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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\\nWe 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!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased 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\nWe 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!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"7795",leadTitle:null,fullTitle:"Artificial Intelligence - Scope and Limitations",title:"Artificial Intelligence",subtitle:"Scope and Limitations",reviewType:"peer-reviewed",abstract:"Artificial intelligence (AI) is a potent buzzword and happening technology which has greatly impacted the lifestyle of every human being either directly or indirectly and is shaping the future of tomorrow. In fact, AI is fast becoming an intrinsic part of our daily life and is not confined to university research labs, even if remarkable progress has been made in this domain. The benefit of this phenomenon is widely recognized in diversified areas, ranging from medicine to security to consumer applications and business, and resulting in improvements in the quality of life of humankind. Every new disruptive technology has its own pros and cons and AI is no exception to this rule. Privacy, data protection, and the rights of individuals pose social and ethical challenges.",isbn:"978-1-78985-936-2",printIsbn:"978-1-78985-935-5",pdfIsbn:"978-1-83962-124-6",doi:"10.5772/intechopen.77611",price:100,priceEur:109,priceUsd:129,slug:"artificial-intelligence-scope-and-limitations",numberOfPages:78,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"7e536b4fe8982ca9015228fe6f58c6ea",bookSignature:"Dinesh G. Harkut",publishedDate:"April 24th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/7795.jpg",numberOfDownloads:5709,numberOfWosCitations:4,numberOfCrossrefCitations:5,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:10,numberOfDimensionsCitationsByBook:1,hasAltmetrics:1,numberOfTotalCitations:19,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 13th 2018",dateEndSecondStepPublish:"July 4th 2018",dateEndThirdStepPublish:"September 2nd 2018",dateEndFourthStepPublish:"November 21st 2018",dateEndFifthStepPublish:"January 20th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"216122",title:"Dr.",name:"Dinesh G.",middleName:null,surname:"Harkut",slug:"dinesh-g.-harkut",fullName:"Dinesh G. Harkut",profilePictureURL:"https://mts.intechopen.com/storage/users/216122/images/system/216122.png",biography:"Dr. Dinesh G. Harkut is Associate Professor at Prof Ram Meghe College of Engineering & Management (PRMCEAM), Badnera, India, in the Computer Science and Engineering Department. He obtained a bachelor’s degree, a master’s of engineering (CSE), and a PhD (CSE) from SGBAU Amravati University, Maharashtra, India. He also holds a master’s degree and PhD in Business Administration.\nHis primary research interests are in artificial intelligence, big data, analytics, embedded systems, and e-commerce. He has supervised eighteen master’s degree and twenty-four bachelor’s degree students. He has published forty-seven papers in refereed journals and published six books with international publishers. He has also organized various workshops, sessions, conferences, and trainings. He has two patents filed and published in his name in India. \nHe is a member of the Board of Studies (Computer Science and Engineering) and a recognized PhD supervisor at SGBAU Amravati University, Maharashtra, India. He holds membership in various professional bodies including the Institution of Electronics and Telecommunication Engineers (IETE), New Delhi; International Society for Technology in Education (ISTE), New Delhi; Universal Association of Computer and Electronics Engineers (UACEE), USA; International Economics Development and Research Center (IEDRC), Hong Kong; International Association of Engineers (IAENG), Hong Kong; and the European Alliance for Innovation, Belgium.",institutionString:"Prof Ram Mehge College of Engineering and Management",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"Sant Gadge Baba Amravati University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"87",title:"Artificial Intelligence",slug:"computer-and-information-science-artificial-intelligence"}],chapters:[{id:"66147",title:"Introductory Chapter: Artificial Intelligence - Challenges and Applications",doi:"10.5772/intechopen.84624",slug:"introductory-chapter-artificial-intelligence-challenges-and-applications",totalDownloads:1616,totalCrossrefCites:4,totalDimensionsCites:6,hasAltmetrics:1,abstract:null,signatures:"Dinesh G. Harkut and Kashmira Kasat",downloadPdfUrl:"/chapter/pdf-download/66147",previewPdfUrl:"/chapter/pdf-preview/66147",authors:[null],corrections:null},{id:"64306",title:"Intention to Use WhatsApp",doi:"10.5772/intechopen.81999",slug:"intention-to-use-whatsapp",totalDownloads:1079,totalCrossrefCites:1,totalDimensionsCites:4,hasAltmetrics:1,abstract:"More than 1.8 billion people use WhatsApp nowadays, out of which 70% uses it daily. In this scenario, this study seeks modeling the variables that positively influence the intention to use WhatsApp. To this end, 579 surveys based on the unified theory of acceptance and use of technology are conducted. The descriptive results show that individuals use WhatsApp mainly motivated by leisure. In this sense, according to the structural equation model, the variable with the greatest influence on behavioral intention is hedonic motivation, followed by social influence, performance expectancy, and effort expectancy. These results indicate that most people use WhatsApp principally because they find it fun, enjoyable, and very entertaining, something more inherent to an entertainment application than to a messaging application. Nevertheless, a cluster analysis indicates the existence of two consumer segments: one showing a certain indifference and disagreement regarding the usefulness of WhatsApp for their activities and duties and the other manifesting that it uses WhatsApp not only for leisure but also for work, academic, and informative reasons. These differences in consumer drivers might have a great impact on WhatsApp and its competition marketing strategies.",signatures:"Cristobal Fernández-Robin, Diego Yáñez and Scott McCoy",downloadPdfUrl:"/chapter/pdf-download/64306",previewPdfUrl:"/chapter/pdf-preview/64306",authors:[null],corrections:null},{id:"65222",title:"Information and Communication Systems Including Artificial Intelligence and Big Data as Objects of International Legal Protection",doi:"10.5772/intechopen.83565",slug:"information-and-communication-systems-including-artificial-intelligence-and-big-data-as-objects-of-i",totalDownloads:984,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The objective of this study is identifying prospective for international legal protection of information and communication systems including artificial intelligence on the universal and regional levels, and analysis of legal instruments for protection of artificial intelligence and Big Data in the context of regulation of relations in the global information society. A complex of general scientific and philosophical methods, including the logical, comparative-legal, formal-legal, systemic-structural, and problematic-theoretical methods, as well as methods of analysis and synthesis, generalization and description were used in the research. It was found that the existing international agreements in the field of intellectual property protection take no account of the particular features of protection of complex objects. Complex objects comprise information and communication systems including artificial intelligence and Big Data. There is an objective necessity to establish a legal regime for complex objects on the universal level. The findings can be used in activities of international organizations in execution of their functions of unification and harmonization of the international information law.",signatures:"Valentina Petrovna Talimonchik",downloadPdfUrl:"/chapter/pdf-download/65222",previewPdfUrl:"/chapter/pdf-preview/65222",authors:[{id:"248931",title:"Dr.",name:"Valentina",surname:"Talimonchik",slug:"valentina-talimonchik",fullName:"Valentina Talimonchik"}],corrections:null},{id:"64350",title:"Prediction of Cancer Patient Outcomes Based on Artificial Intelligence",doi:"10.5772/intechopen.81872",slug:"prediction-of-cancer-patient-outcomes-based-on-artificial-intelligence",totalDownloads:1207,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Knowledge-based outcome predictions are common before radiotherapy. Because there are various treatment techniques, numerous factors must be considered in predicting cancer patient outcomes. As expectations surrounding personalized radiotherapy using complex data have increased, studies on outcome predictions using artificial intelligence have also increased. Representative artificial intelligence techniques used to predict the outcomes of cancer patients in the field of radiation oncology include collecting and processing big data, text mining of clinical literature, and machine learning for implementing prediction models. Here, methods of data preparation and model construction to predict rates of survival and toxicity using artificial intelligence are described.",signatures:"Suk Lee, Eunbin Ju, Suk Woo Choi, Hyungju Lee, Jang Bo Shim,\nKyung Hwan Chang, Kwang Hyeon Kim and Chul Yong Kim",downloadPdfUrl:"/chapter/pdf-download/64350",previewPdfUrl:"/chapter/pdf-preview/64350",authors:[null],corrections:null},{id:"64304",title:"Team Exploration of Environments Using Stochastic Local Search",doi:"10.5772/intechopen.81902",slug:"team-exploration-of-environments-using-stochastic-local-search",totalDownloads:823,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"We investigate the use of Stochastic Local Search (SLS) technique to explore environments where agents? knowledge