\\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\\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:"8796",leadTitle:null,fullTitle:"Environmental Chemistry and Recent Pollution Control Approaches",title:"Environmental Chemistry and Recent Pollution Control Approaches",subtitle:null,reviewType:"peer-reviewed",abstract:"In recent years, there have been significant advances in the techniques of sampling and analysis, which has allowed the more accurate recording of environmental levels of many substances present in the environment. At the same time, processes for the remediation of contaminated matrices have evolved, through the application and/or combination of biological, physical, and chemical procedures.The purpose of this book is to present new studies aimed at determining levels of environmental pollution in various parts of the world. It also shows new alternatives for the remediation of contaminated matrices.",isbn:"978-1-83968-063-2",printIsbn:"978-1-83968-062-5",pdfIsbn:"978-1-83968-064-9",doi:"10.5772/intechopen.80247",price:119,priceEur:129,priceUsd:155,slug:"environmental-chemistry-and-recent-pollution-control-approaches",numberOfPages:224,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"413211c08d7fafecdcaca36f521d4cd6",bookSignature:"Hugo Saldarriaga-Noreña, Mario Alfonso Murillo-Tovar, Robina Farooq, Rajendra Dongre and Sara Riaz",publishedDate:"December 18th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/8796.jpg",numberOfDownloads:12573,numberOfWosCitations:23,numberOfCrossrefCitations:23,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:52,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:98,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"August 30th 2018",dateEndSecondStepPublish:"October 15th 2018",dateEndThirdStepPublish:"December 14th 2018",dateEndFourthStepPublish:"March 4th 2019",dateEndFifthStepPublish:"May 3rd 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"255072",title:"Dr.",name:"Hugo",middleName:null,surname:"Albeiro Saldarriaga Noreña",slug:"hugo-albeiro-saldarriaga-norena",fullName:"Hugo Albeiro Saldarriaga Noreña",profilePictureURL:"https://mts.intechopen.com/storage/users/255072/images/system/255072.png",biography:"Since 1991, Hugo Saldarriaga-Noreña has worked in the environmental pollution field, specifically in water purification. Later in 1995, I joined the University of Antioquia (Colombia), combining research with teaching, until 2001. In 2007, I joined the Center for Research and Assistance in Technology and Design of the State of Jalisco, Mexico, as a leading researcher in the area of air quality. Since 2012, I have been a full-time professor at the Autonomous University of the State of Morelos, Mexico. My research area is environmental chemistry, specifically oriented to the characterization of environmental matrices, through the application of high-performance liquid and gas chromatography, ICP mass spectrometry, nuclear magnetic resonance, and IR among others.",institutionString:"Universidad Autónoma del Estado Morelos",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Universidad Autónoma del Estado de Morelos",institutionURL:null,country:{name:"Mexico"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar",profilePictureURL:"https://mts.intechopen.com/storage/users/255959/images/system/255959.png",biography:"Dr. Mario Alfonso Murillo Tovar is currently working at CIQ-IICBA Universidad Autónoma del Estado de Morelos, Cuernavaca, México as a Professor-Researcher and he is involved in teaching, research, management, and academic work. He received his undergraduate Bachelor of Chemistry degree from Universidad del Valle, Colombia and he obtained his Master´s degree and Doctorate in Chemical Sciences from Universidad Nacional Autónoma de México. His research has focused on the development and validation of analytical methods, chemical characterization of environmental samples, and treatment and removal methods. He has worked on many projects, including determination of trace metal, inorganic species and toxic organic compounds using ICP-MS, GC, and LC tandem MS techniques, identification of emission sources, chemical degradation of emerging compounds and risk assessment.",institutionString:"Universidad Autónoma del Estado de Morelos",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Universidad Autónoma del Estado de Morelos",institutionURL:null,country:{name:"Mexico"}}},coeditorTwo:{id:"173800",title:"Prof.",name:"Robina",middleName:null,surname:"Farooq",slug:"robina-farooq",fullName:"Robina Farooq",profilePictureURL:"https://mts.intechopen.com/storage/users/173800/images/system/173800.jpg",biography:"Dr. Robina Farooq has been involved in teaching, research,\nmanagement, and academic work in numerous distinguished\nuniversities of Britain, China, and Pakistan for the last 28 years.\nCurrently, she is working at COMSATS Institute of Information\nTechnology, Lahore, Pakistan. She has discovered innovative\nand low-cost processes for the treatment of wastewater. She is\nthe author of scientific manuscripts, books, book chapters, and\ngranted patents by USPTO, USA. She is the recipient of Best Innovator, Best University Teacher, and Productive Scientist Awards. She has worked on projects including\nultrasonic decomposition of pollutants, phytoremediation of wastewater, bioelectrochemical synthesis of renewable fuel, bioelectrochemical decomposition of\nwastewater and energy recovery, recovery of heavy metals from effluents, microbial fuel cell technology for wastewater remediation, and retrieval of precious metals\nfrom printed circuit boards.",institutionString:"COMSATS University Islamabad",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"2",institution:null},coeditorThree:{id:"188286",title:"Associate