Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\n
We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
IntechOpen is proud to announce that 179 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\n
Throughout the years, the list has named a total of 252 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\n
We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
\n'}],latestNews:[{slug:"stanford-university-identifies-top-2-scientists-over-1-000-are-intechopen-authors-and-editors-20210122",title:"Stanford University Identifies Top 2% Scientists, Over 1,000 are IntechOpen Authors and Editors"},{slug:"intechopen-authors-included-in-the-highly-cited-researchers-list-for-2020-20210121",title:"IntechOpen Authors Included in the Highly Cited Researchers List for 2020"},{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"}]},book:{item:{type:"book",id:"9415",leadTitle:null,fullTitle:"Advanced Oxidation Processes - Applications, Trends, and Prospects",title:"Advanced Oxidation Processes",subtitle:"Applications, Trends, and Prospects",reviewType:"peer-reviewed",abstract:"Advanced Oxidation Processes – Applications, Trends, and Prospects constitutes a comprehensive resource for civil, chemical, and environmental engineers researching in the field of water and wastewater treatment. The book covers the fundamentals, applications, and future work in Advanced Oxidation Processes (AOPs) as an attractive alternative and a complementary treatment option to conventional methods. This book also presents state-of-the-art research on AOPs and heterogeneous catalysis while covering recent progress and trends, including the application of AOPs at the laboratory, pilot, or industrial scale, the combination of AOPs with other technologies, hybrid processes, process intensification, reactor design, scale-up, and optimization. The book is divided into four sections: Introduction to Advanced Oxidation Processes, General Concepts of Heterogeneous Catalysis, Fenton and Ferrate in Wastewater Treatment, and Industrial Applications, Trends, and Prospects.",isbn:"978-1-78984-891-5",printIsbn:"978-1-78984-890-8",pdfIsbn:"978-1-83880-971-3",doi:"10.5772/intechopen.85681",price:119,priceEur:129,priceUsd:155,slug:"advanced-oxidation-processes-applications-trends-and-prospects",numberOfPages:182,isOpenForSubmission:!1,isInWos:1,hash:"60d177837fbb691b82c80922cd9bb295",bookSignature:"Ciro Bustillo-Lecompte",publishedDate:"June 10th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/9415.jpg",numberOfDownloads:2955,numberOfWosCitations:4,numberOfCrossrefCitations:2,numberOfDimensionsCitations:12,hasAltmetrics:1,numberOfTotalCitations:18,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 6th 2019",dateEndSecondStepPublish:"June 27th 2019",dateEndThirdStepPublish:"August 26th 2019",dateEndFourthStepPublish:"November 14th 2019",dateEndFifthStepPublish:"January 13th 2020",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!0,editors:[{id:"189304",title:"Dr.",name:"Ciro",middleName:"Fernando",surname:"Bustillo-Lecompte",slug:"ciro-bustillo-lecompte",fullName:"Ciro Bustillo-Lecompte",profilePictureURL:"https://mts.intechopen.com/storage/users/189304/images/system/189304.jpeg",biography:"Dr. Ciro Bustillo LeCompte has a multidisciplinary background\nin the areas of civil, environmental, and chemical engineering.\nHe completed his Bachelor of Engineering (2008) at the University of Cartagena, Colombia, and obtained his MASc (2012)\nand PhD (2016) at Ryerson University, Canada. Dr. LeCompte\nis a certified Professional Engineer (PEng), Environmental\nProfessional (EP), a Fraternal Member of the Canadian Institute\nof Public Health Inspectors (CIPHI), and a 2017-2018 Queen Elizabeth Scholar\n(QES). He is currently an Associate Member in the Environmental Applied Science\nand Management Graduate Programs, and a Lecturer in the School of Occupational\nand Public Health at Ryerson University. He has co-authored over twenty peer-reviewed scientific papers, several conference proceedings, chapters, and books. His\nresearch interests include advanced oxidation processes, advanced treatment of\nwater and wastewater, waste minimization, water, soil and air quality, energy and\nresource recovery, water reuse, and heterogeneous catalysis.",institutionString:"Ryerson University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Ryerson University",institutionURL:null,country:{name:"Canada"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1354",title:"Wastewater Engineering",slug:"technology-environmental-engineering-wastewater-engineering"}],chapters:[{id:"70086",title:"Advanced Oxidation Processes: A Powerful Treatment Option for the Removal of Recalcitrant Organic Compounds",doi:"10.5772/intechopen.90192",slug:"advanced-oxidation-processes-a-powerful-treatment-option-for-the-removal-of-recalcitrant-organic-com",totalDownloads:564,totalCrossrefCites:2,totalDimensionsCites:3,signatures:"Damodhar Ghime and Prabir Ghosh",downloadPdfUrl:"/chapter/pdf-download/70086",previewPdfUrl:"/chapter/pdf-preview/70086",authors:[{id:"251470",title:"Dr.",name:"Prabir",surname:"Ghosh",slug:"prabir-ghosh",fullName:"Prabir Ghosh"},{id:"312650",title:"Mr.",name:"Damodhar",surname:"Ghime",slug:"damodhar-ghime",fullName:"Damodhar Ghime"}],corrections:null},{id:"70440",title:"Heterogeneous Catalytic Process for Wastewater Treatment",doi:"10.5772/intechopen.90393",slug:"heterogeneous-catalytic-process-for-wastewater-treatment",totalDownloads:312,totalCrossrefCites:0,totalDimensionsCites:1,signatures:"Ting Zhang",downloadPdfUrl:"/chapter/pdf-download/70440",previewPdfUrl:"/chapter/pdf-preview/70440",authors:[{id:"308235",title:"Dr.",name:"Ting",surname:"Zhang",slug:"ting-zhang",fullName:"Ting Zhang"}],corrections:null},{id:"71660",title:"Applications of Chemical Kinetics in Heterogeneous Catalysis",doi:"10.5772/intechopen.91939",slug:"applications-of-chemical-kinetics-in-heterogeneous-catalysis",totalDownloads:302,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Zhenhua Zhang, Li-Ping Fan and Yue-Juan Wang",downloadPdfUrl:"/chapter/pdf-download/71660",previewPdfUrl:"/chapter/pdf-preview/71660",authors:[{id:"312555",title:"Prof.",name:"Zhenhua",surname:"Zhang",slug:"zhenhua-zhang",fullName:"Zhenhua Zhang"},{id:"316868",title:"Ms.",name:"Li-Ping",surname:"Fan",slug:"li-ping-fan",fullName:"Li-Ping Fan"},{id:"316869",title:"Prof.",name:"Yue-Juan",surname:"Wang",slug:"yue-juan-wang",fullName:"Yue-Juan Wang"}],corrections:null},{id:"70242",title:"Advancements in the Fenton Process for Wastewater Treatment",doi:"10.5772/intechopen.90256",slug:"advancements-in-the-fenton-process-for-wastewater-treatment",totalDownloads:695,totalCrossrefCites:0,totalDimensionsCites:7,signatures:"Min Xu, Changyong Wu and Yuexi Zhou",downloadPdfUrl:"/chapter/pdf-download/70242",previewPdfUrl:"/chapter/pdf-preview/70242",authors:[{id:"307479",title:"Prof.",name:"Changyong",surname:"Wu",slug:"changyong-wu",fullName:"Changyong Wu"},{id:"307546",title:"Prof.",name:"Yuexi",surname:"Zhou",slug:"yuexi-zhou",fullName:"Yuexi Zhou"},{id:"311139",title:"Dr.",name:"Min",surname:"Xu",slug:"min-xu",fullName:"Min Xu"}],corrections:null},{id:"70285",title:"Application of Ferrate for Advanced Water and Wastewater Treatment",doi:"10.5772/intechopen.90231",slug:"application-of-ferrate-for-advanced-water-and-wastewater-treatment",totalDownloads:317,totalCrossrefCites:0,totalDimensionsCites:1,signatures:"Ansaf V. Karim, Sukanya Krishnan, Lakshmi Pisharody and Milan Malhotra",downloadPdfUrl:"/chapter/pdf-download/70285",previewPdfUrl:"/chapter/pdf-preview/70285",authors:[{id:"310802",title:"Ph.D.",name:"Milan",surname:"Malhotra",slug:"milan-malhotra",fullName:"Milan Malhotra"},{id:"312701",title:"Mr.",name:"Ansaf V",surname:"Karim",slug:"ansaf-v-karim",fullName:"Ansaf V Karim"},{id:"312732",title:"Ms.",name:"Lakshmi",surname:"Pisharody",slug:"lakshmi-pisharody",fullName:"Lakshmi Pisharody"},{id:"312733",title:"Ms.",name:"Sukanya",surname:"Krishnan",slug:"sukanya-krishnan",fullName:"Sukanya Krishnan"}],corrections:null},{id:"72151",title:"Application of Advanced Oxidation Process in the Food Industry",doi:"10.5772/intechopen.92355",slug:"application-of-advanced-oxidation-process-in-the-food-industry",totalDownloads:213,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Zhaoran Xin and Lars Rehmann",downloadPdfUrl:"/chapter/pdf-download/72151",previewPdfUrl:"/chapter/pdf-preview/72151",authors:[{id:"316358",title:"Dr.",name:"Lars",surname:"Rehmann",slug:"lars-rehmann",fullName:"Lars Rehmann"},{id:"322088",title:"Dr.",name:"Zhaoran",surname:"Xin",slug:"zhaoran-xin",fullName:"Zhaoran Xin"}],corrections:null},{id:"70153",title:"Catalytic Ozone Oxidation of Petrochemical Secondary Effluent: Mechanism, Application and Future Development",doi:"10.5772/intechopen.90170",slug:"catalytic-ozone-oxidation-of-petrochemical-secondary-effluent-mechanism-application-and-future-devel",totalDownloads:239,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Yu Tan, Liya Fu, Changyong Wu, Yanan Li, Xiumei Sun and Yuexi Zhou",downloadPdfUrl:"/chapter/pdf-download/70153",previewPdfUrl:"/chapter/pdf-preview/70153",authors:[{id:"307479",title:"Prof.",name:"Changyong",surname:"Wu",slug:"changyong-wu",fullName:"Changyong Wu"},{id:"307546",title:"Prof.",name:"Yuexi",surname:"Zhou",slug:"yuexi-zhou",fullName:"Yuexi Zhou"},{id:"307543",title:"Dr.",name:"Yu",surname:"Tan",slug:"yu-tan",fullName:"Yu Tan"},{id:"307544",title:"Dr.",name:"Xiumei",surname:"Sun",slug:"xiumei-sun",fullName:"Xiumei Sun"},{id:"307545",title:"MSc.",name:"Yanan",surname:"Li",slug:"yanan-li",fullName:"Yanan Li"},{id:"322089",title:"Dr.",name:"Liya",surname:"Fu",slug:"liya-fu",fullName:"Liya Fu"}],corrections:null},{id:"71672",title:"Scale-Up and Optimization for Slurry Photoreactors",doi:"10.5772/intechopen.91920",slug:"scale-up-and-optimization-for-slurry-photoreactors",totalDownloads:318,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Gianluca Li Puma, Fiderman Machuca-Martínez, Miguel Mueses, José Colina-Márquez and Ciro Bustillo-Lecompte",downloadPdfUrl:"/chapter/pdf-download/71672",previewPdfUrl:"/chapter/pdf-preview/71672",authors:[{id:"189304",title:"Dr.",name:"Ciro",surname:"Bustillo-Lecompte",slug:"ciro-bustillo-lecompte",fullName:"Ciro Bustillo-Lecompte"},{id:"309822",title:"Prof.",name:"Gianluca",surname:"Li Puma",slug:"gianluca-li-puma",fullName:"Gianluca Li Puma"},{id:"309823",title:"Prof.",name:"Fiderman",surname:"Machuca-Martínez",slug:"fiderman-machuca-martinez",fullName:"Fiderman Machuca-Martínez"},{id:"309826",title:"Prof.",name:"Miguel",surname:"Mueses",slug:"miguel-mueses",fullName:"Miguel Mueses"},{id:"309827",title:"Prof.",name:"José",surname:"Colina-Márquez",slug:"jose-colina-marquez",fullName:"José Colina-Márquez"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},relatedBooks:[{type:"book",id:"6539",title:"Wastewater and Water Quality",subtitle:null,isOpenForSubmission:!1,hash:"011810f6bbc0d25f6590e1169231962f",slug:"wastewater-and-water-quality",bookSignature:"Taner Yonar",coverURL:"https://cdn.intechopen.com/books/images_new/6539.jpg",editedByType:"Edited by",editors:[{id:"32956",title:"Dr.",name:"Taner",surname:"Yonar",slug:"taner-yonar",fullName:"Taner Yonar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6199",title:"Osmotically Driven Membrane Processes",subtitle:"Approach, Development and Current Status",isOpenForSubmission:!1,hash:"bbb718c2b4705962a3388b4cb551d87b",slug:"osmotically-driven-membrane-processes-approach-development-and-current-status",bookSignature:"Hongbo Du, Audie Thompson and Xinying Wang",coverURL:"https://cdn.intechopen.com/books/images_new/6199.jpg",editedByType:"Edited by",editors:[{id:"180165",title:"Dr.",name:"Hongbo",surname:"Du",slug:"hongbo-du",fullName:"Hongbo Du"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7645",title:"Desalination",subtitle:"Challenges and Opportunities",isOpenForSubmission:!1,hash:"79498ce21a56d214786502c9fe4ebd6b",slug:"desalination-challenges-and-opportunities",bookSignature:"Mohammad Hossein Davood Abadi Farahani, Vahid Vatanpour and Amir Hooshang Taheri",coverURL:"https://cdn.intechopen.com/books/images_new/7645.jpg",editedByType:"Edited by",editors:[{id:"249503",title:"Dr.",name:"Mohammad Hossein",surname:"Davood Abadi Farahani",slug:"mohammad-hossein-davood-abadi-farahani",fullName:"Mohammad Hossein Davood Abadi Farahani"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8915",title:"Advances in Membrane Technologies",subtitle:null,isOpenForSubmission:!1,hash:"19febde893f705494f2334d02977fd83",slug:"advances-in-membrane-technologies",bookSignature:"Amira Abdelrasoul",coverURL:"https://cdn.intechopen.com/books/images_new/8915.jpg",editedByType:"Edited by",editors:[{id:"151521",title:"Dr.",name:"Amira",surname:"Abdelrasoul",slug:"amira-abdelrasoul",fullName:"Amira Abdelrasoul"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8804",title:"Water and Wastewater Treatment",subtitle:null,isOpenForSubmission:!1,hash:"ccb46d6518786712b3184b2498fb0cab",slug:"water-and-wastewater-treatment",bookSignature:"Murat Eyvaz",coverURL:"https://cdn.intechopen.com/books/images_new/8804.jpg",editedByType:"Edited by",editors:[{id:"170083",title:"Associate Prof.",name:"Murat",surname:"Eyvaz",slug:"murat-eyvaz",fullName:"Murat Eyvaz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6464",title:"Nanofiltration",subtitle:null,isOpenForSubmission:!1,hash:"ff27f3309a565c3d37afcac907cc7a2e",slug:"nanofiltration",bookSignature:"Muhammad Akhyar Farrukh",coverURL:"https://cdn.intechopen.com/books/images_new/6464.jpg",editedByType:"Edited by",editors:[{id:"63182",title:"Dr.",name:"Muhammad Akhyar",surname:"Farrukh",slug:"muhammad-akhyar-farrukh",fullName:"Muhammad Akhyar Farrukh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{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"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,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"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,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"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,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"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],ofsBooks:[]},correction:{item:{id:"67322",slug:"corrigendum-to-sexual-dysfunction-in-patients-with-systemic-sclerosis",title:"Corrigendum to: Sexual Dysfunction in Patients with Systemic Sclerosis",doi:null,correctionPDFUrl:"https://cdn.intechopen.com/pdfs/67322.pdf",downloadPdfUrl:"/chapter/pdf-download/67322",previewPdfUrl:"/chapter/pdf-preview/67322",totalDownloads:null,totalCrossrefCites:null,bibtexUrl:"/chapter/bibtex/67322",risUrl:"/chapter/ris/67322",chapter:{id:"66966",slug:"sexual-dysfunction-in-patients-with-systemic-sclerosis",signatures:"Barbora Heřmánková",dateSubmitted:"July 16th 2018",dateReviewed:"April 5th 2019",datePrePublished:"May 3rd 2019",datePublished:null,book:{id:"8269",title:"New Insights into Systemic Sclerosis",subtitle:null,fullTitle:"New Insights into Systemic Sclerosis",slug:"new-insights-into-systemic-sclerosis",publishedDate:"September 18th 2019",bookSignature:"Michal Tomcik",coverURL:"https://cdn.intechopen.com/books/images_new/8269.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"193284",title:"Dr.",name:"Michal",middleName:null,surname:"Tomcik",slug:"michal-tomcik",fullName:"Michal Tomcik"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null}},chapter:{id:"66966",slug:"sexual-dysfunction-in-patients-with-systemic-sclerosis",signatures:"Barbora Heřmánková",dateSubmitted:"July 16th 2018",dateReviewed:"April 5th 2019",datePrePublished:"May 3rd 2019",datePublished:null,book:{id:"8269",title:"New Insights into Systemic Sclerosis",subtitle:null,fullTitle:"New Insights into Systemic Sclerosis",slug:"new-insights-into-systemic-sclerosis",publishedDate:"September 18th 2019",bookSignature:"Michal Tomcik",coverURL:"https://cdn.intechopen.com/books/images_new/8269.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"193284",title:"Dr.",name:"Michal",middleName:null,surname:"Tomcik",slug:"michal-tomcik",fullName:"Michal Tomcik"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null},book:{id:"8269",title:"New Insights into Systemic Sclerosis",subtitle:null,fullTitle:"New Insights into Systemic Sclerosis",slug:"new-insights-into-systemic-sclerosis",publishedDate:"September 18th 2019",bookSignature:"Michal Tomcik",coverURL:"https://cdn.intechopen.com/books/images_new/8269.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"193284",title:"Dr.",name:"Michal",middleName:null,surname:"Tomcik",slug:"michal-tomcik",fullName:"Michal Tomcik"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"10706",leadTitle:null,title:"Fighting the COVID-19 Pandemic",subtitle:null,reviewType:"peer-reviewed",abstract:"
\r\n\tNovember 2019 marked a change in human lives that will not be forgotten within a short period of time. We went to sleep in one world and woke up in another very if not totally different one. The appearance and recognition of the first cases of the respiratory disease that was later designated COVID-19 coined the beginning of a worldwide pandemic that changed human behavior and claimed over 1.3 million people in the 21st century. Though much debate has encased most aspects of this disease, facts are starting to unfold with the availability of data from clinical trials. The second wave, though maybe spreading faster with higher numbers of cases, is showing a lower mortality rate than the first wave, which means that we have learned how to better manage cases. We definitely still need to learn much more and what was considered a fact a few months ago might be rendered obsolete shortly.
",isbn:"978-1-83968-217-9",printIsbn:"978-1-83968-216-2",pdfIsbn:"978-1-83968-246-9",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,hash:"1a5246f0b6ba4f0e9ad1fbfa4134c598",bookSignature:"Dr. Manal Mohammad Baddour",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10706.jpg",keywords:"Virus Family, Natural Host, Mode of Transmission, Incubation Times, Classical Clinical Picture, Alternate Clinical Pictures, Commonly Used Protocols, Myths, Adverse Effects, Physical Methods, Vaccine Candidates, Concerns",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"January 29th 2021",dateEndSecondStepPublish:"February 26th 2021",dateEndThirdStepPublish:"April 27th 2021",dateEndFourthStepPublish:"July 16th 2021",dateEndFifthStepPublish:"September 14th 2021",remainingDaysToSecondStep:"9 days",secondStepPassed:!0,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"A dedicated Microbiologist striving to attain optimum patient care through best practices in the Microbiology Lab and Diagnostic Microbiology Research.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"174598",title:"Dr.",name:"Manal Mohammad",middleName:null,surname:"Baddour",slug:"manal-mohammad-baddour",fullName:"Manal Mohammad Baddour",profilePictureURL:"https://mts.intechopen.com/storage/users/174598/images/system/174598.jpeg",biography:"Manal Baddour is Professor of Medical Microbiology and Immunology, Director of the Diagnostic Microbiology Lab in Alexandria University and editorial board member of several international journals. She has published more than 33 papers in reputed journals and has edited and authored several books. She has co-organised and participated in over 50 conferences and workshops. She has supervised many Ph. D. and Master degree theses. She has assessed promotion files for Professors of Microbiology for many candidates from Egypt, Jordan and Saudi Arabia. She has also assessed manuscripts for over 20 journals. She has been a principal investigator/co-investigator in 20 scientific project grants. She is a member of several scientific organisations and supervises several microbiology labs at the University and in private sectors.",institutionString:"Alexandria University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Alexandria University",institutionURL:null,country:{name:"Egypt"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"297737",firstName:"Mateo",lastName:"Pulko",middleName:null,title:"Mr.",imageUrl:"https://mts.intechopen.com/storage/users/297737/images/8492_n.png",email:"mateo.p@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:"5294",title:"Steps Forwards in Diagnosing and Controlling Influenza",subtitle:null,isOpenForSubmission:!1,hash:"15d072595f188560cf6edce50307b529",slug:"steps-forwards-in-diagnosing-and-controlling-influenza",bookSignature:"Manal Mohammad Baddour",coverURL:"https://cdn.intechopen.com/books/images_new/5294.jpg",editedByType:"Edited by",editors:[{id:"174598",title:"Dr.",name:"Manal Mohammad",surname:"Baddour",slug:"manal-mohammad-baddour",fullName:"Manal Mohammad Baddour"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4786",title:"Updates on Brucellosis",subtitle:null,isOpenForSubmission:!1,hash:"dc389e7ef54fb572ca89ae1ac6e5f3ec",slug:"updates-on-brucellosis",bookSignature:"Manal Mohammad Baddour",coverURL:"https://cdn.intechopen.com/books/images_new/4786.jpg",editedByType:"Edited by",editors:[{id:"174598",title:"Dr.",name:"Manal Mohammad",surname:"Baddour",slug:"manal-mohammad-baddour",fullName:"Manal Mohammad Baddour"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7082",title:"Surgical Infections",subtitle:"Some Facts",isOpenForSubmission:!1,hash:"b5cab76ab84efa06f84fce22420ee43d",slug:"surgical-infections-some-facts",bookSignature:"Manal Mohammad Baddour",coverURL:"https://cdn.intechopen.com/books/images_new/7082.jpg",editedByType:"Edited by",editors:[{id:"174598",title:"Dr.",name:"Manal Mohammad",surname:"Baddour",slug:"manal-mohammad-baddour",fullName:"Manal Mohammad Baddour"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6550",title:"Cohort Studies in Health Sciences",subtitle:null,isOpenForSubmission:!1,hash:"01df5aba4fff1a84b37a2fdafa809660",slug:"cohort-studies-in-health-sciences",bookSignature:"R. Mauricio Barría",coverURL:"https://cdn.intechopen.com/books/images_new/6550.jpg",editedByType:"Edited by",editors:[{id:"88861",title:"Dr.",name:"R. Mauricio",surname:"Barría",slug:"r.-mauricio-barria",fullName:"R. Mauricio Barría"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{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"}}]},chapter:{item:{type:"chapter",id:"48484",title:"Role of C1q in Efferocytosis and Self-Tolerance — Links With Autoimmunity",doi:"10.5772/60519",slug:"role-of-c1q-in-efferocytosis-and-self-tolerance-links-with-autoimmunity",body:'
1. Introduction
C1q, the well-known initiator of the classical complement pathway, belongs to a family of soluble pattern recognition receptors (PRRs) called defense collagens comprised of a C-terminal globular region and an N–terminal collagen-like tail. The defense collagens include collectins (collagen containing lectins) such as mannan-binding lectin (MBL), lung surfactant protein A (SP-A), SP-D, CL-K1 CL-L1, conglutinin, collectin-43 and related proteins ficolins. They are capable of recognizing a wide range of microorganisms by binding to their pathogen-associated molecular patterns (PAMPs) [1-3].
C1q differs from the collectins and ficolins members of the defense collagens in that it does not contain a C-type lectin or fibrinogen like recognition domain [4]. Rather, it contains a “jellyroll” beta sandwich fold typical of tumor necrosis factor family [5]. Additionally, C1q is structurally related to some TNF-related proteins such as adiponectin, and the members of CTRP (C1q/TNF-related proteins) family [6], suggesting that C1q could share some “cytokine-like“functions with these molecules.
On the other hand, C1q is classically known for its ability to bind IgG-and IgM-containing immune complexes [7, 8] which initiates the classical complement cascade for microbial killing and phagocytosis.
The traditional view of the biological role of C1q as a first line of innate immunity against pathogens has been reconsidered over the past 15 years with evidences showing that C1q has the ability to sense many altered structures from self, including the pathological form of the prion protein [9, 10], β-amyloid fibrils [11], modified forms of low-density lipoprotein [12, 13] and apoptotic cells [14-16]. Unlike the other complement proteins that are expressed mostly, if not exclusively, in the liver, C1q is predominantly synthesized by myeloid cells such as macrophages and dendritic cells (DC) and also, in smaller quantities, by a wide range of cell types (reviewed in [17] and paragraph 3.2).
Importantly, C1q is one actor of efferocytosis, which is the mechanism of the clearance of altered self-cells and in particular of apoptotic cells, and is essential for development and to maintain tissue homeostasis [18]. C1q is involved in this process, at least as a physical bridge between the phagocyte and its prey. Numerous C1q-binding molecules at both sides of the phagocytic synapse have been characterized today (summarized in Tables 1 and 2), suggesting a multiligand-binding process even if the consequences of their molecular interplay are not deciphered yet.
Consistent with its importance in the fight against pathogens and as for the other complement proteins, genetic deficiency in C1q leads to a plethora of infections [19]. However, in the case of C1q, deficiency is also strongly correlated with autoimmune diseases, such as systemic lupus erythematosus (SLE) and glomerulonephritis, associated with compromised removal of apoptotic cells (as developed in paragraph 7).
A key element that highlights the non-traditional C1q functions, linking it to autoimmunity, is its capacity to regulate immune cells. This includes a wide range of effects such as regulation of dendritic cells and macrophage polarization, phagocytosis enhancement, stimulation of leukocytes, suppression of T and B cells proliferation. This chapter will provide an update of the C1q functions with an emphasis on its role in autoimmunity.
2. The C1q protein and its classical functions in complement activation
The association with a Ca2+-dependent tetramer comprising two copies of two serine proteases, C1r and C1s [20, 21], allows C1q to trigger the classical complement pathway. C1q is a 460-kDa hexameric protein assembled from six heterotrimeric collagen-like fibers (Figure 1), each being prolonged by a C-terminal globular domain. One heterotrimeric fiber consists of 3 distinct but similar polypeptide chains, A, B, C encoded by 3 genes C1QA, C1QB and C1QC localized on human chromosome 1p, and aligned in the same orientation in the order A-C-B. From a structure-function point of view, the collagen-like domain (cC1q) and the globular heads (gC1q) define two well characterized functional domains. The gC1q domain has the ability to sense and engage an amazing variety of ligands that could be part of surface molecular patterns [20, 22] and is considered as the key to the versatility of C1q function [21, 23, 24]. Until even recently, cC1q specificity has been restricted to the interaction with the associated serine proteases C1r-C1s and with the phagocyte endocytic receptor CRT/CD91(LRP1). As the recognition molecule of the classical pathway, C1q is well known to recognize the IgG and IgM Fc fragments of membrane-bound antibodies, but also of aggregated immune complexes. In addition to this best known “classical” property, C1q recognizes C-reactive protein and other pentraxins bound to pathogens and other surfaces, as well as various molecular motifs on several Gram-negative bacteria and viruses (PAMPs), including gp41 or DNA [20, 25-27]. In most cases, recognition of these non-self ligands, as well as Ig and pentraxins, by C1q triggers activation of the classical complement pathway, thereby contributing to their elimination through enhanced phagocytosis, lysis, and inflammation (Figure 2).
Figure 1.
Schematic representation of the assembly of the C1q molecule. C1q is assembled from three polypeptide chains (A, B and C) encoded by 3 different genes (C1QA, C1QB and C1QC). Each chain comprises an N-terminal collagen-like sequence and a C-terminal globular gC1q module, with disulfide bridges linking the N-terminal ends of the A and B chains and two C chains. Each A-B dimer associates with a C chain, resulting in a basic subunit comprised of two disulphide-linked heterotrimeric collagen-like stalks prolonged by globular domains. The association of 3 subunits results in a full-length protein with a typical shape of a bouquet of six flowers, the stalks being held together in their N-terminal half through strong non-covalent interactions and then diverging to form six individual stems, each terminating in a globular head.
Figure 2.
Activation of the classical pathway of complement. C1q binds to microbial surface motifs directly or via or other immune molecules (antibodies, pentraxins) through its globular heads. This multivalent binding triggers sequential activation of the C1r and C1s proteases associated to C1q collagen stalks. Activated C1s cleaves complement components C4 and C2, leading to the assembly of the C3 convertase responsible for C3 cleavage and opsonization of the target by C3b. Activation of the complement cascade generates fragments involved in inflammation, enhancement of phagocytosis and ends in target lysis by the membrane attack complex assembled from complement components C5b, C6, C7, C8 and C9. C1 inhibitor (C1-Inh), a member of the serine protease inhibitor (serpin) family, controls both C1 activation and C1s proteolytic activity.
3. New emerging C1q functions
3.1. A sensor of altered-self structure
One main starting point for revisiting C1q function was probably the work of Korb and Ahearn showing that gC1q binds specifically to apoptotic cells and that binding is important for prevention of autoimmunity in SLE [14]. Since then, numerous experimental proofs have established that C1q is an efficient sensor of self-modifications defined as ACAMPs and DAMPs (for Apoptotic Cells- and Danger-Associated Molecular Patterns, respectively). In contrast to PAMPs, DAMPs and ACAMPs are molecules that can initiate and perpetuate the immune response in a noninfectious inflammatory context. On one way, ACAMPs should be defined as a restricted class of DAMPs which is linked and/or restricted to apoptotic cell membrane modifications. Viewed from another angle, some DAMPs are ACAMPs when they are exposed at the surface of apoptotic cells, the best illustration being probably DNA: it is indeed a mainly intracellular molecule released upon cell damage, but DNA is also anchored at the cell surface in association with histone proteins as a consequence of apoptosis. C1q recognizes the deoxyribose moiety of DNA, through unexpected lectin-like property [28, 29].