and the time to explore such environments are limited. We extend a work that uses evolutionary algorithms to evolve teams in simulated environments. Our work proposes a formalization of the concept of state and neighborhood for SLS and provides evaluation of agents? teams using number of interesting cells. Further, we modify the environments to include goals that are randomly distributed among interesting cells. Agents in this case are then required to search for goals. Experiments using teams of different sizes show the effectiveness of our technique. Teams were able to complete exploration of more than 70% of the environments, while in the best cases, they were able to complete explorations of more than 80% of the environments within limited time steps. These results compare with those of the previous work. It is interesting to note that all teams of agents were able to find on average all the goals in the three environments when the size of the grid is 12. This is a 100% achievement by the agents? teams. However, performance can be seen to degrade as the environments? sizes become larger.",signatures:"Ramoni O. Lasisi and Robert DuPont",downloadPdfUrl:"/chapter/pdf-download/64304",previewPdfUrl:"/chapter/pdf-preview/64304",authors:[null],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"9966",title:"Dynamic Data Assimilation",subtitle:"Beating the Uncertainties",isOpenForSubmission:!1,hash:"e7fde2a36354a2f5a4282fdf9c743380",slug:"dynamic-data-assimilation-beating-the-uncertainties",bookSignature:"Dinesh G. Harkut",coverURL:"https://cdn.intechopen.com/books/images_new/9966.jpg",editedByType:"Edited by",editors:[{id:"216122",title:"Dr.",name:"Dinesh G.",surname:"Harkut",slug:"dinesh-g.-harkut",fullName:"Dinesh G. 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The volume of losses resulting from these events is also growing exponentially, particularly in highly urbanized urban areas, where the effects of intensive land use and climate change are particularly extreme. All this despite our scientific knowledge, technical competence, and computational capacity to develop highly sophisticated and accurate forecasting and simulation models being higher than ever. In order to tackle this global issue, it is fundamental to keep on promoting and developing fundamental and applied research that allows the better targeting of interventions to improve resilience, reduce vulnerability and enhance recovery, as well as assist decision-makers in delivering more effective flood risk-reduction policies. This book will aim at contributing to this goal by gathering recent studies and state-of-the-art methodologies focused on understanding existing and emerging flood risk drivers in a climate change context.
",isbn:"978-1-80356-603-0",printIsbn:"978-1-80356-602-3",pdfIsbn:"978-1-80356-604-7",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"c829bdd1a2a84b4b2c31ce5eaab865e2",bookSignature:"Dr. Tiago Miguel Ferreira and Associate Prof. Haiyun Shi",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11487.jpg",keywords:"Flood Risk, Flood Hazard, Climate Change, Extreme Events, Precipitation Extremes, Extreme Events Statistics, Forecasting, Machine Learning, Statistical Hydrology, Urban Flood Risk, Urban Flood Management, Heritage Buildings",numberOfDownloads:52,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 16th 2022",dateEndSecondStepPublish:"April 13th 2022",dateEndThirdStepPublish:"June 12th 2022",dateEndFourthStepPublish:"August 31st 2022",dateEndFifthStepPublish:"October 30th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"3 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Dr. Ferreira is ranked among the top 2% of scientists in the world in building and construction, with a long track record of publications in the field of urban risk management. Recipient of several awards and over £11 Million attracted in research grants. He has ten years of academic experience in the conservation of historical structures and vulnerability assessment under flood, earthquake, and fire.",coeditorOneBiosketch:"Dr.Shi is a pioneering researcher in the field of hydrology and water resources, mainly focusing on the topics of hydrological extremes (floods and droughts) under climate change. He has served as the main convener of two sessions in the AOGS (Asia Oceania Geosciences Society) annual meeting and the main convener of one session in the AGU (American Geophysical Union) Fall meeting.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"450075",title:null,name:"Tiago Miguel",middleName:null,surname:"Ferreira",slug:"tiago-miguel-ferreira",fullName:"Tiago Miguel Ferreira",profilePictureURL:"https://mts.intechopen.com/storage/users/450075/images/system/450075.jpg",biography:"Dr. Tiago Miguel Ferreira is an Assistant Professor in Civil Engineering at the University of the West of England, United Kingdom, and an invited Assistant Professor at the University of Coimbra, Portugal. Currently, he is an Editor-in-Chief of Conservar Património, a SCOPUS and Web-of-Science indexed journal dedicated to heritage studies, and a Co-Editor-in-Chief of GeoHazards, a multidisciplinary open-access journal devoted to theoretical and applied research across the whole spectrum of geomorphological hazards, namely endogenous and exogenous hazards, and those related to climate change and human activity. Ten years of academic experience in the conservation of historical structures and vulnerability assessment under flood, earthquake, and fire. His research has focused on the vulnerability assessment of urban areas, advanced structural analysis, non-destructive evaluation and diagnosis, and documentation of cultural heritage and historical sites.",institutionString:null,position:null,outsideEditionCount:null,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null}],coeditorOne:{id:"451554",title:"Associate Prof.",name:"Haiyun",middleName:null,surname:"Shi",slug:"haiyun-shi",fullName:"Haiyun Shi",profilePictureURL:"https://mts.intechopen.com/storage/users/451554/images/system/451554.jpg",biography:"Dr. Haiyun Shi is an Associate Professor at Southern University of Science and Technology, Shenzhen, China. He got his Ph.D. degree at Tsinghua University, Beijing, China. He worked previously as a Postdoctoral Fellow/Senior Research Assistant at The University of Hong Kong. His research interests include digital watersheds, hydroinformatics, climate change, hydrological extremes (floods and droughts), and sustainable development. He has been invited as the reviewer of over 30 international journals and the Expert Reviewer of the IPCC Sixth Assessment Report (Working Group II). He has served as the Editorial Board Member/Guest Editor of 5 international journals. He has served as the main convener of 2 sessions in the AOGS (Asia Oceania Geosciences Society) annual meeting and the main convener of 1 session in the AGU (American Geophysical Union) Fall meeting.",institutionString:"Southern University of Science and Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Southern University of Science and Technology",institutionURL:null,country:{name:"China"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"10",title:"Earth and Planetary Sciences",slug:"earth-and-planetary-sciences"}],chapters:[{id:"80843",title:"Understanding the Role of Constructed Wetlands in Stormwater Management",slug:"understanding-the-role-of-constructed-wetlands-in-stormwater-management",totalDownloads:52,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"453624",firstName:"Martina",lastName:"Scerbe",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/453624/images/20399_n.jpg",email:"martina.s@intechopen.com",biography:null}},relatedBooks:[{type:"book",id:"5962",title:"Estuary",subtitle:null,isOpenForSubmission:!1,hash:"43058846a64b270e9167d478e966161a",slug:"estuary",bookSignature:"William Froneman",coverURL:"https://cdn.intechopen.com/books/images_new/5962.jpg",editedByType:"Edited by",editors:[{id:"109336",title:"Prof.",name:"William",surname:"Froneman",slug:"william-froneman",fullName:"William Froneman"}],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:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],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:"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:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"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:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"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:"2270",title:"Fourier Transform",subtitle:"Materials Analysis",isOpenForSubmission:!1,hash:"5e094b066da527193e878e160b4772af",slug:"fourier-transform-materials-analysis",bookSignature:"Salih Mohammed Salih",coverURL:"https://cdn.intechopen.com/books/images_new/2270.jpg",editedByType:"Edited by",editors:[{id:"111691",title:"Dr.Ing.",name:"Salih",surname:"Salih",slug:"salih-salih",fullName:"Salih Salih"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"42337",title:"Exopolysaccharides of Lactic Acid Bacteria for Food and Colon Health Applications",doi:"10.5772/50839",slug:"exopolysaccharides-of-lactic-acid-bacteria-for-food-and-colon-health-applications",body:'Lactic acid bacteria (LAB) are used in many fermented foods, particularly fermented dairy products such as cheese, buttermilk, and fermented milks. LAB produce lactic acid, carbon dioxide, and diacetyl/acetoin that contribute to the flavor, texture, and shelf life of fermented foods. Some LAB produce exopolysaccharide (EPS), and generally, EPS play a major role as natural texturizer in the industrial production of yoghurt, cheese, and milk-based desserts. Recently, EPS produced by LAB have received increasing attention, mainly because of their health benefits. In particular, immune stimulation, antimutagenicity, and the antitumor activity of fermented dairy products prepared with EPS-producing LAB or EPS themselves have been investigated [1-4].