Prof.",name:"Rajendra",middleName:"Sukhadeorao",surname:"Dongre",slug:"rajendra-dongre",fullName:"Rajendra Dongre",profilePictureURL:"https://mts.intechopen.com/storage/users/188286/images/system/188286.jpg",biography:"Rajendra S. Dongre received his M.Sc. from the Department of Chemistry, R.T.M., Nagpur University in 1996 (Gold Medalist) and his PhD in 2010. His research work includes organic synthesis, chitosan bio-composite, assorted dimensional matrix, and remediation of water pollution de-fluoridation; nitrate, chromium, and phosphate lead (II). He has worked as a Scientist-B in the CSIR-LAB, National Environmental Engineering Research Institute (NEERI) Nagpur M.S., India. Overall, he has 25 years of experience in research and development and 18 years of post-graduate teaching experience, which has resulted in 70 international research paper publications. He has guided four research students to pursue their PhD. He received the 6th National Award (runner-up) for Technology Innovation in Petrochemicals and Downstream Plastics Processing Industry, for research in the field of polymer science and technology, handed by the Honorable Ananth Kumar, Petrochemical & Fertilizers Minister of Government of India in 2016. He received the 5th National Science & Technology Award for research contribution in the field of developing science in 2017, by EET-CRS, Noida, India.",institutionString:"RTM Nagpur University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"10",totalChapterViews:"0",totalEditedBooks:"2",institution:null},coeditorFour:{id:"283581",title:"Dr.",name:"Sara",middleName:null,surname:"Riaz",slug:"sara-riaz",fullName:"Sara Riaz",profilePictureURL:"https://mts.intechopen.com/storage/users/283581/images/system/283581.jpg",biography:"Dr Sara Riaz is currently working at COMSATS University Islamabad, Lahore campus as an Assistant Professor and is involved\nin teaching, research, and management in the Department of\nChemistry. She completed her MSc from Bahauddin Zakariya\nUniversity, Multan Pakistan in 2013 in organic synthesis and\nreceived a doctoral degree in 2014 from East China University of\nScience and Technology, Shanghai, P.R. China for her work on\nsynthesis and characterization of novel ubiquinone derivatives and their electrochemical interaction studies with gold nanoparticles. Dr Sara is currently involved\nin projects including bioelectrochemical decomposition of dyes for electricity\ngeneration, synthesis of graphitic nanomaterials and their applications in energy\nstorage devices. and heavy metal ions detection.",institutionString:"COMSATS University Islamabad",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorFive:null,topics:[{id:"887",title:"Bioremediation",slug:"bioremediation"}],chapters:[{id:"63393",title:"Characterization of the Youssoufia-Morocco-MineFluoride-Contaminated Water and Their Detrimental Effects on Human Health",doi:"10.5772/intechopen.80547",slug:"characterization-of-the-youssoufia-morocco-minefluoride-contaminated-water-and-their-detrimental-eff",totalDownloads:856,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:1,abstract:"In Youssoufia, the second phosphate mining center of our country (Morocco), the drinking water needs of the rural population are of underground origins. Indeed, most of Youssoufia’s rural areas feed on traditional wells. The main purpose of this chapter is to evaluate the degree of contamination of mine water along the pumping canal by fluoride. Wells located near this channel were also analyzed to see the influence of the existence of black phosphate in this region on these wells. At the end of this analytical part, it is obvious to conclude that the dewatering waters of the black phosphate mines of Youssoufia, known as dewatering water along the canal, contain significant fluoride concentrations in the order of 3–4 mg/l on average and the waters of the wells located near this canal have fluoride concentrations higher than the standard recommended by the National Office of Drinking Water in Morocco and the World Health Organization which is 1.5 mg/l. Indeed, a number of residents residing in Youssoufia suffer from fluorosis.",signatures:"Moufti Ahmed",downloadPdfUrl:"/chapter/pdf-download/63393",previewPdfUrl:"/chapter/pdf-preview/63393",authors:[null],corrections:null},{id:"69539",title:"Greenhouse Gas Emissions of Agriculture: A Comparative Analysis",doi:"10.5772/intechopen.84208",slug:"greenhouse-gas-emissions-of-agriculture-a-comparative-analysis",totalDownloads:736,totalCrossrefCites:1,totalDimensionsCites:6,hasAltmetrics:0,abstract:"Greenhouse gas emissions are accounted by greenhouse gases inventories, which must be produced by common accounting rules, called Guidelines, which are endorsed by the United Nations Framework Convention on Climate Change (UNFCCC). These inventories are fundamental to analyze the impact of agriculture on emissions, and as example of the difficulty and complexity of implementation of the guidelines, a comparative study is made on emissions from Agricultural Soil Management (CRF category 3D source) utilizing biological nitrogen fixation. The analysis carried out for the N2O emissions under this section of the agrarian sector of Spain, Europe, New Zealand, Canada and the USA, inventories and national communications from Argentina and Brazil permit to observe the wide spectrum of approaches and the importance of the management of the accounting rules to be used mainly if we need that the impact of mitigation policies are captured in a direct way by the inventory. New technologies could introduce changes in the rules and can be utilized for reducing emissions, and examples