At the surface of apoptotic cells, C1q also binds phosphatidylserine (PS), the canonical marker of apoptosis, and calreticulin (CRT) which was characterized as a strong “Eat–me” signal for phagocyte. Growing evidence emphasizes the role of C1q as a sensor and integrator of the self-alteration and the list of recognized molecules summed up in Table I (C1q ligands on apoptotic cells), is probably far from being closed. These interactions are mainly mediated by the globular region of C1q (gC1q) that were shown to contain the binding sites for self-molecules specifically exposed on altered-self cells surface. However, as the C1q collagenous tail (cC1q) is known to interact with several membrane receptors (see paragraph 6), widely distributed on various cell types, C1q can enter into a vast array of interactions by binding of its heads or/and its stalks depending of their accessibility in a particular situation. C1q binding to altered–self structures is not dependent on its associated serum proteases. Indeed, purified C1q freed of the C1r2-C1s2 tetramer, and the isolated gC1q domains retain its binding capacity [14, 28, 30, 31].
\n\t\t
\n\t\t
\n\t\t
\n\t\t
\n\t\t
\n\t\t
\n\t\t\t
\n\t\t\t
\n\t\t\t\tInteraction with C1q domains\n\t\t\t
\n\t\t\t
\n\t\t\t\tFunction(s)\n\t\t\t
\n\t\t\t
\n\t\t\t\tPotential partners in complex(es) \n\t\t\t
C1q ligands characterized on apoptotic cells (ACs).
*These ligands are autoantigens targeted in lupus erythematous. PS, phosphatidylserine; CERT(L), the longer splicing isoform of ceramide transporter protein (CERT); GAPDH, Glyceraldehyde-3-phosphate dehydrogenase;1 determined by X-ray crystallography;2 does not exclude a binding to late ACs;3CD46 was characterized as a “Don’t Eat me” signal (Elward et al, 2005, [35]);4 full length C1q was used in these studies; (?) probable function that remains to be further investigated; ND, not determined.
3.2. A modulator of the phagocyte functions
Other biological functions of C1q with particular emphasis on immune responses have been revealed. They include stimulation of leukocyte oxidative response, chemotaxis of monocytes derived cells, including neutrophils, modulation of lymphocytes proliferation, DC differentiation, cytokines expression by phagocytes (reviewed in [17]) and more recently macrophage M1/M2 polarization [43]. The recent findings that C1q, together with its receptors, is directly involved in the safe removal of self-waste (paragraph 4), also provide strong evidence for a relationship between C1q activity, maintenance of immune tolerance and prevention of autoimmunity (developed in paragraph 7). Importantly, the monocyte lineage includes macrophages and dendritic cells which are key actors for phagocytosis, cytokines production and antigen presentation. This suggests a special place for C1q at the interface of both innate and acquired immunity. Indeed, recent observations by the group of Berhane Ghebrehiwet [44, 45] suggest that C1q functions as a molecular switch dictating the monocyte to dendritic cell transition and arresting DCs in an immature state, which influences the cell response, mainly in a “tolerogenic” way. Although not precisely known, this process seems supported by the oligo heterotrimeric nature of C1q which can bind to gC1q and cC1q receptors which are differentially expressed during monocytes maturation. It should also be mentioned that these interactions are likely differentially modulated by the pathogenic or altered-self nature of gC1q ligands (e. g, PAMPs or DAMPs).
In the same way, C1q influences the M1 pro-inflammatory / M2 pro-resolving macrophage polarization [46]. Specifically, the C1q-stimulated phagocyte is anti-inflammatory (M2-polarized) and this is also observed when C1q-opsonized apoptotic cells are engulfed. In blood, C3 complement component is another actor that, in the presence of C1 (C1q/C1r-C1s complex) helps the clearance of apoptotic debris in an anti-inflammatory manner, through its cleavage fragments C3b and iC3b generated by complement activation. Apoptotic blebs become opsonized by iC3b, which is recognized by complement receptor 3 (CR3, Mac-1) on phagocytes. This induces an immune suppression beneficial to the safe elimination of altered-self structures.
Interestingly, recent studies have also shown that T cell responses to apoptotic cells are regulated by complement in a C3-dependent manner [47, 48]. The group of Marina Botto has demonstrated that C3 bound to dying cells not only facilitates the uptake of apoptotic cells but also influences their intracellular processing, facilitating the MHC II/peptide presentation, and thus dedicates the T cell response to an “apoptotic cell” antigen [48]. This observation contributes to the understanding of how use of the same engulfing machinery yields different responses for a pathogen or an altered-self cell.
Whether C1q alone or C3b-derived opsonins are involved is certainly a key for understanding the cellular response mechanism. Therefore it must be dependent on the local delivery of C1q, i.e. in blood or in the surrounding tissues. Approximately 80% of C1q contained in the plasma is associated with the C1r2–C1s2 tetramer to form the C1 complex which is capable to trigger proteolytic processing of other serum complement components, including C3. Since monocyte-derived cells are the most abundant sources of C1q, local production of C1q in the absence of other complement proteins could induce a specific response, independently of the complement proteolytic cascade. The “phagocytic synapse”, which organizes the information that will trigger a specific signaling event, is one of the micro environments where C1q produced by phagocytes may serve as an autocrine signal to induce specific responses. Interestingly, growing evidence is now in favor of C1q production in various tissues, such as endothelial cells [49], neurons [50], fibroblasts [51], osteoclasts [52], which reinforces the view that it may be involved in distinct functions in the absence of serum complement proteins.
3.3. A role in angiogenesis and development
C1q is produced by endothelial cells (ECs) and in the absence of other complement proteins such as the C1r and C1s proteases, C3 and C4, exerts a proangiogenic effect [49]. C1q is very efficient in inducing new vessel formation in wound healing. The globular region of C1q seems to be implicated in this function by binding specifically to the gC1q membrane receptor (gC1qR) expressed by ECs and mainly restricted to the skin ulcer. These observations provide significant insights in favor of a role of C1q in development, tissue repair and also tumor growth. Importantly, this is a new entry to apprehend the role of C1q in inflammatory processes. Angiogenesis is an essential component of inflammatory and it is related to inflammatory pathologies such as rheumatoid arthritis and other systemic autoimmune diseases [53, 54].
C1q produced by cells of the central nervous system (CNS) has been shown to play an important role in remodeling synaptic connections in the developing visual system by tagging unwanted synapses for elimination. These results suggest that complement-mediated synapse elimination may become aberrantly reactivated in neurodegenerative diseases [55]. In addition a dramatic increase of C1q level in the CNS (as much as 300-fold) during normal aging was demonstrated recently [56]. C1q has also been reported to activate Wnt signaling, a pathway involved in development of many organs and implicated in mammalian aging, thereby possibly promoting aging-associated decline in tissue regeneration [57].
4. Efferocytosis
Efferocytosis (from efferre, Latin for \'to take to the grave’) is now the term admitted to name the mechanism of the clearance of apoptotic cells [58]. Apoptosis occurs throughout life as an essential process during development, tissue homeostasis but also in pathogenic events. Despite the billion of apoptotic cells produced per day in human [59], they were rarely observed in tissue excepted in pathological situations. Efficient removal of apoptotic cells before the onset of necrosis is considered as a pre-requisite for prevention of autoimmune and inflammatory diseases. This fundamental process, which appears to promote immune tolerance to self together with anti-inflammatory effects, is ongoingly studied since at least 15 years at the cellular and molecular levels and is increasingly better characterized. Such knowledge leads to discover signals that play together to modulate the way by which dead cells are recognized, engulfed by phagocytes and also determine the final immunological outcome. Of great interest, it was shown that drug-manipulating apoptosis of tumor cell for therapy could benefit to their elimination possibly in an immunogenic way [60, 61]. This also highlights that the balanced immune response to apoptotic cell death results from a fine regulation of “factors” promoting either immunity or tolerance. In brief, efferocytosis proceeds in successive steps, including (i) the contact between the damaged cell and the phagocyte, that could be affected by release of soluble “Find-me” signals by ACs, (ii) the specific recognition of the target with the organization of the phagocytic synapse, and (iii) the intracellular degradation and processing of the debris that impact the global “immune” response.
Because excellent reviews are available on this subject [18, 62-64], the next paragraphs will only summarize the pivotal steps of efferocytosis, with a particular emphasis on the role of C1q.
4.1. C1q recognizes apoptotic cells rapidly from death induction
If it is now clear that C1q binds to various molecules on “apoptotic surfaces” (see Table 1 and paragraph 3). The “age” of the apoptotic cells (young/early or rather aged/late) concerned by C1q-dependent clearance remains a subject of debate [65-67], essentially because extensive binding to necrotic cells is observed in vitro. Various elements must be taken into account to make up its mind on the question. At first, when does C1q bind to the cell? When does the recognized motif become accessible? An interesting element is the nature of the debris that is engulfed by the phagocyte and, importantly, this is clearly dependent on the type of phagocyte. Some phagocytes (mostly the professional phagocytes i.e. macrophages and DCs) are able to eat the apoptotic cell in whole [68, 69], whereas there are other instances where phagocytes engulf smaller cell fragments proceeding from membrane blebbing. This is one of the observations explaining why C1q has been involved in early or late apoptotic cells uptake, depending on the experimental setup. The efficiency of engulfment itself and the kinetics of the apoptosis process are two other factors that could impact the time course of the C1q effect. The presence of serum complement components (i.e. C3 and C4) is known to amplify the C1q effect. At last, an important point is certainly the nature of the ligands recognized by C1q that could impact its function. It is now known that C1q deficiency correlates with autoimmune diseases characterized by an increased number of non-engulfed apoptotic cells together with production of auto-antibodies (paragraph 7). It was also shown that in the case of patients with systemic lupus erythematosus who present auto-antibodies against C1q, anti-C1q specifically targeted C1q bound on early apoptotic cells [70]. These latter two observations strongly argue for an early action of C1q in the course of apoptosis development, nevertheless it does not preclude that C1q could also act on later stages of induced cell death and necrosis.
In favor of a rapid response during the elimination process of apoptotic cells, it was shown by our group and others that the C1q globular region binds cells with non-yet permeabilized plasma membrane. Among the C1q ligands on the outlet face of the plasma membrane, PS, CRT, DNA, annexins and GAPDH are molecules that become accessible or increase significantly at early stage of apoptosis [71]. In particular, we have observed by confocal microscopy and FRET (Fluorescence Resonance Energy Transfer) measurement that CRT/gC1q interaction occurs mainly on HeLa apoptotic cells without detectable membrane blebs and that this interaction decreases on developed blebs [71]. Additionally, in a study performed with Jurkat cells, gC1q binding was detected before the appearance of PS, which is a hallmark of very early stage of the morphologic changes of apoptosis. Importantly, Obeid and coworkers have shown a preapoptotic translocation of CRT to the plasma membrane [60].
4.2. C1q enhances phagocytosis
Despite numerous studies demonstrating the effect of C1q on phagocytosis, a clear understanding of the molecular events which support its functions is still lacking. Even if the enhancement of uptake was initially reported, it proved to be modest in most cases. Various factors that could modulate this effect have to be taken into account. First, efferocytosis is a very redundant process, involving a large number of molecules, which could partially compensate each other. Second, it depends on either the apoptotic cell or the phagocyte type and third it is conditioned by the cell microenvironment, i.e. the presence of serum proteins. In accordance with the observation that C1q by itself binds ACAMPs, the enhancement of uptake is observed independently from its ability to activate the classical complement pathway. However it was also clearly demonstrated that complement protein iC3b, a proteolytic inactive product of the cleavage of C3, could opsonize the target, resulting in enhanced phagocytosis due to iC3b recognition by phagocyte receptors (CR3) [35]. It cannot also be excluded that in some cases other complement opsonins such as C4b could also be involved.
4.2.1. C1q bridges the phagocyte and its prey
It was first proposed that C1q binds the prey through its globular regions and the phagocyte through its collagen stalks, essentially because CRT with its co-receptor CD91 (LRP1) at the phagocyte surface was characterized as a receptor for the collagen part of C1q, and because C1q binds directly to pathogens as well as damaged self–cells surface via its globular heads. This model is undoubtedly challenged by the increasing number of molecules and receptors known to recognize the globular and/or the collagen part of C1q, which could be exposed at both faces of the phagocytic synapse (reviewed in Tables 1 and 2).
4.2.2. C1q aggregates motifs and potentially helps synapse formation
By its capacity to recognize a large number of molecular motifs, mainly supported by the C1q globular region versatility (paragraph 5) but also by the collagen region, C1q has the potential to aggregate molecules in close proximity to help the phagocytic synapse formation in a way similar to the organization of the immunologic synapse. Beyond its role as a molecular bridge, a large number of studies demonstrate that C1q activates signals stimulating the cell responses, thereby providing evidence for its function as a “transmitter” molecule.
4.2.3. C1q induces cell signaling
An important primary observation was that C1q serves as an activation ligand for cells from the monocyte lineage. Indeed, it was shown that fluid phase or immobilized C1q binds to various membrane receptors, including β1 and β3 integrins and other not yet characterized molecules [72-74]. This binding correlates with various intracellular signaling events, such as integrin activation and platelet aggregation, cell migration and tissue remodeling, and also generation of NF-kappa B complexes, most obviously linked with anti–inflammatory effects and thus directly to efferocytosis. In addition, several independent investigators have analyzed the role of C1q on dendritic cells and proposed that C1q interaction with cC1qR(s), but also with gC1qR/p33 in cooperation with the DC-SIGN receptor, are responsible for the modulation of DC maturation and consequently for the “nonimmunogenic” presentation of self-antigens [75, 76]. Notably, DCs which express elevated levels of C1q co-localized with DC-SIGN-gC1qR are functionally immature, whereas inducing DC maturation with LPS and inflammatory cytokines decreases expression of both C1q and its receptors. A recent work has revealed a shared signaling pathway for C1q and adiponectin in murine macrophages, through the demonstration that C1q utilizes 5’ adenosine mono-phosphate-activated protein kinase (AMPK) to induce MER tyrosine kinase which is a receptor known to regulate efferocytosis [77]. Remarkably, various phagocyte receptors that are linked to efferocytosis have been shown to bind C1q, but so far the consequences of these interactions remain elusive. They include a scavenger receptor expressed by endothelial cell and also in some subsets of DCs (SREC-I/SCARF1), which binds C1q dependently of its interaction with PS on the apoptotic cell surface [51], the leukocyte-associated Ig-like receptor 1 (LAIR1) [78], but also the CD91(LRP1)-CRT complex (see paragraph 6).
4.2.4. C1q modulates cytokine production
It is now unambiguously demonstrated that C1q promotes an anti-inflammatory response and thus probably contributes to the global tolerogenic effect triggered by apoptotic cells. A major contribution was provided by Andrea Tenner and coworkers, who have analyzed the C1q effect on cytokine response during ingestion of apoptotic cells by the various monocyte derived-cells (monocytes, macrophages and DCs) [79]. This effect is mainly supported by increase of the IL-10 anti-inflammatory cytokine, inhibition of the pro-inflammatory NF-kappa B transcription factor [74] and modulation of interferon (IFN)-alpha [80, 81]. It however depends either on the maturation state of the phagocyte or on the nature of the apoptotic cell. In addition, the recent characterization of CRT as a major “Eat-me” signal that enhances phagocytosis of apoptotic cells [60, 82] had shed new light on the “signaling” potentiality of C1q, by showing that it could also trigger an immunogenic response in reaction to proapoptotic/anticancer drugs. CRT is a ligand of both the collagen stems and the heads of C1q and is present on each side of the phagocytic synapse. We have demonstrated the direct interaction between CRT and gC1q [71] on early apoptotic cells and also that decreasing CRT exposure impacts C1q binding [31], together with a modulation of cytokine released by macrophages that have engulfed these cells. We also showed that a deficiency of CRT induces contrasting effects on cytokine release by THP-1 macrophages, by increasing interleukin (IL)-6 and monocyte chemotactic protein 1/CCL2 and decreasing IL-8. Remarkably, these effects were greatly reduced when apoptotic cells were opsonized by C1q, which counterbalanced the effect of CRT deficiency. Most notably, these data emphasize the dual role of C1q on uptake and on signaling events during the elimination of apoptotic cells and highlight the crucial role of C1q in tissue homeostasis in controlling the inflammatory phagocyte status. However, the molecular mechanisms that control this effect remain to be fully elucidated. Interestingly, C1q and CRT share PS as a common ligand, itself characterized as a signal involved in the non-immunogenic handling of apoptotic cells. Other serum PS binding molecules have been shown to regulate C1q function such as factor H and beta 2-glycoprotein 1 [38, 83]. Annexins (II, V) which are PS binding molecules were also reported to interact with C1q [39]. All these observations suggest that these immunomodulatory proteins could interact inside complexes involving both faces of the phagocytic synapse.
5. How C1q interactions modulate its function
As stated above, both cC1q and gC1q can interact with different molecular partners, which modulate C1q function. For example, the C1q classical function is mediated by the cC1q-associated C1r and C1s proteases, whereas the cC1q interaction with the phagocyte endocytic receptor CRT-CD91(LRP1) is believed to occur only in the absence of the proteases. More intriguingly, the gC1q domain has the ability to recognize a wide variety of ligands, but the resulting gC1q-mediated C1 binding does not automatically activate the complement pathway as illustrated in figure 3 [21, 23, 24]. How can the nature of the ligand-binding surface modulate such an activation? We can very briefly sum up a current hypothesis as follows: the catalytic domain of the C1r protease lies inside the C1q cone in a ‘resting dimeric’ configuration preventing its spontaneous auto-activation, as strongly suggested by the combined use of electron microscopy and X-ray structural studies [84]. Therefore, a mechanical signal (or heating) is required to trigger C1 activation [23, 24, 85]). The mobile collagen stems of the C1q molecule can accommodate different positions and transmit molecular distortions to the proteases when binding to a target surface (Fig. 3). The magnitude of the corresponding mechanical stress will vary according to the nature and relative position of the molecular motifs on the surface; it will also be influenced by the position of its binding site on gC1q [29].
Figure 3.
Differential C1 activation in response to various binding surfaces. A) Differential C1 activation by IgG-containing immune complexes, heparin and DNA (from Garlatti et al. 2010 [29]). The non-immune self-ligands DNA and heparin induce almost no complement activation in the presence of physiological concentrations of C1-inhibitor. B) Schematic molecular interpretation in terms of differential activating mechanical stress induced by C1q binding. C) Larger view of the C1 model showing the positions of C1q flexible hinges, of the inner C1r dimeric catalytic domains, and of the proposed immune complex binding site on the B chain (IC) and the non-immune self-ligand binding site on the C chain (ni).
6. C1q receptors on phagocytes
The identity of C1q receptors and their role in C1q-dependent efferocytosis have been a matter of controversy for many years and are still not fully elucidated. These receptors include cC1qR, gC1qR, C1qRp, CR1, the α2β1 integrin and CD91, and several new receptors described during the past two years, including RAGE, CR3, DC-SIGN and LAIR-1. As will be seen below, certain of these receptors interact with each other and the interaction with C1q might involve ternary complexes.
Paradoxically, the first two receptors identified for C1q collagen-like and globular regions (cC1qR/collectin receptor and gC1qR, respectively) [86, 87] turned out to be multifunctional, multi-compartmental proteins normally present in the endoplasmic reticulum (cC1qR/calreticulin/CRT) and in mitochondria (gC1qR/p33), but detected at the surface of a wide variety of cells. Since both proteins neither have transmembrane domain nor membrane anchor, they likely function as co-receptors in association with cell surface transmembrane proteins such as CD91/LRP1 (CRT) and DC-SIGN (gC1qR), which have recently been shown themselves to bind C1q [76, 88]. Both gC1qR and cC1qR have also been proposed to form a signaling complex with integrin β1 on endothelial cells [89], but the possible binding of C1q to this complex was not investigated.
Two other receptors were described later, a receptor called C1qRp (C1q receptor that enhances phagocytosis) [90], further identified as the C-type lectin receptor CD93, and complement receptor 1 (CR1/CD35) [91]. It should be mentioned that CD93 is not considered any more as a C1q receptor due to the lack of direct interaction of the protein with C1q [92]. CR1, also called the immune adherence receptor, was initially identified as a receptor for complement fragments C4b and C3b, acting as a regulator of complement activation. CR1 is expressed on numerous cells, including erythrocytes, eosinophils, neutrophils, monocytes, macrophages, B-lymphocytes, some T cells subsets, follicular dendritic cells and glomerular podocytes (reviewed in [93]). CR1 on red blood cells (ECR1) has been shown to transport complement-tagged particles and immune complexes to the spleen and the liver for phagocytosis by resident macrophages. A marked decline in ECR1 has been observed in autoimmune diseases such as SLE [94]. CR1 was also identified as a receptor for C1q and other defense collagens such as MBL and ficolins [91, 95, 96]. However the involvement of C1q-CR1 interaction in phagocytosis has not been demonstrated so far. This receptor is a multi-modular type I membrane glycoprotein composed of an extracellular stretch of 30 complement control protein (CCP) modules, organized into four long homologous repeats (LHR-A, -B, -C and -D) of 7 CCPs each, a transmembrane domain and a short cytoplasmic tail (43 amino acids). The cytoplasmic tail of CR1 contains two PDZ (postsynaptic density protein, Drosophila disc large tumor suppressor and zonula occludens-1) motifs, allowing interaction of ECR1 with Fas-associated phosphatase 1, a scaffolding protein with tyrosine phosphatase activity [97]. LHR-A contains the major C4b binding site whereas LHR-B and LHR-C contain homologous C4b/C3b binding sites. C1q, MBL and ficolin-2 have been shown to bind LHR-D and their interaction with CR1 proposed to involve major ionic interactions between their collagen stalks and CCP24 and/or CCP25 of CR1 ([96] and unpublished data).
Integrin α2β1 is known as a receptor for extracellular matrix components, including collagen, and is involved in inflammation and immunity (for a review on β1 integrins [98]. It is expressed on many cell types such as epithelial cells, endothelial cells, fibroblasts and hematopoietic cells, including platelets and specific subsets of leukocytes [99]. This integrin has been shown to interact with C1q and other members of the collectin family such as MBL and surfactant protein-A. The C1q-α2β1 interaction has been suggested to play a role in mast cell activation and cytokine secretion [99, 100]. However, its role on other cell types and its potential function in ACs clearance have not been investigated yet. Integrin α2β1 has been shown to interact with calreticulin at the surface of various cells, including platelets [101]. It has been proposed to interact with the collagen-like part of C1q and collectins through its α2 inserted (I) domain, which is involved in collagen binding [100].
CD91/LRP1 (or α2-macroglobulin receptor) is a multifunctional endocytic and cell-signaling receptor of the low density lipoprotein (LDL) receptor family, expressed on both professional (macrophages and dendritic cells) and non-professional phagocytes (epithelial, endothelial cells, fibroblasts, microglia...). It is composed of two non-covalently linked α (85 kDa, C-terminal, membrane-spanning) and β (515 kDa, N-terminal, extracellular) chains. The latter is involved in binding to a wide variety of ligands, including lipoproteins, extracellular matrix proteins or protease/inhibitor complexes [102]. The binding versatility is supported by the modular structure of LRP1 composed of four ligand-binding clusters of LDL receptor type A (LA, also called complement-like) repeats, β-propellers (YWTD repeats) and epidermal growth factor (EGF) modules. Binding of the various ligands was shown to involve mainly clusters II and IV. The cytoplasmic tail of LRP1 consists of 100 amino acids and exhibits diverse potential endocytosis and signaling motifs, including two NPXY motifs, one YXXL motif and two di-leucine motifs. It has been shown to interact with GULP, an adaptor protein involved in engulfment of apoptotic cells.
LRP1 was proposed to use CRT as a coreceptor for engulfment of C1q-opsonized targets, but also to serve as a docking platform for CRT-dependent recognition of dying cells by C1q. However, it has been reported that LRP1 is not always required for C1q-dependent enhancement of AC phagocytosis, suggesting involvement of other C1q receptors [103]. In addition, no direct interaction between isolated LRP1 and CRT has been reported yet while a direct interaction between the LRP1 and C1q molecules has been described, which involves both the collagen-like stalks and the globular heads of C1q [88]. This indicates that the role of LRP1 and CRT in C1q-dependent efferocytosis is more complex than anticipated and needs further clarification.
SREC-I (scavenger receptor (SR) expressed by endothelial cells I, also called SCARF1 or SR-F1) is a class F type scavenger receptor expressed on endothelial cells, macrophages and dendritic cells, that binds various ligands including modified LDL, heat-shock proteins and fungal pathogens. It is characterized by an extracellular domain composed of 6-7 EGF/EGF-like modules, a transmembrane domain and a long (388 amino acids) C-terminal cytoplasmic tail containing serine/proline and glycine rich segments. SREC-I has been shown very recently to play a crucial role in the recognition and engulfment of ACs and in preventing autoimmunity. Most strikingly, this function is mediated through SREC-I interaction with C1q bound to PS exposed at the surface of AC [51]. This C1q-SREC-I efferocytosis pathway, although not fully non-redundant, contributed to AC clearance up to 70%, depending on the phagocyte type, again suggesting involvement of different pathways, depending on cell types and tissue environment. Interestingly, SREC-I has been described as an endocytic receptor for CRT [104], but no interaction was detected recently using isolated proteins [51]. SREC-I has also been shown to trans-interact through its ectodomain with SREC-II, a related type F SR [105], that however does not recognize typical SR ligands and is not involved in C1q-dependent efferocytosis [51]. Identification of protein domains and amino acid residues critical in C1q-SREC-I interaction, the potential existence of trimolecular complexes with CRT, and the signaling pathway triggered by SREC-I binding to C1q-opsonized ACs, remain to be investigated at both molecular and functional levels.
RAGE (receptor for advanced glycation end-products (AGEs) or SR-J) is a 45 kDa receptor of the immunoglobulin (Ig) superfamily comprising an extracellular domain of 3 Ig-like domains (V, C1 and C2 type), a transmembrane domain and a short C-terminal cytoplasmic tail (41 amino acids). RAGE oligomerization is believed to play a role in ligand recognition and signal transduction, which is mediated through association with cytoplasmic adaptor proteins [106]. RAGE is expressed on monocytes, macrophages and dendritic cells, and acts as a pattern recognition receptor for endogenous danger signals including AGEs, high mobility group box 1 (HMGB1), β–amyloid fibrils, S-100 protein and DNA, known to play a pathogenic role in chronic inflammatory diseases [107]. It has also been shown to participate in efferocytosis by acting as a PS receptor [108, 109] and proposed to contribute to the resolution of inflammation. This dual “friend or foe” role appears to depend on the cell context and environment [107]. Of note, soluble forms of RAGE (sRAGE), produced by alternative mRNA splicing or ectodomain shedding, were shown to act as decoys for RAGE ligands [110]. RAGE was shown recently to bind to the globular heads of C1q and to enhance C1q-mediated phagocytosis of ACs, a process suggested to involve formation of a receptor complex with CR3 (see next paragraph) [111]. The RAGE domain and the amino acid residues of both partners participating in the receptor-C1q interaction remain to be determined. Interestingly, RAGE has been shown recently to bind collagen in vitro [112].
The phagocytic receptor CR3 (alias Mac-1, integrin αMβ2, CD11bCD18) is an integrin expressed on most immune cells including neutrophils, dendritic cells and macrophages. It binds to a wide range of ligands including complement C3 fragments C3b/iC3b, extracellular matrix proteins, adhesion molecules (ICAM-1 and -2) and microbial motifs, most of them binding to the inserted (I) domain of the α chain. CR3 inside-out activation leads to a high affinity ligand binding state (extended conformation) allowing target uptake and triggering phagocytosis and signaling [113]. CR3 has been shown to interact extracellularly with other C1q receptors including LRP1 [114] and RAGE [111]. In addition, a direct interaction between CR3 and C1q was reported recently [111]. The receptor and C1q domains involved in the interaction are not known. Interestingly, CR3 has also been shown recently to bind collagens in vitro [115].
DC-SIGN (DC-specific intercellular adhesion molecule (ICAM)-3 grabbing non integrin/CD209) is a C-type lectin receptor with a short N-terminal cytoplasmic tail (37 amino acids) containing recycling and internalization motifs, a transmembrane domain and a C-terminal extracellular domain comprising an extended tetrameric neck region surmounted by a cluster of 4 Ca2+-dependent carbohydrate recognition domains (CRDs). It is expressed by DCs and specific macrophage populations and is a receptor involved in multiple functions including adhesion, pathogen recognition and antigen presentation [116]. Interactions between neutrophils and DCs are mediated through interaction of DC-SIGN with CR3 [117]. DC-SIGN was reported recently to bind C1q, and the interaction proposed to involve the IgG binding site of C1q globular heads and the Ca2+-binding pocket of the lectin domain of DC-SIGN [76]. In addition, C1q and gC1qR were shown to associate with DC-SIGN on the surface of immature DCs and to regulate DC differentiation and function. Interestingly, SIGN-R1, a DC-SIGN homolog expressed on mouse splenic marginal zone macrophages, was shown recently to enhance ACs clearance through interaction with C1q and subsequent complement activation [118]. However, the potential capacity of DC-SIGN to activate the classical complement pathway remains to be investigated.
LAIR-1 (leukocyte-associated immunoglobulin-like receptor-1/CD305) is part of the family of inhibitory immune receptors and is expressed at the surface of both myeloid and lymphoid immune cells. LAIR-1 contains a single extracellular C2-type Ig-like domain, a transmembrane domain and a cytoplasmic tail of 101 amino acids with two immunoreceptor tyrosine-based inhibitory motifs (ITIMs) (reviewed in [119]). When phosphorylated, ITIM motifs can bind the SH2 domain of several SH2-containing phosphatases, leading to down-regulation of immune cell activation. LAIR-1 is a receptor for membrane and matrix collagens and its interaction with collagens is dependent on the presence of hydroxyproline residues [120]. LAIR-1 and its soluble homologue LAIR-2 have been shown to interact with several defense collagens, including C1q, MBL and surfactant protein D through their collagen-like regions [78, 121, 122]. LAIR-2 has been reported to inhibit the classical and MBL-dependent lectin complement pathways [121]. LAIR-1 engagement by C1q has been shown to trigger phosphorylation of LAIR-1 ITIMs in monocytes, which likely represents a mechanism involved in maintaining immunological tolerance [78, 123].
It has been classically considered that C1q binds to the apoptotic cell surface through its globular heads, which leaves the collagen-like stems available for interaction with the C1q receptor at the surface of phagocytes. As mentioned above, recently published results challenge this hypothesis since (i) LRP1 and CRT bind both functional C1q regions and may be present on both AC and phagocyte surfaces and, (ii) two recently identified C1q receptors, RAGE and DC-SIGN, bind the globular regions of C1q. Therefore alternative hypotheses about C1q orientation in the phagocytic synapse should be investigated, taking into account the hexameric structure of C1q, possibly allowing simultaneous interaction of the globular heads with both AC and phagocyte surfaces. Since many receptors seem to function as macromolecular complexes, simultaneous interaction of the C1q molecule with two receptors at the phagocyte surface may also be envisaged, as proposed for the globular heads of C1q within the gC1qR/C1q/DC-SIGN complex [76].