EPS are polysaccharides secreted from the cell, or produced on the outer cell by extracellular enzymes. EPS from LAB are divided into two classes, homo- and hetero-EPS. Homo-EPS are composed of one type of monosaccharide, whereas hetero-EPS consist of regular repeating units of 3-8 different carbohydrate moieties synthesized from intracellular sugar nucleotide precursors [5]. The biosynthesis of homo-EPS and hetero-EPS are different. Homo-EPS are made from sucrose using glucansucrase or levansucrase [6-7], and the synthesis of hetero-EPS involves four major steps, sugar transportation, sugar nucleotide synthesis, repeating unit synthesis, and polymerization of the repeating units [8]. The major physiological function of EPS is believed to be biological defenses against various stresses such as phage attack, toxic metal ions, and desiccation [9], and it is very unlikely that bacteria use EPS as an energy source. However, some potentially probiotic LAB strains have been reported to degrade EPS produced by the other LAB strains [10-11].
The term "probiotic" was first proposed by Fuller [12], and its definition was further refined to "Live microorganisms which when consumed in adequate amounts as part of food confer a health benefit on the host" [13]. Probiotic LAB thus represent a class of live food ingredients that exert a beneficial effect on the health of the host. Beneficial microorganisms in the intestine are enhanced by “prebiotics,” which are defined as "nondigestible food ingredients that beneficially affect the host by selectively stimulating the growth and activity of one or a limited number of bacterial species already resident in the colon, and thus improving host health" [14].
Most of the current prebiotics are low molecular weight except for inulin. As long carbohydrate chains are metabolized more slowly than the short ones, and polysaccharides thus exert prebiotic effects in more distal colonic regions compared to oligosaccharides, which are more rapidly digested in the proximal colon [15]. Therefore, EPS produced by LAB can be used as prebiotics. This chapter reviews the physicochemical properties, genetics, and bioactivities of the EPS produced by LAB.
Some LAB can produce EPS that are either secreted to the environment or attached to the cell surface forming capsules. EPS are classified into two groups: homo-EPS, consisting of a single type of monosaccharide (α-D-glucans, β-D-glucans, fructans, and others represented by polygalactan) and hetero-EPS, composed of different types of monosaccharides, mainly D-glucose, D-galactose, L-rhamnose, and their derivatives [16].
The differences arise between the homopolysaccharides mainly because of the features of their primary structure such as the pattern of main chain bonds, molecular weight, and branch structure. Two important groups of homo-EPS are produced by LAB; (i) α-glucans, mainly composed of α-1,6- and α-1,3-linked glucose residues, namely dextrans, produced by
The formation of dextran from sucrose has been recorded for
Mutan is the glucan synthesized by various serotypes of
Homo-EPS | Main linkage(branching linkage) | Organism |
Glucans | ||
Dextran | ||
Mutan | α-1,3 (α-1,6) | |
Alternan | ||
Fructans | ||
Levan | ||
Inulin | β-2,1 (β-2,6) |
Homo EPS produced by LAB
Alternan has alternate α-1,6 and α-1,3 linkages, and this structure is thought to be responsible for its distinctive physical properties including high solubility and low viscosity. These characteristics provide this glucan with a potential commercial application as a low viscosity texturizer in foods.
Levan is an EPS produced from sucrose. It is fructan composed of β-2,6-linked fructose molecules with some β-2,1-linked branches. Incidentally, inulin is a fructan composed of β-2,1-linked fructose molecules with some β-2,6-linked branches.
The chemical composition of hetero-EPS shows wide variablity. Hetero-EPS are polymerized repeating units mainly composed of D-glucose, D-galactose, and L-rhamnose. The composition of the monosaccharide subunits and the structure of the repeating units are considered not to be species-specific, except in case of
The quantities of hetero-EPS produced by LAB vary greatly. EPS production is 50-350 mg/l for
Fermentation conditions using undefined media have been improved to maximize yields. However, a chemically defined medium containing a carbohydrate source, mineral salts, amino acids, vitamins, and nucleic acid bases is more suitable for investigating the influence of different nutrients on LAB growth and EPS biosynthesis. The total yield of EPS produced by LAB depends on the composition of the medium (carbon and nitrogen sources) and the growth conditions, i.e., temperature, pH, and incubation time.
Under conditions of higher temperatures and slower growth, the production of the polymer per cell in
The effects of alterations to the nitrogen and carbon sources used in EPS production have also been investigated. According to early reports, neither LAB growth nor EPS production was specifically linked to the presence of casein or whey proteins in the growth medium. Garcia et al. [57] reported that EPS production by
It has been shown that an optimal ratio between the carbon and nitrogen is absolutely necessary to achieve high EPS yields [62]. The production of EPS by
Homo EPS are synthesized outside the cell by specific glycosyltransferase (GTF) or fructosyltransferase (FTF) enzymes (commonly named glucansucrases or fructan-sucrases). Homo-EPS producing LAB also use extracellular GTF enzymes to synthesize high-molecular mass α-glucans from sucrose. This process uses sucrose as a specific substrate, and the energy required for the process comes from sucrose hydrolysis. There is no energy requirement for EPS-production other than for enzyme biosynthesis because EPS synthesis by GTF or FTF does not involve active transport processes or the use of activated carbohydrate precursors. Therefore, large amounts of sucrose can easily be converted to EPS.
Glucan synthesis reactions catalysed by GTF can be written as follows (Fig. 1):
sucrose + H2O → glucose + fructose
sucrose + acceptor carbohydrate → oligosaccharide + fructose
sucrose + glucan (n) → glucan (n+1) + fructose
Although GTF enzymes have a high degrees of similarity, lactobacilli produce a broad spectrum of glucans, including polymers with α-1,6 linkages (dextran), α-1,3 linkages (mutan), and both α-1,6 and α-1,4 linkages (alternan). The relative molecular weight of glucans from lactobacilli range from 1 × 106 Da to 5 × 107 Da [6]. In addition, GTF enzymes are not saturated by their substrate, and transfer reactions exceed the sucrose hydrolysis under sucrose concentrations above 100 mM [64].
The dextran synthesis by GTF (dextran sucrase).
The GTF enzymes of streptococci are generally produced constitutively. In contrast, the GTF enzymes of
The fructan synthesis reaction catalyzed by FTF can be written as follows:
sucrose + H2O → fructose + glucose
sucrose + acceptor carbohydrate → oligosaccharide + glucose
sucrose + fructan (n) → fructan (n+1) + glucose
Fructans generally have a relative molecular weight exceeding 5 × 106 Da. Similar to GTFs, FTFs are not saturated by their substrate, namely, sucrose, and transfer reactions exceed the rate of sucrose hydrolysis for sucrose concentrations above 200 mM [5]. FTFs such as Lev, Inu, and LevS from lactobacilli exhibit pH optima of between 5.0 and 5.5. The optimum temperature for enzymes from the thermophilic
Hetero EPS are not synthesized by extracellular enzymes, but are instead synthesized by a complex sequence of interactions involving intracellular enzymes. EPS are made by polymerization of repeating units, and these repeating units are built by a series of addition of sugar nucleotides at the cytoplasmic membrane. Sugars are the starting materials for the synthesize sequence. LAB strains can utilize various monosaccharides and disaccharides as energy sources, via some well-studied sugar uptake systems include primary transport systems, direct coupling of sugar translocation to ATP hydrolysis via a transport-specific ATPase; secondary sugar transport systems, coupling of sugar transport to the transport of ions or other solutes, both as symport and antiport transport systems; and group translocation systems, coupling of sugar transport to phosphorylation via the phosphoenolpyruvate (PEP)-dependent phosphotransferase system (PTS; Fig. 2) [8]. Polysaccharides must be hydrolyzed before uptake. For example, starch is hydrolyzed by α-amylase, and the raction products are subsequently hydrolyzed by the enzymes described above.
