results that were obtained here might not be as expected when done in field condition. For future research, utilization of more local soybean varieties with different soil types both in a controlled environment and on natural field condition would be beneficial to target the development of a site-specific and useful potential soybean inoculant. The data generated in this report would be beneficial for the augmentation of inoculation strategies in the country.
The authors would like to acknowledge the contributions of John Philip Tanay, Emmanuel Victor Buniao, Mary Joy Portin, and Maria Leah Sevilla of Central Luzon State University for their help on some laboratory experiments. This work was supported by the JSPS Grant-in-Aid for Scientific Research (KAKENHI Grant Number: 18K05376).
The authors declare no conflict of interest.
IntechOpen implements a robust policy to minimize and deal with instances of fraud or misconduct. As part of our general commitment to transparency and openness, and in order to maintain high scientific standards, we have a well-defined editorial policy regarding Retractions and Corrections.
",metaTitle:"Retraction and Correction Policy",metaDescription:"Retraction and Correction Policy",metaKeywords:null,canonicalURL:"/page/retraction-and-correction-policy",contentRaw:'[{"type":"htmlEditorComponent","content":"IntechOpen’s Retraction and Correction Policy has been developed in accordance with the Committee on Publication Ethics (COPE) publication guidelines relating to scientific misconduct and research ethics:
\\n\\n1. RETRACTIONS
\\n\\nA Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
\\n\\nA formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
\\n\\nPublishing of a Retraction Notice will adhere to the following guidelines:
\\n\\n1.2. REMOVALS AND CANCELLATIONS
\\n\\n2. STATEMENTS OF CONCERN
\\n\\nA Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
\\n\\nIntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\\n\\n3. CORRECTIONS
\\n\\nA Correction will be issued by the Academic Editor when:
\\n\\n3.1. ERRATUM
\\n\\nAn Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
\\n\\nA published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\\n\\n3.2. CORRIGENDUM
\\n\\nA Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
\\n\\n4. FINAL REMARKS
\\n\\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\\n\\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\\n\\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
\\n\\nAny suggestions or comments on this Policy are welcome and may be sent to permissions@intechopen.com.
\\n\\nPolicy last updated: 2017-09-11
\\n"}]'},components:[{type:"htmlEditorComponent",content:'IntechOpen’s Retraction and Correction Policy has been developed in accordance with the Committee on Publication Ethics (COPE) publication guidelines relating to scientific misconduct and research ethics:
\n\n1. RETRACTIONS
\n\nA Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
\n\nA formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
\n\nPublishing of a Retraction Notice will adhere to the following guidelines:
\n\n1.2. REMOVALS AND CANCELLATIONS
\n\n2. STATEMENTS OF CONCERN
\n\nA Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
\n\nIntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\n\n3. CORRECTIONS
\n\nA Correction will be issued by the Academic Editor when:
\n\n3.1. ERRATUM
\n\nAn Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
\n\nA published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n3.2. CORRIGENDUM
\n\nA Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n4. FINAL REMARKS
\n\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\n\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\n\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
\n\nAny suggestions or comments on this Policy are welcome and may be sent to permissions@intechopen.com.