Another important feature of C1q receptors lies in the existence of soluble counterparts, that may arise from alternative gene splicing (soluble RAGE variants, DC-SIGN isoforms), as a result of gene duplication (LAIR-2), or after receptor proteolytic shedding from the membrane (as reported for LRP1 and CR1). These soluble proteins might act as decoy receptors by competing with membrane-bound receptors for ligand binding and preventing subsequent signal transmission, thereby playing a role in regulation of C1q-dependent clearance of altered self.
KO mice: profound defect in the innate immune response
\n\t\t
\n\t\t
\n\t\t\t
\n\t\t\t\tSREC-I, SCARF1, SR-F\n\t\t\t
\n\t\t\t
Scavenger receptor
\n\t\t\t
6/7 EGF-like modules
\n\t\t\t
?
\n\t\t\t
oxLDL, HSP CRT
\n\t\t\t
KO mice: autoimmunity, deficient AC uptake
\n\t\t
\n\t\t
\n\t\t\t
\n\t\t\t\tRAGE, SR-J\n\t\t\t
\n\t\t\t
Scavenger receptor
\n\t\t\t
3 IgG-like modules (V-C1-C2)
\n\t\t\t
gC1q
\n\t\t\t
HMGB1, AGE, PS, CR3
\n\t\t\t
KO mice: deficient AC uptake
\n\t\t
\n\t\t
\n\t\t\t
\n\t\t\t\tCR3, Mac1, αMβ2 (CD11bCD18)\n\t\t\t
\n\t\t\t
β2 integrin
\n\t\t\t
integrin
\n\t\t\t
?
\n\t\t\t
iC3b, sRAGE, LRP1, collagen
\n\t\t\t
Reduced efferocytosis in CD11b-lupus associated variant
\n\t\t
\n\t\t
\n\t\t\t
\n\t\t\t\tDC-SIGN (CD209)\n\t\t\t
\n\t\t\t
C-type lectin receptor
\n\t\t\t
Tetramer; neck + C-lectin domain
\n\t\t\t
gC1q cC1q?
\n\t\t\t
ICAM-3, gC1qR
\n\t\t\t
SIGNR1 KO mice: delayed AC clearance
\n\t\t
\n\t\t
\n\t\t\t
\n\t\t\t\tLAIR-1 (CD305)\n\t\t\t
\n\t\t\t
Inhibitory immune receptor
\n\t\t\t
Ig-like domain (C2)
\n\t\t\t
cC1q gC1q?
\n\t\t\t
MBL, SP-D, collagens
\n\t\t\t
defective expression and function in B lymphocytes from SLE patients
\n\t\t
\n\t
Table 2.
C1q receptors on phagocytes
7. C1q in autoimmune disease
Numerous studies suggest that C1q has a protective role in lupus erythematosus, an autoimmune disease resulting largely in dysregulation of the adaptive immunity, i.e; loss of tolerance and generation of autoreactive T-cells [124]. Other observations, however, argue in favor of a facilitating role of C1q in SLE (systemic lupus erythematosus) correlating with tissue damage due to complement activation. Indeed, the complement cascade generates pro-inflammatory products such as C3a and C5a but could also contribute to acquired-C1q deficiency. These two hypotheses are not exclusive and in any case this highlights the pivotal function of C1q at the interface of the innate and adaptive immunity.
It is well established that complete genetic deficiency of C1q is the strongest risk factor for development of SLE [125]. More than 90 % of individuals who are homozygous for a mutation impairing the expression of one of the C1Q genes (A, B or C) developed severe clinical manifestations common for SLE (cutaneous lupus and photosensibility, nephritis). It was also reported that partial genetic deficiency, subtle genetic variations (e.g. point mutations that could modify the assembly or function of the C1q molecule) or auto antibodies against C1q [126-128] and to the C1q receptor CRT are associated with SLE [129, 130]. Importantly, targeting genes for C1q in mice resulted in disease susceptibility similar to that observed in human, even if the mice genetic background was shown to contribute to the disease [125, 131, 132]. Of note, deficiencies of the early components of the classical complement pathway predispose to SLE in a hierarchical fashion (C1q>C1rs>C4->C2). In brief, this indicates that C1q deficiency is the most important factor whereas C3 is not critical. A feature that could link the C1q deficiency to the adaptive immune response is its role in prevention of immune precipitation. C1q is essential in keeping antigen–antibody complexes soluble and for their removal from the circulation through the CR1 receptor, thereby preventing inflammatory tissue injury [133]. Another C1q function of significance in autoimmune processes likely resides in its involvement in the removal of apoptotic cells. In agreement with this hypothesis, C1q-deficient mice developed a proliferative glomerulonephritis associated with the presence of multiple apoptotic cell bodies, and apoptotic cells are also observed in lymph node germinal centers in some SLE patients with severe disease [134]. Accordingly, most of the relevant autoantigens in SLE, which are nuclear and cytoplasmic molecules [135], are also found at the surface of apoptotic cells or blebs [136]. As previously mentioned, it is interesting to note that among the autoantigens in various forms of lupus are calreticulin, an “Eat–me” signal recognized by the gC1q domain also acting as a cC1q receptor on phagocyte, or C1q itself when bound to apoptotic surfaces.
The other major effect of C1q modulation of immune responses concerns its function in regulating cells from the immune system, independently from the binding to apoptotic bodies and the uptake mechanism. This includes the role of C1q on the function of the neutrophil. In particular, calreticulin is released from activated neutrophils [137] and, as it was previously shown that C1q-CRT interaction modulates the cytokine release by macrophages, it might be hypothesized that this could interfere with neutrophil-mediated inflammatory processes. Of interest, we have shown that CRT recognizes proteinase 3 (PR3), a member of the family of neutrophil-derived serine proteases, released from azurophilic granules but also present in secretory vesicles and membrane-exposed on viable and apoptotic neutrophils [138]. PR3 is a pro-inflammatory factor whose membrane expression can potentiate chronic inflammatory diseases such as anti-neutrophil cytoplasmic antibodies systemic vasculitis (AAV) or rheumatoid arthritis [139]. In addition, the role of C1q on the biology of the monocyte-derived cells and particularly DCs is probably of primary importance [140], because the presence of C1q influences the DC and macrophage responses mainly in a “tolerogenic” way [46, 141]. The interaction of C1q with B and T cells [142-144], which modulates cell proliferation, has also been shown to participate both in the activation and inhibition of T cells, and in the negative selection of B autoreactive-cells through mechanisms that remain to be elucidated.
8. How manipulating C1q could help autoimmune disease treatment, hopes and difficulties
Undoubtedly, the aforementioned observations strongly highlight that C1q has a central role in maintaining tissue homeostasis. In this respect, the fact that complement deficiencies, including C1q, are relatively rare according to national and supranational registries (1 to 10 % of all primary immunodeficiencies) [145] together with the observation that an abnormal C1q content generally induces autoimmunity, is one element that also argues for a critical role of this protein. In our opinion, its function in efferocytosis by helping the rapid elimination of cell debris together with its impact on the response developed by the phagocyte makes it a prime target for resolving autoimmune diseases. Indeed, it can be hypothesized that restoring an efficient engulfment of apoptotic cells would decrease the number of not properly cleared dead cells and thus diminish the release of intracellular autoantigens which are strongly correlated to chronic systemic autoimmune disease. Accordingly, apoptotic cell-based therapy has been developed to limit the graft rejection in transplantation [146]. Because all defects in apoptotic cell clearance are not systematically related to immune disease (CD14 or MBL deficiencies for example) [147, 148], this stresses the dual function of C1q in the uptake process and in modulating the phagocyte signaling response in a tolerogenic way, thus reinforcing its therapeutic potential.
However the fact that C1q reacts with a large spectrum of molecules and membrane receptors which will likely induce mutiple, possibly antagonist functions adds complexity for its potential use in therapy. A 2001 pilot study including 8 patients suggested that SLE might be treated successfully by immunoadsorption of plasma with a C1q column [149]. The parameters of SLE clinical disease activity improved upon removing from the circulation molecules that bind to and consume C1q, i. e. immune complexes, anti-C1q autoantibodies and inflammatory proteins such as pentraxins. More recently, administration of plasma in a SLE patient with complete C1q deficiency has been therapeutically successful [150] with reestablishment of complement haemolytic activity and absence of anti-C1q antibodies, suggesting that targeting C1q/C1q pathway could be a valid therapeutic option.
The fact remains that a better understanding of the molecular details that control the C1q interaction with its targets is a primary need. One major breakthrough for future strategies was clearly the recent success in production of a recombinant full length C1q molecule [151]. This now allows the production of mutated forms of the molecule to map the amino acid residues involved in the recognition of its different targets and receptors. Importantly, this opens the way to produce C1q variants devoid of a particular interaction or sensing property, as exemplified by the lysines B61 and C58 mutants of the collagen stalks which are both unable to trigger complement activation but retain other C1q binding functions. Recombinant C1q devoid of binding capacity for antibodies recognition motifs could represent an efficient tool to disconnect C1q binding to apoptotic bodies from pathways involved in pathogen recognition or in the clearance of immune complexes. Mutated forms targeting binding to specific receptors such as LRP1/CD91 and CRT, DC-SIGN, SCARF1, gC1qR present on various monocytes-derived cells and DCs would provide powerful tools to modulate their specific functions discussed previously. More than ever, producing engineered C1q paves the way to target efferocytosis in order to gain in or to restore a tolerogenic and efficient elimination of apoptotic cells.
9. Conclusion
Over the past 15 years, the status of the C1q molecule has changed from its classical primary role in the initiation of the classical complement pathway, acting in the first line of the immune defense against pathogens, to an essential molecule for maintaining tissue homeostasis, functioning at the crossroad between innate and adaptive immunity. This relatively new finding is undoubtedly one explanation why the primitive C1q status resisted over time. Thanks to an incredible number of studies, not all reported in this chapter, C1q is now known for its involvement in a multiplicity of immunologic functions and other tissue homeostasis-related mechanisms that, when defective, could induce autoimmune and inflammatory diseases as well as cancer. This was emphasized by the discovery of its roles in several steps of the safe clearance of altered-self cells which elicits a global tolerogenic immune response. In our opinion, these properties of C1q arise from its multivalent heterotrimeric structure which supports its amazing ability to recognize and to interpret multiple molecular motifs that, taken individually, would possibly not be sufficient to yield a comprehensive signal. C1q appears to act either as a sensor or a transmitter of subtle changes that must be considered for a balanced appropriate response in numerous physiological processes, including immunity and inflammation.
This remarkable property to interact which a very large number of targets and receptors, involved in various biological processes, is also the major difficulty for its use in therapy. In this respect the recent success in the production of functional full-length recombinant C1q opens new avenues. Indeed, it paves the way for its engineering, first to decipher its molecular mechanisms of action, and second for developing new strategies by specifically targeting one C1q pathway, without undesirable side effects associated with other pathways. We are only at the beginning of what is possible to imagine or of imagining what is possible.
\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/48484.pdf",chapterXML:"https://mts.intechopen.com/source/xml/48484.xml",downloadPdfUrl:"/chapter/pdf-download/48484",previewPdfUrl:"/chapter/pdf-preview/48484",totalDownloads:1610,totalViews:477,totalCrossrefCites:4,totalDimensionsCites:6,hasAltmetrics:0,dateSubmitted:"June 18th 2014",dateReviewed:"March 17th 2015",datePrePublished:null,datePublished:"June 17th 2015",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/48484",risUrl:"/chapter/ris/48484",book:{slug:"autoimmunity-pathogenesis-clinical-aspects-and-therapy-of-specific-autoimmune-diseases"},signatures:"Philippe Frachet, Pascale Tacnet-Delorme, Christine Gaboriaud and\nNicole M. Thielens",authors:[{id:"172578",title:"Dr.",name:"Philippe",middleName:null,surname:"Frachet",fullName:"Philippe Frachet",slug:"philippe-frachet",email:"philippe.frachet@ibs.fr",position:null,institution:{name:"Grenoble Alpes University",institutionURL:null,country:{name:"France"}}},{id:"174451",title:"Dr.",name:"Pascale",middleName:null,surname:"Tacnet-Delorme",fullName:"Pascale Tacnet-Delorme",slug:"pascale-tacnet-delorme",email:"pascale.tacnet@ibs.fr",position:null,institution:null},{id:"174453",title:"Dr.",name:"Christine",middleName:null,surname:"Gaboriaud",fullName:"Christine Gaboriaud",slug:"christine-gaboriaud",email:"christine.gaboriaud@ibs.fr",position:null,institution:null},{id:"174454",title:"Dr.",name:"Nicole",middleName:null,surname:"Thielens",fullName:"Nicole Thielens",slug:"nicole-thielens",email:"nicole.thielens@ibs.fr",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. The C1q protein and its classical functions in complement activation",level:"1"},{id:"sec_3",title:"3. New emerging C1q functions",level:"1"},{id:"sec_3_2",title:"3.1. A sensor of altered-self structure",level:"2"},{id:"sec_4_2",title:"3.2. A modulator of the phagocyte functions",level:"2"},{id:"sec_5_2",title:"3.3. A role in angiogenesis and development",level:"2"},{id:"sec_7",title:"4. Efferocytosis",level:"1"},{id:"sec_7_2",title:"4.1. C1q recognizes apoptotic cells rapidly from death induction",level:"2"},{id:"sec_8_2",title:"4.2. C1q enhances phagocytosis",level:"2"},{id:"sec_8_3",title:"4.2.1. C1q bridges the phagocyte and its prey",level:"3"},{id:"sec_9_3",title:"4.2.2. C1q aggregates motifs and potentially helps synapse formation",level:"3"},{id:"sec_10_3",title:"4.2.3. C1q induces cell signaling",level:"3"},{id:"sec_11_3",title:"4.2.4. C1q modulates cytokine production",level:"3"},{id:"sec_14",title:"5. How C1q interactions modulate its function",level:"1"},{id:"sec_15",title:"6. C1q receptors on phagocytes",level:"1"},{id:"sec_16",title:"7. C1q in autoimmune disease",level:"1"},{id:"sec_17",title:"8. How manipulating C1q could help autoimmune disease treatment, hopes and difficulties",level:"1"},{id:"sec_18",title:"9. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Holmskov U, Malhotra R, Sim RB, Jensenius JC: Collectins: collagenous C-type lectins of the innate immune defense system. Immunol Today 1994, 15:67-74.'},{id:"B2",body:'Holmskov U, Thiel S, Jensenius JC: Collections and ficolins: humoral lectins of the innate immune defense. Annu Rev Immunol 2003, 21:547-578.'},{id:"B3",body:'Selman L, Hansen S: Structure and function of collectin liver 1 (CL-L1) and collectin 11 (CL-11, CL-K1). Immunobiology 2012, 217:851-863.'},{id:"B4",body:'Hoppe HJ, Reid KB: Collectins--soluble proteins containing collagenous regions and lectin domains--and their roles in innate immunity. Protein Sci 1994, 3:1143-1158.'},{id:"B5",body:'Shapiro L, Scherer PE: The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor. Curr Biol 1998, 8:335-338.'},{id:"B6",body:'Schaffler A, Buechler C: CTRP family: linking immunity to metabolism. Trends Endocrinol Metab 2012, 23:194-204.'},{id:"B7",body:'Lu J, Wiedemann H, Timpl R, Reid KB: Similarity in structure between C1q and the collectins as judged by electron microscopy. Behring Inst Mitt 1993:6-16.'},{id:"B8",body:'Gadjeva MG, Rouseva MM, Zlatarova AS, Reid KB, Kishore U, Kojouharova MS: Interaction of human C1q with IgG and IgM: revisited. Biochemistry 2008, 47:13093-13102.'},{id:"B9",body:'Klein MA, Kaeser PS, Schwarz P, Weyd H, Xenarios I, Zinkernagel RM, Carroll MC, Verbeek JS, Botto M, Walport MJ, et al.: Complement facilitates early prion pathogenesis. Nat Med 2001, 7:488-492.'},{id:"B10",body:'Erlich P, Dumestre-Perard C, Ling WL, Lemaire-Vieille C, Schoehn G, Arlaud GJ, Thielens NM, Gagnon J, Cesbron JY: Complement protein C1q forms a complex with cytotoxic prion protein oligomers. J Biol Chem 2010, 285:19267-19276.'},{id:"B11",body:'Tacnet-Delorme P, Chevallier S, Arlaud GJ: Beta-amyloid fibrils activate the C1 complex of complement under physiological conditions: evidence for a binding site for A beta on the C1q globular regions. J Immunol 2001, 167:6374-6381.'},{id:"B12",body:'Biro A, Ling WL, Arlaud GJ: Complement protein C1q recognizes enzymatically modified low-density lipoprotein through unesterified fatty acids generated by cholesterol esterase. Biochemistry 2010, 49:2167-2176.'},{id:"B13",body:'Biro A, Thielens NM, Cervenak L, Prohaszka Z, Fust G, Arlaud GJ: Modified low density lipoproteins differentially bind and activate the C1 complex of complement. Mol Immunol 2007, 44:1169-1177.'},{id:"B14",body:'Korb LC, Ahearn JM: C1q binds directly and specifically to surface blebs of apoptotic human keratinocytes: complement deficiency and systemic lupus erythematosus revisited. J Immunol 1997, 158:4525-4528.'},{id:"B15",body:'Taylor PR, Carugati A, Fadok VA, Cook HT, Andrews M, Carroll MC, Savill JS, Henson PM, Botto M, Walport MJ: A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo. J Exp Med 2000, 192:359-366.'},{id:"B16",body:'Navratil JS, Watkins SC, Wisnieski JJ, Ahearn JM: The globular heads of C1q specifically recognize surface blebs of apoptotic vascular endothelial cells. J Immunol 2001, 166:3231-3239.'},{id:"B17",body:'Ghebrehiwet B, Hosszu KK, Valentino A, Peerschke EI: The C1q family of proteins: insights into the emerging non-traditional functions. Front Immunol 2012, 3.'},{id:"B18",body:'Hochreiter-Hufford A, Ravichandran KS: Clearing the dead: apoptotic cell sensing, recognition, engulfment, and digestion. Cold Spring Harb Perspect Biol 2013, 5:a008748.'},{id:"B19",body:'Nishino H, Shibuya K, Nishida Y, Mushimoto M: Lupus erythematosus-like syndrome with selective complete deficiency of C1q. Ann Intern Med 1981, 95:322-324.'},{id:"B20",body:'Cooper NR: The classical complement pathway: activation and regulation of the first complement component. Adv Immunol 1985, 37:151-216.'},{id:"B21",body:'Gaboriaud C, Thielens NM, Gregory LA, Rossi V, Fontecilla-Camps JC, Arlaud GJ: Structure and activation of the C1 complex of complement: unraveling the puzzle. Trends Immunol 2004, 25:368-373.'},{id:"B22",body:'Kishore U, Gaboriaud C, Waters P, Shrive AK, Greenhough TJ, Reid KB, Sim RB, Arlaud GJ: C1q and tumor necrosis factor superfamily: modularity and versatility. Trends Immunol 2004, 25:551-561.'},{id:"B23",body:'Gaboriaud C, Juanhuix J, Gruez A, Lacroix M, Darnault C, Pignol D, Verger D, Fontecilla-Camps JC, Arlaud GJ: The crystal structure of the globular head of complement protein C1q provides a basis for its versatile recognition properties. J Biol Chem 2003, 278:46974-46982.'},{id:"B24",body:'Gaboriaud C, Frachet P, Thielens NM, Arlaud GJ: The human c1q globular domain: structure and recognition of non-immune self ligands. Front Immunol 2011, 2:92.'},{id:"B25",body:'Ebenbichler CF, Thielens NM, Vornhagen R, Marschang P, Arlaud GJ, Dierich MP: Human immunodeficiency virus type 1 activates the classical pathway of complement by direct C1 binding through specific sites in the transmembrane glycoprotein gp41. J Exp Med 1991, 174:1417-1424.'},{id:"B26",body:'Szalai AJ, Agrawal A, Greenhough TJ, Volanakis JE: C-reactive protein: structural biology and host defense function. Clin Chem Lab Med 1999, 37:265-270.'},{id:"B27",body:'Thielens NM, Tacnet-Delorme P, Arlaud GJ: Interaction of C1q and mannan-binding lectin with viruses. Immunobiology 2002, 205:563-574.'},{id:"B28",body:'Paidassi H, Tacnet-Delorme P, Lunardi T, Arlaud GJ, Thielens NM, Frachet P: The lectin-like activity of human C1q and its implication in DNA and apoptotic cell recognition. FEBS Lett 2008, 582:3111-3116.'},{id:"B29",body:'Garlatti V, Chouquet A, Lunardi T, Vives R, Paidassi H, Lortat-Jacob H, Thielens NM, Arlaud GJ, Gaboriaud C: Cutting edge: C1q binds deoxyribose and heparan sulfate through neighboring sites of its recognition domain. J Immunol 2010, 185:808-812.'},{id:"B30",body:'Paidassi H, Tacnet-Delorme P, Garlatti V, Darnault C, Ghebrehiwet B, Gaboriaud C, Arlaud GJ, Frachet P: C1q binds phosphatidylserine and likely acts as a multiligand-bridging molecule in apoptotic cell recognition. J Immunol 2008, 180:2329-2338.'},{id:"B31",body:'Paidassi H, Tacnet-Delorme P, Verneret M, Gaboriaud C, Houen G, Duus K, Ling WL, Arlaud GJ, Frachet P: Investigations on the C1q-calreticulin-phosphatidylserine interactions yield new insights into apoptotic cell recognition. J Mol Biol 2011, 408:277-290.'},{id:"B32",body:'Jiang H, Cooper B, Robey FA, Gewurz H: DNA binds and activates complement via residues 14-26 of the human C1q A chain. J Biol Chem 1992, 267:25597-25601.'},{id:"B33",body:'Tissot B, Daniel R, Place C: Interaction of the C1 complex of complement with sulfated polysaccharide and DNA probed by single molecule fluorescence microscopy. Eur J Biochem 2003, 270:4714-4720.'},{id:"B34",body:'Palaniyar N, Nadesalingam J, Clark H, Shih MJ, Dodds AW, Reid KB: Nucleic acid is a novel ligand for innate, immune pattern recognition collectins surfactant proteins A and D and mannose-binding lectin. J Biol Chem 2004, 279:32728-32736.'},{id:"B35",body:'Elward K, Griffiths M, Mizuno M, Harris CL, Neal JW, Morgan BP, Gasque P: CD46 plays a key role in tailoring innate immune recognition of apoptotic and necrotic cells. J Biol Chem 2005, 280:36342-36354.'},{id:"B36",body:'Verneret M, Tacnet-Delorme P, Laurin D, Aspord C, Thielens N, Kleman JP, Frachet P: Investigations on the cell surface calreticulin-C1q interactions and their involvement in the uptake of apoptotic cells. Mol Immunol 2011, 48:1706-1706.'},{id:"B37",body:'Donnelly S, Roake W, Brown S, Young P, Naik H, Wordsworth P, Isenberg DA, Reid KB, Eggleton P: Impaired recognition of apoptotic neutrophils by the C1q/calreticulin and CD91 pathway in systemic lupus erythematosus. Arthritis Rheum 2006, 54:1543-1556.'},{id:"B38",body:'Tan LA, Yu B, Sim FC, Kishore U, Sim RB: Complement activation by phospholipids: the interplay of factor H and C1q. Protein Cell 2010, 1:1033-1049.'},{id:"B39",body:'Martin M, Leffler J, Blom AM: Annexin A2 and A5 serve as new ligands for C1q on apoptotic cells. J Biol Chem 2012, 287:33733-33744.'},{id:"B40",body:'Leffler J, Herbert AP, Norstrom E, Schmidt CQ, Barlow PN, Blom AM, Martin M: Annexin-II, DNA, and histones serve as factor H ligands on the surface of apoptotic cells. J Biol Chem 2010, 285:3766-3776.'},{id:"B41",body:'Terrasse R, Tacnet-Delorme P, Moriscot C, Perard J, Schoehn G, Vernet T, Thielens NM, Di Guilmi AM, Frachet P: Human and pneumococcal cell surface glyceraldehyde-3-phosphate dehydrogenase (GAPDH) proteins are both ligands of human C1q protein. J Biol Chem 2012, 287:42620-42633.'},{id:"B42",body:'Bode GH, Losen M, Buurman WA, Veerhuis R, Molenaar PC, Steinbusch HW, De Baets MH, Daha MR, Martinez-Martinez P: Complement activation by ceramide transporter proteins. J Immunol 2014, 192:1154-1161.'},{id:"B43",body:'Benoit ME, Clarke EV, Morgado P, Fraser DA, Tenner AJ: Complement protein C1q directs macrophage polarization and limits inflammasome activity during the uptake of apoptotic cells. J Immunol 2012, 188:5682-5693.'},{id:"B44",body:'Hosszu KK, Santiago-Schwarz F, Peerschke EI, Ghebrehiwet B: Evidence that a C1q/C1qR system regulates monocyte-derived dendritic cell differentiation at the interface of innate and acquired immunity. Innate Immun 2010, 16:115-127.'},{id:"B45",body:'Hosszu KK, Valentino A, Ji Y, Matkovic M, Pednekar L, Rehage N, Tumma N, Peerschke EI, Ghebrehiwet B: Cell surface expression and function of the macromolecular c1 complex on the surface of human monocytes. Front Immunol 2012, 3:38.'},{id:"B46",body:'Bohlson SS, O\'Conner SD, Hulsebus HJ, Ho MM, Fraser DA: Complement, c1q, and c1q-related molecules regulate macrophage polarization. Front Immunol 2014, 5:402.'},{id:"B47",body:'Kemper C, Atkinson JP: T-cell regulation: with complements from innate immunity. Nat Rev Immunol 2007, 7:9-18.'},{id:"B48",body:'Baudino L, Sardini A, Ruseva MM, Fossati-Jimack L, Cook HT, Scott D, Simpson E, Botto M: C3 opsonization regulates endocytic handling of apoptotic cells resulting in enhanced T-cell responses to cargo-derived antigens. Proc Natl Acad Sci U S A 2014, 111:1503-1508.'},{id:"B49",body:'Bossi F, Tripodo C, Rizzi L, Bulla R, Agostinis C, Guarnotta C, Munaut C, Baldassarre G, Papa G, Zorzet S, et al.: C1q as a unique player in angiogenesis with therapeutic implication in wound healing. Proc Natl Acad Sci U S A 2014, 111:4209-4214.'},{id:"B50",body:'Bialas AR, Stevens B: TGF-beta signaling regulates neuronal C1q expression and developmental synaptic refinement. Nat Neurosci 2013, 16:1773-1782.'},{id:"B51",body:'Ramirez-Ortiz ZG, Pendergraft WF, 3rd, Prasad A, Byrne MH, Iram T, Blanchette CJ, Luster AD, Hacohen N, El Khoury J, Means TK: The scavenger receptor SCARF1 mediates the clearance of apoptotic cells and prevents autoimmunity. Nat Immunol 2013, 14:917-926.'},{id:"B52",body:'Teo BH, Bobryshev YV, Teh BK, Wong SH, Lu J: Complement C1q production by osteoclasts and its regulation of osteoclast development. Biochem J 2012, 447:229-237.'},{id:"B53",body:'Szekanecz Z, Koch AE: Mechanisms of Disease: angiogenesis in inflammatory diseases. Nat Clin Pract Rheumatol 2007, 3:635-643.'},{id:"B54",body:'Imhof BA, Aurrand-Lions M: Angiogenesis and inflammation face off. Nat Med 2006, 12:171-172.'},{id:"B55",body:'Stevens B, Allen NJ, Vazquez LE, Howell GR, Christopherson KS, Nouri N, Micheva KD, Mehalow AK, Huberman AD, Stafford B, et al.: The classical complement cascade mediates CNS synapse elimination. Cell 2007, 131:1164-1178.'},{id:"B56",body:'Stephan AH, Madison DV, Mateos JM, Fraser DA, Lovelett EA, Coutellier L, Kim L, Tsai HH, Huang EJ, Rowitch DH, et al.: A dramatic increase of C1q protein in the CNS during normal aging. J Neurosci 2013, 33:13460-13474.'},{id:"B57",body:'Naito AT, Sumida T, Nomura S, Liu ML, Higo T, Nakagawa A, Okada K, Sakai T, Hashimoto A, Hara Y, et al.: Complement C1q activates canonical Wnt signaling and promotes aging-related phenotypes. Cell 2012, 149:1298-1313.'},{id:"B58",body:'deCathelineau AM, Henson PM: The final step in programmed cell death: phagocytes carry apoptotic cells to the grave. Essays Biochem 2003, 39:105-117.'},{id:"B59",body:'Ravichandran KS: Find-me and eat-me signals in apoptotic cell clearance: progress and conundrums. J Exp Med 2010, 207:1807-1817.'