After the addition of a hetero-EPS repeating unit, the unit is exported through the cell membrane and becomes polymerized into the final hetero-EPS. Hence, several enzymes and proteins are involved in the biosynthesis and secretion of heterotype EPS, and the enzymes and proteins involved in these processes may not be unique to hetero-EPS anabolism.
Sugars taken into the cell are converted into sugar nucleotides. Iintracellular monosaccharides are converted to sugar nucleotide substrates for polymerization reactions, including UDP (uridine diphosphate), dNTP (thymidine diphosphate), and GDP (guanosine diphosphate). Such polymerization reactions are catalyzed by glycosyl pyrophosphorylases.
Glu-1P (Gal-1P) + UTP → UDP-Glu (UDP-Gal) + pyrophosphate
UDP-glucose is then converted to UDP-galactose by epimerases such as UDP-glucose-4-epimerase. This reaction is reversible.
UDP-glucose ↔ UDP-galactose
Glycosidic linkages are formed on membranes in the cytoplasm. A sugar moiety is transferred to C55-polyprenyl phosphate, a carrier lipid and component of the membrane, by priming glycosyl transferases. This transfer triggers the addition of a repeating unit to the hetero-EPS molecule. Disruption of the priming glycosyl transferase gene generates non-EPS-producing mutants [66]. Thus, priming glycosyl transferases are thought to be crucial for EPS biosynthesis. The addition of the repeating unit is completed by the action of glycosyl transferase on the sugar residue attached to C55-polyprenyl phosphate. Therefore, the type and number of glycosyl transferases available determine the range of repeating units in hetero-EPS. C55-polyprenyl phosphate is also involved in bacterial cell wall biosynthesis, and therefore, cell wall biosynthesis and EPS synthesis compete for this substrate. The repeating unit is exported through the bacterial membrane, and is polymerized to become a hetero-EPS (Fig. 3).
Pathway of lactose fermentation in lactic acid bacteria.
Outline of biosynthesis of hetero EPS.PGM: α-phosphoglucomutase, UGP: UDP-glucose pyrophospholyraseUGE: UDP-galactose 4-epimerase, TGP: dTDP-glucose pyrophospholyraseTRS: dTDP-rhamnose synthetic enzyme system, PMI: phosphomannoisomerasePMM: phosphomannomutase, GMP: GDP-mannose pyrophospholyrase
The instability of hetero-EPS production has been reviewed by de Vuyst et al. [8]. Briefly, a loss in the ability to produce slime may be caused by repeated subculture of bacterial strains or incubation at high temperatures. The loss of plasmids from ropy mesophilic LAB strains is generally the reason for loss of slime production. On the other hand, thermophilic LAB, namely,
Priming glycosyl transferases are thought to be crucial for EPS biosynthesis and disruption of the priming glycosyl transferase gene generates non-EPS-producing mutants. Tsuda et al. generated the EPS-producing mutant strain 301102S from the non-EPS-producing
EPS produced by LAB have various functional roles in human or animal health including immunomodulatory properties, antiviral activity, antioxidant activity, and antihypertensive activity [1, 55, 71, 72], and have also been used as food additives for texture improvement. These properties have been extensively reviewed [8, 9, 56, 73, 74]. Besides these properties, prebiotics based on LAB and oligosaccharides have other health benefits. Prebiotics are usually non-digestible oligosaccharides that selectively stimulate the growth and activity of a limited number of bacterial species in the colon, such as bifidobacteria and lactobacilli, and therefore, improve host health. Detrimental bacteria may form substances such as ammonia, hydrogen sulfide, indles, and amines that are noxious to the host. However, beneficial bacteria such as bifidobacteria and lactobacilli inhibit the proliferation of detrimental bacteria, and their cell components stimulate the host immune system [75]. Gastrointestinal microflora consist of approximately 1014 colony forming units (cfu)/g of various types of both detrimental and beneficial bacteria, and the numbers and composition vary greatly along the gastrointestinal tract. The balance of the gastrointestinal micro flora influences different aspects of host health such as bowel movement, tympanites flatulence, and the absorption of nutrients. Many factors may upset this balance, including stress, consumption of antibiotics, infection, food poisoning, and the natural ageing process. To redress this balance, the growth and activities of beneficial bacteria may be enhanced by specific ingredients in foods.
Speceis | Strain | Glc | Gal | Rha | Fuc | NAc Gal | GlcA | Gly | Reference |
CNCMI 733 | 1 | 2 | 1 | [25] | |||||
SFi39 | 1 | 1 | [26] | ||||||
SFi12 | 1 | 3 | 2 | [26] | |||||
LY03 | 1 | 4 | [27] | ||||||
OR901 | 5 | 2 | [28] | ||||||
MR-1C | 5 | 2 | 1 | [29] | |||||
NIZO B891 | 3 | 2 | [30] | ||||||
Ropy352 | 2 | 3 | [31] | ||||||
NIZO B39 | 2 | 3 | 2 | [32] | |||||
SBT 0495 | 2 | 2 | 1 | [33] | |||||
OLL 1073R-1 | 1 | 1.6 | [34] | ||||||
NCFB 2772 | 1 | 2.4 | [35] | ||||||
Lb18 | 1 | 1 | [36] | ||||||
EU23 | 1 | 1 | [37] | ||||||
rr | 1 | 5 | 1 | [38] | |||||
NCFB 2772 | 1 | 7 | 0.8 | [35] | |||||
TN-4 | 1 | 1 | [39] | ||||||
766 | 2 | 1 | [40] | ||||||
2091 | 1 | 2 | [41] | ||||||
Lb161 | 5 | 2 | [42] | ||||||
RW-9595M | 2 | 1 | 4 | [43] | |||||
GG | 1 | 4 | 1 | [44] | |||||
EP56 | 3 | 1 | 1 | [45] | |||||
EP56 | 3 | 1 | 1 | [45] | |||||
LPS26 | 1 | 2 | 2 | [46] | |||||
34-1 | 3 | 1 | 1 | [47] | |||||
K1 | 1 | 1 | [48] | ||||||
0-1 | 3 | 2 | [49] |
Monosaccharide ratio in hetero EPSGlc: glucose, Gal: galactose, Rha: rhamnose, Fuc: fucose, NAc Glu: N-acetyl glucosamine, NAc Gal: N-acetyl galactosamine, GlcA: glucuronic acid.
Various oligosaccharides have been identified as prebiotics, that can increase the number of
The food for specified health use (FOSHU) system was introduced in Japan in 1991. FOSHU refers to foods containing ingredients that provide health benefits and have officially approved physiological effects on the human body. FOSHU is intended to be consumed for the maintenance or promotion of health or for special health uses, for example, to control conditions such as blood pressure or blood cholesterol. To be defined as FOSHU, it is important to assess the safety of the food as well as the effectiveness of health promotion, and this assessment must be approved by the Ministry of Health, Labour and Welfare in Japan. At present (2012), 990 foods are recognized as FOSHU, and of these, 86 provide gastrointestinal health benefit. Foods for balancing gastrointestinal micro flora contain galactosylsucrose, soy oligosaccharides, lactulose, GOS, FOS, isomalto-oligosaccharides, raffinose, xylo-oligosaccharides, mannobiose, and brewer\'s yeast cell wall as functional ingredients.
GOS are well-known type of prebiotic oligosaccharides found in human milk. The concentration of oligosaccharides is 100 times higher in human breast milk than in bovine milk [76]. Many studies have shown that breast-fed infants have intestinal microflora dominated by bifidobacteria. The reason for this phenomenon is thought to be that the oligosaccharides in breast milk, including GOS, can reach the upper gut without being digested where the bifidobacteria can utilize them. At present, GOS is produced by the enzymatic treatment of lactose by β-galactosidase. GOS produced in this manner usually have degrees of polymerization (DP) between 2 and 10. Furthermore, the type of glycosidic linkage is determined by the reaction conditions: final products usually possess β-1,2, β-1,3, or β-1,4 linkages. GOS is given a caloric value of 2 kcal/g in Japan and Europe for food-labelling purpose.