\n\nPolicy last updated: 2017-09-11
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. From 2004 to 2011, he was a Research Assistant with the Communications Engineering Department at the University of Málaga. In 2011, he became an Assistant Professor in the same department. From 2012 to 2015, he was with Ericsson Spain, where he was working on geo-location\ntools for third generation mobile networks. Since 2015, he is a Marie-Curie fellow at the Denmark Technical University. His current research interests include the areas of mobile communication systems and channel modeling in addition to atmospheric optical communications, adaptive optics and statistics",institutionString:null,institution:{name:"University of Malaga",country:{name:"Spain"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5681},{group:"region",caption:"Middle and South America",value:2,count:5161},{group:"region",caption:"Africa",value:3,count:1683},{group:"region",caption:"Asia",value:4,count:10200},{group:"region",caption:"Australia and Oceania",value:5,count:886},{group:"region",caption:"Europe",value:6,count:15610}],offset:12,limit:12,total:117095},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{sort:"dateEndThirdStepPublish",topicId:"25"},books:[{type:"book",id:"8737",title:"Rabies Virus",subtitle:null,isOpenForSubmission:!0,hash:"49cce3f548da548c718c865feb343509",slug:null,bookSignature:"Dr. Sergey Tkachev",coverURL:"https://cdn.intechopen.com/books/images_new/8737.jpg",editedByType:null,editors:[{id:"61139",title:"Dr.",name:"Sergey",surname:"Tkachev",slug:"sergey-tkachev",fullName:"Sergey Tkachev"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10830",title:"Animal Feed Science",subtitle:null,isOpenForSubmission:!0,hash:"b6091426454b1c484f4d38efc722d6dd",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10830.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10496",title:"Feed Additives in Animal Nutrition",subtitle:null,isOpenForSubmission:!0,hash:"8ffe43a82ac48b309abc3632bbf3efd0",slug:null,bookSignature:"Prof. László Babinszky",coverURL:"https://cdn.intechopen.com/books/images_new/10496.jpg",editedByType:null,editors:[{id:"53998",title:"Prof.",name:"László",surname:"Babinszky",slug:"laszlo-babinszky",fullName:"László Babinszky"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:9},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:17},{group:"topic",caption:"Business, Management and Economics",value:7,count:2},{group:"topic",caption:"Chemistry",value:8,count:7},{group:"topic",caption:"Computer and Information Science",value:9,count:10},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:5},{group:"topic",caption:"Engineering",value:11,count:15},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:5},{group:"topic",caption:"Materials Science",value:14,count:4},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:60},{group:"topic",caption:"Nanotechnology and Nanomaterials",value:17,count:1},{group:"topic",caption:"Neuroscience",value:18,count:1},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:6},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:3},{group:"topic",caption:"Robotics",value:22,count:1},{group:"topic",caption:"Social Sciences",value:23,count:3},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:2}],offset:12,limit:12,total:3},popularBooks:{featuredBooks:[{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7769",title:"Medical Isotopes",subtitle:null,isOpenForSubmission:!1,hash:"f8d3c5a6c9a42398e56b4e82264753f7",slug:"medical-isotopes",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9376",title:"Contemporary Developments and Perspectives in International Health Security",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"b9a00b84cd04aae458fb1d6c65795601",slug:"contemporary-developments-and-perspectives-in-international-health-security-volume-1",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, Sagar C. Galwankar, Ricardo Izurieta and Thomas Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/9376.