},{id:"B60",body:'Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini JL, Castedo M, Mignot G, Panaretakis T, Casares N, et al.: Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 2007, 13:54-61.'},{id:"B61",body:'Kroemer G, Galluzzi L, Kepp O, Zitvogel L: Immunogenic cell death in cancer therapy. Annu Rev Immunol 2013, 31:51-72.'},{id:"B62",body:'Savill J, Dransfield I, Gregory C, Haslett C: A blast from the past: clearance of apoptotic cells regulates immune responses. Nat Rev Immunol 2002, 2:965-975.'},{id:"B63",body:'Paidassi H, Tacnet-Delorme P, Arlaud GJ, Frachet P: How Phagocytes Track Down and Respond to Apoptotic Cells. Crit Rev Immunol 2009, 29:111-130.'},{id:"B64",body:'Poon IK, Lucas CD, Rossi AG, Ravichandran KS: Apoptotic cell clearance: basic biology and therapeutic potential. Nat Rev Immunol 2014, 14:166-180.'},{id:"B65",body:'Liang YY, Arnold T, Michlmayr A, Rainprecht D, Perticevic B, Spittler A, Oehler R: Serum-dependent processing of late apoptotic cells for enhanced efferocytosis. Cell Death Dis 2014, 5:e1264.'},{id:"B66",body:'Gaipl US, Kuenkele S, Voll RE, Beyer TD, Kolowos W, Heyder P, Kalden JR, Herrmann M: Complement binding is an early feature of necrotic and a rather late event during apoptotic cell death. Cell Death Differ 2001, 8:327-334.'},{id:"B67",body:'Nauta AJ, Trouw LA, Daha MR, Tijsma O, Nieuwland R, Schwaeble WJ, Gingras AR, Mantovani A, Hack EC, Roos A: Direct binding of C1q to apoptotic cells and cell blebs induces complement activation. Eur J Immunol 2002, 32:1726-1736.'},{id:"B68",body:'Wood W, Turmaine M, Weber R, Camp V, Maki RA, McKercher SR, Martin P: Mesenchymal cells engulf and clear apoptotic footplate cells in macrophageless PU.1 null mouse embryos. Development 2000, 127:5245-5252.'},{id:"B69",body:'Parnaik R, Raff MC, Scholes J: Differences between the clearance of apoptotic cells by professional and non-professional phagocytes. Curr Biol 2000, 10:857-860.'},{id:"B70",body:'Bigler C, Schaller M, Perahud I, Osthoff M, Trendelenburg M: Autoantibodies against complement C1q specifically target C1q bound on early apoptotic cells. J Immunol 2009, 183:3512-3521.'},{id:"B71",body:'Verneret M, Tacnet-Delorme P, Osman R, Awad R, Grichine A, Kleman JP, Frachet P: Relative contribution of c1q and apoptotic cell-surface calreticulin to macrophage phagocytosis. J Innate Immun 2014, 6:426-434.'},{id:"B72",body:'Peerschke EI, Reid KB, Ghebrehiwet B: Platelet activation by C1q results in the induction of alpha IIb/beta 3 integrins (GPIIb-IIIa) and the expression of P-selectin and procoagulant activity. J Exp Med 1993, 178:579-587.'},{id:"B73",body:'Agostinis C, Bulla R, Tripodo C, Gismondi A, Stabile H, Bossi F, Guarnotta C, Garlanda C, De Seta F, Spessotto P, et al.: An alternative role of C1q in cell migration and tissue remodeling: contribution to trophoblast invasion and placental development. J Immunol 2010, 185:4420-4429.'},{id:"B74",body:'Fraser DA, Arora M, Bohlson SS, Lozano E, Tenner AJ: Generation of inhibitory NFkappaB complexes and phosphorylated cAMP response element-binding protein correlates with the anti-inflammatory activity of complement protein C1q in human monocytes. J Biol Chem 2007, 282:7360-7367.'},{id:"B75",body:'Castellano G, Woltman AM, Nauta AJ, Roos A, Trouw LA, Seelen MA, Schena FP, Daha MR, van Kooten C: Maturation of dendritic cells abrogates C1q production in vivo and in vitro. Blood 2004, 103:3813-3820.'},{id:"B76",body:'Hosszu KK, Valentino A, Vinayagasundaram U, Vinayagasundaram R, Joyce MG, Ji Y, Peerschke EI, Ghebrehiwet B: DC-SIGN, C1q, and gC1qR form a trimolecular receptor complex on the surface of monocyte-derived immature dendritic cells. Blood 2012, 120:1228-1236.'},{id:"B77",body:'Galvan MD, Hulsebus H, Heitker T, Zeng E, Bohlson SS: Complement Protein C1q and Adiponectin Stimulate Mer Tyrosine Kinase-Dependent Engulfment of Apoptotic Cells through a Shared Pathway. J Innate Immun 2014, 6:780-792.'},{id:"B78",body:'Son M, Santiago-Schwarz F, Al-Abed Y, Diamond B: C1q limits dendritic cell differentiation and activation by engaging LAIR-1. Proc Natl Acad Sci U S A 2012, 109:E3160-3167.'},{id:"B79",body:'Fraser DA, Laust AK, Nelson EL, Tenner AJ: C1q differentially modulates phagocytosis and cytokine responses during ingestion of apoptotic cells by human monocytes, macrophages, and dendritic cells. J Immunol 2009, 183:6175-6185.'},{id:"B80",body:'Santer DM, Hall BE, George TC, Tangsombatvisit S, Liu CL, Arkwright PD, Elkon KB: C1q deficiency leads to the defective suppression of IFN-alpha in response to nucleoprotein containing immune complexes. J Immunol 2010, 185:4738-4749.'},{id:"B81",body:'Lood C, Gullstrand B, Truedsson L, Olin AI, Alm GV, Ronnblom L, Sturfelt G, Eloranta ML, Bengtsson AA: C1q inhibits immune complex-induced interferon-alpha production in plasmacytoid dendritic cells: a novel link between C1q deficiency and systemic lupus erythematosus pathogenesis. Arthritis Rheum 2009, 60:3081-3090.'},{id:"B82",body:'Gardai SJ, McPhillips KA, Frasch SC, Janssen WJ, Starefeldt A, Murphy-Ullrich JE, Bratton DL, Oldenborg PA, Michalak M, Henson PM: Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte. Cell 2005, 123:321-334.'},{id:"B83",body:'Tan LA, Yang AC, Kishore U, Sim RB: Interactions of complement proteins C1q and factor H with lipid A and Escherichia coli: further evidence that factor H regulates the classical complement pathway. Protein Cell 2011, 2:320-332.'},{id:"B84",body:'Budayova-Spano M, Lacroix M, Thielens NM, Arlaud GJ, Fontecilla-Camps JC, Gaboriaud C: The crystal structure of the zymogen catalytic domain of complement protease C1r reveals that a disruptive mechanical stress is required to trigger activation of the C1 complex. Embo J 2002, 21:231-239.'},{id:"B85",body:"Gaboriaud C, Ling, W, Thielens, N. M., Bally, I, and Rossi, V Deciphering the fine details of C1 assembly and activation mechanisms: 'mission impossible'? Front. Immunol 2014. doi: 10.3389"},{id:"B86",body:'Malhotra R, Willis AC, Jensenius JC, Jackson J, Sim RB: Structure and homology of human C1q receptor (collectin receptor). Immunology 1993, 78:341-348.'},{id:"B87",body:'Ghebrehiwet B, Lim BL, Peerschke EI, Willis AC, Reid KB: Isolation, cDNA cloning, and overexpression of a 33-kD cell surface glycoprotein that binds to the globular "heads" of C1q. J Exp Med 1994, 179:1809-1821.'},{id:"B88",body:'Duus K, Hansen EW, Tacnet P, Frachet P, Arlaud GJ, Thielens NM, Houen G: Direct interaction between CD91 and C1q. FEBS J 2010, 277:3526-3537.'},{id:"B89",body:'Feng X, Tonnesen MG, Peerschke EI, Ghebrehiwet B: Cooperation of C1q receptors and integrins in C1q-mediated endothelial cell adhesion and spreading. J Immunol 2002, 168:2441-2448.'},{id:"B90",body:'Nepomuceno RR, Henschen-Edman AH, Burgess WH, Tenner AJ: cDNA cloning and primary structure analysis of C1qR(P), the human C1q/MBL/SPA receptor that mediates enhanced phagocytosis in vitro. Immunity 1997, 6:119-129.'},{id:"B91",body:'Klickstein LB, Barbashov SF, Liu T, Jack RM, Nicholson-Weller A: Complement receptor type 1 (CR1, CD35) is a receptor for C1q. Immunity 1997, 7:345-355.'},{id:"B92",body:'McGreal EP, Ikewaki N, Akatsu H, Morgan BP, Gasque P: Human C1qRp is identical with CD93 and the mNI-11 antigen but does not bind C1q. J Immunol 2002, 168:5222-5232.'},{id:"B93",body:'Liu D, Niu ZX: The structure, genetic polymorphisms, expression and biological functions of complement receptor type 1 (CR1/CD35). Immunopharmacol Immunotoxicol 2009, 31:524-535.'},{id:"B94",body:'Khera R, Das N: Complement Receptor 1: disease associations and therapeutic implications. Mol Immunol 2009, 46:761-772.'},{id:"B95",body:'Ghiran I, Barbashov SF, Klickstein LB, Tas SW, Jensenius JC, Nicholson-Weller A: Complement receptor 1/CD35 is a receptor for mannan-binding lectin. J Exp Med 2000, 192:1797-1808.'},{id:"B96",body:'Jacquet M, Lacroix M, Ancelet S, Gout E, Gaboriaud C, Thielens NM, Rossi V: Deciphering complement receptor type 1 interactions with recognition proteins of the lectin complement pathway. J Immunol 2013, 190:3721-3731.'},{id:"B97",body:'Ghiran I, Glodek AM, Weaver G, Klickstein LB, Nicholson-Weller A: Ligation of erythrocyte CR1 induces its clustering in complex with scaffolding protein FAP-1. Blood 2008, 112:3465-3473.'},{id:"B98",body:'Margadant C, Monsuur HN, Norman JC, Sonnenberg A: Mechanisms of integrin activation and trafficking. Curr Opin Cell Biol 2011, 23:607-614.'},{id:"B99",body:'Zutter MM, Edelson BT: The alpha2beta1 integrin: a novel collectin/C1q receptor. Immunobiology 2007, 212:343-353.'},{id:"B100",body:'Edelson BT, Stricker TP, Li Z, Dickeson SK, Shepherd VL, Santoro SA, Zutter MM: Novel collectin/C1q receptor mediates mast cell activation and innate immunity. Blood 2006, 107:143-150.'},{id:"B101",body:'Elton CM, Smethurst PA, Eggleton P, Farndale RW: Physical and functional interaction between cell-surface calreticulin and the collagen receptors integrin alpha2beta1 and glycoprotein VI in human platelets. Thromb Haemost 2002, 88:648-654.'},{id:"B102",body:'Herz J, Strickland DK: LRP: a multifunctional scavenger and signaling receptor. J Clin Invest 2001, 108:779-784.'},{id:"B103",body:'Lillis AP, Greenlee MC, Mikhailenko I, Pizzo SV, Tenner AJ, Strickland DK, Bohlson SS: Murine low-density lipoprotein receptor-related protein 1 (LRP) is required for phagocytosis of targets bearing LRP ligands but is not required for C1q-triggered enhancement of phagocytosis. J Immunol 2008, 181:364-373.'},{id:"B104",body:'Berwin B, Delneste Y, Lovingood RV, Post SR, Pizzo SV: SREC-I, a type F scavenger receptor, is an endocytic receptor for calreticulin. J Biol Chem 2004, 279:51250-51257.'},{id:"B105",body:'Ishii J, Adachi H, Aoki J, Koizumi H, Tomita S, Suzuki T, Tsujimoto M, Inoue K, Arai H: SREC-II, a new member of the scavenger receptor type F family, trans-interacts with SREC-I through its extracellular domain. J Biol Chem 2002, 277:39696-39702.'},{id:"B106",body:'Fritz G: RAGE: a single receptor fits multiple ligands. Trends Biochem Sci 2011, 36:625-632.'},{id:"B107",body:'Sorci G, Riuzzi F, Giambanco I, Donato R: RAGE in tissue homeostasis, repair and regeneration. Biochim Biophys Acta 2013, 1833:101-109.'},{id:"B108",body:'Friggeri A, Banerjee S, Biswas S, de Freitas A, Liu G, Bierhaus A, Abraham E: Participation of the receptor for advanced glycation end products in efferocytosis. J Immunol 2011, 186:6191-6198.'},{id:"B109",body:'He M, Kubo H, Morimoto K, Fujino N, Suzuki T, Takahasi T, Yamada M, Yamaya M, Maekawa T, Yamamoto Y, et al.: Receptor for advanced glycation end products binds to phosphatidylserine and assists in the clearance of apoptotic cells. EMBO Rep 2011, 12:358-364.'},{id:"B110",body:'Santilli F, Vazzana N, Bucciarelli LG, Davi G: Soluble forms of RAGE in human diseases: clinical and therapeutical implications. Curr Med Chem 2009, 16:940-952.'},{id:"B111",body:'Ma W, Rai V, Hudson BI, Song F, Schmidt AM, Barile GR: RAGE binds C1q and enhances C1q-mediated phagocytosis. Cell Immunol 2012, 274:72-82.'},{id:"B112",body:'Milutinovic PS, Englert JM, Crum LT, Mason NS, Ramsgaard L, Enghild JJ, Sparvero LJ, Lotze MT, Oury TD: Clearance kinetics and matrix binding partners of the receptor for advanced glycation end products. PLoS One 2014, 9:e88259.'},{id:"B113",body:'Dupuy AG, Caron E: Integrin-dependent phagocytosis: spreading from microadhesion to new concepts. J Cell Sci 2008, 121:1773-1783.'},{id:"B114",body:'Ranganathan S, Cao C, Catania J, Migliorini M, Zhang L, Strickland DK: Molecular basis for the interaction of low density lipoprotein receptor-related protein 1 (LRP1) with integrin alphaMbeta2: identification of binding sites within alphaMbeta2 for LRP1. J Biol Chem 2011, 286:30535-30541.'},{id:"B115",body:'Lahti M, Heino J, Kapyla J: Leukocyte integrins alphaLbeta2, alphaMbeta2 and alphaXbeta2 as collagen receptors--receptor activation and recognition of GFOGER motif. Int J Biochem Cell Biol 2013, 45:1204-1211.'},{id:"B116",body:'Garcia-Vallejo JJ, van Kooyk Y: The physiological role of DC-SIGN: a tale of mice and men. Trends Immunol 2013, 34:482-486.'},{id:"B117",body:'Ludwig IS, Geijtenbeek TB, van Kooyk Y: Two way communication between neutrophils and dendritic cells. Curr Opin Pharmacol 2006, 6:408-413.'},{id:"B118",body:'Prabagar MG, Do Y, Ryu S, Park JY, Choi HJ, Choi WS, Yun TJ, Moon J, Choi IS, Ko K, et al.: SIGN-R1, a C-type lectin, enhances apoptotic cell clearance through the complement deposition pathway by interacting with C1q in the spleen. Cell Death Differ 2013, 20:535-545.'},{id:"B119",body:'Meyaard L: The inhibitory collagen receptor LAIR-1 (CD305). J Leukoc Biol 2008, 83:799-803.'},{id:"B120",body:'Lebbink RJ, de Ruiter T, Adelmeijer J, Brenkman AB, van Helvoort JM, Koch M, Farndale RW, Lisman T, Sonnenberg A, Lenting PJ, et al.: Collagens are functional, high affinity ligands for the inhibitory immune receptor LAIR-1. J Exp Med 2006, 203:1419-1425.'},{id:"B121",body:'Olde Nordkamp MJ, Boross P, Yildiz C, Jansen JH, Leusen JH, Wouters D, Urbanus RT, Hack CE, Meyaard L: Inhibition of the classical and lectin pathway of the complement system by recombinant LAIR-2. J Innate Immun 2014, 6:284-292.'},{id:"B122",body:'Olde Nordkamp MJ, van Eijk M, Urbanus RT, Bont L, Haagsman HP, Meyaard L: Leukocyte-associated Ig-like receptor-1 is a novel inhibitory receptor for surfactant protein D. J Leukoc Biol 2014, 96:105-111.'},{id:"B123",body:'Son M, Diamond B: C1q-mediated repression of human monocytes is regulated by LAIR-1. Mol Med 2014.'},{id:"B124",body:'Morgan BP, Walport MJ: Complement deficiency and disease. Immunol Today 1991, 12:301-306.'},{id:"B125",body:'Manderson AP, Botto M, Walport MJ: The role of complement in the development of systemic lupus erythematosus. Annu Rev Immunol 2004, 22:431-456.'},{id:"B126",body:'Trendelenburg M, Lopez-Trascasa M, Potlukova E, Moll S, Regenass S, Fremeaux-Bacchi V, Martinez-Ara J, Jancova E, Picazo ML, Honsova E, et al.: High prevalence of anti-C1q antibodies in biopsy-proven active lupus nephritis. Nephrol Dial Transplant 2006, 21:3115-3121.'},{id:"B127",body:'Siegert C, Daha M, Westedt ML, van der Voort E, Breedveld F: IgG autoantibodies against C1q are correlated with nephritis, hypocomplementemia, and dsDNA antibodies in systemic lupus erythematosus. J Rheumatol 1991, 18:230-234.'},{id:"B128",body:'Schaller M, Bigler C, Danner D, Ditzel HJ, Trendelenburg M: Autoantibodies against C1q in systemic lupus erythematosus are antigen-driven. J Immunol 2009, 183:8225-8231.'},{id:"B129",body:'van den Berg RH, Siegert CE, Faber-Krol MC, Huizinga TW, van Es LA, Daha MR: Anti-C1q receptor/calreticulin autoantibodies in patients with systemic lupus erythematosus (SLE). Clin Exp Immunol 1998, 111:359-364.'},{id:"B130",body:'Roumenina LT, Sene D, Radanova M, Blouin J, Halbwachs-Mecarelli L, Dragon-Durey MA, Fridman WH, Fremeaux-Bacchi V: Functional complement C1q abnormality leads to impaired immune complexes and apoptotic cell clearance. J Immunol 2011, 187:4369-4373.'},{id:"B131",body:'Botto M: C1q knock-out mice for the study of complement deficiency in autoimmune disease. Exp Clin Immunogenet 1998, 15:231-234.'},{id:"B132",body:'Botto M, Walport MJ: C1q, autoimmunity and apoptosis. Immunobiology 2002, 205:395-406.'},{id:"B133",body:'Nash JT, Taylor PR, Botto M, Norsworthy PJ, Davies KA, Walport MJ: Immune complex processing in C1q-deficient mice. Clin Exp Immunol 2001, 123:196-202.'},{id:"B134",body:'Baumann I, Kolowos W, Voll RE, Manger B, Gaipl U, Neuhuber WL, Kirchner T, Kalden JR, Herrmann M: Impaired uptake of apoptotic cells into tingible body macrophages in germinal centers of patients with systemic lupus erythematosus. Arthritis Rheum 2002, 46:191-201.'},{id:"B135",body:'Ippolito A, Wallace DJ, Gladman D, Fortin PR, Urowitz M, Werth V, Costner M, Gordon C, Alarcon GS, Ramsey-Goldman R, et al.: Autoantibodies in systemic lupus erythematosus: comparison of historical and current assessment of seropositivity. Lupus 2011, 20:250-255.'},{id:"B136",body:'Eggleton P, Ukoumunne OC, Cottrell I, Khan A, Maqsood S, Thornes J, Perry E, Isenberg D: Autoantibodies against C1q as a Diagnostic Measure of Lupus Nephritis: Systematic Review and Meta-analysis. J Clin Cell Immunol 2014, 5:210.'},{id:"B137",body:'Kishore U, Sontheimer RD, Sastry KN, Zappi EG, Hughes GR, Khamashta MA, Reid KB, Eggleton P: The systemic lupus erythematosus (SLE) disease autoantigen-calreticulin can inhibit C1q association with immune complexes. Clin Exp Immunol 1997, 108:181-190.'},{id:"B138",body:'Gabillet J, Millet A, Pederzoli-Ribeil M, Tacnet-Delorme P, Guillevin L, Mouthon L, Frachet P, Witko-Sarsat V: Proteinase 3, the autoantigen in granulomatosis with polyangiitis, associates with calreticulin on apoptotic neutrophils, impairs macrophage phagocytosis, and promotes inflammation. J Immunol 2012, 189:2574-2583.'},{id:"B139",body:'Witko-Sarsat V, Reuter N, Mouthon L: Interaction of proteinase 3 with its associated partners: implications in the pathogenesis of Wegener\'s granulomatosis. Curr Opin Rheumatol 2010, 22:1-7.'},{id:"B140",body:'Ghebrehiwet B, Hosszu KK, Valentino A, Ji Y, Peerschke EI: Monocyte Expressed Macromolecular C1 and C1q Receptors as Molecular Sensors of Danger: Implications in SLE. Front Immunol 2014, 5:278.'},{id:"B141",body:'Castellano G, Woltman AM, Schlagwein N, Xu W, Schena FP, Daha MR, van Kooten C: Immune modulation of human dendritic cells by complement. Eur J Immunol 2007, 37:2803-2811.'},{id:"B142",body:'Peerschke EI, Ghebrehiwet B: Modulation of platelet responses to collagen by Clq receptors. J Immunol 1990, 144:221-225.'},{id:"B143",body:'Jiang K, Chen Y, Xu CS, Jarvis JN: T cell activation by soluble C1q-bearing immune complexes: implications for the pathogenesis of rheumatoid arthritis. Clin Exp Immunol 2003, 131:61-67.'},{id:"B144",body:'Barilla-LaBarca ML, Atkinson JP: Rheumatic syndromes associated with complement deficiency. Curr Opin Rheumatol 2003, 15:55-60.'},{id:"B145",body:'Grumach AS, Kirschfink M: Are complement deficiencies really rare? Overview on prevalence, clinical importance and modern diagnostic approach. Mol Immunol 2014, 61:110-117.'},{id:"B146",body:'Morelli AE, Larregina AT: Apoptotic cell-based therapies against transplant rejection: role of recipient\'s dendritic cells. Apoptosis 2010, 15:1083-1097.'},{id:"B147",body:'Devitt A, Parker KG, Ogden CA, Oldreive C, Clay MF, Melville LA, Bellamy CO, Lacy-Hulbert A, Gangloff SC, Goyert SM, et al.: Persistence of apoptotic cells without autoimmune disease or inflammation in CD14-/- mice. J Cell Biol 2004, 167:1161-1170.'},{id:"B148",body:'Stuart LM, Takahashi K, Shi L, Savill J, Ezekowitz RA: Mannose-binding lectin-deficient mice display defective apoptotic cell clearance but no autoimmune phenotype. J Immunol 2005, 174:3220-3226.'},{id:"B149",body:'Pfueller B, Wolbart K, Bruns A, Burmester GR, Hiepe F: Successful treatment of patients with systemic lupus erythematosus by immunoadsorption with a C1q column: a pilot study. Arthritis Rheum 2001, 44:1962-1963.'},{id:"B150",body:'Mehta P, Norsworthy PJ, Hall AE, Kelly SJ, Walport MJ, Botto M, Pickering MC: SLE with C1q deficiency treated with fresh frozen plasma: a 10-year experience. Rheumatology (Oxford) 2010, 49:823-824.'},{id:"B151",body:'Bally I, Ancelet S, Moriscot C, Gonnet F, Mantovani A, Daniel R, Schoehn G, Arlaud GJ, Thielens NM: Expression of recombinant human complement C1q allows identification of the C1r/C1s-binding sites. Proc Natl Acad Sci U S A 2013, 110:8650-8655.'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Philippe Frachet",address:"philippe.frachet@ibs.fr",affiliation:'
Immune Response to Pathogens and Altered Self (IRPAS) Group, Université Grenoble Alpes, CNRS and CEA, Institut de Biologie Structurale (IBS), Grenoble, France
Immune Response to Pathogens and Altered Self (IRPAS) Group, Université Grenoble Alpes, CNRS and CEA, Institut de Biologie Structurale (IBS), Grenoble, France
Immune Response to Pathogens and Altered Self (IRPAS) Group, Université Grenoble Alpes, CNRS and CEA, Institut de Biologie Structurale (IBS), Grenoble, France
'},{corresp:null,contributorFullName:"Nicole M. Thielens",address:null,affiliation:'
Immune Response to Pathogens and Altered Self (IRPAS) Group, Université Grenoble Alpes, CNRS and CEA, Institut de Biologie Structurale (IBS), Grenoble, France
'}],corrections:null},book:{id:"4560",title:"Autoimmunity",subtitle:"Pathogenesis, Clinical Aspects and Therapy of Specific Autoimmune Diseases",fullTitle:"Autoimmunity - Pathogenesis, Clinical Aspects and Therapy of Specific Autoimmune Diseases",slug:"autoimmunity-pathogenesis-clinical-aspects-and-therapy-of-specific-autoimmune-diseases",publishedDate:"June 17th 2015",bookSignature:"Katerina Chatzidionysiou",coverURL:"https://cdn.intechopen.com/books/images_new/4560.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"138809",title:"Dr.",name:"Katerina",middleName:null,surname:"Chatzidionysiou",slug:"katerina-chatzidionysiou",fullName:"Katerina Chatzidionysiou"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"48526",title:"Crosstalk Between Oxidative Stress, Autophagy and Cell Death — Pathogenesis of Autoimmune Disease",slug:"crosstalk-between-oxidative-stress-autophagy-and-cell-death-pathogenesis-of-autoimmune-disease",totalDownloads:1411,totalCrossrefCites:0,signatures:"Dilip Shah, Dheeraj Mohania, Nidhi Mahajan, Sangita Sah,\nBishnuhari Paudyal and Swapan K. Nath",authors:[{id:"142238",title:"Dr.",name:"Dilip",middleName:null,surname:"Shah",fullName:"Dilip Shah",slug:"dilip-shah"},{id:"155220",title:"Prof.",name:"Swapan K.",middleName:null,surname:"Nath",fullName:"Swapan K. Nath",slug:"swapan-k.-nath"},{id:"172952",title:"Prof.",name:"Swapan",middleName:null,surname:"Nath",fullName:"Swapan Nath",slug:"swapan-nath"},{id:"172953",title:"Dr.",name:"Dheeraj",middleName:null,surname:"Mohania",fullName:"Dheeraj Mohania",slug:"dheeraj-mohania"},{id:"173497",title:"Dr.",name:"Nidhi",middleName:null,surname:"Mahajan",fullName:"Nidhi Mahajan",slug:"nidhi-mahajan"}]},{id:"48484",title:"Role of C1q in Efferocytosis and Self-Tolerance — Links With Autoimmunity",slug:"role-of-c1q-in-efferocytosis-and-self-tolerance-links-with-autoimmunity",totalDownloads:1610,totalCrossrefCites:4,signatures:"Philippe Frachet, Pascale Tacnet-Delorme, Christine Gaboriaud and\nNicole M. Thielens",authors:[{id:"172578",title:"Dr.",name:"Philippe",middleName:null,surname:"Frachet",fullName:"Philippe Frachet",slug:"philippe-frachet"},{id:"174451",title:"Dr.",name:"Pascale",middleName:null,surname:"Tacnet-Delorme",fullName:"Pascale Tacnet-Delorme",slug:"pascale-tacnet-delorme"},{id:"174453",title:"Dr.",name:"Christine",middleName:null,surname:"Gaboriaud",fullName:"Christine Gaboriaud",slug:"christine-gaboriaud"},{id:"174454",title:"Dr.",name:"Nicole",middleName:null,surname:"Thielens",fullName:"Nicole Thielens",slug:"nicole-thielens"}]},{id:"47991",title:"Implication of Regional Activation of Toll-Like Receptor 3/ Interferon-β Signaling in Human Mesangial Cells — Possible Involvement in the Pathogenesis of Lupus Nephritis",slug:"implication-of-regional-activation-of-toll-like-receptor-3-interferon-signaling-in-human-mesangial-c",totalDownloads:768,totalCrossrefCites:0,signatures:"Hiroshi Tanaka, Kazushi Tsuruga and Tadaatsu Imaizumi",authors:[{id:"175882",title:"Dr.",name:"Hiroshi",middleName:null,surname:"Tanaka",fullName:"Hiroshi Tanaka",slug:"hiroshi-tanaka"}]},{id:"48537",title:"Autoimmunity in Children with Primary Immunodeficiency – Diagnosis, Management and Therapy",slug:"autoimmunity-in-children-with-primary-immunodeficiency-diagnosis-management-and-therapy",totalDownloads:1024,totalCrossrefCites:1,signatures:"Anna Pituch-Noworolska",authors:[{id:"146338",title:"Dr",name:"Anna",middleName:null,surname:"Pituch-Noworolska",fullName:"Anna Pituch-Noworolska",slug:"anna-pituch-noworolska"}]},{id:"48381",title:"A Concise Review of Autoimmune Liver Diseases",slug:"a-concise-review-of-autoimmune-liver-diseases",totalDownloads:2194,totalCrossrefCites:2,signatures:"Nwe Ni Than and Ye Htun Oo",authors:[{id:"172180",title:"Dr.",name:"Ye Htun",middleName:null,surname:"Oo",fullName:"Ye Htun Oo",slug:"ye-htun-oo"},{id:"172780",title:"Dr.",name:"Nwe Ni",middleName:null,surname:"Than",fullName:"Nwe Ni Than",slug:"nwe-ni-than"}]},{id:"48538",title:"Celiac Disease and Other Autoimmune Disorders",slug:"celiac-disease-and-other-autoimmune-disorders",totalDownloads:1350,totalCrossrefCites:1,signatures:"M.I. Torres, T. Palomeque and P. Lorite",authors:[{id:"34102",title:"Dr.",name:"Mª Isabel",middleName:null,surname:"Torres",fullName:"Mª Isabel Torres",slug:"ma-isabel-torres"}]},{id:"47867",title:"Vitiligo – A Complex Autoimmune Skin Depigmenting Disease",slug:"vitiligo-a-complex-autoimmune-skin-depigmenting-disease",totalDownloads:1657,totalCrossrefCites:2,signatures:"Mitesh Dwivedi, Naresh C. Laddha, Anthony P. Weetman,\nRasheedunnisa Begum and Helen Kemp",authors:[{id:"172546",title:"Dr.",name:"Mitesh",middleName:"Kumar",surname:"Dwivedi",fullName:"Mitesh Dwivedi",slug:"mitesh-dwivedi"}]},{id:"48143",title:"Will Understanding Methotrexate Modes of Action Teach us About Rheumatoid Arthritis?",slug:"will-understanding-methotrexate-modes-of-action-teach-us-about-rheumatoid-arthritis-",totalDownloads:1099,totalCrossrefCites:0,signatures:"Charles F. Spurlock III, Nancy J. Olsen and Thomas M. Aune",authors:[{id:"172784",title:"Prof.",name:"Thomas",middleName:null,surname:"Aune",fullName:"Thomas Aune",slug:"thomas-aune"}]}]},relatedBooks:[{type:"book",id:"1388",title:"Autoimmune Disorders",subtitle:"Current Concepts and Advances from Bedside to Mechanistic Insights",isOpenForSubmission:!1,hash:"f3365e915e5d7c7299da6c076aa5cf24",slug:"autoimmune-disorders-current-concepts-and-advances-from-bedside-to-mechanistic-insights",bookSignature:"Fang-Ping Huang",coverURL:"https://cdn.intechopen.com/books/images_new/1388.jpg",editedByType:"Edited by",editors:[{id:"42618",title:"Dr.",name:"Fang-Ping",surname:"Huang",slug:"fang-ping-huang",fullName:"Fang-Ping Huang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"20659",title:"Autoimmune Disorders Associated to Type 1 Diabetes Mellitus in Children and Adolescents",slug:"autoimmune-disorders-associated-to-type-1-diabetes-mellitus-in-children-and-adolescents",signatures:"Giuseppe d’Annunzio and Chiara Russo, Ramona Tallone and Renata Lorini",authors:[{id:"39758",title:"Dr.",name:"Giuseppe",middleName:null,surname:"D'Annunzio",fullName:"Giuseppe D'Annunzio",slug:"giuseppe-d'annunzio"},{id:"52571",title:"Dr.",name:"Chiara",middleName:null,surname:"Russo",fullName:"Chiara Russo",slug:"chiara-russo"},{id:"52572",title:"Prof.",name:"Renata",middleName:null,surname:"Lorini",fullName:"Renata Lorini",slug:"renata-lorini"},{id:"53744",title:"Dr.",name:"Ramona",middleName:null,surname:"Tallone",fullName:"Ramona Tallone",slug:"ramona-tallone"}]},{id:"20660",title:"Hashimoto's Thyroiditis in Children and Adolescents",slug:"hashimoto-s-thyroiditis-in-children-and-adolescents",signatures:"Erkan Sarı, Abdulbaki Karaoglu and Ediz Yeşilkaya",authors:[{id:"59265",title:"Dr.",name:"Ediz",middleName:null,surname:"Yesilkaya",fullName:"Ediz Yesilkaya",slug:"ediz-yesilkaya"},{id:"59267",title:"Dr.",name:"Erkan",middleName:null,surname:"Sari",fullName:"Erkan