The effect of GOS on defecation has been studied in healthy volunteers. Defecation frequency was significantly increased, and faeces became significantly softer after the subjects drank a beverage containing 5.0 g of GOS, on a daily basis. Therefore, consumption of a beverage containing 5.0 g of GOS can improve defecation in individuals with a tendency for constipation [77]. Ishikawa et al. reported that the number of faecal bifidobacteria increased significantly after subjects consumed 2.5 g of GOS/day for 3 weeks [78]. GOS utilization by enterobacteria was further investigated in vitro. The trisaccharide forms of GOS were utilized by
The use of beneficial bacteria or their enzymes in the synthesis of prebiotics may be a good way to produce prebiotics with high specificity. Rabiu reported that five different GOS were produced using β-galactosidase extracted from five different
FOS is used as a generic term for all β-2,1 linear fructans with a variable DP. Inulin and oligofructose are common forms of FOS that are widely found in nature. Chicory inulin has a DP of 2-60, and the product of its partial enzymatic hydrolysis is oligofructose or FOS with a DP of 2-10.
The effect of FOS intake on intestinal microflora was studied in humans. The number of bifidobacteria in faeces was significantly increased during the FOS intake (1 g/d) period, and a significant increase in stool frequency and a softening effect on stool were observed [84]. FOS increased the level of bifidobacteria in faeces, whereas that of bacteroides, clostridia, and fusobacteria decreased in subjects that were fed FOS (15 g/d) for 15 days [85]. Another study measured the increase in number of
It is not clear which oligosaccharides are the most suitable substrates for the selective growth of specific beneficial species or strains. Several research group have suggested useful methods to investigate the potential prebiotic activity of oligosaccharides [88-92]. Potential prebiotic activities were determined on the basis of the changes in the growth of beneficial and undesirable bacteria, such as bifidobacteria, lactobacilli, clostridia, and bacteroides. Such methods can evaluate the ability of specific strains to utilize a particular prebiotic, and a comparison of the prebiotic activities of oligosaccharides by using these methods could help in the choice of prebiotics for improving the gastrointestinal microflora on an individual basis. However, it is important to understand that only a limited group of bacteria can be chosen from the gastrointestinal microflora by using these methods, and that polysaccharides and oligo-saccharides are fermented by numerous species in the gastrointestinal tract.
Oligosaccharides produced by beneficial bacteria or their enzymes may enhance the growth of beneficial bacteria. A novel GOS mixture produced using
The dietary fiber, arabinoxylan is the predominant hemicellulose from cereals and exhibits prebiotic activity [96]. The addition of water-unextractable arabinoxylans increased the population of bifidobacteria and bacteroides in a medium inoculated with faecal slurry. Polysaccharides are not usually utilized by microorganisms. Remarkably, however,
Poly- and hetero-oligosaccharides produced by LAB may be potential prebiotics. Studies on the production of polysaccharides and oligosaccharides by enzymes in beneficial microorganisms may lead to the production of highly selective prebiotics, although in vitro evaluation may be difficult because of degradation and utilization of polysaccharides by various microorganisms in the gastrointestinal tract. Administration of synbiotic food containing a combination of a probiotic bacterial strain and the prebiotic sugar produced by that strain could be effective in improving human health.
The human immune system has two major divisions: innate and acquired. We will talk about innate immunity. Innate immunity can be defined as the first line of defense against pathogens, which represents a great machinery to create an adequate and definitive systemic response to prevent infections and maintain homeostasis of the organism. The elements of innate immunity include external physical barriers, humoral and cellular effector mechanisms. This type of immunity recognizes pathogens such as bacteria and viruses. This works thanks to the phagocytosis of the pathogens with the consequent induction of inflammatory reactions. It also has a critical role in the activation and regulation of adaptive immunity. This immunity has the ability to develop an induced response during primoinfection. This response is specific due to the expression of cell surface pattern recognition (PRR) receptors, which are capable of recognizing complex polysaccharides, glycolipids, lipoproteins, and nucleic acids. We know that pathogens contain in their structure various components that act as substances strange (antigens) and this in turn will induce an innate immune response that will subsequently activate the adaptive response. It is imperative to recognize that the important exploration of these innate mechanisms is essential for the understanding of the complex events involved in human innate immunity and is also crucial for the discovery of new antimicrobials, antitumor drugs, and immunomodulators with therapeutic applications [1]. Innate immunity, which is considered a simple immune system, is essential for the onset of acquired immunity and has been found to play an important role in the pathogenesis of the disease age [2]. Among them, it recognizes nucleic acids derived from pathogens. The innate immune pattern recognition (PRR) receptor recognizes self-derived nucleic acids. Innate pattern recognition receptors regulate antigens for the presentation and subsequent responses of B cells and T cells, for example, physiological management of autoantigens, induction of immature dendritic cells to detect tolerant signals to T cells. The activation of toll-like receptors (TLR), NOD type receptors (NLR) or Helicases similar to RIG (RLH) by molecular agents associated with pathogens where the patterns will induce dendritic cell maturation, costimulation.
T cell activation and production of antibodies by B cells. Therefore, recognition of innate patterns is now being considered as a central element of immunity modulation. There are at least 80 different autoimmune diseases discovered so far, which in the US alone, affect 20 million people [3]. These pathologies are established systemically or in a specific organ, but require for their expression certain conditions that are the result of multifactorial processes that involve a deregulation of the innate immune system and therefore adaptive that lead the body to erroneous responses with the subsequent attack itself of their own tissues. The innate immune system as discussed above is the first line of immediate defense against invading microorganisms that links to the adaptive response. Specific cells of the innate immune system, which are dendritic cells (DC) (antigen presenting), which are cells with an important and critical role in promoting the responses of B and T cells. This type of immunity is critical to maintain homeostasis and prevent microbial invasion, eliminating a wide variety of pathogens and contributing to the activation of the adaptive immune response.
It is the control point. A dendritic type receptor that bears the title of “access gate” for innate cellular immunity: this basically consists of a type of toll-like receptor. It has been found that it plays a fundamental role as a sensor in the recognition of pathogens in the innate immune system [4].
This pattern recognition receptor acts on bacteria and viruses (PAMP) [5]. The innate immune response in immunological terms controls the infection and prevents its spread. And more recently it is known that to induce this series of reactions against pathogens, in addition to the existence of antigens, another series of molecules in the pathogens is required. These molecules are known as pathogen-associated molecular patterns (PAMPs). PAMPs play and interact with a series of receptors that are mainly present in phagocytic cells (macrophages), and these “gate” receptors have been called recognition patterns to pathogen-associated molecular patterns (PRRs). These receptors contain other subfamilies where we can find toll type receptors (TLRs), NOD type receptors (NLRs), RIG-1 type receptors (RLRs), and lectin C type (CLRs). This molecular pattern related to the associated damage known as DAMP comes to behave as a type of alert that recognizes signals and most importantly this does not involve pathogen detection. The main molecular recognition patterns (PRRs) include TLR and NLR receptors, also known as nucleotide binding oligomerization domains. TLR is the homologous receptor that has already been identified in the Drosophila genetic code, and that to date some TLRs have been found in humans mainly in the cell surface, membrane, and lipids [6]. Types 1, 2, 4, 5, and 6 are those that recognize proteins, nucleic acids located in the endoplasmic reticulum and those that are found in the endosomal membranes. 3, 7, 8, and 9 detect lipopolysaccharides in the outer membrane of gram-negative bacteria (endotoxins). The TLR4 type, which transmits inflammatory signals, is the best known in general and the most studied of the TLR. This receptor responds to MyD88, which becomes a station at the central point of the inflammation signal, and corresponds to the first phase of activation of the transcription factor NF-κB pathway (nuclear factor-kappa B), which a In turn, production begins and a kind of “chain reaction” of inflammatory cytokines to eliminate pathogens [7]. Meanwhile, these TLR receptors are incorporated into PAMPs, which by recognizing nucleic acids act as an inflammatory cytokine. Receptors that mediate innate immune responses, such as toll-like receptors (TLR) and specific C-type lectin receptors (CLR) that recognize associated molecular patterns (PAMP), have been implicated in autoimmune disease mechanisms, both directly through self-recognition ligands and indirectly through the regulation of immune homeostasis [8, 9].