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9279",title:"Concepts, Applications and Emerging Opportunities in Industrial Engineering",subtitle:null,isOpenForSubmission:!1,hash:"9bfa87f9b627a5468b7c1e30b0eea07a",slug:"concepts-applications-and-emerging-opportunities-in-industrial-engineering",bookSignature:"Gary Moynihan",coverURL:"https://cdn.intechopen.com/books/images_new/9279.jpg",editors:[{id:"16974",title:"Dr.",name:"Gary",middleName:null,surname:"Moynihan",slug:"gary-moynihan",fullName:"Gary Moynihan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7807",title:"A Closer Look at Organizational Culture in Action",subtitle:null,isOpenForSubmission:!1,hash:"05c608b9271cc2bc711f4b28748b247b",slug:"a-closer-look-at-organizational-culture-in-action",bookSignature:"Süleyman Davut Göker",coverURL:"https://cdn.intechopen.com/books/images_new/7807.jpg",editors:[{id:"190035",title:"Associate Prof.",name:"Süleyman Davut",middleName:null,surname:"Göker",slug:"suleyman-davut-goker",fullName:"Süleyman Davut Göker"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7796",title:"Human 4.0",subtitle:"From Biology to Cybernetic",isOpenForSubmission:!1,hash:"5ac5c052d3a593d5c4f4df66d005e5af",slug:"human-4-0-from-biology-to-cybernetic",bookSignature:"Yves Rybarczyk",coverURL:"https://cdn.intechopen.com/books/images_new/7796.jpg",editors:[{id:"72920",title:"Prof.",name:"Yves",middleName:"Philippe",surname:"Rybarczyk",slug:"yves-rybarczyk",fullName:"Yves Rybarczyk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9711",title:"Pests, Weeds and Diseases in Agricultural Crop and Animal Husbandry Production",subtitle:null,isOpenForSubmission:!1,hash:"12cf675f1e433135dd5bf5df7cec124f",slug:"pests-weeds-and-diseases-in-agricultural-crop-and-animal-husbandry-production",bookSignature:"Dimitrios Kontogiannatos, Anna Kourti and Kassio Ferreira Mendes",coverURL:"https://cdn.intechopen.com/books/images_new/9711.jpg",editors:[{id:"196691",title:"Dr.",name:"Dimitrios",middleName:null,surname:"Kontogiannatos",slug:"dimitrios-kontogiannatos",fullName:"Dimitrios Kontogiannatos"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10178",title:"Environmental Emissions",subtitle:null,isOpenForSubmission:!1,hash:"febf21ec717bfe20ae25a9dab9b5d438",slug:"environmental-emissions",bookSignature:"Richard Viskup",coverURL:"https://cdn.intechopen.com/books/images_new/10178.jpg",editors:[{id:"103742",title:"Dr.",name:"Richard",middleName:null,surname:"Viskup",slug:"richard-viskup",fullName:"Richard Viskup"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8511",title:"Cyberspace",subtitle:null,isOpenForSubmission:!1,hash:"8c1cdeb133dbe6cc1151367061c1bba6",slug:"cyberspace",bookSignature:"Evon Abu-Taieh, Abdelkrim El Mouatasim and Issam H. Al Hadid",coverURL:"https://cdn.intechopen.com/books/images_new/8511.jpg",editors:[{id:"223522",title:"Dr.",name:"Evon",middleName:"M.O.",surname:"Abu-Taieh",slug:"evon-abu-taieh",fullName:"Evon Abu-Taieh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9534",title:"Banking and Finance",subtitle:null,isOpenForSubmission:!1,hash:"af14229738af402c3b595d7e124dce82",slug:"banking-and-finance",bookSignature:"Razali Haron, Maizaitulaidawati Md Husin and Michael Murg",coverURL:"https://cdn.intechopen.com/books/images_new/9534.jpg",editors:[{id:"206517",title:"Prof.",name:"Razali",middleName:null,surname:"Haron",slug:"razali-haron",fullName:"Razali Haron"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"2160",title:"MATLAB",subtitle:"A Fundamental Tool for Scientific Computing and Engineering Applications - Volume 