are also analyzed.",signatures:"Dionisio Rodríguez",downloadPdfUrl:"/chapter/pdf-download/69539",previewPdfUrl:"/chapter/pdf-preview/69539",authors:[null],corrections:null},{id:"65795",title:"Progressive Research in the Molecular Mechanisms of Chronic Fluorosis",doi:"10.5772/intechopen.84548",slug:"progressive-research-in-the-molecular-mechanisms-of-chronic-fluorosis",totalDownloads:1128,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:1,abstract:"Long-term excessive intake of fluoride (F) leads to chronic fluorosis, resulting in dental fluorosis and skeletal fluorosis. Chronic exposure to high doses of fluoride can also cause damage to soft tissues, especially when it passes through the blood-brain, blood-testis, and blood-placenta barrier, causing damage to the corresponding tissues. Fluorosis has become a public health problem in some countries or regions around the world. Understanding the pathogenesis of fluorosis is very important. Although the exact mechanism of fluorosis has not been fully elucidated, various mechanisms of fluoride-induced toxicity have been proposed. In this chapter, we will introduce the research progress of the mechanism of fluorosis, focusing on dental fluorosis, skeletal fluorosis, nervous and reproductive system toxicity, and influential factors related to fluoride toxicity (i.e., genetic background, co-exposure with other element). In addition, the application of proteomics and metabolomics in the study of the pathogenesis of fluorosis is also introduced. Currently, there is still no specific treatment for fluorosis. However, since fluorosis is caused by excessive intake of fluoride, avoiding excessive fluoride intake is the critical measure to prevent the disease. In endemic regions, health education and supplement diet with vitamins C, D and E, and calcium and antioxidant compounds are important.",signatures:"Liming Shen, Chengyun Feng, Sijian Xia, Yan Wei, Hua Zhang, Danqing Zhao, Fang Yao, Xukun Liu, Yuxi Zhao and Huajie Zhang",downloadPdfUrl:"/chapter/pdf-download/65795",previewPdfUrl:"/chapter/pdf-preview/65795",authors:[null],corrections:null},{id:"68804",title:"Polymer Hydrogels for Wastewater Treatment",doi:"10.5772/intechopen.89000",slug:"polymer-hydrogels-for-wastewater-treatment",totalDownloads:1065,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"The pollution of water resources turns into a worldwide problem because of the indiscriminate disposal of pollutants both organic and inorganic in nature. It stays hard to manner or control the purification of wastewater before it flows to water reservoirs. The growing interest in the improvement and application of novel hydrogels in wastewater remedy is due to its particular chemical characteristics along with hydrophilicity, sensitivity, and functionality. Hydrogels exhibit superior overall performance inside the adsorptive removal of a wide variety of aqueous pollutants along with heavy metals, nutrients, and toxic dyes. In this chapter, we are focusing on the behavior and importance of the hydrogels used so far for the removal of both organic and inorganic pollutants from wastewater. With this contribution, we will be able to elaborate the answer for why these hydrogels are superior than other materials used for the same purpose. More attention is given to the removal of heavy metal ions from wastewater using different hydrogel systems.",signatures:"Luqman Ali Shah and Sher Ali Khan",downloadPdfUrl:"/chapter/pdf-download/68804",previewPdfUrl:"/chapter/pdf-preview/68804",authors:[null],corrections:null},{id:"68504",title:"Biological Remediation of Phenoxy Herbicide-Contaminated Environments",doi:"10.5772/intechopen.88256",slug:"biological-remediation-of-phenoxy-herbicide-contaminated-environments",totalDownloads:1013,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Phenoxy herbicides such as 2,4-dichlorophenoxyacetic acid (2,4-D) and 2-methyl-4-chlorophenoxyacetic acid (MCPA) are widely used in agriculture to control broadleaf weeds. Although their application has helped to increase the yield and value of crops, they are also recognized as a source of emerging environmental contamination. Their extensive use may promote contamination of soil, surface, and groundwater and lead to increased inhibition of plant development and soil toxicity. Hence, there is an urgent need to identify nature-based methods based on appropriate biological remediation techniques, such as bio-, phyto-, and rhizoremediation, that enable the effective elimination of phenoxy herbicides from the environment. Bioremediation typically harnesses microorganisms and their ability to utilize recalcitrant contaminants in complete degradation processes, while phytoremediation is a cost-effective, environmentally friendly strategy that uses plants to transform or mineralize xenobiotics to less or nontoxic compounds. Rhizoremediation (microbe-assisted phytoremediation), in turn, is based on the interactions between plant roots, root exudates enriched in plant secondary metabolites, soil, and microorganisms. Based on the above, this chapter presents current knowledge on the properties of phenoxy herbicides, as well as the concentrations detected in the environment, their toxicity, and the biological remediation techniques used for safe removal of the compounds of interest from the environment.",signatures:"Magdalena Urbaniak and Elżbieta Mierzejewska",downloadPdfUrl:"/chapter/pdf-download/68504",previewPdfUrl:"/chapter/pdf-preview/68504",authors:[null],corrections:null},{id:"65819",title:"Biodegradation of Sheep Wool Geotextiles Designed for Erosion Control",doi:"10.5772/intechopen.84334",slug:"biodegradation-of-sheep-wool-geotextiles-designed-for-erosion-control",totalDownloads:1029,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Wool