Sari",slug:"erkan-sari"},{id:"91048",title:"Dr.",name:"Abdulbaki",middleName:null,surname:"Karaoglu",fullName:"Abdulbaki Karaoglu",slug:"abdulbaki-karaoglu"}]},{id:"20661",title:"Primary Sjögren’s Syndrome: Current Pathophysiological, Diagnostic and Therapeutic Advances",slug:"primary-sjo-gren-s-syndrome-current-pathophysiological-diagnostic-and-therapeutic-advances",signatures:"Christine Delporte, Jason Perret and Muhammad S. Soyfoo",authors:[{id:"40743",title:"Prof.",name:"Christine",middleName:null,surname:"Delporte",fullName:"Christine Delporte",slug:"christine-delporte"},{id:"51555",title:"Prof.",name:"Jason",middleName:null,surname:"Perret",fullName:"Jason Perret",slug:"jason-perret"},{id:"51556",title:"Dr",name:"Muhammad",middleName:"Shahnawaz",surname:"Soyfoo",fullName:"Muhammad Soyfoo",slug:"muhammad-soyfoo"}]},{id:"20662",title:"Changing Spectrum of Chronic Immune Thrombocytopenic Purpura: New Face for an Old Disease",slug:"changing-spectrum-of-chronic-immune-thrombocytopenic-purpura-new-face-for-an-old-disease",signatures:"Indu Sabnani and Patricia Tsang",authors:[{id:"53121",title:"Dr.",name:"Indu",middleName:null,surname:"Sabnani",fullName:"Indu Sabnani",slug:"indu-sabnani"},{id:"53153",title:"Dr.",name:"Patricia",middleName:null,surname:"Tsang",fullName:"Patricia Tsang",slug:"patricia-tsang"}]},{id:"23462",title:"Autoimmune-Associated Hemophagocytic Syndrome/Macrophage Activation Syndrome",slug:"autoimmune-associated-hemophagocytic-syndrome-macrophage-activation-syndrome",signatures:"Maciej Machaczka, Wojciech Sydor, Małgorzata Rucińska, Marta Szostek and Jacek Musiał",authors:[{id:"37510",title:"Dr.",name:"Maciej",middleName:"J.",surname:"Machaczka",fullName:"Maciej Machaczka",slug:"maciej-machaczka"},{id:"53497",title:"Dr.",name:"Malgorzata",middleName:"Maria",surname:"Rucinska",fullName:"Malgorzata Rucinska",slug:"malgorzata-rucinska"},{id:"93873",title:"Dr.",name:"Wojciech",middleName:"J.",surname:"Sydor",fullName:"Wojciech Sydor",slug:"wojciech-sydor"},{id:"93874",title:"Dr.",name:"Marta",middleName:null,surname:"Szostek",fullName:"Marta Szostek",slug:"marta-szostek"},{id:"93875",title:"Prof.",name:"Jacek",middleName:null,surname:"Musial",fullName:"Jacek Musial",slug:"jacek-musial"}]},{id:"20664",title:"Ocular Myasthenia Analysis of Diagnostic and Treatment Options",slug:"ocular-myasthenia-analysis-of-diagnostic-and-treatment-options",signatures:"Austin Hake and Henry J. Kaminski",authors:[{id:"40795",title:"Dr.",name:"Henry",middleName:null,surname:"Kaminski",fullName:"Henry Kaminski",slug:"henry-kaminski"},{id:"136016",title:"Prof.",name:"Austin",middleName:null,surname:"Hake",fullName:"Austin Hake",slug:"austin-hake"}]},{id:"20665",title:"Sweet Syndrome",slug:"sweet-syndrome",signatures:"Manuel Ginarte and Jaime Toribio",authors:[{id:"35090",title:"Dr.",name:"Manuel",middleName:null,surname:"Ginarte",fullName:"Manuel Ginarte",slug:"manuel-ginarte"},{id:"136018",title:"Dr.",name:"Jaime",middleName:null,surname:"Toribio",fullName:"Jaime Toribio",slug:"jaime-toribio"}]},{id:"20666",title:"Validation of Protein Biomarkers to Advance the Management of Autoimmune Disorders",slug:"validation-of-protein-biomarkers-to-advance-the-management-of-autoimmune-disorders",signatures:"David S. Gibson, Sorcha Finnegan, Stephen Pennington, Ji Qiu, Joshua LaBaer, Madeleine E. Rooney and Mark W. Duncan",authors:[{id:"40972",title:"Dr.",name:"David",middleName:null,surname:"Gibson",fullName:"David Gibson",slug:"david-gibson"},{id:"40988",title:"Prof.",name:"Mark",middleName:null,surname:"Duncan",fullName:"Mark Duncan",slug:"mark-duncan"},{id:"89331",title:"Dr",name:"Sorcha",middleName:null,surname:"Finnegan",fullName:"Sorcha Finnegan",slug:"sorcha-finnegan"},{id:"89714",title:"Dr.",name:"Madeleine",middleName:null,surname:"Rooney",fullName:"Madeleine Rooney",slug:"madeleine-rooney"},{id:"89766",title:"Prof.",name:"Stephen",middleName:null,surname:"Pennington",fullName:"Stephen Pennington",slug:"stephen-pennington"},{id:"89767",title:"Dr.",name:"Ji",middleName:null,surname:"Qiu",fullName:"Ji Qiu",slug:"ji-qiu"},{id:"90269",title:"Prof.",name:"Joshua",middleName:null,surname:"LaBaer",fullName:"Joshua LaBaer",slug:"joshua-labaer"}]},{id:"20667",title:"Relevance of Autoantibodies for the Classification and Pathogenesis of Neurological Diseases",slug:"relevance-of-autoantibodies-for-the-classification-and-pathogenesis-of-neurological-diseases",signatures:"Simone Mader, Benjamin Obholzer and Markus Reindl",authors:[{id:"39318",title:"Prof.",name:"Markus",middleName:null,surname:"Reindl",fullName:"Markus Reindl",slug:"markus-reindl"},{id:"39330",title:"Dr.",name:"Simone",middleName:null,surname:"Mader",fullName:"Simone Mader",slug:"simone-mader"},{id:"93770",title:"MSc.",name:"Benjamin",middleName:null,surname:"Obholzer",fullName:"Benjamin Obholzer",slug:"benjamin-obholzer"}]},{id:"20668",title:"Preclinical and Predictive Algorithms in Monitoring Patients with Autoimmune Diseases and Their Relatives-at-Risks",slug:"preclinical-and-predictive-algorithms-in-monitoring-patients-with-autoimmune-diseases-and-their-rela",signatures:"Sergey Suchkov, Dmitry Kostyushev, Dmitry Gnatenko, Sevindzh Gadzhieva and Mikhail Paltsev",authors:[{id:"40368",title:"Prof.",name:"Sergey",middleName:"Victorovich",surname:"Suchkov",fullName:"Sergey Suchkov",slug:"sergey-suchkov"},{id:"49152",title:"Dr.",name:"Dmitry",middleName:"Sergeevich",surname:"Kostyushev",fullName:"Dmitry Kostyushev",slug:"dmitry-kostyushev"},{id:"49153",title:"Prof.",name:"Dmitrii",middleName:null,surname:"Gnatenko",fullName:"Dmitrii Gnatenko",slug:"dmitrii-gnatenko"},{id:"49154",title:"Dr.",name:"Sevindj",middleName:null,surname:"Gadjieva",fullName:"Sevindj Gadjieva",slug:"sevindj-gadjieva"},{id:"49155",title:"Prof.",name:"Mihail",middleName:null,surname:"Paltsev",fullName:"Mihail Paltsev",slug:"mihail-paltsev"}]},{id:"20669",title:"Application of Novel Quantitative Proteomic Technologies to Identify New Serological Biomarkers in Autoimmune Diseases",slug:"application-of-novel-quantitative-proteomic-technologies-to-identify-new-serological-biomarkers-in-a",signatures:"Soyoung Lee, Satoshi Serada, Minoru Fujimoto and Tetsuji Naka",authors:[{id:"40263",title:"Prof.",name:"Tetsuji",middleName:null,surname:"Naka",fullName:"Tetsuji Naka",slug:"tetsuji-naka"},{id:"54042",title:"Prof.",name:"Satoshi",middleName:null,surname:"Serada",fullName:"Satoshi Serada",slug:"satoshi-serada"},{id:"54043",title:"Prof.",name:"Minoru",middleName:null,surname:"Fujimoto",fullName:"Minoru Fujimoto",slug:"minoru-fujimoto"},{id:"64673",title:"Dr.",name:"Soyoung",middleName:null,surname:"Lee",fullName:"Soyoung Lee",slug:"soyoung-lee"}]},{id:"20670",title:"Application of Monoclonal Antibody Therapies in Autoimmune Diseases",slug:"application-of-monoclonal-antibody-therapies-in-autoimmune-diseases",signatures:"Adrienn Angyal, Jozsef Prechl, Gyorgy Nagy and Gabriella Sarmay",authors:[{id:"54397",title:"Dr",name:"Adrienn",middleName:null,surname:"Angyal",fullName:"Adrienn Angyal",slug:"adrienn-angyal"},{id:"54406",title:"Prof.",name:"Jozsef",middleName:null,surname:"Prechl",fullName:"Jozsef Prechl",slug:"jozsef-prechl"},{id:"54407",title:"Prof.",name:"Gabriella",middleName:null,surname:"Sarmay",fullName:"Gabriella Sarmay",slug:"gabriella-sarmay"},{id:"145362",title:"Prof.",name:"György M.",middleName:null,surname:"Nagy",fullName:"György M. Nagy",slug:"gyorgy-m.-nagy"}]},{id:"20671",title:"The Emerging Role of Monoclonal Antibodies in the Treatmentof Systemic Lupus Erythematosus",slug:"the-emerging-role-of-monoclonal-antibodies-in-the-treatmentof-systemic-lupus-erythematosus",signatures:"Ewa Robak and Tadeusz Robak",authors:[{id:"34135",title:"Prof.",name:"Tadeusz",middleName:null,surname:"Robak",fullName:"Tadeusz Robak",slug:"tadeusz-robak"},{id:"34143",title:"Prof.",name:"Ewa",middleName:null,surname:"Robak",fullName:"Ewa Robak",slug:"ewa-robak"}]},{id:"20672",title:"Treatment of Pediatric-Onset Lupus Nephritis: A New Option of Less Cytotoxic Immunosuppressive Therapy",slug:"treatment-of-pediatric-onset-lupus-nephritis-a-new-option-of-less-cytotoxic-immunosuppressive-therap",signatures:"Hiroshi Tanaka and Tadaatsu Imaizumi",authors:[{id:"37530",title:"Dr.",name:"Hiroshi",middleName:null,surname:"Tanaka",fullName:"Hiroshi Tanaka",slug:"hiroshi-tanaka"},{id:"52589",title:"Dr.",name:"Tadaatsu",middleName:null,surname:"Imaizumi",fullName:"Tadaatsu Imaizumi",slug:"tadaatsu-imaizumi"}]},{id:"20673",title:"Recent Advances in the Treatment of Neurological Autoimmune Disorders",slug:"recent-advances-in-the-treatment-of-neurological-autoimmune-disorders",signatures:"Jagat R. Kanwar, Bhasker Sriramoju and Rupinder K. Kanwar",authors:[{id:"40068",title:"Prof.",name:"Jagat",middleName:"Rakesh",surname:"Kanwar",fullName:"Jagat Kanwar",slug:"jagat-kanwar"},{id:"53589",title:"Dr.",name:"Rupinder",middleName:null,surname:"Kanwar",fullName:"Rupinder Kanwar",slug:"rupinder-kanwar"}]},{id:"20674",title:"Synthetic Glucocorticoids Modulate Function of Neural Cells: Implications in Autoimmune Neurological Disorders",slug:"synthetic-glucocorticoids-modulate-function-of-neural-cells-implications-in-autoimmune-neurological-",signatures:"Oscar Gonzalez-Perez, Norma A. Moy-Lopez and Jorge Guzman-Muniz",authors:[{id:"35161",title:"Prof.",name:"Oscar",middleName:null,surname:"Gonzalez-Perez",fullName:"Oscar Gonzalez-Perez",slug:"oscar-gonzalez-perez"},{id:"94114",title:"Dr.",name:"Norma",middleName:null,surname:"Moy-Lopez",fullName:"Norma Moy-Lopez",slug:"norma-moy-lopez"},{id:"94115",title:"MSc.",name:"Jorge",middleName:null,surname:"Guzman-Muniz",fullName:"Jorge Guzman-Muniz",slug:"jorge-guzman-muniz"}]},{id:"20675",title:"Intravenous Immunoglobulins in Neurological Diseases: Established and Novel Clinical Applications",slug:"intravenous-immunoglobulins-in-neurological-diseases-established-and-novel-clinical-applications",signatures:"Konstantina G. Yiannopoulou",authors:[{id:"52626",title:"Dr.",name:"Konstantina",middleName:null,surname:"Yiannopoulou",fullName:"Konstantina Yiannopoulou",slug:"konstantina-yiannopoulou"}]},{id:"20676",title:"Cellular Based Therapies for the Treatment of Multiple Sclerosis",slug:"cellular-based-therapies-for-the-treatment-of-multiple-sclerosis",signatures:"James Crooks, Guang-Xian Zhang and Bruno Gran",authors:[{id:"38513",title:"Prof.",name:"Guang-Xian",middleName:null,surname:"Zhang",fullName:"Guang-Xian Zhang",slug:"guang-xian-zhang"},{id:"38803",title:"Dr.",name:"Bruno",middleName:null,surname:"Gran",fullName:"Bruno Gran",slug:"bruno-gran"},{id:"38804",title:"Mr.",name:"James",middleName:null,surname:"Crooks",fullName:"James Crooks",slug:"james-crooks"}]},{id:"20677",title:"Haematopoietic Cell Transplantation and Immunotherapy for Autoimmune Diseases in Children and Adults",slug:"haematopoietic-cell-transplantation-and-immunotherapy-for-autoimmune-diseases-in-children-and-adults",signatures:"Menachem Bitan",authors:[{id:"39092",title:"Dr.",name:"Menachem",middleName:null,surname:"Bitan",fullName:"Menachem Bitan",slug:"menachem-bitan"}]},{id:"20678",title:"Thionamides-Related Vasculitis in Autoimmune Thyroid Disorders: Review of Current Literature and Case Reports",slug:"thionamides-related-vasculitis-in-autoimmune-thyroid-disorders-review-of-current-literature-and-case",signatures:"Elisabetta L. Romeo, Giuseppina T. Russo, Annalisa Giandalia, Provvidenza Villari, Angela A. Mirto, Mariapaola Cucinotta, Giuseppa Perdichizzi and Domenico Cucinotta",authors:[{id:"53938",title:"Dr.",name:"Giuseppina T.",middleName:null,surname:"Russo",fullName:"Giuseppina T. Russo",slug:"giuseppina-t.-russo"},{id:"53940",title:"Dr.",name:"Elisabetta L.",middleName:null,surname:"Romeo",fullName:"Elisabetta L. Romeo",slug:"elisabetta-l.-romeo"},{id:"53941",title:"Dr.",name:"Annalisa",middleName:null,surname:"Giandalia",fullName:"Annalisa Giandalia",slug:"annalisa-giandalia"},{id:"95745",title:"Dr.",name:"Mariapaola",middleName:null,surname:"Cucinotta",fullName:"Mariapaola Cucinotta",slug:"mariapaola-cucinotta"},{id:"95746",title:"Prof.",name:"Giuseppa",middleName:null,surname:"Perdichizzi",fullName:"Giuseppa Perdichizzi",slug:"giuseppa-perdichizzi"},{id:"95749",title:"Prof.",name:"Domenico",middleName:null,surname:"Cucinotta",fullName:"Domenico Cucinotta",slug:"domenico-cucinotta"},{id:"115595",title:"Dr.",name:"Provvidenza",middleName:null,surname:"Villari",fullName:"Provvidenza Villari",slug:"provvidenza-villari"},{id:"115964",title:"Dr.",name:"Angela A.",middleName:null,surname:"Mirto",fullName:"Angela A. Mirto",slug:"angela-a.-mirto"}]},{id:"22843",title:"The Ectopic Germinal Centre Response in Autoimmune Disease and Cancer",slug:"the-ectopic-germinal-centre-response-in-autoimmune-disease-and-cancer",signatures:"David I. Stott and Donna McIntyre",authors:[{id:"110862",title:"Prof.",name:"David",middleName:"Ian",surname:"Stott",fullName:"David Stott",slug:"david-stott"},{id:"136021",title:"Dr.",name:"Donna",middleName:null,surname:"McIntyre",fullName:"Donna McIntyre",slug:"donna-mcintyre"}]},{id:"20680",title:"Myasthenia Gravis: New Insights into the Effect of MuSK Antibodies and Acetylcholinesterase Inhibitors",slug:"myasthenia-gravis-new-insights-into-the-effect-of-musk-antibodies-and-acetylcholinesterase-inhibitor",signatures:"Anna Rostedt Punga",authors:[{id:"38872",title:"Dr.",name:"Anna",middleName:"Rostedt",surname:"Punga",fullName:"Anna Punga",slug:"anna-punga"}]},{id:"20681",title:"Vasoactive Neuropeptides in Autoimmune Diseases",slug:"vasoactive-neuropeptides-in-autoimmune-diseases",signatures:"Ekua W. Brenu, Lotti Tajouri, Donald R. Staines and Sonya M. Marshall-Gradisnik",authors:[{id:"41142",title:"Ms",name:"Ekua",middleName:"Weba",surname:"Brenu",fullName:"Ekua Brenu",slug:"ekua-brenu"},{id:"53185",title:"Prof.",name:"Lotti",middleName:null,surname:"Tajouri",fullName:"Lotti Tajouri",slug:"lotti-tajouri"},{id:"53186",title:"Prof.",name:"Sonya",middleName:null,surname:"Marshall-Gradisnik",fullName:"Sonya Marshall-Gradisnik",slug:"sonya-marshall-gradisnik"},{id:"53187",title:"Prof.",name:"Don",middleName:null,surname:"Staines",fullName:"Don Staines",slug:"don-staines"}]},{id:"20682",title:"Antibody-Proteases in the Pathogenesis of Autoimmune Demyelination and Monitoring Patients with Multiple Sclerosis",slug:"antibody-proteases-in-the-pathogenesis-of-autoimmune-demyelination-and-monitoring-patients-with-mult",signatures:"Dmitry Kostyushev, Dmitry Gnatenko, Mikhail Paltsev, Aleksandr Gabibov and Sergey Suchkov",authors:[{id:"40368",title:"Prof.",name:"Sergey",middleName:"Victorovich",surname:"Suchkov",fullName:"Sergey Suchkov",slug:"sergey-suchkov"},{id:"49152",title:"Dr.",name:"Dmitry",middleName:"Sergeevich",surname:"Kostyushev",fullName:"Dmitry Kostyushev",slug:"dmitry-kostyushev"},{id:"49166",title:"Prof.",name:"Gabibov",middleName:null,surname:"Aleksandr",fullName:"Gabibov Aleksandr",slug:"gabibov-aleksandr"},{id:"107360",title:"Prof.",name:"Dmitrii",middleName:null,surname:"Gnatenko",fullName:"Dmitrii Gnatenko",slug:"dmitrii-gnatenko"},{id:"107467",title:"Prof.",name:"Mikhail",middleName:null,surname:"Paltsev",fullName:"Mikhail Paltsev",slug:"mikhail-paltsev"}]},{id:"20683",title:"Role of Fatty Acids in the Resolution of Autoimmune and Inflammatory Diseases",slug:"role-of-fatty-acids-in-the-resolution-of-autoimmune-and-inflammatory-diseases",signatures:"Elena Puertollano, María A. Puertollano, Gerardo Álvarez de Cienfuegos and Manuel A. de Pablo",authors:[{id:"35125",title:"Dr.",name:"Manuel Antonio",middleName:null,surname:"de Pablo",fullName:"Manuel Antonio de Pablo",slug:"manuel-antonio-de-pablo"},{id:"45341",title:"Dr.",name:"M. Angeles",middleName:null,surname:"Puertollano",fullName:"M. Angeles Puertollano",slug:"m.-angeles-puertollano"},{id:"45342",title:"Dr",name:"Elena",middleName:null,surname:"Puertollano",fullName:"Elena Puertollano",slug:"elena-puertollano"},{id:"45343",title:"Dr.",name:"Gerardo",middleName:null,surname:"Alvarez de Cienfuegos",fullName:"Gerardo Alvarez de Cienfuegos",slug:"gerardo-alvarez-de-cienfuegos"}]},{id:"20684",title:"Autoimmune Disorder and Autism",slug:"autoimmune-disorder-and-autism",signatures:"Xiaohong Li and Hua Zou",authors:[{id:"50228",title:"Dr.",name:"Xiaohong",middleName:null,surname:"Li",fullName:"Xiaohong Li",slug:"xiaohong-li"},{id:"50235",title:"Dr.",name:"Hua",middleName:null,surname:"Zou",fullName:"Hua Zou",slug:"hua-zou"}]},{id:"20685",title:"Chronobiology of and Chronotherapy for Rheumatoid Arthritis",slug:"chronobiology-of-and-chronotherapy-for-rheumatoid-arthritis",signatures:"Hideto To",authors:[{id:"45740",title:"Prof.",name:"Hideto",middleName:null,surname:"To",fullName:"Hideto To",slug:"hideto-to"}]},{id:"20686",title:"Four Aspects of Autoimmunity and How to Regain Tolerance to Self From an Autoimmune Disease Utilizing the Modified Vaccination Technique",slug:"four-aspects-of-autoimmunity-and-how-to-regain-tolerance-to-self-from-an-autoimmune-disease-utilizin",signatures:"Arpad Z. Barabas, Chad D. Cole, Arpad D. Barabas, Rene Lafreniere and Donald M. Weir",authors:[{id:"40002",title:"Dr.",name:"Arpad Z.",middleName:null,surname:"Barabas",fullName:"Arpad Z. Barabas",slug:"arpad-z.-barabas"},{id:"137145",title:"Dr.",name:"Chad",middleName:null,surname:"Cole",fullName:"Chad Cole",slug:"chad-cole"}]},{id:"20687",title:"Parasitic Helminths as Potential Therapeutic Agents Against Autoimmune Disorders",slug:"parasitic-helminths-as-potential-therapeutic-agents-against-autoimmune-disorders",signatures:"Yoshio Osada",authors:[{id:"44076",title:"Dr.",name:"Yoshio",middleName:null,surname:"Osada",fullName:"Yoshio Osada",slug:"yoshio-osada"}]}]}]},onlineFirst:{chapter:{type:"chapter",id:"73448",title:"Nutritional Approaches for Attenuating Muscle Atrophy",doi:"10.5772/intechopen.94009",slug:"nutritional-approaches-for-attenuating-muscle-atrophy",body:'
1. Introduction
Muscle mass and strength have been linked to overall health and mortality [1, 2], and improvements in skeletal muscle properties and the prevention of muscle wasting with disuse/atrophy are essential for all individuals, particularly inactive older adults [3]. Sarcopenia is characterized by the loss of skeletal muscle mass and physical function (muscle strength or physical performance) with advancing age [4, 5, 6]. It is associated with physical disability, poor quality of life, and increased mortality in older adults [5]. Although the loss of muscle mass and physical function is associated with aging, rates of decline vary across the population [7]. Therefore, modifiable behavioral factors, such as diet, may influence the development of sarcopenia. Since a poor diet and nutritional status are common among the elderly [8, 9, 10], improvements in these factors may contribute to the prevention and treatment of sarcopenia, thereby promoting better health in later life for this population [11].
The term diet quality describes how well an individual’s diet conforms to dietary recommendations using a principal component or factor analysis [12, 13]. In older adults, a higher quality diet leads to several positive health outcomes, including a reduced risk of common age-related diseases and greater longevity. For example, a high quality diet is associated with a significantly reduced risk of all-cause mortality, cardiovascular disease, cancer, type 2 diabetes, and neurodegenerative disease, as well as reduced mortality in cancer survivors [14, 15, 16, 17].
While there is growing evidence linking healthier diets with greater muscle strength and better physical performance outcomes in older adults, limited information is currently available on how diet quality influences sarcopenia in older adults [11, 18]. A recent systematic review concluded that the number of longitudinal studies was too small to reach concrete conclusions; however, there is growing evidence for the benefits of adhering to a Mediterranean diet [19, 20, 21]. The next section summarizes current epidemiological evidence for the relationship between diet quality and sarcopenia in older adults.
2. Nutritional approaches for attenuating muscle atrophy
2.1 Nutritional epidemiology evidence related to sarcopenia
The world’s population is getting older [22]. Based on a 2017 report, the number of adults aged 60 years and older will increase worldwide, from 962 million (or one in eight individuals) in 2017 to 2.1 billion (one in five) by the middle of the 21st century [23]. Several environmental and lifestyle factors may modify the aging process [24], including physical activity [25, 26] and diet [27, 28, 29].
A large number of observational and intervention studies have used a single-nutrient approach to investigate the relationship between diet and muscle health in aging. However, difficulties are associated with isolating the influence of one dietary component on health outcomes from other components as well as obtaining a clearer understanding of how dietary components interact within a whole diet to affect health outcomes. Previous studies using a whole-diet approach were conducted to clarify the role diet quality plays in muscle health with aging [30, 31, 32, 33].
Two main methods of defining diet quality—a priori (hypothesis-driven) and a posteriori (data driven)—have been used to investigate the relationships between diet quality and muscle health in epidemiological studies on muscle aging. The a priori method defines diet quality as adherence to predefined dietary scores or indices based on current knowledge on what constitutes a healthy diet for a particular health condition (e.g., cardiovascular disease or diabetes). In this method, higher scores reflect the greater consumption of beneficial foods (e.g., fruits, vegetables, lean meat, fish, nuts, and low-fat foods) and lower consumption of nutrient-poor foods (e.g., sweets, processed meat, refined grains, and trans-fats) [34, 35, 36]. In contrast, the a posteriori method is exploratory, using all available dietary data to define diet quality. This method may be used to describe a population’s normal diet, which may or may not be related to particular health outcomes. In this method, multivariate statistical tools (e.g., a factor principal component analysis [PCA] and cluster analysis) may be used to assess diet quality. While these two tools follow markedly different procedures, they may be used in tandem to improve the interpretability of the data obtained from each method [37].
We reviewed nutritional epidemiology studies on the role of diet quality in muscle health and function in older adults (Table 1). Only eight studies reported a relationship between diet quality (i.e., the amount of nutrients consumed and/or the uptake of specific nutrients from foods) and sarcopenia components [38, 39, 40, 41, 42, 43, 44, 45]. Five of these studies were cross-sectional, while three were longitudinal. Study sample sizes ranged between 156 and 2983 participants. The majority of studies were conducted in a community setting (e.g., a nursing home or care facility) and with participants whose mean age ranged between 65 and 75 years.
n = 791 men (n = 302) and women (n = 489), living either at home or in a care facility, 68.7 ± 0.3 years
Longitudinal
Three dietary patterns were identified. a. DP1, High Red Meat b. DP2, Low Meat c. DP3, High Butter
Men in DP1 had worse overall hand grip strength and slower timed up and go than those in DP2. Women in DP3 had slower timed up and go than those in DP2. Men in DP3 had a steeper decline in hand grip strength than those in DP1.
n = 1241 community-dwelling men (n = 646) and women (n = 595), 74.6 ± 5.5 years
Cross-sectional
Three dietary patterns were identified. a. DP1, high factor loading for fish, tofu, vegetables, and fruits b DP2, high factor loading for fish, rice, and miso soup c. DP3, high factor loading for noodles
Men with the lowest tertile of the DP1 score had a higher likelihood of being sarcopenic. Women with the lowest tertile of the DP2 score had a moderate likelihood of being sarcopenic.
Table 1.
Summary of diet quality and physical function in older adults.
Robinson et al. examined the relationship between diet quality and grip strength in older men and women [38]. A food frequency questionnaire (FFQ) based on the European Prospective Investigation of Cancer (EPIC) questionnaire was used to assess the subject’s diet. They used the FFQ that contained 129 foods and food groups and assessed the average frequency of the consumption of the listed foods over the three months preceding the interview. Nutrient intake for each food item consumed was calculated by multiplying the nutrient content listed in the UK national food composition database or manufacturer composition data. The 129 foods listed in the FFQ were divided into 54 food groups based on similarity and nutrient compositions. The PCA of the reported weekly consumption frequencies of these food groups was used to define diet patterns. The prudent diet was characterized by the high consumption of fruit, vegetables, whole grain cereals, and fatty fish and by the low consumption of white bread, chips, sugar, and full-fat dairy products. Participants with higher prudent diet scores had stronger grip strengths. In addition, an increase was observed in grip strength of 0.43 kg in men and 0.48 kg in women for each additional fatty fish portion consumed per week.
Martin et al. investigated the relationship between diet and physical performance (measured using a short physical performance battery) in a group of men and women living in West Hertfordshire who were part of the Hertfordshire Cohort Study [39]. Nutrient intake for each food item consumed was calculated by multiplying the nutrient content listed in the UK national food composition database or manufacturer composition data. Higher prudent diet scores were related to shorter three-meter walk times and shorter chair-rise times in women. Additionally, inverse relationships were observed between physical function and the consumption of vegetables, whitefish, shellfish, and oily fish. These findings indicate that a relationship exists between diet variations in community-dwelling older women and differences in physical performance. However, further studies are needed to clarify the role of diet variations in physical performance, particularly in men.
Bollwein et al. examined whether the risk of frailty was significantly reduced in participants who scored in the highest quartile for Mediterranean diet consumption (MED) [40]. This scoring is an alternative to the MED scoring used by Fung et al. [46], who adapted the original MED score used by Trichopoulou et al. [47] for a non-Mediterranean population. They combined FFQ foods into nine nutritional characteristics, classified as either beneficial (vegetables, legumes, fruits, unrefined cereals, nuts, fish, high monounsaturated fatty acid [MUFA]/saturated fatty acid [SFA] foods, and moderate alcohol consumption) or detrimental (red and processed meats) to health, to calculate the score, and found an inverse correlation between a low walking speed and MED scores. Moreover, a relationship was observed between high diet quality (high MED score) and slow walking speed in older men and women.