1",isOpenForSubmission:!1,hash:"dd9c658341fbd264ed4f8d9e6aa8ca29",slug:"matlab-a-fundamental-tool-for-scientific-computing-and-engineering-applications-volume-1",bookSignature:"Vasilios N. Katsikis",coverURL:"https://cdn.intechopen.com/books/images_new/2160.jpg",editors:[{id:"12289",title:"Prof.",name:"Vasilios",middleName:"N.",surname:"Katsikis",slug:"vasilios-katsikis",fullName:"Vasilios Katsikis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5126},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7769",title:"Medical Isotopes",subtitle:null,isOpenForSubmission:!1,hash:"f8d3c5a6c9a42398e56b4e82264753f7",slug:"medical-isotopes",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9376",title:"Contemporary Developments and Perspectives in International Health Security",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"b9a00b84cd04aae458fb1d6c65795601",slug:"contemporary-developments-and-perspectives-in-international-health-security-volume-1",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, Sagar C. Galwankar, Ricardo Izurieta and Thomas Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/9376.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9279",title:"Concepts, Applications and Emerging Opportunities in Industrial Engineering",subtitle:null,isOpenForSubmission:!1,hash:"9bfa87f9b627a5468b7c1e30b0eea07a",slug:"concepts-applications-and-emerging-opportunities-in-industrial-engineering",bookSignature:"Gary Moynihan",coverURL:"https://cdn.intechopen.com/books/images_new/9279.jpg",editors:[{id:"16974",title:"Dr.",name:"Gary",middleName:null,surname:"Moynihan",slug:"gary-moynihan",fullName:"Gary Moynihan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7807",title:"A Closer Look at Organizational Culture in Action",subtitle:null,isOpenForSubmission:!1,hash:"05c608b9271cc2bc711f4b28748b247b",slug:"a-closer-look-at-organizational-culture-in-action",bookSignature:"Süleyman Davut Göker",coverURL:"https://cdn.intechopen.com/books/images_new/7807.jpg",editors:[{id:"190035",title:"Associate Prof.",name:"Süleyman Davut",middleName:null,surname:"Göker",slug:"suleyman-davut-goker",fullName:"Süleyman Davut Göker"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7796",title:"Human 4.0",subtitle:"From Biology to Cybernetic",isOpenForSubmission:!1,hash:"5ac5c052d3a593d5c4f4df66d005e5af",slug:"human-4-0-from-biology-to-cybernetic",bookSignature:"Yves Rybarczyk",coverURL:"https://cdn.intechopen.com/books/images_new/7796.jpg",editors:[{id:"72920",title:"Prof.",name:"Yves",middleName:"Philippe",surname:"Rybarczyk",slug:"yves-rybarczyk",fullName:"Yves Rybarczyk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9711",title:"Pests, Weeds and Diseases in Agricultural Crop and Animal Husbandry Production",subtitle:null,isOpenForSubmission:!1,hash:"12cf675f1e433135dd5bf5df7cec124f",slug:"pests-weeds-and-diseases-in-agricultural-crop-and-animal-husbandry-production",bookSignature:"Dimitrios Kontogiannatos, Anna Kourti and Kassio Ferreira Mendes",coverURL:"https://cdn.intechopen.com/books/images_new/9711.jpg",editors:[{id:"196691",title:"Dr.",name:"Dimitrios",middleName:null,surname:"Kontogiannatos",slug:"dimitrios-kontogiannatos",fullName:"Dimitrios Kontogiannatos"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10178",title:"Environmental Emissions",subtitle:null,isOpenForSubmission:!1,hash:"febf21ec717bfe20ae25a9dab9b5d438",slug:"environmental-emissions",bookSignature:"Richard Viskup",coverURL:"https://cdn.intechopen.com/books/images_new/10178.jpg",editors:[{id:"103742",title:"Dr.",name:"Richard",middleName:null,surname:"Viskup",slug:"richard-viskup",fullName:"Richard Viskup"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8511",title:"Cyberspace",subtitle:null,isOpenForSubmission:!1,hash:"8c1cdeb133dbe6cc1151367061c1bba6",slug:"cyberspace",bookSignature:"Evon