geotextiles were formed from the meandrically arranged thick ropes and used as erosion control products. The geotextiles were installed in the experimental sites to protect the endangered slopes and the bank of ditches. Additionally, as a reinforcement of the soil, loose wool fibres were applied. The progress of wool biodegradation on the slope was investigated. Changes in the outer appearance, mechanical parameters, molecular structure and fibre morphology were analysed. Moreover, the nitrogen content in the soil and the effect of compounds released into soil on the grass growth were studied. The measurements revealed that the biodegradation starts at the cleavage of disulphide bonds, followed by disruption of the peptide bonds. Degradation is initiated in the outer cuticle and is followed by the decomposition of the inner cortical cells. During biodegradation, the nitrogen-rich compounds are released. The compounds act as an effective fertiliser which supports the growth of grass and significantly accelerates the greening of the slope.",signatures:"Jan Broda",downloadPdfUrl:"/chapter/pdf-download/65819",previewPdfUrl:"/chapter/pdf-preview/65819",authors:[{id:"104226",title:"Prof.",name:"Jan",surname:"Broda",slug:"jan-broda",fullName:"Jan Broda"}],corrections:null},{id:"63252",title:"Adsorptive Removal of Fluoride onto Different Waste Materials: Orange Juice Residue, Waste Seaweed, and Spent Cation-Exchange Resin",doi:"10.5772/intechopen.80448",slug:"adsorptive-removal-of-fluoride-onto-different-waste-materials-orange-juice-residue-waste-seaweed-and",totalDownloads:1087,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"To effectively use waste materials in developing a sustainable society, adsorbents for removing trace or low concentrations of fluoride, which is difficult to be removed by conventional techniques, were prepared from three waste materials: orange juice residue, waste sea weed, and spent cation exchange resin. These adsorbents were loaded with tri- or tetravalent metal ions such as iron(III) and zirconium(IV), of which zirconium(IV) was found to be most suitable as the loaded metal ion. From the pH effect on adsorption, the adsorption mechanism was inferred, and adsorption and desorption was found to be controlled by changing pH values. The maximum adsorption capacities on zirconium(IV)-loaded orange juice residue, waste sea weed, and spent cation exchange resin were evaluated as 33.1, 18.1, and 37.6 mg/g, respectively, which were higher than those of most other adsorbents reported in literatures. They exhibited high selectivity for fluoride over other anionic species and high durability. Tests to remove trace concentrations of fluoride from actual waste plating solutions revealed that the concentration could be reduced below the acceptable level using small amounts of these adsorbents, i.e., it was reduced lower than 1.5 mg/dm3 (WHO standard) by adding 1 g of the adsorbents into 1 dm3 test solution.",signatures:"Katsutoshi Inoue, Hari Paudyal, Hidetaka Kawakita and Keisuke Ohto",downloadPdfUrl:"/chapter/pdf-download/63252",previewPdfUrl:"/chapter/pdf-preview/63252",authors:[null],corrections:null},{id:"68347",title:"Bioremediation of Heavy Metals",doi:"10.5772/intechopen.88339",slug:"bioremediation-of-heavy-metals",totalDownloads:1512,totalCrossrefCites:4,totalDimensionsCites:9,hasAltmetrics:0,abstract:"Exposure to lead (Pb), zinc (Zn), cadmium (Cd), copper (Cu), and selenite (SeO3−2) consider the main heavy metals that threat human health. These heavy metals can interfere with the function of vital cellular components. Soil heavy metal contamination represents risks to humans and the ecosystem through drinking of contaminated groundwater, direct ingestion or the food chain, and reduction in food quality. Bioremediation means cleanup of polluted environment via transformation of toxic heavy metals into less toxic form by microbes or its enzymes. Otherwise, bioremediation by microbes has limitations like production of toxic metabolites. The efflux of metal ions outside the cell, biosorption to the cell walls and entrapment in extracellular capsules, precipitation, and reduction of the heavy metal ions to a less toxic state are mechanisms to metals’ resistance.",signatures:"Medhat Rehan and Abdullah S. Alsohim",downloadPdfUrl:"/chapter/pdf-download/68347",previewPdfUrl:"/chapter/pdf-preview/68347",authors:[{id:"175766",title:"Dr.",name:"Medhat",surname:"Rehan",slug:"medhat-rehan",fullName:"Medhat Rehan"}],corrections:null},{id:"70249",title:"Bioremediation of Petroleum-Contaminated Soil",doi:"10.5772/intechopen.90289",slug:"bioremediation-of-petroleum-contaminated-soil",totalDownloads:1141,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Petroleum is not only an important energy resource to boost the economic development, but also a major pollutant of the soil. The toxicity of petroleum can cause a negative impact on ecosystem, as well as the negative effects related to its carcinogenic for both animals and humans. In the present study, bioremediation as an alternative tool for restoration petroleum-contaminated soils was set forth, and focusing on the phytoremediatior plants, petroleum-biodegradable microorganism are responsible for the biodegradation of petroleum. In the present chapter, the bioremediation of petroleum-contaminated soil, as well as the influence factors of bioremediation are elaborated based on the recently studies. This will provide a novel understanding on bioremediation and help improve strategies for petroleum-contaminated soils remediation.",signatures:"Shuisen Chen and Ming