In intracellular infections, in addition to antigens and PAMPs, the participation of another series of molecules that participate in the activation of the immune response is necessary. Recently, some studies have shown that cells can die from a type of immunogenic “apoptosis” and thus expose their nuclear or cytoplasmic molecules to their membrane. These have a way of stimulating the immune response, thanks to their activity. They are also released during the process of necrosis and have been given the name of molecular patterns associated with damage or warning signs, the famous DAMPs. The NLR receptor is present in the cytoplasm. It has the particularity of recognizing not only PAMP but also several DAMP among them [uric acid, cholesterol, sterols crystals, extracellular ATP (adenosine triphosphate), silica] or even recognizing exogenous DAMP such as asbestos, origin of aseptic inflammation, such as gout, arteriosclerosis, and silicosis [10]. It is clear that it is a cause and attracts attention. The abnormalities in the immune system that are the basis and fertilizer for autoimmune diseases are mainly caused by an abnormal acquired immunity [11]. In recent years, in contrast to the concept that autoimmune or auto-inflammatory diseases are mainly due to abnormal innate immunity, it is attracting more attention.
Dendritic cells, macrophages, and other myeloid cells also play an important role in the innate immune response, both as antigen presenting cells as effector cells that mediate the tissue damage [12, 13, 14]. Therefore, they are fundamental and will be as in conflicts, “the first line of defense” in the face of a bacterial or other stimulus. We will also take them into account in relation to autoimmune diseases, because of their responsiveness and because they are important mediators of innate immunity, an interest has arisen in this potential to contribute to the pathology of these diseases. Proinflammatory cytokines: mainly TNFa (tumor necrosis factor alpha), induce the activation of endothelial cells, resulting in an increase in the expression of different adhesion molecules (CD62E, CD62P, ICAM-1, and VCAM-1). This causes the leukocytes to roll over them, and during this bearing, they are activated by the intracellular signals that are generated through their adhesion molecules and different chemokine receptors, which interact with the ligands found on the surface of the cells endothelial. Subsequently, these activated leukocytes adhere firmly to the endothelium, change their morphology (cell polarization) and carry out their transendothelial migration, and then migrate to the inflammatory focus, guided by the gradient of chemotactic substances that are released. Macrophages are multifunctional antigen presenting cells, with an important role in innate immunity and, therefore, in the inflammation process [15]. Macrophages are found in almost all organs, and recent studies have demonstrated their multifunctionality and heterogeneous capacities established by their numerous subpopulations, adaptation in specific tissue microenvironments and different stages of maturation. For example, during a bacterial infection, classically activated macrophages show inflammatory functions (type 1 or M1 macrophages), while with alternative activation (by Th2 type cytokines, such as IL-4 or IL-13), macrophages acquire anti-inflammatory functions (type 2 macrophages or M2). In addition to depletion or inhibition of macrophage function, reprogramming of M2 has also been explored. Recently, it has been shown that paracoccin, a protein contained in a fungal human pathogen, induces the repolarization of M1 macrophages through interaction with toll as a receptor (TLR) 4, being a new possible immunotherapeutic agent for pathologies related to M2 macrophages. Macrophage-related therapies have been proposed for various autoimmune and inflammatory pathologies. In the case of PPARγ and PPARδ, which are nuclear receptors that control different genes associated with M2 macrophages, and their agonists have been proposed as a therapy directed at macrophages to induce M2 pathways. In addition, the demonstration that TLR9 receptor signaling can reverse the aberrant M2 macrophage phenotype.
Dendritic cells (DC) are professional antigen presenting cells (APC), often referred to as “orchestra directors of the innate immune response” due to their ability to capture, process, and present antigens to T cells. Depending on the nature of the antigen may exhibit an immunogenic or tolerogenic effect, which will be defined by cytokine secretion. They are often considered tolerogenic, because they have autoantigens in the absence of costimulation and, together with anti-inflammatory stimuli, (TGF-β), can promote the induction of regulatory T cells and/or induce anergy of T cells [16]. After activation by proinflammatory stimuli, they mature and generate an expression of costimulatory molecules and the major histocompatibility complex (HCM) class II, which causes a potent response of specific T cells to the antigens. Therefore, they play a fundamental role in maintaining self-tolerance, and on the other hand, they initiate the response against foreign antigens for their subsequent elimination by effector immune cells. In a state of aberrant hyperreactivity, they could contribute to perpetuating immune responses, backed by evidence of a high frequency of immunogenic infiltration [17]. Due to their ability to modulate the cellular response, they have been considered a powerful target for immune modulation. Strategies such as pharmacological modulation to affect their maturation status and genetic engineering to improve their tolerance or immunogenic properties for the treatment of autoimmune diseases have been studied. In several murine models, they were transduced to express IL-4 and were able to prevent disease in 12-week NOD mice. In a murine model of collagen-induced arthritis (CIA), it was shown that the injection of dendritic cells with tolerogenic activity improves the clinical and the outcome of the disease. Although the treatment was found to be safe and feasible, other studies are needed to evaluate the efficacy of cellular treatment in autoimmunity.
They are a growing family of immune cells that reflect the phenotypes and functions of T cells. Natural killer cells (NK) can be considered innate homologs of cytotoxic CD8 + T cells, while ILC1, ILC2, and ILC3 correspond to innate homologs of T cells CD4 + (TH1), TH2, and TH17. However, in contrast to T cells, they do not express antigen receptors or undergo clonal selection and expansion when stimulated [4]. The ILCs react and respond to the signs of tissue damage and produce a series of cytokines, which direct the immune response and this adapts to contain the lesion. Therefore, these cells can control or unleash the immune response. As with B cells and T cells, these also originate from the common lymphoid lineage but the specific transcription factors of these suppress and modify their development until the generation of the different types of ILC. The precursors of these can migrate from their primary production site in infected and injured tissues, where they complete their maturation, in a process very similar to the differentiation of virgin T cells into TH effectors. The cytokines produced by local cells, as well as some trauma and stress response ligands as well as bacterial and dietary compounds regulate the maturation and activation of ILC in effectors that play an important role in early immune responses to pathogens in particular has been found relationship with symbionts, helminths, and allergens. The cytokines they produce induce innate responses in stromal, epithelial, and myeloid cells that in turn will regulate the activity of dendritic cells and will also play a central role in the transfer of information between ILC and T cells. ILCs by activating DC found in tissues to migrate to the lymph nodes, where they cause specific T-type cellular responses. ILCs also regulate T cells directly through the presentation of peptide antigens through CMH type II. However, ILCs are also involved in autoimmunity, because their cytokine production can exacerbate and exaggerate the inflammatory process.