Abu-Taieh, Abdelkrim El Mouatasim and Issam H. Al Hadid",coverURL:"https://cdn.intechopen.com/books/images_new/8511.jpg",editors:[{id:"223522",title:"Dr.",name:"Evon",middleName:"M.O.",surname:"Abu-Taieh",slug:"evon-abu-taieh",fullName:"Evon Abu-Taieh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"8468",title:"Sheep Farming",subtitle:"An Approach to Feed, Growth and Sanity",isOpenForSubmission:!1,hash:"838f08594850bc04aa14ec873ed1b96f",slug:"sheep-farming-an-approach-to-feed-growth-and-sanity",bookSignature:"António Monteiro",coverURL:"https://cdn.intechopen.com/books/images_new/8468.jpg",editedByType:"Edited by",editors:[{id:"190314",title:"Prof.",name:"António",middleName:"Cardoso",surname:"Monteiro",slug:"antonio-monteiro",fullName:"António Monteiro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9523",title:"Oral and Maxillofacial Surgery",subtitle:null,isOpenForSubmission:!1,hash:"5eb6ec2db961a6c8965d11180a58d5c1",slug:"oral-and-maxillofacial-surgery",bookSignature:"Gokul Sridharan",coverURL:"https://cdn.intechopen.com/books/images_new/9523.jpg",editedByType:"Edited by",editors:[{id:"82453",title:"Dr.",name:"Gokul",middleName:null,surname:"Sridharan",slug:"gokul-sridharan",fullName:"Gokul Sridharan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editedByType:"Edited by",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9018",title:"Some RNA Viruses",subtitle:null,isOpenForSubmission:!1,hash:"a5cae846dbe3692495fc4add2f60fd84",slug:"some-rna-viruses",bookSignature:"Yogendra Shah and Eltayb Abuelzein",coverURL:"https://cdn.intechopen.com/books/images_new/9018.jpg",editedByType:"Edited by",editors:[{id:"278914",title:"Ph.D.",name:"Yogendra",middleName:null,surname:"Shah",slug:"yogendra-shah",fullName:"Yogendra Shah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8816",title:"Financial Crises",subtitle:"A Selection of Readings",isOpenForSubmission:!1,hash:"6f2f49fb903656e4e54280c79fabd10c",slug:"financial-crises-a-selection-of-readings",bookSignature:"Stelios Markoulis",coverURL:"https://cdn.intechopen.com/books/images_new/8816.jpg",editedByType:"Edited by",editors:[{id:"237863",title:"Dr.",name:"Stelios",middleName:null,surname:"Markoulis",slug:"stelios-markoulis",fullName:"Stelios Markoulis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9585",title:"Advances in Complex Valvular Disease",subtitle:null,isOpenForSubmission:!1,hash:"ef64f11e211621ecfe69c46e60e7ca3d",slug:"advances-in-complex-valvular-disease",bookSignature:"Michael S. Firstenberg and Imran Khan",coverURL:"https://cdn.intechopen.com/books/images_new/9585.jpg",editedByType:"Edited by",editors:[{id:"64343",title:null,name:"Michael S.",middleName:"S",surname:"Firstenberg",slug:"michael-s.-firstenberg",fullName:"Michael S. Firstenberg"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10150",title:"Smart Manufacturing",subtitle:"When Artificial Intelligence Meets the Internet of Things",isOpenForSubmission:!1,hash:"87004a19de13702d042f8ff96d454698",slug:"smart-manufacturing-when-artificial-intelligence-meets-the-internet-of-things",bookSignature:"Tan Yen Kheng",coverURL:"https://cdn.intechopen.com/books/images_new/10150.jpg",editedByType:"Edited by",editors:[{id:"78857",title:"Dr.",name:"Tan Yen",middleName:null,surname:"Kheng",slug:"tan-yen-kheng",fullName:"Tan Yen Kheng"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9386",title:"Direct Numerical Simulations",subtitle:"An Introduction and Applications",isOpenForSubmission:!1,hash:"158a3a0fdba295d21ff23326f5a072d5",slug:"direct-numerical-simulations-an-introduction-and-applications",bookSignature:"Srinivasa Rao",coverURL:"https://cdn.intechopen.com/books/images_new/9386.jpg",editedByType:"Edited