Zhong",downloadPdfUrl:"/chapter/pdf-download/70249",previewPdfUrl:"/chapter/pdf-preview/70249",authors:[null],corrections:null},{id:"65862",title:"Mycoremediation in Soil",doi:"10.5772/intechopen.84777",slug:"mycoremediation-in-soil",totalDownloads:1912,totalCrossrefCites:7,totalDimensionsCites:14,hasAltmetrics:1,abstract:"The chapter reviews the most important researches on the use of micro- and macrofungi in the bioremediation of contaminated soils. In particular, the main classes of soil pollutants in Europe (heavy metals, mineral oils, polycyclic aromatic hydrocarbons (PAHs), monoaromatic hydrocarbons, phenols and chlorinated hydrocarbons (CHCs)), together with the emerging contaminants (i.e. endocrine-disrupting chemicals (EDCs) and pharmaceutical-personal care products (PPCPs)) are considered. A description of the fungal species (saprotrophic and biotrophic basidiomycetes) and biodegradative extracellular (laccases and class II peroxidases) and intracellular (cytochrome P450 monooxygenases and glutathione transferases) enzyme classes is reported. Moreover, the chemical-physical parameters that influence the biodegradation process are examined, and the biostimulation and bioaugmentation strategies are described. A specific attention is paid to the microcosm studies, at the laboratory scale, which are an essential approach to evaluate the feasibility of a biodegradation process.",signatures:"Francesca Bosco and Chiara Mollea",downloadPdfUrl:"/chapter/pdf-download/65862",previewPdfUrl:"/chapter/pdf-preview/65862",authors:[{id:"93865",title:"Dr.",name:"Francesca",surname:"Bosco",slug:"francesca-bosco",fullName:"Francesca Bosco"},{id:"96159",title:"Dr.",name:"Chiara",surname:"Mollea",slug:"chiara-mollea",fullName:"Chiara Mollea"}],corrections:null},{id:"68268",title:"Arsenic Phytoremediation: Finally a Feasible Approach in the Near Future",doi:"10.5772/intechopen.88207",slug:"arsenic-phytoremediation-finally-a-feasible-approach-in-the-near-future",totalDownloads:1099,totalCrossrefCites:2,totalDimensionsCites:8,hasAltmetrics:0,abstract:"Arsenic, a class-1 carcinogenic, is a ubiquitous metalloid found in the atmosphere, soils, natural waters, and organisms. The World Health Organization (WHO) estimates that hundred million people worldwide might be chronically exposed to arsenic in drinking water at concentrations above the safety standard. Conventionally applied techniques to remove arsenic species show low removal efficiency, high operational costs, and high-energy requirements. The biological methods, especially phytoremediation, could be cost-effective for protecting human health and the environment from toxic metal contamination. Plants, as sessile organisms, have developed an extraordinary capacity to tolerate arsenic through three main strategies: uptake repression, sequestration into the vacuole, or extrusion. Therefore, arsenic perception and tolerance require a coordinated response that involves arsenic transporters, extrusion pumps, vacuole transporters, and the activation of the phytochelatin biosynthetic pathway. For phytoremediation to become a feasible strategy for arsenic removal from contaminated sites, it is essential to completely understand the molecular mechanisms of arsenic uptake, extrusion, and sequestration, as well as how this response is coordinated. 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Beghi",authors:[{id:"41947",title:"Prof.",name:"Marco G.",middleName:null,surname:"Beghi",fullName:"Marco G. Beghi",slug:"marco-g.-beghi"}]},{id:"45568",title:"On Universal Modeling of the Bulk Acoustic Wave Devices",slug:"on-universal-modeling-of-the-bulk-acoustic-wave-devices",signatures:"Boris Sveshnikov, Sergey Nikitov and Sergey Suchkov",authors:[{id:"11533",title:"Dr.",name:"Boris",middleName:"V.",surname:"Sveshnikov",fullName:"Boris Sveshnikov",slug:"boris-sveshnikov"},{id:"166911",title:"Prof.",name:"Sergey",middleName:null,surname:"Nikitov",fullName:"Sergey Nikitov",slug:"sergey-nikitov"},{id:"166912",title:"Prof.",name:"Sergey",middleName:null,surname:"Suchkov",fullName:"Sergey Suchkov",slug:"sergey-suchkov"}]},{id:"45608",title:"Progress in Theoretical and Numerical Tools Devoted to Understanding of Acoustic Devices Behavior",slug:"progress-in-theoretical-and-numerical-tools-devoted-to-understanding-of-acoustic-devices-behavior",signatures:"T. Laroche and S. Ballandras",authors:[{id:"31933",title:"Dr.",name:"Sylvain",middleName:null,surname:"Ballandras",fullName:"Sylvain Ballandras",slug:"sylvain-ballandras"},{id:"44765",title:"Dr.",name:"Thierry",middleName:null,surname:"Laroche",fullName:"Thierry Laroche",slug:"thierry-laroche"}]},{id:"45585",title:"Precise Analysis and Design of Multi-Layered Acoustic Wave Devices with Bragg Cell",slug:"precise-analysis-and-design-of-multi-layered-acoustic-wave-devices-with-bragg-cell",signatures:"Yongqiang Guo and Weiqiu Chen",authors:[{id:"11654",title:"Dr.",name:"Yongqiang",middleName:null,surname:"Guo",fullName:"Yongqiang Guo",slug:"yongqiang-guo"},{id:"125695",title:"Prof.",name:"Weiqiu",middleName:null,surname:"Chen",fullName:"Weiqiu Chen",slug:"weiqiu-chen"}]},{id:"45583",title:"High-Overtone Bulk Acoustic Resonator",slug:"high-overtone-bulk-acoustic-resonator",signatures:"T. Baron, E. Lebrasseur, F. Bassignot, G. Martin,\nV. Pétrini and S. Ballandras",authors:[{id:"149751",title:"Dr.",name:"Thomas",middleName:null,surname:"Baron",fullName:"Thomas Baron",slug:"thomas-baron"}]},{id:"45580",title:"Modeling and Design of BAW Resonators and Filters for Integration in a UMTS Transmitter",slug:"modeling-and-design-of-baw-resonators-and-filters-for-integration-in-a-umts-transmitter",signatures:"Matthieu Chatras , Stéphane Bila, Sylvain Giraud, Lise Catherinot,\nJi Fan, Dominique Cros, Michel Aubourg, Axel Flament,\nAntoine