Recent research has revealed new knowledge about the respective roles of these cells in relation to cellular and humoral immunity as well as the extension to adaptive immunity [18]. There is talk of a recent study in which a genetically modified mouse prototype model was developed with an autoimmune disease similar to lupus that does not require to express the adaptive immune system machinery, but is triggered directly by the innate immune response [19]. For many autoimmune diseases, we largely know the roles that key cells (T cells and B cells) play and for example are evident in the success of existing therapies (anti-CD3 and anti-CD20). Then knowing this, each of the functions of myeloid cells, and in general of the innate immune response cells, can “autoimmune” disease occur in the absence of adaptive immunity and these cells act as effectors in disease progression? The answer to this could be yes [20]. The most recent example is the study of mice eaten by moths that have been genetically modified to have deficiencies in hematopoietic cells, and to express an autoimmune disease characterized by alopecia (giving a “peeled or eaten by moths”) and edema in their legs. These were also accompanied by high antibody titers, with renal and pulmonary functions being compromised due to immune complex deposits [21, 22]. However, in another study, mice with deficiency in hematopoietic cell phosphatase were crossed with mice that lack the recombinase-1 activator gene (RAG-1) that caused a subsequent deficiency in the production of T and B cells and found that the disease autoimmune had progressed normally in the absence of an adaptive immune response [22, 23] even though these mice lacked high antibody titers and immune complex deposits, and they exhibited all other symptoms of the disease. Subsequently, although the onset and progression of the disease could not be defined, it was concluded that the autoimmune disease of this type of mice was mediated by an aggressive response of macrophages and other myeloid cells. Now, a study with murine models is also described, with mice with a genetic alteration associated with the deficiency in the enzyme α-mannosidase type II (αM-II) where there is premature aging with the clinical expression and the characteristic symptoms of SLE and Lupus nephritis (high titers of anti-DNA antibodies, glomerulonephritis, and renal compromise due to deposition of immunoglobulins in the kidney) that seems to be driven by a mechanism that also seems to involve the innate immune system [12, 24, 25]. In the case of the murine model, evidence was provided that the abnormal presence of hybrid glycoprotein structures acts as a trigger for the induction of an innate immune response mediated by members of the C-type lectin family that is specific for mannose. Serum mannose-binding lectins (MBL-A and MBL-B) are soluble lectins that mediate innate immunity to pathogenic bacteria and fungi that express glucans (mannose). It is also believed that the macrophage of the mannose receptor cell surface (MMR) participates in innate immune responses, and its expression has been documented in mesangial renal cells [26, 27]. In mice with αM-II deficiency, MBL lectins are deposited in renal glomeruli which, when they express high levels of mannose glucans in mesangial cells, also express higher levels of MMR, which can bind mannose ligands in the serum. Monocyte chemoattractant protein 1 (MCP-1) levels, produced by activated mesangial cells, represent the entry of activated macrophages. By aberrantly expressing mannose-containing glucans in mice with αMII deficiency, they act as triggers for an innate immune response mediated by mannose-specific C-type lectins programmed to recognize mannose glucans as PAMP.
The second point in importance is the role of antibodies in stimulating the innate immune response. How can this be to the production of autoantibodies in autoimmune diseases, such as our old friend, lupus? Systemic lupus erythematosus (SLE) is an autoimmune disease that translates inflammation and exaggerated immune responses and thus with a large generalized associated tissue damage. We are clear that innate immunity plays a great role in its development and sequentially its clinical expression, and it has been shown that defects found in any of the immune recognition pathways will promote autoimmunity. First, dendritic cells and macrophages activated by TLR receptors can regulate the differentiation of self-reactive B cells through the expression of CD40 and the action of IL-6. Second, by nucleic acids. These can activate and in a powerful and disorderly way certain TLR and RLH receptors; therefore, these are normally protected from immune recognition by multiple mechanisms (epigenetic modifications, nuclear compartmentalization, and the rapid elimination of cells that have entered apoptosis and extracellular compartments by a type of DNase and RNAse enzymes). These immune complexes containing chromatin or circulating RNA particles can avoid being “digested” by these enzymes in the extracellular space and facilitate the uptake of the complex in intracellular compartments through Fc receptor-mediated endocytosis (FcR) in dendritic cell-mediated uptake or by B cell receptor (BCR) in B cells. And it has also been confirmed by studies with lupus-prone mice deficient in TLR receptors and their respective signaling molecules. As an exception, mice with TLR-9 deficiency with a predisposition to lupus produce more autoantibodies against it, indicating that TLR-9s have additional functions in the regulation of systemic autoimmunity. Innate pattern recognition (PRR) receptors regulate the production of autoantibodies associated with lupus and self-reactive T cells by modulating the presentation of autoantigens and also contribute directly to the end result that is tissue or organ injury secondary to autoimmunity. In general, it is believed that this “injury” or tissue damage is generated from the deposition of the immune complex, complement activation, and subsequent release of cytokines and chemokines to trigger local inflammation. This concept has been redefined. For example in glomerulonephritis, in the glomerular immune complex, deposits are not always associated with innate and adaptive immune responses. These are traditionally seen as separated from each other, but emerging evidence suggests that they overlap and interact with each other. Recently discovered cell types, particularly innate lymphoid cells and myeloid cell-derived suppressors that are gaining increasing attention. It is a rapidly evolving field with molecular pathways and new types of discovered cells and multiple constantly changing paradigms. In general, it is believed that many autoimmune diseases are triggered by aggressive responses of adaptive immunity by an automatic antigen system, resulting in tissue damage and pathological sequelae.
The third point is undoubtedly the role of infectious agents, which have the potential to trigger an exaggerated immune response, through molecular imitation, polyclonal activation or antigen release. For example, there are certain diseases that respond to certain infectious autoantigen peptides. This is the case of multiple sclerosis, where T cells are activated by Epstein-Barr virus peptides, type A flu, and human papilloma and that react with the myelin autoantigen peptide [28]. In this case, the viral infection could cause the activation of the lymphocytes, and the autoantigen could maintain this activation, even after the eradication of the infectious agent. Microbial infection can also cause polyclonal activation of lymphocytes, and this is the underlying mechanism in increasing the incidence of autoimmunity in murine models exposed to microbial pathogens [29]. Microbes (viruses or bacteria) that destroy cells also cause an inflammatory response and also the release of antigens that have been previously captured and this could also result in autoimmunity. There is another important point. Inflammation, even in the absence of infection, can trigger polyclonal activation and self-activity. This is that through the activation of annergic cells, by inflammatory mediators or the activation of new self-reactive cells in an inflammatory environment for example in the context of ischemia of any tissue, tissue autoreactivity could be caused and because not at a systematic level [3]. Within non-infectious detonators, we have those of the hormonal type that in many autoimmune diseases are more common in women than in men. Drugs can also alter the immune repertoire. One of the most common and studied procainamide induces antinuclear antibodies and sometimes induces a lupus-like syndrome. And even some substances produced by the same cells can act as haptens and make autoantigens immunogenic, for example, CD1 T cells, with receptors (gamma/delta), CD4+, CD25+, and cytokine-producing agents that monitor activity, reduce, and control self-reactive cells, and they can become pathogenic. As some must complete their maturation in the thymus, and others the activation of autoantigens in the periphery, in these processes alterations in the number and function of regulatory cells that can contribute to autoimmunization can be generated.
Upon contact with the stimulus, whether microbial or of any substance, the recruitment and activation of macrophages will begin. The macrophages will serve as the primary effector cells that cause tissue damage and loss. And it has been concluded that the vast majority of autoimmune diseases could be explained by an aberrant adaptation as an immune response to the antigens themselves. On the other hand, autoimmunity as a disease contrasts with innate immunity. The first in which the term autoinflammatory was used was the periodic fever syndrome related to the TNF receptor (tumor necrosis factor), whose causative gene is TRAPS 4 and which was directly related to the presence of genetic abnormalities associated with innate immunity autoinflammatory diseases that are generally considered as a group of diseases where we can find an active responsibility for aberrant innate immunity and in which T cells are not detected and include TRAPS, cryopyrine-associated syndrome (secondary to mutations in the NLRP3 gene in children) (CAPS), Familial Mediterranean Fever (FMF), Bechet’s disease, Still’s disease in adults, Crohn’s disease, Gout, Type 2 diabetes, and various metabolic disorders [30]. The mechanism of its many initiation is still unclear, but the symptoms and diseases themselves are caused by the collapse of immune tolerance. Thymus autoreactivity and subsequent and completely abnormal inactivation of receptive and regulatory (Th) T cells suppress the reaction to the foreign antigen. The other part of the aberrant response of the innate immune response is carried out in the recipients of recognition of autoimmune patterns and diseases recognized by nucleic acids (PRR). This recognition is transmembrane due to its location in the cell and is divided into two general and cytoplasmic phases. This receptor is found in the endoplasmic reticulum or endosome and is directly related to autoimmune diseases (SLE = TLR7/9). When comparing the sequence of own nucleic acids and pathogen derivatives by means of the TLR7/9TLR9 receptors, it is noted that it contains unmethylated CpG sequences, and these are derived from pathogens that in turn recognize a type of single stranded DNA. TLR7 on the other hand recognizes single stranded RNA derived from viruses and other types, as well as messenger RNA (mRNA). From this, TLR7/9 is self-sufficient, and this receptor can strictly distinguish between conventional nucleic acids and pathogen derivatives. Stimulates an immune response in response to auto-nucleic acid. In other words, viruses and infected cells are captured by endosomes, and these nucleic acids are recognized by TLR7/9. In the case of SLE, the TLR7/9 receptor, due to the genetic modification secondary to the aberrant response to the own nucleic acids that were released and transferred to the endosome and therefore increases the genetic expression of the type I IFN and is known as the “IFN signature.” This signature of IFN is directly related to SLE, rheumatoid arthritis (RA), and systemic sclerosis (SSc) and its effects, suggesting the importance of type I IFN in autoimmune disease [31]. It also activates and stimulates plasma cells that in turn produce large amounts of type I IFN.