Rahi et al. investigated the relationship between diet quality and muscle strength changes over three years in diabetic participants aged 67 to 84 years [41]. Diet quality was evaluated at recruitment using the validated Diet Quality Index-Canada and nine-item Canadian Healthy Eating Index (C-HEI) [48]. Diet quality was calculated using data from the mean of three, non-consecutive, 24-hour dietary recalls collected using the five-step, multiple-pass method [49]. The C-HEI has nine components. The first four components evaluate the extent to which respondents meet age and gender-based recommendations for the number of portions eaten from each of the four groups of Canada’s Food Guide (grain products, vegetables and fruits, milk and alternatives, and meat and alternatives). The next four items reflect Canadian nutritional recommendations for moderation: the daily percentage of energy from total fat, the daily percentage of energy from saturated fat, cholesterol intake (mg), and sodium intake (mg). The final component, dietary variety (adapted from the Dietary Diversity Score), was assessed as the daily consumption of at least one food from each food group. The findings obtained indicated that the combination of a high diet quality with stable or increased physical activity minimized muscle strength losses in diabetic older males over the three-year follow-up period.
Hashemi et al. investigated whether adherence to a particular dietary pattern was associated with sarcopenia among elderly adults in a district of Teheran, Iran [42]. A semiquantitative FFQ was used to survey the dietary intake of 300 randomly-selected older men and women. They evaluated the dietary patterns of participants using PCA. Participants in the highest tertile of the Mediterranean dietary pattern had a lower odds ratio for developing sarcopenia than those in the lowest tertile. In contrast, adherence to the Western dietary pattern (characterized by the high consumption of sugar, soy, and fast foods) and mixed dietary pattern (characterized by the high consumption of animal proteins, potatoes, and refined grains) did not affect the odds of developing sarcopenia. These findings suggested that Mediterranean diet adherence was associated with a lower odds ratio for the development of sarcopenia among older Iranian individuals.
Granic et al. examined the relationship between previously established dietary patterns and declines in muscle strength and physical performance among older adults [43]. In total, 791 participants were followed for five years to detect changes in grip strength and timed up and go test (TUG) scores. Trained research nurses kept a detailed record of food intake on the previous day for each participant on two different days of the week, at least one week apart. Each food had a unique food code (>2000), and intakes were entered into a Microsoft Access-based dietary data system, then further grouped into 118 food groups based on McCance and Widdowson’s composition of foods [50, 51]. These 118 groups were combined into 33 food groups based on food/nutrient composition similarities and then classified as either absent or present in each participant’s food intake. Participants were divided into three groups: dietary pattern 1 (DP1; high red meat); dietary pattern 2 (DP2; low meat); and dietary pattern 3 (DP3; high butter). The findings obtained showed that men in DP1 had worse overall grip strength, whereas those in DP3 had steeper grip strength declines than those in DP2. Additionally, TUG scores were significantly longer for men in DP1 and women in DP3 than those in DP2. Therefore, diets high in red meats, potatoes, gravy, and butter appear to adversely affect muscle strength and physical performance in later life.
Perälä et al. researched whether the consumption of a healthy Nordic diet for 10 years was associated with improved physical performance measures [44]. After the diets of 1072 participants (mean age 67 years) had been examined using a validated 128-item FFQ, the a priori Nordic diet score was calculated. The diet items checked included Nordic fruits and berries, vegetables, cereals, low-fat milk, fish, red and processed meat, alcohol, polyunsaturated omega-3 fatty acids (PUFA)/SFA and trans-fatty acids ratios, and total fat. Since participants had a mean age of 71 years, their physical performance was measured using the Senior Fitness Test (SFT), and an overall SFT score was calculated. The findings obtained revealed that women with the highest diet scores had 17% better in that of walk, 16% better in that of arm curl, and 20% better in that of chair-stand than women with the lowest diet scores. These findings indicated that women who consumed a healthy Nordic diet had better physical performance (i.e., better aerobic endurance and upper and lower body strength) 10 years later.
Suthutvoravut et al. investigated the relationship between dietary patterns and sarcopenia in a sample of older community-dwelling Japanese adults [45]. The sample included 1241 older adults aged 65 years and older who were not eligible for long-term care. Dietary intake by participants was assessed using the brief self-administered diet history questionnaire. Dietary patterns were identified using both PCA and Japanese diet scores (soybeans and soybean products, fish, vegetables, pickles, mushrooms, seaweeds, and fruits). Participants were classified into three groups: dietary pattern 1 (DP1; high factor loading for the consumption of fish, tofu, vegetables, and fruits found in typical Japanese side dishes); dietary pattern 2 (DP2; high factor loading for fish, rice, and miso soup found in typical Japanese main dishes); and dietary pattern 3 (DP3; high factor loading for noodles). The findings obtained showed that men with the lowest tertile DP1 score had a higher likelihood of being sarcopenic, while women with the lowest tertile DP2 score had a moderate likelihood of being sarcopenic. Additionally, low adherence to Japanese dietary patterns increased with the prevalence of sarcopenia in both genders.
Many traditional regional diets may have similar benefits to those described here. We then focused on diets with demonstrated effects on muscle mass, reported by randomized controlled trials that investigated diet quality using precise parameters. For example, the traditional diets of Korea and China may be beneficial for preventing sarcopenia in the populations of these countries. Healthier diets are higher in plant-based food and lower in animal-based foods than Western diets. Further epidemiological studies are needed to investigate the relationship between healthy diets and development of sarcopenia throughout the world, particularly in developing countries.
2.2 Nutrient supplementation for attenuating sarcopenia
Skeletal muscle is a dynamic, plastic tissue with a mass that is regulated by the balance between the rates of muscle protein synthesis and breakdown. Adopting an appropriate dietary strategy is crucial for facilitating an anabolic response that may prevent muscle wasting with atrophy by suppressing the breakdown of muscle protein. An adequate nutrient intake is essential for maintaining and improving muscle properties. Many supplements have been proposed to enhance muscle mass and strength. More than 50% of adults in the United States take some form of dietary supplement to improve their health or well-being [52]. However, there is no scientific evidence for the effectiveness of many of these supplements. In some cases, their use has been linked to serious adverse side effects. This section summarizes the effects of several popular nutritional supplements when administered under strict dietary controls, either alone or in combination with other supplements.
In a randomized study, Tieland et al. examined the effects of 24 weeks of dietary protein supplementation on muscle mass, strength, and physical performance in a sample of frail older adults [53]. This study included 65 frail participants who were allocated to either the daily protein supplementation group (15 g protein consumed at breakfast and lunch) or placebo group (0 g protein at breakfast and lunch). Participants recorded their food intake for three days with the help of trained dieticians. Dietary intake data were coded (the type of food, time of intake, and amount), and energy and macronutrient intakes were calculated using a food-calculation system from the 2006 Dutch food composition database. The findings obtained indicated that skeletal muscle mass did not change in either the protein or placebo group following the 24-week intervention. However, leg extension strength increased more in the protein group than in the placebo group. Furthermore, physical performance significantly improved (from 8.9 to 10.0 points) in the protein group, but not in the placebo group. Therefore, while dietary protein supplementation appeared to improve physical performance in frail older adults, it did not increase their skeletal muscle mass.
Kim et al. investigated whether protein-energy supplementation prevented functional declines in frail older adults with a low socioeconomic status [54]. In that study, 84 frail elderly participants were assigned to either an intervention or control group. The intervention group received two 200-ml cans of commercial liquid formula (an additional 400 kcal of energy, 25 g of protein, 9.4 g of essential amino acids, and 400 ml of water) each day for 12 weeks, while the control group did not. Dietary intake was assessed in three, non-consecutive 24-hour recall sessions (one face-to-face and two by telephone; weekday and weekend ratio of 2:1) to show the nutritional status. The same research dietitian coded dietary data, and a nutrient analysis was performed using CAN-Pro 3.0. No significant changes were observed in grip strength in either group; however, physical functioning, usual gait speed, and TUG scores were significantly better in the protein group than in the control group. Therefore, protein-energy supplementation administered to frail older adults with a low socioeconomic status appeared to reduce the progression of functional decline.
Veronese et al. investigated whether 12 weeks of oral magnesium supplementation improved physical performance in healthy older women [55]. In that study, 124 participants were grouped into either a treatment group (300 mg of magnesium/day) or control group (no treatment). A dietary assessment was examined by a modified method including an estimated three-day record and a questionnaire about the frequency that participants generally ate certain foods. They used the data from the previous month as a reference and calculated the macronutrients and micronutrients of usual food intake by a national food composition table. After 12 weeks of supplementation with magnesium, the treatment group had significantly higher total short physical performance battery scores, chair-stand times, and four-minute walking speeds than the control group. These findings indicated that magnesium supplementation prevented or delayed age-related physical performance declines.
Roma et al. examined the effects of PUFA supplementation on the parameters of body composition, muscle strength, and physical performance in the elderly [56]. Fifty participants were randomly assigned to a PUFA-treated group (receiving 1.3 g of PUFA and 10 mg of vitamin E) or control group (receiving 11 mg of vitamin E). Participants were assessed using the mini nutritional assessment (composed of six questions related to decreased food intake in the three months before the test) and a 12-question survey on diet (number of meals consumed and consumption of protein, fruits, vegetables, and liquids) and the ability to feed themselves. No significant between-group differences were observed in muscle mass, grip strength, or TUG scores. Therefore, the 12-week PUFA supplementation did not appear to affect the parameters evaluated in elderly individuals with a decreased muscle mass.
Bauer et al. sought to test the hypothesis that a specific oral nutritional supplement may improve selected sarcopenia measures [57]. The active group (n = 184) consumed a vitamin D and leucine-enriched whey protein nutritional supplement twice daily for 13 weeks. The control group (n = 196) consumed an iso-caloric control product twice daily for 13 weeks. A dietary assessment was completed at baseline and week 13 using three-day prospective diet records for two weekdays and one weekend day. Additional energy and protein intakes from both supplements were added to habitual three-day intakes to assess total intake. The active group gained more appendicular muscle mass and performed better in the chair-stand test than the control group. These findings demonstrated that specific nutritional supplementation alone may benefit geriatric patients, particularly those unable to exercise.
Porter et al. investigated whether participants following an enhanced protein regimen have greater functional status improvements and better lean muscle mass preservation than control group participants [58]. In that study, 67 obese older adults were randomly assigned to either a traditional weight loss regimen (control group) or one with a higher protein intake at each meal (protein group). Control group participants were prescribed a 500-kcal deficit diet (15% protein, 30% fat, and 55% carbohydrate), which met the recommended dietary allowance (RDA) for protein intake (0.8 g/kg of body weight). Protein group participants were also prescribed a 500-kcal deficit, but with a macronutrient distribution of 30% protein, 30% fat, and 40% carbohydrate, for a total prescribed protein intake of 1.2 g/kg. Both groups exhibited significant weight loss at the six-month endpoint. However, while both groups had improved muscle function, the Short Physical Performance Battery response was greater in the protein group than in the control group. These findings indicated that functionally limited obese adults undergoing a six-month weight loss intervention that included a meal-based protein enhancement lost similar amounts of weight, but had better functional improvements than the control group.
Only one of the studies used an iso-caloric control supplement to investigate the efficacy of a vitamin D and leucine-enriched whey protein nutritional supplement (not combined with exercise) for attenuating sarcopenia. To produce the most useful data, future studies that investigate whether a simple nutrient supplement contributes to the prevention of sarcopenia will need to use dietary control in a sample of more than 100 elderly participants. Evidence from two in vivo studies showed that calorie restriction or fasting may help to prevent reductions in muscle mass or strength [59, 60]. Future human studies need to focus on the effects of the removal of some nutrients from the diet, instead of solely assessing the effects of their addition, in order to obtain more useful data (Table 2).
300 mg magnesium/day for 12 wks vs. non-supplemental control
No change in hand grip strength in both groups
Significantly improved Short Physical Performance Battery score, chair-stand times, and 4-m walking speeds in the magnesium group, but not in the control group
n = 67 obese older adults with a Short Physical Performance Battery (SPPB) score of 4–10, 68.2 ± 5.6 years
1458 kcal/day, 55% CHO, 30% fat, 15% protein (0.8 g protein/kg/day)
30 g protein × 3 times/day for 6 mo vs. non-supplemental control
No differences in lean body mass or hand grip in both groups
Significantly improved total and chair-stand scores in the protein group from those in the control group
Table 2.
Summary of effects of nutrient supplementation for attenuating sarcopenia.
2.3 Nutrient supplementation effects on muscle mass and strength during muscle disuse
A number of conditions, such as recovery from injury or illness or space flight, require prolonged periods of muscle disuse (i.e., unloading) in otherwise healthy individuals, resulting in the progressive loss of skeletal muscle mass that impairs functional strength, reduces the basal metabolic rate, and increases body fat mass. Therefore, prolonged muscle disuse is a significant health concern, particularly in aging populations. While nutrition is an important factor regulating muscle mass, the development of effective nutritional strategies that attenuate muscle loss during periods of muscle disuse warrants further efforts. Table 3 shows an overview of studies that have assessed the efficacy of nutritional interventions for attenuating muscle disuse atrophy under controlled diet quality.
n = 20 young men, One-legged immobilization (8 days)
2521 kcal/day (1.0 g protein/kg/day)
23.7 g × 3 times/day amino acids vs. 23.7 g × 3 times/day maltodextrin (iso-caloric control)
Significantly lower decrease of 3.1% in amino acids than in control (2.4% down) in quadriceps muscle volume
No difference in both groups in peak leg isometric torque
Table 3.
Summary of effects of nutritional interventions on muscle mass and strength during a period of muscle disuse.
Paddon-Jones et al. examined whether supplementation with essential amino acids and carbohydrates offset the catabolic response to 28 days of bed rest [61]. Thirteen healthy male participants were randomly assigned to either the experimental or control groups. The control group consumed nutritionally mixed meals three times a day. The experimental group consumed the same meals plus 30 g of carbohydrate and 16.5 g of essential amino acids three times a day. The Harris-Benedict equation was used to estimate daily caloric requirements, according to the following formula: daily energy requirement (kcal) = [66 + (13.7 × kg) + (5 × cm) – (6.8 × yr)] × 1.3 (activity factor for bed rest). Participants were placed on a three-day rotating diet with daily nutrient intake evenly distributed between the three meals. The findings obtained revealed that the experimental group maintained lean leg mass throughout bed rest (+0.2 kg), whereas the control group lost mass (−0.4 kg). In addition, strength loss was more pronounced in the control group (exp group, −8.8 kg; cont group, −17.8 kg). Therefore, supplementation with essential amino acids and carbohydrates during bed rest appeared to provide an anabolic stimulus that ameliorated lean muscle mass loss in an otherwise catabolic environment. However, it currently remains unclear whether additional energy intake contributed to these findings.
Trappe et al. investigated whether nutritional countermeasures, consisting of additional protein and free leucine, reduced volume and strength losses in lower-limb skeletal muscle during 60 days of simulated weightlessness [62]. Young women were assigned to either the bed rest group (control) or the bedrest plus a nutrition countermeasure group (intervention). Dietary staff prepared all meals for both groups. These meals contained controlled amounts of total energy and macronutrients. The findings obtained demonstrated that thigh muscle (quadriceps femoris) volume decreased in both the control (−21%) and intervention groups (−24%). Moreover, both groups exhibited similar large decreases in isometric and dynamic (centric force, eccentric force, power, and work) muscle strength for the supine squat (−19% to −33%). Therefore, the nutrition countermeasure did not appear to be effective at offsetting volume or strength losses in lower-limb muscles. Furthermore, exercise countermeasures may need to be modified to protect the calf muscles of participants.
Ferrando et al. examined the effects of an increasing protein intake (through essential amino acid supplementation) in older individuals subjected to 10 days of bed rest on their lean body mass and muscle function [63]. Participants received either a placebo or 15 g of essential amino acids, three times a day throughout 10 days of bed rest. The placebo was a non-caloric diet soda. During diet stabilization and bed rest, subjects consumed a lacto-ovo vegetarian diet providing the RDA for protein (0.8 g/kg of protein per day). The diet consisted of a three-day rotation based on the Harris-Benedict equation designed to maintain body weight throughout the study. An activity factor of 1.3 was used to estimate daily energy requirements during bed rest. The findings obtained indicated that essential amino acids did not affect the maintenance of total or leg lean muscle mass. However, stair ascent power and standing plantar flexion appeared to be maintained with essential amino acid supplementation. Therefore, increasing protein intake above the RDA may preserve muscle function in elderly individuals during compulsory inactivity. However, this protocol may need to be operated under iso-caloric nutritional interventions.
Deutz et al. attempted to clarify whether beta-hydroxy-beta-methylbutyrate (HMB), a leucine metabolite, was capable of attenuating muscle decline in healthy older adults during 10 days of bed rest [64]. Healthy older adults were randomly assigned to a control group or HMB group (Ca-HMB, 1.5 g twice daily, total 3 g/day). Participants were fed a metabolically controlled diet for diet stabilization, providing the RDA for protein intake (0.8 g protein/kg of body weight per day). Total calorie needs were estimated using the Harris–Benedict equation for resting energy expenditure. An activity factor of 1.35 was used to estimate daily energy requirements during bedrest. The study protocol significantly decreased total lean body mass in the control group. In contrast, the treatment with HMB prevented these declines in all but one participant in the HMB group. However, differences in functional parameters were not observed between the two groups. These findings indicated that HMB supplementation contributed to the preservation of muscle mass during 10 days of bed rest. Further studies using larger samples and iso-calorie conditions for nutritional interventions are needed to clarify the preventative effects of HMB on the acute decline in muscle mass.
Dirks et al. investigated whether protein supplementation preserved muscle mass during a short period of limb immobilization [65]. Healthy older men were subjected to five days of one-legged knee immobilization using a full-leg cast with or without the twice-daily administration of a dietary protein supplement (20.7 g of protein, 9.3 g of carbohydrate, and 3.0 g of fat). Weighted dietary intake records were completed by participants for the five-day immobilization period and on a separate consecutive five-day occasion, either before or after the immobilization period. Immobilization decreased the quadricep cross-sectional area by 1.5 and 2.0%, and muscle strength by 8.3 and 9.3% in the control and protein groups, respectively. These findings indicated that dietary protein supplementation (~20 g twice daily) did not attenuate muscle loss during short-term muscle disuse in healthy older men.
English et al. investigated whether leucine protects skeletal muscle health during bed rest [66]. In that study, a group of middle-aged adults were randomly assigned to a leucine group (4.5 g leucine × 3 times/day) or alanine group (4.5 g alanine × 3 times/day). Participants were fed controlled isoenergetic diets with protein intake evenly distributed across three daily meals for diet stabilization. Daily energy requirements were estimated using the Harris-Benedict equation. An activity factor of 1.3 was used during the bedrest period. The findings obtained indicated that while leg lean mass significantly decreased in both groups, leucine supplementation protected knee extensor peak torque more than in the alanine group. Therefore, leucine supplementation appeared to protect muscle health during relatively brief periods of physical inactivity. The parameters of this study allowed for the strict control of diets and nutritional supplementation under energy-matched conditions; therefore, leucine supplementation may help protect muscle function in muscle disuse atrophy.
Holloway et al. examined the safety, tolerability, and atrophy-mitigating effects of a novel amino acid composition (containing essential amino acids and arginine, glutamine, and N-acetylcysteine) during single-limb immobilization [67]. Twenty young men were randomly assigned to receive either the amino acid mixture or an energy-matched, non-amino acid-containing placebo three times a day (two hours after breakfast, lunch, and dinner) for consecutive days. Diets were designed to achieve an energy balance, and meal plans included protein derived from dairy sources held constant at 1.0 g/kg/day. The reduction in the cross-sectional area of the quadriceps muscle was significantly lower in the amino acid group than in the placebo group. However, immobilization resulted in similar relative declines in peak torque in both groups. These findings indicated that the daily consumption of an amino acid mixture (three times a day for 28 days) attenuated muscle atrophy, and are bolstered by the use of well-controlled diets and nutritional supplementation with energy-matched conditions.
A number of human studies examined the effects of nutritional interventions on muscle mass and strength during a period of muscle disuse [68, 69]. Due to insufficient dietary control, these studies were not sufficient to clarify the nutritional value of such supplements. Despite these deficits, many studies have reported the efficacy of nutritional supplementation for preventing the loss of muscle mass and strength during a period of muscle disuse in vivo [70, 71, 72]. Future studies are needed to clarify whether these candidates for nutritional supplementation preserve muscle mass during disuse. These studies must control diet quality and modify the nutritional intervention period (e.g., expand the duration of nutritional administration before muscle disuse) to provide sufficient evidence.
3. Conclusions
In this chapter, we (a) summarized nutritional epidemiology evidence related to sarcopenia from recent systematic reviews; (b) reviewed the role nutrient supplementation plays in attenuating sarcopenia through dietary control; (c) provided evidence for the efficacy of nutrient supplementation for treating disuse muscle atrophy under controlled diet quality conditions.
Dietary patterns of adequate quality for older adults (i.e., ensuring a sufficient intake of beneficial foods, such as fruits, vegetables, whole grain products, fish, nuts, and low-fat foods) are useful for preventing sarcopenia. While the Mediterranean diet has been touted as a healthy diet, other diets (healthy Nordic or traditional Asian diets) also help prevent sarcopenia in older adults.
Vitamin D and leucine-enriched whey protein supplement may be useful for attenuating sarcopenia in geriatric patients, particularly in those unable to exercise.
Further studies are needed to clarify the effects of protein and amino acid supplementation on muscle mass and strength.
Based on the strong evidence linking nutrition to muscle mass and function, nutrition plays a crucial role in both the prevention and management of sarcopenia. Further high quality studies, particularly those using large sample sizes, controlled diet quality, and iso-caloric placebo supplementation, are needed to provide a clear understanding of the dose and duration effects of nutrients on muscle atrophy.
Conflict of interest
The authors declare no conflict of interest.