Frappé, Bruno Stefanelli, Andreas Kaiser, Andreia Cathelin,\nJean Baptiste David, Alexandre Reinhardt, Laurent Leyssenne and\nEric Kerhervé",authors:[{id:"149671",title:"Dr.",name:"Matthieu",middleName:null,surname:"Chatras",fullName:"Matthieu Chatras",slug:"matthieu-chatras"}]},{id:"45586",title:"Surface Acoustic Wave Based Magnetic Sensors",slug:"surface-acoustic-wave-based-magnetic-sensors",signatures:"Bodong Li, Hommood Al Rowais and Jürgen Kosel",authors:[{id:"141848",title:"Prof.",name:"Jurgen",middleName:null,surname:"Kosel",fullName:"Jurgen Kosel",slug:"jurgen-kosel"},{id:"143722",title:"MSc.",name:"Bodong",middleName:null,surname:"Li",fullName:"Bodong Li",slug:"bodong-li"},{id:"146392",title:"MSc.",name:"Hommood",middleName:null,surname:"Al Rowais",fullName:"Hommood Al Rowais",slug:"hommood-al-rowais"}]},{id:"45577",title:"Electromagnetic and Acoustic Transformation of Surface Acoustic Waves and Its Application in Various Tasks",slug:"electromagnetic-and-acoustic-transformation-of-surface-acoustic-waves-and-its-application-in-various",signatures:"Sergey E. Babkin",authors:[{id:"150021",title:"Dr",name:null,middleName:null,surname:"Babkin",fullName:"Babkin",slug:"babkin"}]},{id:"45573",title:"Acoustics in Optical Fiber",slug:"acoustics-in-optical-fiber",signatures:"Abhilash Mandloi and Vivekanand Mishra",authors:[{id:"143426",title:"Dr.",name:"Vivekanand",middleName:null,surname:"Mishra",fullName:"Vivekanand Mishra",slug:"vivekanand-mishra"},{id:"146960",title:"Mr.",name:"Abhilash",middleName:null,surname:"Mandloi",fullName:"Abhilash Mandloi",slug:"abhilash-mandloi"}]},{id:"45570",title:"Techniques for Tuning BAW-SMR Resonators for the 4th Generation of Mobile Communications",slug:"techniques-for-tuning-baw-smr-resonators-for-the-4th-generation-of-mobile-communications",signatures:"M. El Hassan, E. Kerherve, Y. Deval, K. Baraka,\nJ.B. David and D. Belot",authors:[{id:"61815",title:"Prof.",name:"Jean-Baptiste",middleName:null,surname:"David",fullName:"Jean-Baptiste David",slug:"jean-baptiste-david"},{id:"143096",title:"Dr.",name:"Moustapha",middleName:null,surname:"El Hassan",fullName:"Moustapha El Hassan",slug:"moustapha-el-hassan"},{id:"146675",title:"Prof.",name:"Eric",middleName:null,surname:"Kerherve",fullName:"Eric Kerherve",slug:"eric-kerherve"},{id:"146676",title:"Prof.",name:"Yann",middleName:null,surname:"Deval",fullName:"Yann Deval",slug:"yann-deval"},{id:"146679",title:"Mr.",name:"Didier",middleName:null,surname:"Belot",fullName:"Didier Belot",slug:"didier-belot"},{id:"156246",title:"Dr.",name:"Kamal",middleName:null,surname:"Baraka",fullName:"Kamal Baraka",slug:"kamal-baraka"}]},{id:"45581",title:"Seismic Vibration Sensor with Acoustic Surface Wave",slug:"seismic-vibration-sensor-with-acoustic-surface-wave",signatures:"Jerzy Filipiak and Grzegorz Steczko",authors:[{id:"146520",title:"Prof.",name:"Jerzy",middleName:null,surname:"Fllipiak",fullName:"Jerzy Fllipiak",slug:"jerzy-fllipiak"},{id:"146533",title:"Dr.",name:"Grzegorz",middleName:null,surname:"Steczko",fullName:"Grzegorz Steczko",slug:"grzegorz-steczko"}]},{id:"45571",title:"Acoustics and Vibro-Acoustics Applied in Space Industry",slug:"acoustics-and-vibro-acoustics-applied-in-space-industry",signatures:"Rogério Pirk, Carlos d´Andrade Souto,\nGustavo Paulinelli Guimarães and Luiz Carlos Sandoval Góes",authors:[{id:"143133",title:"Dr.",name:"Rogerio",middleName:null,surname:"Pirk",fullName:"Rogerio Pirk",slug:"rogerio-pirk"},{id:"169101",title:"Dr.",name:"Carlos",middleName:null,surname:"d´Andrade Souto",fullName:"Carlos d´Andrade Souto",slug:"carlos-dandrade-souto"},{id:"169102",title:"Dr.",name:"Gustavo",middleName:null,surname:"Paulinelli Guimarães",fullName:"Gustavo Paulinelli Guimarães",slug:"gustavo-paulinelli-guimaraes"},{id:"169103",title:"Dr.",name:"Luiz Carlos",middleName:null,surname:"Sandoval Góes",fullName:"Luiz Carlos Sandoval Góes",slug:"luiz-carlos-sandoval-goes"}]},{id:"45575",title:"Acoustic Wave Based Microfluidics and Lab-on-a-Chip",slug:"acoustic-wave-based-microfluidics-and-lab-on-a-chip",signatures:"J. K. Luo, Y. Q. Fu and W. I. Milne",authors:[{id:"145624",title:"Prof.",name:"Jack",middleName:null,surname:"Luo",fullName:"Jack Luo",slug:"jack-luo"},{id:"146419",title:"Dr.",name:"Richard",middleName:null,surname:"Fu",fullName:"Richard Fu",slug:"richard-fu"},{id:"146420",title:"Prof.",name:"Williams I",middleName:null,surname:"Milne",fullName:"Williams I Milne",slug:"williams-i-milne"}]},{id:"45579",title:"Underwater Acoustics Modeling in Finite Depth Shallow Waters",slug:"underwater-acoustics-modeling-in-finite-depth-shallow-waters",signatures:"Emerson de Sousa Costa, Eduardo Bauzer Medeiros\nand João Batista Carvalho Filardi",authors:[{id:"149966",title:"M.Sc.",name:"Emerson",middleName:"De Sousa",surname:"Costa",fullName:"Emerson Costa",slug:"emerson-costa"},{id:"149967",title:"Dr.",name:"Eduardo",middleName:null,surname:"Bauzer Medeiros",fullName:"Eduardo Bauzer Medeiros",slug:"eduardo-bauzer-medeiros"},{id:"168716",title:"MSc.",name:"João",middleName:null,surname:"Batista Carvalho Filardi",fullName:"João Batista Carvalho Filardi",slug:"joao-batista-carvalho-filardi"}]},{id:"45578",title:"Ray Trace Modeling of Underwater Sound Propagation",slug:"ray-trace-modeling-of-underwater-sound-propagation",signatures:"Jens M. Hovem",authors:[{id:"46063",title:"Prof.",name:"Jens",middleName:"Martin",surname:"Hovem",fullName:"Jens Hovem",slug:"jens-hovem"}]}]}],publishedBooks:[{type:"book",id:"521",title:"Acoustic Waves",subtitle:"From Microdevices to Helioseismology",isOpenForSubmission:!1,hash:"54432e5ff2c93e574f225da232e79c8c",slug:"acoustic-waves-from-microdevices-to-helioseismology",bookSignature:"Marco G. Beghi",coverURL:"https://cdn.intechopen.com/books/images_new/521.jpg",editedByType:"Edited by",editors:[{id:"41947",title:"Prof.",name:"Marco G.",surname:"Beghi",slug:"marco-g.