The TLR7/9 receptor also mediates the response of plasmacytoid cells and is considered an IFN type I producing cell, which through the TLR7/9 Fc receptor activates the signal to induce the production of non-protein IFN type I histone in the core (HMGB1), to subsequently activate DAMP. The balance between TLR7 and TLR9 is also considered important for inflammation and immune response. The other transmembrane PRR receptors TLR3 and TLR8 also recognize double stranded and single stranded RNA. On the other hand, the cytoplasmic PRR receptor, type RIG-I, and MDA-5 normally identifies a specific structure of single stranded RNA. By recognizing double-stranded RNA, the specific proteins of these DAI, IFI16, and DDX41 receptors induce the production of IFN and inflamasome and, in turn, the production of IL-1β and IL-18.
“The authors declare no conflict of interest.”
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This chapter will discuss an innovation in seaweed cultivation of the genus Eucheuma, which is the prime marine commodity in the tropical regions of the world. Research conducted during 2015-2017 and 2019 in Southeast Sulawesi Province, Indonesia, provided an overview of the use of floating cage that showed very significant growth results. The research result showed that the growth rates of Eucheuma denticulatum and Kappaphycus alvarezii in floating cage seemed faster and resulted in better thallus morphology. Daily production of E. denticulatum and K. alvarezii that were cultivated in floating cage was higher than daily production of E. denticulatum and K. alvarezii cultivated on longline. Specific growth rate (SGR) of E. denticulatum and K. alvarezii cultivated by using floating cage method was also higher than E. denticulatum and K. alvarezii cultivated by using longline method. Moreover, the cultivation by using floating cages produces good growth rates with no effect of herbivore attacks.",book:{id:"8928",slug:"emerging-technologies-environment-and-research-for-sustainable-aquaculture",title:"Emerging Technologies, Environment and Research for Sustainable Aquaculture",fullTitle:"Emerging Technologies, Environment and Research for Sustainable Aquaculture"},signatures:"Ma’ruf Kasim, Abdul Muis Balubi, Ahmad Mustafa, Rahman Nurdin, Rahmad Sofyan Patadjai and Wardha Jalil",authors:[{id:"309893",title:"Prof.",name:"Maruf",middleName:null,surname:"Kasim",slug:"maruf-kasim",fullName:"Maruf Kasim"},{id:"313040",title:"MSc.",name:"Abdul Muis",middleName:null,surname:"Balubi",slug:"abdul-muis-balubi",fullName:"Abdul Muis Balubi"},{id:"313041",title:"MSc.",name:"Wardha",middleName:null,surname:"Jalil",slug:"wardha-jalil",fullName:"Wardha Jalil"},{id:"313042",title:"MSc.",name:"Ahmad",middleName:null,surname:"Mustafa",slug:"ahmad-mustafa",fullName:"Ahmad Mustafa"},{id:"313043",title:"MSc.",name:"Rahman",middleName:null,surname:"Nurdin",slug:"rahman-nurdin",fullName:"Rahman Nurdin"},{id:"313044",title:"MSc.",name:"Rahmat Sofyan",middleName:null,surname:"Patadjai",slug:"rahmat-sofyan-patadjai",fullName:"Rahmat Sofyan Patadjai"}]},{id:"62842",title:"Integrated Rice and Aquaculture Farming",slug:"integrated-rice-and-aquaculture-farming",totalDownloads:1889,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"The burning problems like scarcity of food for ever-growing human population in the present world are addressed by adapting various methods for production of protein, carbohydrate, oils and other food materials. One of the methods to produce high amount of food is integrated farming including rice-aquaculture farming, which produces protein and carbohydrate as major components besides others. Rice-aquaculture farming produces grain (carbohydrate) and animal protein without affecting the quality and quantity of rice yield on the same piece of land and renders additional financial gain besides main crop (rice) like conventional monoculture. The aquatic species grown in the integrated culture are mainly distinct types of fishes, selected crustaceans and other selected species. Profitable rice-aquaculture integrated farming is popular in Asian countries than in Western countries. However, the integrated rice-aquaculture farming has its own limitations. The type of methods, culture species, influencing factors, and pros and cons of rice-aquaculture integrated farming are discussed in the present chapter.",book:{id:"7229",slug:"aquaculture-plants-and-invertebrates",title:"Aquaculture",fullTitle:"Aquaculture - Plants and Invertebrates"},signatures:"Pamuru Ramachandra Reddy and Battina Kishori",authors:[{id:"242524",title:"Dr.",name:"Ramachandra Reddy",middleName:null,surname:"Pamuru",slug:"ramachandra-reddy-pamuru",fullName:"Ramachandra Reddy Pamuru"},{id:"255022",title:"Dr.",name:"Kishori",middleName:null,surname:"Battina",slug:"kishori-battina",fullName:"Kishori Battina"}]},{id:"24074",title:"Embryonic and Larval Development of Freshwater Fish",slug:"embryonic-and-larval-development-of-freshwater-fish",totalDownloads:7448,totalCrossrefCites:1,totalDimensionsCites:2,abstract:null,book:{id:"612",slug:"recent-advances-in-fish-farms",title:"Recent Advances in Fish Farms",fullTitle:"Recent Advances in Fish Farms"},signatures:"Faruk Aral, Erdinç Şahınöz and Zafer Doğu",authors:[{id:"25600",title:"Prof.",name:"Faruk",middleName:null,surname:"Aral",slug:"faruk-aral",fullName:"Faruk Aral"},{id:"29132",title:"Dr.",name:"Zafer",middleName:null,surname:"Dogu",slug:"zafer-dogu",fullName:"Zafer Dogu"},{id:"39952",title:"Dr.",name:"Erdinc",middleName:null,surname:"Sahinoz",slug:"erdinc-sahinoz",fullName:"Erdinc Sahinoz"}]},{id:"68966",title:"Novel Biofloc Technology (BFT) for Ammonia Assimilation and Reuse in Aquaculture In Situ",slug:"novel-biofloc-technology-bft-for-ammonia-assimilation-and-reuse-in-aquaculture-in-situ",totalDownloads:1926,totalCrossrefCites:1,totalDimensionsCites:7,abstract:"Ammonia is one of the most harmful risks for success of fish and shrimp culture. There is no effective solution for harmlessness of ammonia in traditional aquaculture operations except exchanging water, which would bring negative effects on environment, or fixing expensive equipment. Biofloc technology (BFT) that appeared in recent years supplies a novel solution for this issue without exchanging huge water and fixing equipment. This technology could assimilate ammonia almost in real time with many other supplemental benefits. Because of the very high nutritional value for fish and shrimp, bioflocs, the by-product of BFT, could also be reused as a complemented food in situ or a gradient for feedstuff to replace expensive fishmeal or be processed to pellet diet to feed fish and shrimp directly. However, some aspects with regard to the effective use of biofloc as a food source for fish and shrimp, such as high lipid content, productivity, and palatability, need to be further researched in detail.",book:{id:"8928",slug:"emerging-technologies-environment-and-research-for-sustainable-aquaculture",title:"Emerging Technologies, Environment and Research for Sustainable Aquaculture",fullTitle:"Emerging Technologies, Environment and Research for Sustainable Aquaculture"},signatures:"Hai-Hong Huang",authors:[{id:"305215",title:"Dr.",name:"Hai-Hong",middleName:null,surname:"Huang",slug:"hai-hong-huang",fullName:"Hai-Hong Huang"}]}],onlineFirstChaptersFilter:{topicId:"32",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:31,numberOfPublishedChapters:315,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:14,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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