by",editors:[{id:"6897",title:"Dr.",name:"Srinivasa",middleName:"P",surname:"Rao",slug:"srinivasa-rao",fullName:"Srinivasa Rao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editedByType:"Edited by",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editedByType:"Edited by",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"52",title:"Genetic Epidemiology",slug:"genetic-epidemiology",parent:{title:"Biochemistry, Genetics and Molecular Biology",slug:"biochemistry-genetics-and-molecular-biology"},numberOfBooks:1,numberOfAuthorsAndEditors:22,numberOfWosCitations:26,numberOfCrossrefCitations:13,numberOfDimensionsCitations:45,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"genetic-epidemiology",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"2556",title:"Methylation",subtitle:"From DNA, RNA and Histones to Diseases and Treatment",isOpenForSubmission:!1,hash:"ab598a9444e1ee2f8ad04109f1cb898d",slug:"methylation-from-dna-rna-and-histones-to-diseases-and-treatment",bookSignature:"Anica Dricu",coverURL:"https://cdn.intechopen.com/books/images_new/2556.jpg",editedByType:"Edited by",editors:[{id:"106758",title:"Prof.",name:"Anica",middleName:null,surname:"Dricu",slug:"anica-dricu",fullName:"Anica Dricu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:1,mostCitedChapters:[{id:"38950",doi:"10.5772/51774",title:"The Methylation of Metals and Metalloids in Aquatic Systems",slug:"the-methylation-of-metals-and-metalloids-in-aquatic-systems",totalDownloads:2019,totalCrossrefCites:4,totalDimensionsCites:11,book:{slug:"methylation-from-dna-rna-and-histones-to-diseases-and-treatment",title:"Methylation",fullTitle:"Methylation - From DNA, RNA and Histones to Diseases and Treatment"},signatures:"Robert P. Mason",authors:[{id:"152418",title:"Dr.",name:"Robert",middleName:"Peter",surname:"Mason",slug:"robert-mason",fullName:"Robert Mason"}]},{id:"38530",doi:"10.5772/51691",title:"Host-Mimicking Strategies in DNA Methylation for Improved Bacterial Transformation",slug:"host-mimicking-strategies-in-dna-methylation-for-improved-bacterial-transformation",totalDownloads:2064,totalCrossrefCites:4,totalDimensionsCites:10,book:{slug:"methylation-from-dna-rna-and-histones-to-diseases-and-treatment",title:"Methylation",fullTitle:"Methylation - From DNA, RNA and Histones to Diseases and Treatment"},signatures:"Hirokazu Suzuki",authors:[{id:"152236",title:"Ph.D.",name:"Hirokazu",middleName:null,surname:"Suzuki",slug:"hirokazu-suzuki",fullName:"Hirokazu Suzuki"}]},{id:"38575",doi:"10.5772/51419",title:"Circulating Methylated DNA as Biomarkers for Cancer Detection",slug:"circulating-methylated-dna-as-biomarkers-for-cancer-detection",totalDownloads:3086,totalCrossrefCites:0,totalDimensionsCites:7,book:{slug:"methylation-from-dna-rna-and-histones-to-diseases-and-treatment",title:"Methylation",fullTitle:"Methylation - From DNA, RNA and Histones to Diseases and Treatment"},signatures:"Hongchuan Jin, Yanning Ma, Qi Shen and Xian Wang",authors:[{id:"40131",title:"Dr.",name:"Xian",middleName:null,surname:"Wang",slug:"xian-wang",fullName:"Xian Wang"},{id:"163999",title:"Prof.",name:"Hongchuan",middleName:null,surname:"Jin",slug:"hongchuan-jin",fullName:"Hongchuan Jin"}]}],mostDownloadedChaptersLast30Days:[{id:"38575",title:"Circulating Methylated DNA as Biomarkers for Cancer Detection",slug:"circulating-methylated-dna-as-biomarkers-for-cancer-detection",totalDownloads:3086,totalCrossrefCites:0,totalDimensionsCites:7,book:{slug:"methylation-from-dna-rna-and-histones-to-diseases-and-treatment",title:"Methylation",fullTitle:"Methylation - From DNA, RNA and Histones to Diseases and Treatment"},signatures:"Hongchuan Jin, Yanning Ma, Qi Shen and Xian Wang",authors:[{id:"40131",title:"Dr.",name:"Xian",middleName:null,surname:"Wang",slug:"xian-wang",fullName:"Xian