-beghi",fullName:"Marco G. Beghi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10042",title:"Noise and Environment",subtitle:null,isOpenForSubmission:!1,hash:"11e8fca2f0f623d87dfbc3cf2b185e0d",slug:"noise-and-environment",bookSignature:"Daniela Siano and Alice Elizabeth González",coverURL:"https://cdn.intechopen.com/books/images_new/10042.jpg",editedByType:"Edited by",editors:[{id:"9960",title:"Dr.",name:"Daniela",surname:"Siano",slug:"daniela-siano",fullName:"Daniela Siano"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10966",title:"Acoustic Emission",subtitle:"New Perspectives and Applications",isOpenForSubmission:!1,hash:"e4cbf5fe77dcf581393247bd9ac4277a",slug:"acoustic-emission-new-perspectives-and-applications",bookSignature:"Mahmut Reyhanoglu",coverURL:"https://cdn.intechopen.com/books/images_new/10966.jpg",editedByType:"Edited by",editors:[{id:"15068",title:"Dr.",name:"Mahmut",surname:"Reyhanoglu",slug:"mahmut-reyhanoglu",fullName:"Mahmut Reyhanoglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8679",title:"Inverse Heat Conduction and Heat Exchangers",subtitle:null,isOpenForSubmission:!1,hash:"a994b17ac471c6d414d63c74a7ab74de",slug:"inverse-heat-conduction-and-heat-exchangers",bookSignature:"Suvanjan Bhattacharya, Mohammad Moghimi Ardekani, Ranjib Biswas and R. C. Mehta",coverURL:"https://cdn.intechopen.com/books/images_new/8679.jpg",editedByType:"Edited by",editors:[{id:"233630",title:"Dr.",name:"Suvanjan",surname:"Bhattacharyya",slug:"suvanjan-bhattacharyya",fullName:"Suvanjan Bhattacharyya"}],equalEditorOne:{id:"56358",title:"Dr.",name:"Rakhab",surname:"Mehta",slug:"rakhab-mehta",fullName:"Rakhab Mehta"},equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],publishedBooksByAuthor:[{type:"book",id:"521",title:"Acoustic Waves",subtitle:"From Microdevices to Helioseismology",isOpenForSubmission:!1,hash:"54432e5ff2c93e574f225da232e79c8c",slug:"acoustic-waves-from-microdevices-to-helioseismology",bookSignature:"Marco G. Beghi",coverURL:"https://cdn.intechopen.com/books/images_new/521.jpg",editedByType:"Edited by",editors:[{id:"41947",title:"Prof.",name:"Marco G.",surname:"Beghi",slug:"marco-g.-beghi",fullName:"Marco G. Beghi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},onlineFirst:{chapter:{type:"chapter",id:"82439",title:"Cellular Cytotoxicity and Multiple Sclerosis",doi:"10.5772/intechopen.105681",slug:"cellular-cytotoxicity-and-multiple-sclerosis",body:'Multiple sclerosis (MS) is the most prevalent neurological disease among young adults in developed countries, with approximately 2.8 million people being affected worldwide [1]. It principally affects women in their prime, with diagnosis typically occurring between the ages of 20 and 40. The disease is debilitating due to central nervous system (CNS) damage resulting from activated lymphocytes migrating across the blood brain barrier (BBB) and engaging in a proinflammatory response. This causes cells to attack and destroy the myelin sheaths that coat the axons of neurons of the brain, spinal cord and optic nerve, as well as the myelinating cells or oligodendrocytes, and the axons themselves [2]. As neurons receive sensory input from external sources and send motor commands to the muscles by relaying interneuron electrical impulses, breakdown causes interruption to the signals being sent around the body, and dependent on where the damage occurs, results in different signs and symptoms. These can include vision impairment, muscle spasms and numbness, bladder and bowel issues, fatigue and difficulty walking [3]. Most people with MS have progressive neurological disability which, though not usual, can culminate in death [4]. The area of damage or scarring caused by the immune system attack is called a lesion or plaque, and can be visualised by magnetic resonance imaging (MRI). A definitive diagnosis of MS is made when these plaques are shown to be reoccurring and when there is the clear presence of clinical symptoms [3].
Two major types of MS have been recognised, primary progressive multiple sclerosis (PPMS), diagnosed in approximately 15% of patients and which results in steady progression of disease from onset, and relapsing remitting multiple sclerosis (RRMS), which affects approximately 80% of patients and is characterised by periods of relapse separated by periods of remit without worsening of symptoms [5, 6, 7]. Most patients with an initial diagnosis of RRMS will, within 20 years of diagnosis, progress to secondary progressive multiple sclerosis (SPMS) where the stages between relapse and remit shorten and there is a steady decline with an increase in symptoms and disease progression [8]. Up to approximately 5% of MS patients have progressive relapsing multiple sclerosis (PRMS) and this characterised by steady disease progression with occasional relapses [9].
The exact cause of MS is still unknown, however research has determined that it is an autoimmune disease, arising from complex interactions between environmental and genetic influences. There is a latitude incidence variance, with prevalence of MS increased the further one is from the equator; sunlight and vitamin D are therefore being investigated as disease triggers [1, 10, 11, 12]. Childhood exposure to bacteria and viruses have also been investigated, due to a person’s disease risk being set as the incidence of the region they moved to prior to puberty [13, 14]. Of note, every patient with MS have previously been exposed to Epstein–Barr virus (EBV) [15, 16]. Smoking also increases a person’s risk and worsens symptoms following diagnosis [17].