\n',keywords:"diet quality, muscle atrophy, disuse, sarcopenia, epidemiology",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/73448.pdf",chapterXML:"https://mts.intechopen.com/source/xml/73448.xml",downloadPdfUrl:"/chapter/pdf-download/73448",previewPdfUrl:"/chapter/pdf-preview/73448",totalDownloads:89,totalViews:0,totalCrossrefCites:0,dateSubmitted:"May 14th 2020",dateReviewed:"September 13th 2020",datePrePublished:"October 5th 2020",datePublished:"March 3rd 2021",dateFinished:"October 5th 2020",readingETA:"0",abstract:"Muscle atrophy occurs under a number of different conditions, including disuse and aging accompanied by the onset of sarcopenia. Although muscle mass is reduced by decreased protein synthesis and/or increased protein degradation, the mechanisms of disuse muscle atrophy and sarcopenia differ. Therefore, nutrition strategies need to be customized for each type of muscle atrophy. Difficulties are associated with assessing the efficacy of nutrients for preventing sarcopenia due to uncontrolled factors in human studies. We herein (a) summarize nutritional epidemiology evidence related to sarcopenia from recent systematic reviews, (b) review nutrient supplementation for attenuating sarcopenia through dietary control, and (c) provide evidence for the efficacy of nutrient supplementation for treating disuse muscle atrophy under dietary control. Epidemiological studies have indicated that diets with a sufficient intake of beneficial foods are useful for preventing sarcopenia. Supplementation with vitamin D and leucine-enriched whey protein have been suggested to help attenuate sarcopenia in geriatric patients, particularly those who are unable to exercise. Further studies are needed to clarify the effects of protein and amino acid supplementation on muscle mass and strength. High-quality studies with controlled diets and physical activities are required to clarify the effects of nutritional interventions on both types of muscle atrophy.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/73448",risUrl:"/chapter/ris/73448",signatures:"Muneshige Shimizu and Kunihiro Sakuma",book:{id:"10192",title:"Background and Management of Muscular Atrophy",subtitle:null,fullTitle:"Background and Management of Muscular Atrophy",slug:"background-and-management-of-muscular-atrophy",publishedDate:"March 3rd 2021",bookSignature:"Julianna Cseri",coverURL:"https://cdn.intechopen.com/books/images_new/10192.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"135579",title:"Dr.",name:"Julianna",middleName:null,surname:"Cseri",slug:"julianna-cseri",fullName:"Julianna Cseri"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",fullName:"Kunihiro Sakuma",slug:"kunihiro-sakuma",email:"sakuma.k.ac@m.titech.ac.jp",position:null,institution:{name:"Tokyo Institute of Technology",institutionURL:null,country:{name:"Japan"}}},{id:"321387",title:"Ph.D.",name:"Muneshige",middleName:null,surname:"Shimizu",fullName:"Muneshige Shimizu",slug:"muneshige-shimizu",email:"shimizu.muneshige@tsc.u-tokai.ac.jp",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Nutritional approaches for attenuating muscle atrophy",level:"1"},{id:"sec_2_2",title:"2.1 Nutritional epidemiology evidence related to sarcopenia",level:"2"},{id:"sec_3_2",title:"2.2 Nutrient supplementation for attenuating sarcopenia",level:"2"},{id:"sec_4_2",title:"2.3 Nutrient supplementation effects on muscle mass and strength during muscle disuse",level:"2"},{id:"sec_6",title:"3. Conclusions",level:"1"},{id:"sec_10",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Spahillari A, Mukamal K, DeFilippi C, Kizer JR, Gottdiener JS, Djoussé L, Lyles MF, Bartz TM, Murthy VL, Shah RV: The association of lean and fat mass with all-cause mortality in older adults: the cardiovascular health study. Nutr Metab Cardiovasc Dis. 2016, 26, 1039-1047'},{id:"B2",body:'Volakilis KA, Halle M, Meisinger C: Muscular strength as a strong predictor of mortality: a narrative review. Eur J Intern Med. 2015, 26, 303-310'},{id:"B3",body:'Egan B, Zierath JR: Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell Metab. 2013, 17, 162-164'},{id:"B4",body:'Shaw SC, Dennison EM, Cooper C: Epidemiology of Sarcopenia: Determinants Throughout the Lifecourse. Calcif Tissue Int. 2017, 101, 229-247'},{id:"B5",body:'Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, Martin FC, Michel JP, Rolland Y, Schneider SM, Topinková E, Vandewoude M, Zamboni M; European Working Group on Sarcopenia in Older People. Age Ageing, 2010, 39, 412-423'},{id:"B6",body:'Sayer AA: Sarcopenia the new geriatric giant: Time to translate research findings into clinical practice. Age Ageing. 2014, 43, 736-737'},{id:"B7",body:'Dodds RM, Syddall HE, Cooper R, Benzeval M, Deary IJ, Dennison EM, Der G, Gale CR, Inskip HM, Jagger C, Kirkwood TB, Lawlor DA, Robinson SM, Starr JM, Steptoe A, Tilling K, Kuh D, Cooper C, Sayer AA: Grip Strength across the Life Course: Normative data from Twelve British Studies. PLoS ONE. 2014, Dec4, 9(12) e113637'},{id:"B8",body:'Maynard M, Gunnell D, Ness AR, Abraham L, Bates CJ, Blane D: What influences diet in early old age? Prospective and cross-sectional analyses of the Boyd Orr cohort. Eur J Public Health. 2006, 16, 316-324'},{id:"B9",body:'Elia M, Russell CA, Stratton RJ: Malnutrition in the UK: Policies to address the problem. Proc Nutr Soc. 2010, 69, 470-476'},{id:"B10",body:'Margetts BM, Thompson RL, Elia M, Jackson AA: Prevalence of risk of undernutrition is associated with poor health status in older people in the UK. Eur J Clin Nutr. 2003, 57, 69-74'},{id:"B11",body:'Robinson S, Cooper C, Aihie SA: Nutrition and sarcopenia: A review of the evidence and implications for preventive strategies. J Aging Res. 2012, 2012, 510801'},{id:"B12",body:'Waijers PM, Feskens EJ, Ocké MC: A critical review of predefined diet quality scores. Br J Nutr. 2007, 97, 219-231'},{id:"B13",body:'Hu FB: Dietary pattern analysis: A new direction in nutritional epidemiology. Curr Opin Lipidol. 2002, 13, 3-9'},{id:"B14",body:'Schwingshackl L, Bogensberger B, Hoffmann G: Diet quality as assessed by the healthy eating index, alternate healthy eating index, dietary approaches to stop hypertension score, and health outcomes: An updated systematic review and meta-analysis of cohort studies. J Acad Nutr Diet. 2018, 118, 74-100'},{id:"B15",body:'Schwedhelm C, Boeing H, Hoffmann G, Aleksandrova K, Schwingshackl L: Effect of diet on mortality and cancer recurrence among cancer survivors: A systematic review and meta-analysis of cohort studies. Nutr Rev. 2016, 74, 737-748'},{id:"B16",body:'McNaughton SA, Bates CJ, Mishra GD: Diet quality is associated with all-cause mortality in adults aged 65 years and older. J Nutr. 2012, 142, 320-325'},{id:"B17",body:'McNaughton SA, Dunstan DW, Ball K, Shaw J, Crawford D: Dietary quality is associated with diabetes and cardio-metabolic risk factors. J Nutr. 2009, 139, 734-742'},{id:"B18",body:'Robinson SM, Reginster JY, Rizzoli R, Shaw SC, Kanis JA, Bautmans I, Bischoff-Ferrari H, Bruyère O, Cesari M, Dawson-Hughes B, Fielding RA, Kaufman JM, Landi F, Malafarina V, Rolland Y, van Loon LJ, Vellas B, Visser M, Cooper C, ESCEO working group: Does nutrition play a role in the prevention and management of sarcopenia? Clin Nutr. 2018, 37, 1121-1132'},{id:"B19",body:'Willcox DC, Scapagnini G, Willcox BJ: Healthy aging diets other than the Mediterranean: A focus on the Okinawan diet. Mech Ageing Dev. 2014, 136-137, 148-162'},{id:"B20",body:'Craig JV, Bunn DK, Hayhoe RP, Appleyard WO, Lenaghan EA, Welch AA: Relationship between the Mediterranean dietary pattern and musculoskeletal health in children, adolescents, and adults: Systematic review and evidence map. Nutr. Rev. 2017, 75, 830-857'},{id:"B21",body:'Silva R, Pizato N, DaMata F, Figueiredo A, Ito M, Pereira MG: Mediterranean diet and musculoskeletal-functional outcomes in community-dwelling older people: A systematic review and meta-analysis. J Nutr Health Aging, 2018, 22, 655-663'},{id:"B22",body:'United Nations: Department of economic and social affairs, population division. world population ageing 2017. http://www.un.org/en/development/desa/ population/publications/pdf/ageing/WPA2017_Highlights.pdf'},{id:"B23",body:'Steves CJ, Spector TD, Jackson SH: Ageing, genes, environment and epigenetics: What twin studies tell us now, and in the future. Age Ageing 2012, 41, 581-586'},{id:"B24",body:'Daskalopoulou C, Stubbs B, Kralj C, Koukounari A, Prince M, Prina AM: Physical activity and healthy ageing: A systematic review and meta-analysis of longitudinal cohort studies. Ageing Res Rev. 2017, 38, 6-17'},{id:"B25",body:'McPhee JS, French DP, Jackson D, Nazroo J, Pendleton N, Degens H: Physical activity in older age: Perspectives for healthy ageing and frailty. Biogerontology 2016, 17, 567-580'},{id:"B26",body:'Fontana L, Partridge L: Promoting health and longevity through diet: From model organisms to humans. Cell 2015, 161, 106-118'},{id:"B27",body:'Kiefte-de Jong JC, Mathers JC, Franco OH: Nutrition and healthy ageing: The key ingredients. Proc Nutr Soc. 2014, 73, 249-259'},{id:"B28",body:'Witard OC, McGlory C, Hamilton DL, Phillips SM: Growing older with health and vitality: A nexus of physical activity, exercise and nutrition. Biogerontology 2016, 17, 529-546'},{id:"B29",body:'Sofi F, Macchi C, Abbate R, Gensini GF, Casini A: Mediterranean diet and health status: An updated meta-analysis and a proposal for a literature-based adherence score. Pub Health Nutr. 2014, 17, 2769-2782'},{id:"B30",body:'Deutz NE, Bauer JM, Barazzoni R, Biolo G, Boirie Y, Bosy-Westphal A, Cederholm T, Cruz-Jentoft A, Krznariç Z, Nair KS, Singer P, Teta D, Tipton K, Calder PC: Protein intake and exercise for optimal muscle function with aging: Recommendations from the ESPEN Expert Group. Clin. Nutr. 2014, 33, 929-936'},{id:"B31",body:'Deer RR, Volpi E: Protein intake and muscle function in older adults. Curr Opin Clin Nutr Metab Care. 2015, 18, 248-253'},{id:"B32",body:'Beasley JM, Shikany JM, Thomson CA: The role of dietary protein intake in the prevention of sarcopenia of aging. Nutr Clin Pract. 2013, 28, 684-690'},{id:"B33",body:'Muir SW, Montero-Odasso M: Effect of vitamin D supplementation on muscle strength, gait and balance in older adults: A systematic review and meta-analysis. J Am Geriatr Soc. 2011, 59, 2291-2300'},{id:"B34",body:'Reedy J, Krebs-Smith SM, Miller PE, Liese AD, Kahle LL, Park Y, Subar AF: Higher diet quality is associated with decreased risk of all-cause, cardiovascular disease, and cancer mortality among older adults. J Nutr. 2014, 144, 881-889'},{id:"B35",body:'Guasch-Ferre M, Salas-Salvado J, Ros E, Estruch R, Corella D, Fito M, Martinez-Gonzalez MA: The PREMIED trial, Mediterranean diet and health outcomes: How strong is the evidence? Nutr Metab Cardiovasc Dis. 2017, 27 624-632'},{id:"B36",body:'Schwingshackl L, Hoffmann G: Diet quality as assessed by the healthy eating index, the alternate healthy eating index, the dietary approaches to stop hypertension score, and health outcomes: A systematic review and meta-analysis of cohort studies. J Acad Nutr Diet. 2015, 115, 780-800'},{id:"B37",body:'Gorman BS, Primavera LH: The complimentary use of cluster and factor analysis methods. J Exp Educ. 1983, 51, 165-168'},{id:"B38",body:'Robinson SM, Jameson KA, Batelaan SF, Martin HJ, Syddall HE, Dennison EM, Cooper C, Sayer AA, Hertfordshire Cohort Study Group: Diet and its relationship with grip strength in community-dwelling older men and women: The Hertfordshire cohort study. J Am Geriatr Soc. 2008, 56, 84-90'},{id:"B39",body:'Martin H, Aihie-Sayer A, Jameson K, Syddall H, Dennison EM, Cooper C, Robinson S: Does diet influence physical performance in community-dwelling older people? Findings from the Hertfordshire Cohort Study. Age Ageing 2011, 40, 181-186'},{id:"B40",body:'Bollwein J, Diekmann R, Kaiser MJ, Bauer JM, Uter W, Sieber CC, Volkert D: Dietary quality is related to frailty in community-dwelling older adults. J Gerontol Ser A Biol Sci Med Sci. 2013, 68, 483-489'},{id:"B41",body:'Rahi B, Morais JA, Dionne IJ, Gaudreau P, Payette H, Shatenstein B: The combined effects of diet quality and physical activity on maintenance of muscle strength among diabetic older adults from the NuAge cohort. Exp. Gerontol. 2014, 49, 40-46'},{id:"B42",body:'Hashemi R, Motlagh AD, Heshmat R, Esmaillzadeh A, Payab M, Yousefinia M, Siassi F, Pasalar P, Baygi F: Diet and its relationship to sarcopenia in community dwelling Iranian elderly: A cross sectional study. Nutrition 2015, 31, 97-104'},{id:"B43",body:'Granic A, Jagger C, Davies K, Adamson A, Kirkwood T, Hill TR, Siervo M, Mathers JC, Sayer AA: Effect of Dietary Patterns on Muscle Strength and Physical Performance in the Very Old: Findings from the Newcastle 85+ Study. PLoS ONE 2016, 11, e0149699'},{id:"B44",body:'Perala MM, Von-Bonsdorff M, Mannisto S, Salonen MK, Simonen M, Kanerva N, Pohjolainen P, Kajantie E, Rantanen T, Eriksson JG: A healthy Nordic diet and physical performance in old age: Findings from the longitudinal Helsinki Birth Cohort Study. Br J Nutr. 2016, 115, 878-886'},{id:"B45",body:'Suthuvoravut U, Takahashi K, Murayama H, Tanaka T, Akishita M, Iijima K: Association between traditional Japanese diet washoku and sarcopenia in community-dwelling older adults: findings from the Kashiwa study. J Nutr Health Aging 2020, 24, 282-289'},{id:"B46",body:'Fung TT, McCullough ML, Newby PK, Manson JE, Meigs JB, Rifai N, Willett WC, Hu FB: Diet-quality scores and plasma concentrations of markers of inflammation and endothelial dysfunction. Am J Clin Nutr. 2005, 82, 163-173'},{id:"B47",body:'Trichopoulou A, Costacou T, Bamia C, Trichopoulos D: Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med. 2003, 348, 2599-2608'},{id:"B48",body:'Shatenstein B, Nadon S, Godin C, Ferland G: Diet quality of Montreal-area adultsneeds improvement: estimates from a self-administered food frequency question-naire furnishing a dietary indicator score. J Am Diet Assoc. 2005, 105, 1251-1260'},{id:"B49",body:'Moshfegh AJ, Borrud L, Perloff B, LaComb R: Improved method for the 24-hour dietary recall for use in national surveys. FASEB J. 1999, 13, A603'},{id:"B50",body:'Granic A, Davies K, Adamson A, Kirkwood T, Hill T, Siervo M, Mathers JC, Jagger C: Dietary patterns and socioeconomic status in the very old: the Newcastle 85+ Study. PLoS One 2015, 10, e0139713'},{id:"B51",body:'Food Standards Agency: McCance and Widdowson\'s the composition of foods, sixth summary edition. Cambridge, Royal Society of Chemistry 2002'},{id:"B52",body:'Ronis MJJ, Pedersen KB, Watt J: Adverse effects of nutraceuticals and dietary supplements. Annu Rev Pharmacol Toxicol. 2018, 58, 583-601'},{id:"B53",body:'Tieland M, van de Rest O, Dirks ML, van der Zwaluw N, Mensink M, van Loon LJ, de Groot LC: Protein supplementation improves physical performance in frail elderly people: a randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc. 2012, 13, 720-726'},{id:"B54",body:'Kim CO, Lee KR: Preventive effect of protein-energy supplementation on the functional decline of frail older adults with low socioeconomic status: A community-based randomized controlled study. J Gerontol A Biol Sci Med Sci. 2013, 68, 309-16'},{id:"B55",body:'Veronese N, Berton L, Carraro S, Bolzetta F, de Rui M, Perissinotto E, Toffanello ED, Bano G, Pizzato S, Miotto F, Coin A, Manzato E, Sergi G: Effect of oral magunesium supplementation on physical performance in healthy elderly women involved in weekly exercise program: a randomized controlled trial. Am J Clin Nutr. 2014, 100, 974-981'},{id:"B56",body:'Roma KS, Natasza C, Marta L, Ewa Z, Aleksandra S, Janusz W, Katarzyna WT, The effect of a 12-week omega-3 supplementation on bidy composition, muscle strength and physical performance in elderly individuals with decreased muscle mass. Int J Environ Res Public Health 2015, 12, 10558-10574'},{id:"B57",body:'Bauer JM, Verlaan S, Bautmans I, Brandt K, Donini LM, Maggio M, McMurdo ME, Mets T, Seal C, Wijers SL, Ceda GP, de Vito G, Donders G, Drey M, Greig C, Holmbäck U, Narici M, McPhee J, Poggiogalle E, Power D, Scafoglieri A, Schultz R, Sieber CC, Cederholm T: Effects of a vitamin D and leucine-enriced whey protein nutritional supplement on measures of sarcopenia in older adults, the PROVIDE study: a randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc. 2015, 16, 740-747'},{id:"B58",body:'Porter SKN, Pieper CF, Orenduff MC, McDonald SR, McClure LB, Zhou R, Payne ME, Bales CW: Improved function with enhanced protein intake per meal: a pilot study of weight reduction in frail, obese older adults. J Gerontol A Biol Sci Med Sci. 2016, 71, 1369-1375'},{id:"B59",body:'Rhoads TW, Clark JP, Gustafson GE, Miller KN, Conklin MW, DeMuth TM, Berres ME, Eliceiri KW, Vaughan LK, Lary CW, Beasley TM, Colman RJ, Anderson RM: Molecular and functional networks linked to sarcopenia prevention by caloric restriction in rhesus monkeys. Cell Syst. 2020, 26, 156-168'},{id:"B60",body:'Alirezaei M, Kemball CC, Flynn CA, Wood MR, Whitton JL, Kiosses WB: Short-term fasting induced profound neuronal autophagy. Autophagy, 2010, 6, 702-710'},{id:"B61",body:'Paddon-Jones D, Sheffield-Moore M, Urban RJ, Sanford AP, Aarsland A, Wolfe RR, Ferrando AA: Essential amino acid and carbohydrate supplementation ameliorates muscle protein loss in humans during 28 days bedrest. J Clin Endocrinol Metab. 2004, 89, 4351-4358'},{id:"B62",body:'Trappe TA, Burd NA, Louis ES, Lee GA, Trappe SW: Influence of concurrent exercise or nutrition countermeasures on thigh and calf muscle size and function during 60 days of bed rest in women. Acta Physiol, 2007, 191, 147-159'},{id:"B63",body:'Ferrando AA, Paddon-Jones D, Hays NP, Kortebein P, Ronsen O, Williams RH, McComb A, Symons TB, Wolfe RR, Evans W: EAA supplementation to increase nitrogen intake improves muscle function during bed rest in the elderly. Clin Nutr. 2010, 29, 18-23'},{id:"B64",body:'Deutz NEP, Pereira SL, Hays NP, Oliver JS, Edens NK, Evans CM, Wolfe RR: Effect of beta-hydroxy-beta-methylbutyrate (HMB) on lean body mass during 10 days of bed rest in older adults. Clin Nutr. 2013, 32, 704-712'},{id:"B65",body:'Dirks ML, Wall BT, Nilwik R, Weerts DHJM, Verdijk LB, van Loon LJC: Skeletal muscle disuse atrophy is not attenuated by dietary protein supplementation in healthy older men. J Nutr. 2014, 144, 1196-1203'},{id:"B66",body:'English KL, Mettler JA, Ellison JB, Mamerow MM, Arentson-Lantz E, Pattarini JM, Ploutz-Snyder R, Sheffield-Moore M, Paddon-Jones D: Leucine partially protects muscle mass and function during bed rest in middle-aged adults. Am J Clin Nutr. 2016, 103, 465-473'},{id:"B67",body:'Holloway TM, McGlory C, McKellar S, Morgan A, Hamill M, Afeyan R, Comb W, Confer S, Zhao P, Hinton M, Kubassova O, Chakravarthy MV, Philips SM: A novel amino acid composition ameliorates short-term muscle disuse atrophy in healthy young men. Front Nutr. 2019, 10, 6, 105'},{id:"B68",body:'Biolo G, Ciocchi B, Stulle M, Bosutti A, Barazzoni R, Zanetti M, Antonione R, Lebenstedt M, Platen P, Heer M, Guarnieri G: Calorie restriction accelerates the catabolism of lean body mass during 2wk of bed rest. Am J Clin Nutr. 2007, 86, 366-372'},{id:"B69",body:'Johnston APW, Burke DG, Macneil LG, Candow DG: Effect of creatine supplementation during cast-induced immobilization on the preservation of muscle mass, strength, and endurance. J Strength Cond Res. 2009, 23, 116-120'},{id:"B70",body:'Abe T, Kohno S, Yama T, Ochi A, Suto T, Hirasaka K, Ohno A, Teshima-Kondo S, Okumura Y, Oarada M, Choi I, Mukai R, Terao J, Nikawa T: Soy glycinin contains a functional inhibitory sequence against muscle-atrophy-associated ubiquitin ligase Cbl-b. Int J Endocrinol. 2013, 907565'},{id:"B71",body:'Asami Y, Aizawa M, Kinoshita M, Ishikawa J, Sakuma K: Resveratrol attenuates denervation-induced muscle atrophy due to the blockade of atrogin-1 and p62 accumulation. Int J Med Sci. 2018, 3, 628-637'},{id:"B72",body:'Tabata S, Aizawa M, Kinoshita M, Ito Y, Kawamura Y, Takebe M, Pan W, Sakuma K: The influence of isoflavone for denervation-induced muscle atrophy. Eur J Nutr. 2019, 58, 291-300'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Muneshige Shimizu",address:"shimizu.muneshige@tsc.u-tokai.ac.jp",affiliation:'
Department of Fisheries, School of Marine Science and Technology, Tokai University, 3-20-1 Orido, Shimizu-ku, Japan
Institute for Liberal Arts, Environment and Society, Tokyo Institute of Technology, W9-2, 2-12-1 Oookayama, Meguro-ku, Japan
'}],corrections:null},book:{id:"10192",title:"Background and Management of Muscular Atrophy",subtitle:null,fullTitle:"Background and Management of Muscular Atrophy",slug:"background-and-management-of-muscular-atrophy",publishedDate:"March 3rd 2021",bookSignature:"Julianna Cseri",coverURL:"https://cdn.intechopen.com/books/images_new/10192.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"135579",title:"Dr.",name:"Julianna",middleName:null,surname:"Cseri",slug:"julianna-cseri",fullName:"Julianna Cseri"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"291953",title:"MSc.",name:"Adriana",middleName:null,surname:"Alves",email:"adriana.alves@madeira.gov.pt",fullName:"Adriana Alves",slug:"adriana-alves",position:null,biography:null,institutionString:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"1",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:null},booksEdited:[],chaptersAuthored:[{title:"Artisanal Harvest of Shellfish in the Northeastern Atlantic: The Example of Limpet and Topshell Fisheries in the Archipelago of Madeira",slug:"artisanal-harvest-of-shellfish-in-the-northeastern-atlantic-the-example-of-limpet-and-topshell-fishe",abstract:"The harvesting of littoral benthic shellfish in the archipelago of Madeira dates back to the fifteenth century when the Portuguese discovered and colonized the archipelago. The consumption of littoral shellfish is part of the gastronomic cultural heritage of this region, appreciated by the local population and tourists, and has a high social and economic importance. Therefore, harvesting pressure on these resources is one of the greatest concerns, and as such, a sustainable exploitation based on proper regulation, considering the biological and ecological specificities of these species in their particular habitat, is crucial to promote the preservation of species and habitats at medium and long terms. This study presents the current harvesting management regime for gastropods in the archipelago of Madeira and characterizes the artisanal harvest through a period of 27 years (1990–2017) providing new insights for future research in these topics. This artisanal harvesting operates mostly by small vessels (<10 m), with low tonnage and capacity, in nearby areas preferentially in the North coast of Madeira and around Desertas Islands. During the studied period, management actions resulted in the reduction of 50% of the vessels operating in the harvesting of limpets and in slight recovery of the stocks of limpets. The economic impact of limpets gradually increased over the years, representing in 2017 96% of the economic value landed for molluscs and 2% of the total landings in this region. The present characterization provides a comprehensive outlook of the evolution of the marine gastropod harvest in the archipelago of Madeira and allows future comparisons with other regions where gastropods are commercially exploited.",signatures:"Ricardo Sousa, Rodrigo Riera, Joana Vasconcelos, Lídia Gouveia, Ana Rita Pinto, João Delgado, Adriana Alves, José A. González, Mafalda Freitas and Paulo Henriques",authors:[{id:"200407",title:"MSc.",name:"Paulo",surname:"Henriques",fullName:"Paulo Henriques",slug:"paulo-henriques",email:"paulomvh@gmail.com"},{id:"200915",title:"MSc.",name:"Ricardo",surname:"Sousa",fullName:"Ricardo Sousa",slug:"ricardo-sousa",email:"ricardo.sousa@oom.arditi.pt"},{id:"291944",title:"MSc.",name:"João",surname:"Delgado",fullName:"João Delgado",slug:"joao-delgado",email:"joao.delgado@madeira.gov.pt"},{id:"291945",title:"Dr.",name:"Joana",surname:"Vasconcelos",fullName:"Joana Vasconcelos",slug:"joana-vasconcelos",email:"joana.vasco@gmail.com"},{id:"291946",title:"Prof.",name:"Rodrigo",surname:"Riera",fullName:"Rodrigo Riera",slug:"rodrigo-riera",email:"roriera@gmail.com"},{id:"291951",title:"MSc.",name:"Ana Rita",surname:"Pinto",fullName:"Ana Rita Pinto",slug:"ana-rita-pinto",email:"ana.gois@madeira.gov.pt"},{id:"291952",title:"MSc.",name:"Lídia",surname:"Gouveia",fullName:"Lídia Gouveia",slug:"lidia-gouveia",email:"lidia.gouveia@madeira.gov.pt"},{id:"291953",title:"MSc.",name:"Adriana",surname:"Alves",fullName:"Adriana Alves",slug:"adriana-alves",email:"adriana.alves@madeira.gov.pt"},{id:"291954",title:"Prof.",name:"José António",surname:"González",fullName:"José António González",slug:"jose-antonio-gonzalez",email:"pepe.solea@ulpgc.es"},{id:"291955",title:"MSc.",name:"Mafalda",surname:"Freitas",fullName:"Mafalda Freitas",slug:"mafalda-freitas",email:"mafalda.freitas@cm-funchal.pt"}],book:{title:"Invertebrates",slug:"invertebrates-ecophysiology-and-management",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"200407",title:"MSc.",name:"Paulo",surname:"Henriques",slug:"paulo-henriques",fullName:"Paulo Henriques",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Madeira",institutionURL:null,country:{name:"Portugal"}}},{id:"217091",title:"M.Sc.",name:"Laura",surname:"Borden",slug:"laura-borden",fullName:"Laura Borden",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"245773",title:"Dr.",name:"José Manuel",surname:"Mazón-Suástegui",slug:"jose-manuel-mazon-suastegui",fullName:"José Manuel Mazón-Suástegui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/no_image.jpg",biography:null,institutionString:null,institution:null},{id:"255063",title:"Dr.",name:"Avilés-Quevedo",surname:"María Araceli",slug:"aviles-quevedo-maria-araceli",fullName:"Avilés-Quevedo María Araceli",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"269027",title:"Dr.",name:"Jeffrey",surname:"Marliave",slug:"jeffrey-marliave",fullName:"Jeffrey Marliave",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"279002",title:"MSc.",name:"Jessica",surname:"Schultz",slug:"jessica-schultz",fullName:"Jessica Schultz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"279004",title:"Mrs.",name:"Donna",surname:"Gibbs",slug:"donna-gibbs",fullName:"Donna Gibbs",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"279005",title:"Mr.",name:"Glen",surname:"Dennison",slug:"glen-dennison",fullName:"Glen Dennison",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"280776",title:"Prof.",name:"Abel",surname:"Betanzos-Vega",slug:"abel-betanzos-vega",fullName:"Abel Betanzos-Vega",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"280777",title:"Dr.",name:"Mario",surname:"Formoso-García",slug:"mario-formoso-garcia",fullName:"Mario Formoso-García",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null}]},generic:{page:{slug:"OA-publishing-fees",title:"Open Access Publishing Fees",intro:"
The Open Access model is applied to all of our publications and is designed to eliminate subscriptions and pay-per-view fees. This approach ensures free, immediate access to full text versions of your research.
As a gold Open Access publisher, an Open Access Publishing Fee is payable on acceptance following peer review of the manuscript. In return, we provide high quality publishing services and exclusive benefits for all contributors. IntechOpen is the trusted publishing partner of over 118,000 international scientists and researchers.
\\n\\n
The Open Access Publishing Fee (OAPF) is payable only after your full chapter, monograph or Compacts monograph is accepted for publication.
\\n\\n
OAPF Publishing Options
\\n\\n
\\n\\t
1,400 GBP Chapter - Edited Volume
\\n\\t
10,000 GBP Monograph - Long Form
\\n\\t
4,000 GBP Compacts Monograph - Short Form
\\n
\\n\\n
*These prices do not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT as long as provision of the VAT registration number is made during the application process. This is made possible by the EU reverse charge method.
\\n\\n
Services included are:
\\n\\n
\\n\\t
An online manuscript tracking system to facilitate your work
\\n\\t
Personal contact and support throughout the publishing process from your dedicated Author Service Manager
\\n\\t
Assurance that your manuscript meets the highest publishing standards
\\n\\t
English language copyediting and proofreading, including the correction of grammatical, spelling, and other common errors
\\n\\t
XML Typesetting and pagination - web (PDF, HTML) and print files preparation
\\n\\t
Discoverability - electronic citation and linking via DOI
\\n\\t
Permanent and unrestricted online access to your work
What isn't covered by the Open Access Publishing Fee?
\\n\\n
If your manuscript:
\\n\\n
\\n\\t
Exceeds 20 pages (for chapters in Edited Volumes), an additional fee of 40 GBP per page will be required
\\n\\t
If a manuscript requires Heavy Editing or Language Polishing, this will incur additional fees.
\\n
\\n\\n
Your Author Service Manager will inform you of any items not covered by the OAPF and provide exact information regarding those additional costs before proceeding.
\\n\\n
Open Access Funding
\\n\\n
To explore funding opportunities and learn more about how you can finance your IntechOpen publication, go to our Open Access Funding page. IntechOpen offers expert assistance to all of its Authors. We can support you in approaching funding bodies and institutions in relation to publishing fees by providing information about compliance with the Open Access policies of your funder or institution. We can also assist with communicating the benefits of Open Access in order to support and strengthen your funding request and provide personal guidance through your application process. You can contact us at oapf@intechopen.com for further details or assistance.
\\n\\n
For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
\\n\\n
Added Value of Publishing with IntechOpen
\\n\\n
Choosing to publish with IntechOpen ensures the following benefits:
\\n\\n
\\n\\t
Indexing and listing across major repositories, see details ...
\\n\\t
Long-term archiving
\\n\\t
Visibility on the world's strongest OA platform
\\n\\t
Live Performance Metrics to track readership and the impact of your chapter
\\n\\t
Dissemination and Promotion
\\n
\\n\\n
Benefits of Publishing with IntechOpen
\\n\\n
\\n\\t
Proven world leader in Open Access book publishing with over 10 years experience
\\n\\t
+4,800 OA books published
\\n\\t
Most competitive prices in the market
\\n\\t
Fully compliant with OA funding requirements
\\n\\t
Optimized processes, enabling publication between 8 and 12 months
\\n\\t
Personal support during every step of the publication process
\\n\\t
+146,150 citations in Web of Science databases
\\n\\t
Currently strongest OA platform with over 130 million downloads
As a gold Open Access publisher, an Open Access Publishing Fee is payable on acceptance following peer review of the manuscript. In return, we provide high quality publishing services and exclusive benefits for all contributors. IntechOpen is the trusted publishing partner of over 118,000 international scientists and researchers.
\n\n
The Open Access Publishing Fee (OAPF) is payable only after your full chapter, monograph or Compacts monograph is accepted for publication.
\n\n
OAPF Publishing Options
\n\n
\n\t
1,400 GBP Chapter - Edited Volume
\n\t
10,000 GBP Monograph - Long Form
\n\t
4,000 GBP Compacts Monograph - Short Form
\n
\n\n
*These prices do not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT as long as provision of the VAT registration number is made during the application process. This is made possible by the EU reverse charge method.
\n\n
Services included are:
\n\n
\n\t
An online manuscript tracking system to facilitate your work
\n\t
Personal contact and support throughout the publishing process from your dedicated Author Service Manager
\n\t
Assurance that your manuscript meets the highest publishing standards
\n\t
English language copyediting and proofreading, including the correction of grammatical, spelling, and other common errors
\n\t
XML Typesetting and pagination - web (PDF, HTML) and print files preparation
\n\t
Discoverability - electronic citation and linking via DOI
\n\t
Permanent and unrestricted online access to your work
What isn't covered by the Open Access Publishing Fee?
\n\n
If your manuscript:
\n\n
\n\t
Exceeds 20 pages (for chapters in Edited Volumes), an additional fee of 40 GBP per page will be required
\n\t
If a manuscript requires Heavy Editing or Language Polishing, this will incur additional fees.
\n
\n\n
Your Author Service Manager will inform you of any items not covered by the OAPF and provide exact information regarding those additional costs before proceeding.
\n\n
Open Access Funding
\n\n
To explore funding opportunities and learn more about how you can finance your IntechOpen publication, go to our Open Access Funding page. IntechOpen offers expert assistance to all of its Authors. We can support you in approaching funding bodies and institutions in relation to publishing fees by providing information about compliance with the Open Access policies of your funder or institution. We can also assist with communicating the benefits of Open Access in order to support and strengthen your funding request and provide personal guidance through your application process. You can contact us at oapf@intechopen.com for further details or assistance.
\n\n
For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
\n\n
Added Value of Publishing with IntechOpen
\n\n
Choosing to publish with IntechOpen ensures the following benefits:
\n\n
\n\t
Indexing and listing across major repositories, see details ...