Wang"},{id:"163999",title:"Prof.",name:"Hongchuan",middleName:null,surname:"Jin",slug:"hongchuan-jin",fullName:"Hongchuan Jin"}]},{id:"38950",title:"The Methylation of Metals and Metalloids in Aquatic Systems",slug:"the-methylation-of-metals-and-metalloids-in-aquatic-systems",totalDownloads:2019,totalCrossrefCites:4,totalDimensionsCites:11,book:{slug:"methylation-from-dna-rna-and-histones-to-diseases-and-treatment",title:"Methylation",fullTitle:"Methylation - From DNA, RNA and Histones to Diseases and Treatment"},signatures:"Robert P. Mason",authors:[{id:"152418",title:"Dr.",name:"Robert",middleName:"Peter",surname:"Mason",slug:"robert-mason",fullName:"Robert Mason"}]},{id:"38180",title:"Bifunctional Prokaryotic DNA-Methyltransferases",slug:"bifunctional-prokaryotic-dna-methyltransferases",totalDownloads:1450,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"methylation-from-dna-rna-and-histones-to-diseases-and-treatment",title:"Methylation",fullTitle:"Methylation - From DNA, RNA and Histones to Diseases and Treatment"},signatures:"Dmitry V. Nikitin, Attila Kertesz-Farkas, Alexander S. Solonin and Marina L. Mokrishcheva",authors:[{id:"151694",title:"Dr.",name:"Dmitri",middleName:null,surname:"Nikitin",slug:"dmitri-nikitin",fullName:"Dmitri Nikitin"},{id:"152806",title:"Dr.",name:"Attila",middleName:null,surname:"Kertesz-Farkas2",slug:"attila-kertesz-farkas2",fullName:"Attila Kertesz-Farkas2"},{id:"152807",title:"Dr.",name:"Alexander",middleName:null,surname:"Solonin",slug:"alexander-solonin",fullName:"Alexander Solonin"},{id:"152808",title:"Dr.",name:"Marina",middleName:null,surname:"Mokrishcheva",slug:"marina-mokrishcheva",fullName:"Marina Mokrishcheva"}]},{id:"38530",title:"Host-Mimicking Strategies in DNA Methylation for Improved Bacterial Transformation",slug:"host-mimicking-strategies-in-dna-methylation-for-improved-bacterial-transformation",totalDownloads:2064,totalCrossrefCites:4,totalDimensionsCites:10,book:{slug:"methylation-from-dna-rna-and-histones-to-diseases-and-treatment",title:"Methylation",fullTitle:"Methylation - From DNA, RNA and Histones to Diseases and Treatment"},signatures:"Hirokazu Suzuki",authors:[{id:"152236",title:"Ph.D.",name:"Hirokazu",middleName:null,surname:"Suzuki",slug:"hirokazu-suzuki",fullName:"Hirokazu Suzuki"}]},{id:"41211",title:"Messenger RNA Cap Methylation in Vesicular Stomatitis Virus, a Prototype of Non‐Segmented Negative‐Sense RNA Virus",slug:"messenger-rna-cap-methylation-in-vesicular-stomatitis-virus-a-prototype-of-non-segmented-negative-se",totalDownloads:2801,totalCrossrefCites:2,totalDimensionsCites:2,book:{slug:"methylation-from-dna-rna-and-histones-to-diseases-and-treatment",title:"Methylation",fullTitle:"Methylation - From DNA, RNA and Histones to Diseases and Treatment"},signatures:"Jianrong Li and Yu Zhang",authors:[{id:"153206",title:"Dr.",name:"Jianrong",middleName:null,surname:"Li",slug:"jianrong-li",fullName:"Jianrong Li"}]},{id:"40284",title:"Deciphering Protein Arginine Methylation in Mammals",slug:"deciphering-protein-arginine-methylation-in-mammals",totalDownloads:2114,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"methylation-from-dna-rna-and-histones-to-diseases-and-treatment",title:"Methylation",fullTitle:"Methylation - From DNA, RNA and Histones to Diseases and Treatment"},signatures:"Ruben Esse, Paula Leandro, Isabel Rivera, Isabel Tavares de Almeida, Henk J Blom and Rita Castro",authors:[{id:"151778",title:"Prof.",name:"Rita",middleName:null,surname:"Castro",slug:"rita-castro",fullName:"Rita Castro"}]},{id:"39269",title:"DNA Methylation in the Pathogenesis of Head and Neck Cancer",slug:"dna-methylation-in-the-pathogenesis-of-head-and-neck-cancer",totalDownloads:2169,totalCrossrefCites:1,totalDimensionsCites:4,book:{slug:"methylation-from-dna-rna-and-histones-to-diseases-and-treatment",title:"Methylation",fullTitle:"Methylation - From DNA, RNA and Histones to Diseases and Treatment"},signatures:"Zvonko Magić, Gordana Supić, Mirjana Branković-Magić and Nebojša Jovic",authors:[{id:"40933",title:"Dr.",name:"Gordana",middleName:null,surname:"Supic",slug:"gordana-supic",fullName:"Gordana Supic"},{id:"153134",title:"Prof.",name:"Zvonko",middleName:null,surname:"Magic",slug:"zvonko-magic",fullName:"Zvonko Magic"},{id:"162918",title:"Prof.",name:"Nebojsa",middleName:null,surname:"Jovic",slug:"nebojsa-jovic",fullName:"Nebojsa Jovic"},{id:"162919",title:"Dr.",name:"Mirjana",middleName:null,surname:"Brankovic-Magic",slug:"mirjana-brankovic-magic",fullName:"Mirjana Brankovic-Magic"}]},{id:"41250",title:"Breaking the Silence: The Interplay Between Transcription Factors and DNA Methylation",slug:"breaking-the-silence-the-interplay-between-transcription-factors-and-dna-methylation",totalDownloads:2570,totalCrossrefCites:2,totalDimensionsCites:5,book:{slug:"methylation-from-dna-rna-and-histones-to-diseases-and-treatment",title:"Methylation",fullTitle:"Methylation - From DNA, RNA and Histones to Diseases and Treatment"},signatures:"Byron Baron",authors:[{id:"100140",title:"Dr.",name:"Byron",middleName:null,surname:"Baron",slug:"byron-baron",fullName:"Byron Baron"}]},{id:"41225",title:"Diverse Domains of (Cytosine-5)-DNA Methyltransferases: Structural and Functional Characterization",slug:"diverse-domains-of-cytosine-5-dna-methyltransferases-structural-and-functional-characterization",totalDownloads:2372,totalCrossrefCites:0,totalDimensionsCites:5,book:{slug:"methylation-from-dna-rna-and-histones-to-diseases-and-treatment",title:"Methylation",fullTitle:"Methylation - From DNA, RNA and Histones to Diseases and Treatment"},signatures:"A. Yu. Ryazanova, L. A. Abrosimova, T. S. Oretskaya and E. A. Kubareva",authors:[{id:"152990",title:"Prof.",name:"Elena",middleName:null,surname:"Kubareva",slug:"elena-kubareva",fullName:"Elena Kubareva"},{id:"153059",title:"Dr.",name:"Alexandra",middleName:null,surname:"Ryazanova",slug:"alexandra-ryazanova",fullName:"Alexandra Ryazanova"},{id:"153060",title:"Ms.",name:"Liudmila",middleName:null,surname:"Abrosimova",slug:"liudmila-abrosimova",fullName:"Liudmila Abrosimova"},{id:"153063",title:"Prof.",name:"Tatiana",middleName:null,surname:"Oretskaya",slug:"tatiana-oretskaya",fullName:"Tatiana Oretskaya"}]},{id:"41210",title:"DNA Methylation, Stem Cells and Cancer",slug:"dna-methylation-stem-cells-and-cancer",totalDownloads:1875,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"methylation-from-dna-rna-and-histones-to-diseases-and-treatment",title:"Methylation",fullTitle:"Methylation - From DNA, RNA and Histones to Diseases and Treatment"},signatures:"Anica Dricu, Stefana Oana Purcaru, Alice Sandra Buteica, Daniela Elise Tache, Oana Daianu, Bogdan Stoleru, Amelia Mihaela Dobrescu, Tiberiu Daianu and Ligia Gabriela Tataranu",authors:[{id:"106758",title:"Prof.",name:"Anica",middleName:null,surname:"Dricu",slug:"anica-dricu",fullName:"Anica Dricu"}]}],onlineFirstChaptersFilter:{topicSlug:"genetic-epidemiology",limit:3,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"10176",title:"Microgrids and Local Energy Systems",subtitle:null,isOpenForSubmission:!0,hash:"c32b4a5351a88f263074b0d0ca813a9c",slug:null,bookSignature:"Prof. Nick Jenkins",coverURL:"https://cdn.intechopen.com/books/images_new/10176.jpg",editedByType:null,editors:[{id:"55219",title:"Prof.",name:"Nick",middleName:null,surname:"Jenkins",slug:"nick-jenkins",fullName:"Nick Jenkins"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:1},route:{name:"profile.detail",path:"/profiles/114983/katrina-wendel",hash:"",query:{},params:{id:"114983",slug:"katrina-wendel"},fullPath:"/profiles/114983/katrina-wendel",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()