\n\t
Long-term archiving
\n\t
Visibility on the world's strongest OA platform
\n\t
Live Performance Metrics to track readership and the impact of your chapter
\n\t
Dissemination and Promotion
\n
\n\n
Benefits of Publishing with IntechOpen
\n\n
\n\t
Proven world leader in Open Access book publishing with over 10 years experience
\n\t
+4,800 OA books published
\n\t
Most competitive prices in the market
\n\t
Fully compliant with OA funding requirements
\n\t
Optimized processes, enabling publication between 8 and 12 months
\n\t
Personal support during every step of the publication process
\n\t
+146,150 citations in Web of Science databases
\n\t
Currently strongest OA platform with over 130 million downloads
\n
\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:5774},{group:"region",caption:"Middle and South America",value:2,count:5239},{group:"region",caption:"Africa",value:3,count:1721},{group:"region",caption:"Asia",value:4,count:10411},{group:"region",caption:"Australia and Oceania",value:5,count:897},{group:"region",caption:"Europe",value:6,count:15810}],offset:12,limit:12,total:118377},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{hasNoEditors:"1",sort:"dateEndThirdStepPublish"},books:[{type:"book",id:"10231",title:"Proton Therapy",subtitle:null,isOpenForSubmission:!0,hash:"f4a9009287953c8d1d89f0fa9b7597b0",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10231.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10652",title:"Visual Object Tracking",subtitle:null,isOpenForSubmission:!0,hash:"96f3ee634a7ba49fa195e50475412af4",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10652.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10653",title:"Optimization Algorithms",subtitle:null,isOpenForSubmission:!0,hash:"753812dbb9a6f6b57645431063114f6c",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10653.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10655",title:"Motion Planning",subtitle:null,isOpenForSubmission:!0,hash:"809b5e290cf2dade9e7e0a5ae0ef3df0",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10655.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10657",title:"Service Robots",subtitle:null,isOpenForSubmission:!0,hash:"5f81b9eea6eb3f9af984031b7af35588",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10657.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10662",title:"Pedagogy",subtitle:null,isOpenForSubmission:!0,hash:"c858e1c6fb878d3b895acbacec624576",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10662.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10673",title:"The Psychology of Trust",subtitle:null,isOpenForSubmission:!0,hash:"1f6cac41fd145f718ac0866264499cc8",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10673.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10675",title:"Hydrostatics",subtitle:null,isOpenForSubmission:!0,hash:"c86c2fa9f835d4ad5e7efd8b01921866",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10675.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10677",title:"Topology",subtitle:null,isOpenForSubmission:!0,hash:"85eac84b173d785f989522397616124e",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10677.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10678",title:"Biostatistics",subtitle:null,isOpenForSubmission:!0,hash:"f63db439474a574454a66894db8b394c",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10678.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10679",title:"Mass Production",subtitle:null,isOpenForSubmission:!0,hash:"2dae91102099b1a07be1a36a68852829",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10679.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10689",title:"Risk Management in Construction",subtitle:null,isOpenForSubmission:!0,hash:"e3805b3d2fceb9d33e1fa805687cd296",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10689.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:6},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:6},{group:"topic",caption:"Business, Management and Economics",value:7,count:4},{group:"topic",caption:"Chemistry",value:8,count:1},{group:"topic",caption:"Computer and Information Science",value:9,count:5},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:3},{group:"topic",caption:"Engineering",value:11,count:4},{group:"topic",caption:"Environmental Sciences",value:12,count:4},{group:"topic",caption:"Immunology and Microbiology",value:13,count:2},{group:"topic",caption:"Mathematics",value:15,count:2},{group:"topic",caption:"Medicine",value:16,count:26},{group:"topic",caption:"Neuroscience",value:18,count:1},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:3},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:3},{group:"topic",caption:"Robotics",value:22,count:4},{group:"topic",caption:"Social Sciences",value:23,count:3},{group:"topic",caption:"Technology",value:24,count:1}],offset:12,limit:12,total:81},popularBooks:{featuredBooks:[{type:"book",id:"9521",title:"Antimicrobial Resistance",subtitle:"A One Health Perspective",isOpenForSubmission:!1,hash:"30949e78832e1afba5606634b52056ab",slug:"antimicrobial-resistance-a-one-health-perspective",bookSignature:"Mihai Mareș, Swee Hua Erin Lim, Kok-Song Lai and Romeo-Teodor Cristina",coverURL:"https://cdn.intechopen.com/books/images_new/9521.jpg",editors:[{id:"88785",title:"Prof.",name:"Mihai",middleName:null,surname:"Mares",slug:"mihai-mares",fullName:"Mihai Mares"}],equalEditorOne:{id:"190224",title:"Dr.",name:"Swee Hua Erin",middleName:null,surname:"Lim",slug:"swee-hua-erin-lim",fullName:"Swee Hua Erin Lim",profilePictureURL:"https://mts.intechopen.com/storage/users/190224/images/system/190224.png",biography:"Dr. Erin Lim is presently working as an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates and is affiliated as an Associate Professor to Perdana University-Royal College of Surgeons in Ireland, Selangor, Malaysia. She obtained her Ph.D. from Universiti Putra Malaysia in 2010 with a National Science Fellowship awarded from the Ministry of Science, Technology and Innovation Malaysia and has been actively involved in research ever since. Her main research interests include analysis of carriage and transmission of multidrug resistant bacteria in non-conventional settings, besides an interest in natural products for antimicrobial testing. She is heavily involved in the elucidation of mechanisms of reversal of resistance in bacteria in addition to investigating the immunological analyses of diseases, development of vaccination and treatment models in animals. She hopes her work will support the discovery of therapeutics in the clinical setting and assist in the combat against the burden of antibiotic resistance.",institutionString:"Abu Dhabi Women’s College",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Perdana University",institutionURL:null,country:{name:"Malaysia"}}},equalEditorTwo:{id:"221544",title:"Dr.",name:"Kok-Song",middleName:null,surname:"Lai",slug:"kok-song-lai",fullName:"Kok-Song Lai",profilePictureURL:"https://mts.intechopen.com/storage/users/221544/images/system/221544.jpeg",biography:"Dr. Lai Kok Song is an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates. He obtained his Ph.D. in Biological Sciences from Nara Institute of Science and Technology, Japan in 2012. Prior to his academic appointment, Dr. Lai worked as a Senior Scientist at the Ministry of Science, Technology and Innovation, Malaysia. His current research areas include antimicrobial resistance and plant-pathogen interaction. His particular interest lies in the study of the antimicrobial mechanism via membrane disruption of essential oils against multi-drug resistance bacteria through various biochemical, molecular and proteomic approaches. Ultimately, he hopes to uncover and determine novel biomarkers related to antibiotic resistance that can be developed into new therapeutic strategies.",institutionString:"Higher Colleges of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Higher Colleges of Technology",institutionURL:null,country:{name:"United Arab Emirates"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10020",title:"Operations Management",subtitle:"Emerging Trend in the Digital Era",isOpenForSubmission:!1,hash:"526f0dbdc7e4d85b82ce8383ab894b4c",slug:"operations-management-emerging-trend-in-the-digital-era",bookSignature:"Antonella Petrillo, Fabio De Felice, Germano Lambert-Torres and Erik Bonaldi",coverURL:"https://cdn.intechopen.com/books/images_new/10020.jpg",editors:[{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9560",title:"Creativity",subtitle:"A Force to Innovation",isOpenForSubmission:!1,hash:"58f740bc17807d5d88d647c525857b11",slug:"creativity-a-force-to-innovation",bookSignature:"Pooja Jain",coverURL:"https://cdn.intechopen.com/books/images_new/9560.jpg",editors:[{id:"316765",title:"Dr.",name:"Pooja",middleName:null,surname:"Jain",slug:"pooja-jain",fullName:"Pooja Jain"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10192",title:"Background and Management of Muscular Atrophy",subtitle:null,isOpenForSubmission:!1,hash:"eca24028d89912b5efea56e179dff089",slug:"background-and-management-of-muscular-atrophy",bookSignature:"Julianna Cseri",coverURL:"https://cdn.intechopen.com/books/images_new/10192.jpg",editors:[{id:"135579",title:"Dr.",name:"Julianna",middleName:null,surname:"Cseri",slug:"julianna-cseri",fullName:"Julianna Cseri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9243",title:"Coastal Environments",subtitle:null,isOpenForSubmission:!1,hash:"8e05e5f631e935eef366980f2e28295d",slug:"coastal-environments",bookSignature:"Yuanzhi Zhang and X. San Liang",coverURL:"https://cdn.intechopen.com/books/images_new/9243.jpg",editors:[{id:"77597",title:"Prof.",name:"Yuanzhi",middleName:null,surname:"Zhang",slug:"yuanzhi-zhang",fullName:"Yuanzhi Zhang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9644",title:"Glaciers and the Polar Environment",subtitle:null,isOpenForSubmission:!1,hash:"e8cfdc161794e3753ced54e6ff30873b",slug:"glaciers-and-the-polar-environment",bookSignature:"Masaki Kanao, Danilo Godone and Niccolò Dematteis",coverURL:"https://cdn.intechopen.com/books/images_new/9644.jpg",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9550",title:"Entrepreneurship",subtitle:"Contemporary Issues",isOpenForSubmission:!1,hash:"9b4ac1ee5b743abf6f88495452b1e5e7",slug:"entrepreneurship-contemporary-issues",bookSignature:"Mladen Turuk",coverURL:"https://cdn.intechopen.com/books/images_new/9550.jpg",editors:[{id:"319755",title:"Prof.",name:"Mladen",middleName:null,surname:"Turuk",slug:"mladen-turuk",fullName:"Mladen Turuk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9027",title:"Human Blood Group Systems and Haemoglobinopathies",subtitle:null,isOpenForSubmission:!1,hash:"d00d8e40b11cfb2547d1122866531c7e",slug:"human-blood-group-systems-and-haemoglobinopathies",bookSignature:"Osaro Erhabor and Anjana Munshi",coverURL:"https://cdn.intechopen.com/books/images_new/9027.jpg",editors:[{id:"35140",title:null,name:"Osaro",middleName:null,surname:"Erhabor",slug:"osaro-erhabor",fullName:"Osaro Erhabor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8558",title:"Aerodynamics",subtitle:null,isOpenForSubmission:!1,hash:"db7263fc198dfb539073ba0260a7f1aa",slug:"aerodynamics",bookSignature:"Mofid Gorji-Bandpy and Aly-Mousaad Aly",coverURL:"https://cdn.intechopen.com/books/images_new/8558.jpg",editors:[{id:"35542",title:"Prof.",name:"Mofid",middleName:null,surname:"Gorji-Bandpy",slug:"mofid-gorji-bandpy",fullName:"Mofid Gorji-Bandpy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5249},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9521",title:"Antimicrobial Resistance",subtitle:"A One Health Perspective",isOpenForSubmission:!1,hash:"30949e78832e1afba5606634b52056ab",slug:"antimicrobial-resistance-a-one-health-perspective",bookSignature:"Mihai Mareș, Swee Hua Erin Lim, Kok-Song Lai and Romeo-Teodor Cristina",coverURL:"https://cdn.intechopen.com/books/images_new/9521.jpg",editors:[{id:"88785",title:"Prof.",name:"Mihai",middleName:null,surname:"Mares",slug:"mihai-mares",fullName:"Mihai Mares"}],equalEditorOne:{id:"190224",title:"Dr.",name:"Swee Hua Erin",middleName:null,surname:"Lim",slug:"swee-hua-erin-lim",fullName:"Swee Hua Erin Lim",profilePictureURL:"https://mts.intechopen.com/storage/users/190224/images/system/190224.png",biography:"Dr. Erin Lim is presently working as an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates and is affiliated as an Associate Professor to Perdana University-Royal College of Surgeons in Ireland, Selangor, Malaysia. She obtained her Ph.D. from Universiti Putra Malaysia in 2010 with a National Science Fellowship awarded from the Ministry of Science, Technology and Innovation Malaysia and has been actively involved in research ever since. Her main research interests include analysis of carriage and transmission of multidrug resistant bacteria in non-conventional settings, besides an interest in natural products for antimicrobial testing. She is heavily involved in the elucidation of mechanisms of reversal of resistance in bacteria in addition to investigating the immunological analyses of diseases, development of vaccination and treatment models in animals. She hopes her work will support the discovery of therapeutics in the clinical setting and assist in the combat against the burden of antibiotic resistance.",institutionString:"Abu Dhabi Women’s College",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Perdana University",institutionURL:null,country:{name:"Malaysia"}}},equalEditorTwo:{id:"221544",title:"Dr.",name:"Kok-Song",middleName:null,surname:"Lai",slug:"kok-song-lai",fullName:"Kok-Song Lai",profilePictureURL:"https://mts.intechopen.com/storage/users/221544/images/system/221544.jpeg",biography:"Dr. Lai Kok Song is an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates. He obtained his Ph.D. in Biological Sciences from Nara Institute of Science and Technology, Japan in 2012. Prior to his academic appointment, Dr. Lai worked as a Senior Scientist at the Ministry of Science, Technology and Innovation, Malaysia. His current research areas include antimicrobial resistance and plant-pathogen interaction. His particular interest lies in the study of the antimicrobial mechanism via membrane disruption of essential oils against multi-drug resistance bacteria through various biochemical, molecular and proteomic approaches. Ultimately, he hopes to uncover and determine novel biomarkers related to antibiotic resistance that can be developed into new therapeutic strategies.",institutionString:"Higher Colleges of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Higher Colleges of Technology",institutionURL:null,country:{name:"United Arab Emirates"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10020",title:"Operations Management",subtitle:"Emerging Trend in the Digital Era",isOpenForSubmission:!1,hash:"526f0dbdc7e4d85b82ce8383ab894b4c",slug:"operations-management-emerging-trend-in-the-digital-era",bookSignature:"Antonella Petrillo, Fabio De Felice, Germano Lambert-Torres and Erik Bonaldi",coverURL:"https://cdn.intechopen.com/books/images_new/10020.jpg",editors:[{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9560",title:"Creativity",subtitle:"A Force to Innovation",isOpenForSubmission:!1,hash:"58f740bc17807d5d88d647c525857b11",slug:"creativity-a-force-to-innovation",bookSignature:"Pooja Jain",coverURL:"https://cdn.intechopen.com/books/images_new/9560.jpg",editors:[{id:"316765",title:"Dr.",name:"Pooja",middleName:null,surname:"Jain",slug:"pooja-jain",fullName:"Pooja Jain"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10192",title:"Background and Management of Muscular Atrophy",subtitle:null,isOpenForSubmission:!1,hash:"eca24028d89912b5efea56e179dff089",slug:"background-and-management-of-muscular-atrophy",bookSignature:"Julianna Cseri",coverURL:"https://cdn.intechopen.com/books/images_new/10192.jpg",editors:[{id:"135579",title:"Dr.",name:"Julianna",middleName:null,surname:"Cseri",slug:"julianna-cseri",fullName:"Julianna Cseri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9243",title:"Coastal Environments",subtitle:null,isOpenForSubmission:!1,hash:"8e05e5f631e935eef366980f2e28295d",slug:"coastal-environments",bookSignature:"Yuanzhi Zhang and X. San Liang",coverURL:"https://cdn.intechopen.com/books/images_new/9243.jpg",editors:[{id:"77597",title:"Prof.",name:"Yuanzhi",middleName:null,surname:"Zhang",slug:"yuanzhi-zhang",fullName:"Yuanzhi Zhang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9644",title:"Glaciers and the Polar Environment",subtitle:null,isOpenForSubmission:!1,hash:"e8cfdc161794e3753ced54e6ff30873b",slug:"glaciers-and-the-polar-environment",bookSignature:"Masaki Kanao, Danilo Godone and Niccolò Dematteis",coverURL:"https://cdn.intechopen.com/books/images_new/9644.jpg",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9550",title:"Entrepreneurship",subtitle:"Contemporary Issues",isOpenForSubmission:!1,hash:"9b4ac1ee5b743abf6f88495452b1e5e7",slug:"entrepreneurship-contemporary-issues",bookSignature:"Mladen Turuk",coverURL:"https://cdn.intechopen.com/books/images_new/9550.jpg",editors:[{id:"319755",title:"Prof.",name:"Mladen",middleName:null,surname:"Turuk",slug:"mladen-turuk",fullName:"Mladen Turuk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"9243",title:"Coastal Environments",subtitle:null,isOpenForSubmission:!1,hash:"8e05e5f631e935eef366980f2e28295d",slug:"coastal-environments",bookSignature:"Yuanzhi Zhang and X. San Liang",coverURL:"https://cdn.intechopen.com/books/images_new/9243.jpg",editedByType:"Edited by",editors:[{id:"77597",title:"Prof.",name:"Yuanzhi",middleName:null,surname:"Zhang",slug:"yuanzhi-zhang",fullName:"Yuanzhi Zhang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10020",title:"Operations Management",subtitle:"Emerging Trend in the Digital Era",isOpenForSubmission:!1,hash:"526f0dbdc7e4d85b82ce8383ab894b4c",slug:"operations-management-emerging-trend-in-the-digital-era",bookSignature:"Antonella Petrillo, Fabio De Felice, Germano Lambert-Torres and Erik Bonaldi",coverURL:"https://cdn.intechopen.com/books/images_new/10020.jpg",editedByType:"Edited by",editors:[{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9521",title:"Antimicrobial Resistance",subtitle:"A One Health Perspective",isOpenForSubmission:!1,hash:"30949e78832e1afba5606634b52056ab",slug:"antimicrobial-resistance-a-one-health-perspective",bookSignature:"Mihai Mareș, Swee Hua Erin Lim, Kok-Song Lai and Romeo-Teodor Cristina",coverURL:"https://cdn.intechopen.com/books/images_new/9521.jpg",editedByType:"Edited by",editors:[{id:"88785",title:"Prof.",name:"Mihai",middleName:null,surname:"Mares",slug:"mihai-mares",fullName:"Mihai Mares"}],equalEditorOne:{id:"190224",title:"Dr.",name:"Swee Hua Erin",middleName:null,surname:"Lim",slug:"swee-hua-erin-lim",fullName:"Swee Hua Erin Lim",profilePictureURL:"https://mts.intechopen.com/storage/users/190224/images/system/190224.png",biography:"Dr. Erin Lim is presently working as an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates and is affiliated as an Associate Professor to Perdana University-Royal College of Surgeons in Ireland, Selangor, Malaysia. She obtained her Ph.D. from Universiti Putra Malaysia in 2010 with a National Science Fellowship awarded from the Ministry of Science, Technology and Innovation Malaysia and has been actively involved in research ever since. Her main research interests include analysis of carriage and transmission of multidrug resistant bacteria in non-conventional settings, besides an interest in natural products for antimicrobial testing. She is heavily involved in the elucidation of mechanisms of reversal of resistance in bacteria in addition to investigating the immunological analyses of diseases, development of vaccination and treatment models in animals. She hopes her work will support the discovery of therapeutics in the clinical setting and assist in the combat against the burden of antibiotic resistance.",institutionString:"Abu Dhabi Women’s College",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Perdana University",institutionURL:null,country:{name:"Malaysia"}}},equalEditorTwo:{id:"221544",title:"Dr.",name:"Kok-Song",middleName:null,surname:"Lai",slug:"kok-song-lai",fullName:"Kok-Song Lai",profilePictureURL:"https://mts.intechopen.com/storage/users/221544/images/system/221544.jpeg",biography:"Dr. Lai Kok Song is an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates. He obtained his Ph.D. in Biological Sciences from Nara Institute of Science and Technology, Japan in 2012. Prior to his academic appointment, Dr. Lai worked as a Senior Scientist at the Ministry of Science, Technology and Innovation, Malaysia. His current research areas include antimicrobial resistance and plant-pathogen interaction. His particular interest lies in the study of the antimicrobial mechanism via membrane disruption of essential oils against multi-drug resistance bacteria through various biochemical, molecular and proteomic approaches. Ultimately, he hopes to uncover and determine novel biomarkers related to antibiotic resistance that can be developed into new therapeutic strategies.",institutionString:"Higher Colleges of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Higher Colleges of Technology",institutionURL:null,country:{name:"United Arab Emirates"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9560",title:"Creativity",subtitle:"A Force to Innovation",isOpenForSubmission:!1,hash:"58f740bc17807d5d88d647c525857b11",slug:"creativity-a-force-to-innovation",bookSignature:"Pooja Jain",coverURL:"https://cdn.intechopen.com/books/images_new/9560.jpg",editedByType:"Edited by",editors:[{id:"316765",title:"Dr.",name:"Pooja",middleName:null,surname:"Jain",slug:"pooja-jain",fullName:"Pooja Jain"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9669",title:"Recent Advances in Rice Research",subtitle:null,isOpenForSubmission:!1,hash:"12b06cc73e89af1e104399321cc16a75",slug:"recent-advances-in-rice-research",bookSignature:"Mahmood-ur- Rahman Ansari",coverURL:"https://cdn.intechopen.com/books/images_new/9669.jpg",editedByType:"Edited by",editors:[{id:"185476",title:"Dr.",name:"Mahmood-Ur-",middleName:null,surname:"Rahman Ansari",slug:"mahmood-ur-rahman-ansari",fullName:"Mahmood-Ur- Rahman Ansari"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10192",title:"Background and Management of Muscular Atrophy",subtitle:null,isOpenForSubmission:!1,hash:"eca24028d89912b5efea56e179dff089",slug:"background-and-management-of-muscular-atrophy",bookSignature:"Julianna Cseri",coverURL:"https://cdn.intechopen.com/books/images_new/10192.jpg",editedByType:"Edited by",editors:[{id:"135579",title:"Dr.",name:"Julianna",middleName:null,surname:"Cseri",slug:"julianna-cseri",fullName:"Julianna Cseri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9550",title:"Entrepreneurship",subtitle:"Contemporary Issues",isOpenForSubmission:!1,hash:"9b4ac1ee5b743abf6f88495452b1e5e7",slug:"entrepreneurship-contemporary-issues",bookSignature:"Mladen Turuk",coverURL:"https://cdn.intechopen.com/books/images_new/9550.jpg",editedByType:"Edited by",editors:[{id:"319755",title:"Prof.",name:"Mladen",middleName:null,surname:"Turuk",slug:"mladen-turuk",fullName:"Mladen Turuk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editedByType:"Edited by",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9313",title:"Clay Science and Technology",subtitle:null,isOpenForSubmission:!1,hash:"6fa7e70396ff10620e032bb6cfa6fb72",slug:"clay-science-and-technology",bookSignature:"Gustavo Morari Do Nascimento",coverURL:"https://cdn.intechopen.com/books/images_new/9313.jpg",editedByType:"Edited by",editors:[{id:"7153",title:"Prof.",name:"Gustavo",middleName:null,surname:"Morari Do Nascimento",slug:"gustavo-morari-do-nascimento",fullName:"Gustavo Morari Do Nascimento"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9888",title:"Nuclear Power Plants",subtitle:"The Processes from the Cradle to the Grave",isOpenForSubmission:!1,hash:"c2c8773e586f62155ab8221ebb72a849",slug:"nuclear-power-plants-the-processes-from-the-cradle-to-the-grave",bookSignature:"Nasser Awwad",coverURL:"https://cdn.intechopen.com/books/images_new/9888.jpg",editedByType:"Edited by",editors:[{id:"145209",title:"Prof.",name:"Nasser",middleName:"S",surname:"Awwad",slug:"nasser-awwad",fullName:"Nasser Awwad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"277",title:"Social Policy",slug:"social-policy",parent:{title:"Social Sciences",slug:"social-sciences"},numberOfBooks:4,numberOfAuthorsAndEditors:37,numberOfWosCitations:14,numberOfCrossrefCitations:18,numberOfDimensionsCitations:28,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"social-policy",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"8090",title:"Who Wants to Retire and Who Can Afford to Retire?",subtitle:null,isOpenForSubmission:!1,hash:"90fe30d224594414bb156e42afa47f5e",slug:"who-wants-to-retire-and-who-can-afford-to-retire-",bookSignature:"Ingrid Muenstermann",coverURL:"https://cdn.intechopen.com/books/images_new/8090.jpg",editedByType:"Edited by",editors:[{id:"77112",title:"Dr.",name:"Ingrid",middleName:null,surname:"Muenstermann",slug:"ingrid-muenstermann",fullName:"Ingrid Muenstermann"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6682",title:"The Relevance of Hygiene to Health in Developing Countries",subtitle:null,isOpenForSubmission:!1,hash:"c6bce9af9756cd41e5d336fa8945b2ea",slug:"the-relevance-of-hygiene-to-health-in-developing-countries",bookSignature:"Natasha Potgieter and Afsatou Ndama Traore Hoffman",coverURL:"https://cdn.intechopen.com/books/images_new/6682.jpg",editedByType:"Edited by",editors:[{id:"55305",title:"Prof.",name:"Natasha",middleName:null,surname:"Potgieter",slug:"natasha-potgieter",fullName:"Natasha Potgieter"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6938",title:"Elections",subtitle:"A Global Perspective",isOpenForSubmission:!1,hash:"4a122ebf3b961d2c46bbfc8def2916fe",slug:"elections-a-global-perspective",bookSignature:"Ryan M. Yonk",coverURL:"https://cdn.intechopen.com/books/images_new/6938.jpg",editedByType:"Edited by",editors:[{id:"196259",title:"Dr.",name:"Ryan Merlin",middleName:null,surname:"Yonk",slug:"ryan-merlin-yonk",fullName:"Ryan Merlin Yonk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5392",title:"An Analysis of Contemporary Social Welfare Issues",subtitle:null,isOpenForSubmission:!1,hash:"4a9795772c4001a5a648421ebf11cee7",slug:"an-analysis-of-contemporary-social-welfare-issues",bookSignature:"Rosario Laratta",coverURL:"https://cdn.intechopen.com/books/images_new/5392.jpg",editedByType:"Edited by",editors:[{id:"118227",title:"Dr.",name:"Rosario",middleName:null,surname:"Laratta",slug:"rosario-laratta",fullName:"Rosario Laratta"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:4,mostCitedChapters:[{id:"63707",doi:"10.5772/intechopen.80780",title:"Drinking Water Treatment and Challenges in Developing Countries",slug:"drinking-water-treatment-and-challenges-in-developing-countries",totalDownloads:2757,totalCrossrefCites:6,totalDimensionsCites:9,book:{slug:"the-relevance-of-hygiene-to-health-in-developing-countries",title:"The Relevance of Hygiene to Health in Developing Countries",fullTitle:"The Relevance of Hygiene to Health in Developing Countries"},signatures:"Josephine Treacy",authors:[{id:"238173",title:"Dr.",name:"Josephine",middleName:null,surname:"Treacy",slug:"josephine-treacy",fullName:"Josephine Treacy"}]},{id:"63322",doi:"10.5772/intechopen.80355",title:"Challenges to Hygiene Improvement in Developing Countries",slug:"challenges-to-hygiene-improvement-in-developing-countries",totalDownloads:1621,totalCrossrefCites:3,totalDimensionsCites:6,book:{slug:"the-relevance-of-hygiene-to-health-in-developing-countries",title:"The Relevance of Hygiene to Health in Developing Countries",fullTitle:"The Relevance of Hygiene to Health in Developing Countries"},signatures:"Save Kumwenda",authors:[{id:"233913",title:"Mr.",name:"Save",middleName:null,surname:"Kumwenda",slug:"save-kumwenda",fullName:"Save Kumwenda"}]},{id:"52475",doi:"10.5772/65462",title:"Teenage Pregnancies: A Worldwide Social and Medical Problem",slug:"teenage-pregnancies-a-worldwide-social-and-medical-problem",totalDownloads:5893,totalCrossrefCites:4,totalDimensionsCites:4,book:{slug:"an-analysis-of-contemporary-social-welfare-issues",title:"An Analysis of Contemporary Social Welfare Issues",fullTitle:"An Analysis of Contemporary Social Welfare Issues"},signatures:"Sylvia Kirchengast",authors:[{id:"188289",title:"Prof.",name:"Sylvia",middleName:null,surname:"Kirchengast",slug:"sylvia-kirchengast",fullName:"Sylvia Kirchengast"}]}],mostDownloadedChaptersLast30Days:[{id:"52475",title:"Teenage Pregnancies: A Worldwide Social and Medical Problem",slug:"teenage-pregnancies-a-worldwide-social-and-medical-problem",totalDownloads:5902,totalCrossrefCites:4,totalDimensionsCites:4,book:{slug:"an-analysis-of-contemporary-social-welfare-issues",title:"An Analysis of Contemporary Social Welfare Issues",fullTitle:"An Analysis of Contemporary Social Welfare Issues"},signatures:"Sylvia Kirchengast",authors:[{id:"188289",title:"Prof.",name:"Sylvia",middleName:null,surname:"Kirchengast",slug:"sylvia-kirchengast",fullName:"Sylvia Kirchengast"}]},{id:"63707",title:"Drinking Water Treatment and Challenges in Developing Countries",slug:"drinking-water-treatment-and-challenges-in-developing-countries",totalDownloads:2761,totalCrossrefCites:6,totalDimensionsCites:9,book:{slug:"the-relevance-of-hygiene-to-health-in-developing-countries",title:"The Relevance of Hygiene to Health in Developing Countries",fullTitle:"The Relevance of Hygiene to Health in Developing Countries"},signatures:"Josephine Treacy",authors:[{id:"238173",title:"Dr.",name:"Josephine",middleName:null,surname:"Treacy",slug:"josephine-treacy",fullName:"Josephine Treacy"}]},{id:"63322",title:"Challenges to Hygiene Improvement in Developing Countries",slug:"challenges-to-hygiene-improvement-in-developing-countries",totalDownloads:1625,totalCrossrefCites:3,totalDimensionsCites:6,book:{slug:"the-relevance-of-hygiene-to-health-in-developing-countries",title:"The Relevance of Hygiene to Health in Developing Countries",fullTitle:"The Relevance of Hygiene to Health in Developing Countries"},signatures:"Save Kumwenda",authors:[{id:"233913",title:"Mr.",name:"Save",middleName:null,surname:"Kumwenda",slug:"save-kumwenda",fullName:"Save Kumwenda"}]},{id:"52455",title:"Introductory Chapter: An Overview of the Book",slug:"introductory-chapter-an-overview-of-the-book",totalDownloads:1034,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"an-analysis-of-contemporary-social-welfare-issues",title:"An Analysis of Contemporary Social Welfare Issues",fullTitle:"An Analysis of Contemporary Social Welfare Issues"},signatures:"Rosario Laratta",authors:[{id:"118227",title:"Dr.",name:"Rosario",middleName:null,surname:"Laratta",slug:"rosario-laratta",fullName:"Rosario Laratta"}]},{id:"63851",title:"Electoral Behavior and Politics of Stomach Infrastructure in Ekiti State (Nigeria)",slug:"electoral-behavior-and-politics-of-stomach-infrastructure-in-ekiti-state-nigeria-",totalDownloads:577,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"elections-a-global-perspective",title:"Elections",fullTitle:"Elections - A Global Perspective"},signatures:"Mike Omilusi",authors:[{id:"256067",title:"Dr.",name:"Mike",middleName:null,surname:"Omilusi",slug:"mike-omilusi",fullName:"Mike Omilusi"}]},{id:"63923",title:"The Electoral Cycle and Grassroots Realities in Cameroon: The Omnipresent, Overbearing and Contested Political Elite",slug:"the-electoral-cycle-and-grassroots-realities-in-cameroon-the-omnipresent-overbearing-and-contested-p",totalDownloads:457,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"elections-a-global-perspective",title:"Elections",fullTitle:"Elections - A Global Perspective"},signatures:"Numvi Gwaibi",authors:[{id:"256697",title:"Dr.",name:"Wallace",middleName:null,surname:"Numvi Gwaibi",slug:"wallace-numvi-gwaibi",fullName:"Wallace Numvi Gwaibi"}]},{id:"64192",title:"Who Does Not Vote and Why? Implication for New Democracies",slug:"who-does-not-vote-and-why-implication-for-new-democracies",totalDownloads:505,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"elections-a-global-perspective",title:"Elections",fullTitle:"Elections - A Global Perspective"},signatures:"Elvis Bisong Tambe",authors:[{id:"255692",title:"Dr.",name:"Elvis Bisong",middleName:null,surname:"Tambe",slug:"elvis-bisong-tambe",fullName:"Elvis Bisong Tambe"}]},{id:"61814",title:"Inequalities in Households’ Environmental Sanitation Practices in a Developing Nation’s City: The Example of Ile-Ife, Nigeria",slug:"inequalities-in-households-environmental-sanitation-practices-in-a-developing-nation-s-city-the-exam",totalDownloads:490,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"the-relevance-of-hygiene-to-health-in-developing-countries",title:"The Relevance of Hygiene to Health in Developing Countries",fullTitle:"The Relevance of Hygiene to Health in Developing Countries"},signatures:"Faniran Gbemiga and Ojo Deborah",authors:[{id:"232193",title:"Dr.",name:"Gbemiga",middleName:null,surname:"Faniran",slug:"gbemiga-faniran",fullName:"Gbemiga Faniran"},{id:"233650",title:"Mrs.",name:"Deborah",middleName:null,surname:"Ojo",slug:"deborah-ojo",fullName:"Deborah Ojo"}]},{id:"52198",title:"Unemployment and Causes of Hospital Admission Considering Different Analytical Approaches",slug:"unemployment-and-causes-of-hospital-admission-considering-different-analytical-approaches",totalDownloads:929,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"an-analysis-of-contemporary-social-welfare-issues",title:"An Analysis of Contemporary Social Welfare Issues",fullTitle:"An Analysis of Contemporary Social Welfare Issues"},signatures:"Gabriele Berg-Beckhoff, Gabriel Gulis, Carsten Kronborg Bak and\nPernille Tanggaard Andersen",authors:[{id:"188461",title:"Dr.",name:"Gabriele",middleName:null,surname:"Berg-Beckhoff",slug:"gabriele-berg-beckhoff",fullName:"Gabriele Berg-Beckhoff"},{id:"188463",title:"Dr.",name:"Gabriel",middleName:null,surname:"Gulis",slug:"gabriel-gulis",fullName:"Gabriel Gulis"},{id:"188465",title:"Dr.",name:"Carsten",middleName:null,surname:"Kronborg Bak",slug:"carsten-kronborg-bak",fullName:"Carsten Kronborg Bak"},{id:"188466",title:"Dr.",name:"Pernille",middleName:null,surname:"Tangaard Andersen",slug:"pernille-tangaard-andersen",fullName:"Pernille Tangaard Andersen"}]},{id:"63191",title:"Household Water Handling Practices in the Arid and Semi-Arid Lands in Kenya",slug:"household-water-handling-practices-in-the-arid-and-semi-arid-lands-in-kenya",totalDownloads:438,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"the-relevance-of-hygiene-to-health-in-developing-countries",title:"The Relevance of Hygiene to Health in Developing Countries",fullTitle:"The Relevance of Hygiene to Health in Developing Countries"},signatures:"Edith J. Kurui, George M. Ogendi, Wilkister N. Moturi\nand Dishon O. Nyawanga",authors:[{id:"78236",title:"Dr.",name:"Wilkister",middleName:null,surname:"Moturi",slug:"wilkister-moturi",fullName:"Wilkister Moturi"},{id:"234029",title:"M.Sc.",name:"Edith",middleName:null,surname:"Kurui",slug:"edith-kurui",fullName:"Edith Kurui"},{id:"247927",title:"Dr.",name:"George",middleName:null,surname:"Ogendi",slug:"george-ogendi",fullName:"George Ogendi"},{id:"247930",title:"Mr.",name:"Dishon",middleName:null,surname:"Nyawanga",slug:"dishon-nyawanga",fullName:"Dishon Nyawanga"}]}],onlineFirstChaptersFilter:{topicSlug:"social-policy",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/291953/adriana-alves",hash:"",query:{},params:{id:"291953",slug:"adriana-alves"},fullPath:"/profiles/291953/adriana-alves",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)}()