Although the disease is not inherited, it has a genetic component, with those having an affected first degree relative exhibiting an increased incidence of disease [18], and twin studies indicate that there is a 30% chance of developing disease in the second twin if the first has been diagnosed with MS [19]. Genome wide association studies (GWAS) have identified more than 230 genes associated with a person’s MS risk, several being immune genes, particularly those of T cells, B cells, natural killer (NK) cells, monocytes and microglia, implicating involvement of both major branches of the immune system, the innate and adaptive immune responses, in initiation and progression of disease [20, 21, 22, 23]. These studies are supported by several human and animal model functional studies [24, 25, 26].
Cellular toxicity, or the ability to kill other cells, is an important effector mechanisms of the immune system to protect us from infections, cancer or autoimmune diseases. There is a close association between inflammation and neurodegeneration, and cellular toxicity has been implicated as a having a major role in MS [27]. The main players are CD8, or cytotoxic, T cells and NK cells. Cellular toxicity can operate by many mechanisms including NK cell release of lytic granules containing perforin or granzymes to kill directly, or by inducing death receptor-mediated apoptosis via tumour necrosis factor (ligand) superfamily member 10 (TRAIL) or Fas Ligand (FasL) expression on CD8 T cells [28]. There are also antibody-dependent cell-mediated cytotoxic mechanisms (ADCC), where B cells produce antigen specific antibodies or immunoglobulins, that will coat a pathogen or foreign body, marking them for killing or destruction through cell to cell cytoloysis by effector immune cells expressing FcγRIIIA (CD16A), including classical NK cells, monocytes/macrophages, neutrophils, eosinophils, NKT cells, or γδT cells (reviewed in [29]).
The immune system of vertebrates is commonly divided into two main complementary parts, innate and adaptive immunity, the bridge between which is critical for an efficient and effective immune response.
The innate immune system is evolutionary the most primitive, where there is non-specific response to a broad class of antigens. The haematopoietic cells involved include macrophages, dendritic cells, mast cells, neutrophils, eosinophils, NK cells and NKT cells. Although 1908 Nobel Prize winner, Elie Metchnikoff, first described an important role for the innate immune system [30], it is only now being recognised as a critical regulator of human inflammatory disease. Innate immunity involves the recognition of infected cells through surface recognition receptors. These are termed pattern recognition receptors (PRRs) which recognise pathogen associated molecular patterns (PAMPs) unique to non-vertebrate cells, including bacteria and fungi. They are also on internal vesicle membranes for recognition of viral ssRNA and dsRNA and for distinguishing lysed bacterial components [31]. Cytotoxic innate lymphocytes can lyse abnormal or infected cells through the release of cytotoxic granules containing perforin or granzymes, and antigen presenting cells (APCs) can be activated by the innate immune system to present pathogen antigens on their surface. Once activated they will migrate to secondary lymph organs to present their antigen to T cells, and in so doing also activate the adaptive immune system response [32, 33]. The innate immune system therefore functions through a combination of cellular defences and humoral components to defend against nonspecific antigens before activating B and T cells, triggering an adaptive immune response. Speed is the main advantage of innate immunity, with a protective inflammatory response being generated within minutes of pathogen exposure.
Another part of innate immunity is the complement system, which is made up of several small proteins that have been synthesised in the liver and circulate in the blood as active precursors that when stimulated are proteolytically cleaved to release cytokines, leading to a cascade of reactions, ultimately resulting in complement activation or fixation [34]. As the name suggests, they complement or enhance the ability of antibodies and phagocytic cells to clear damaged or diseased cells by promoting inflammation and attack of the cell membrane of the pathogen. Antibodies, generated by the adaptive immune system, can activate the complement system.
Adaptive immunity, sometimes referred to as acquired immunity, is highly specialised and helps to protect the body by recognising antigens, whether they are foreign to the host’s immune system (exogenous), produced by intracellular bacteria or viruses (intracellular) or produced by the host (autoantigen). The adaptive immune system also remembers previously encountered antigens, leading to quicker response times [35]. T and B lymphocytes are the main cells mediating adaptive immunity, with T cells being further divided into the cytotoxic CD8 T cells and CD4 T cells that constitute several classes of what are commonly referred to as “helper T cells”. These cell have produced highly specific receptors for recognition of hundreds or even thousands of antigens through genetic recombination, and this facilitates pathogen specific immunologic effectors pathways, the generation of immunological memory and the regulation of host immune homoeostasis [36].
CD8 T cells recognise infected cells through interaction of T cell receptors with antigens presented by major histocompatibility complex (MHC) class I on the infected cell. The target cell is then killed by the release of cytotoxins, such as perforin and granzymes, from the CD8 T cell [28]. CD4 T cells, on the other hand, recognise antigens presented in the context of MHC II on an APC. Binding to MHC II molecules activates CD4 T cells to release cytokines, which can stimulate CD8 T cells, macrophages and B cells to form an immune response (reviewed in [37]). They can, for example, release cytokines as instructors to CD8 T cells to release cytotoxins, or to B cells to produce pathogen specific antibodies. They therefore instigate and shape adaptive immune responses dependent on the cytokines they release. These can be mainly Th1, or inflammatory, in nature, such as IFN-γ and IL-12, responsible for the control of intracellular pathogens, or polarised to a more anti-inflammatory Th2 response, where cytokines such as IL-4, IL-5 or IL-13 are produced [38, 39]. A disturbance in this Th1/Th2 response can have severe consequences, be they more Th2 in nature, driving asthma and allergy, or Th1 driven, resulting in autoimmune diseases, including MS (reviewed in [40]). A couple of the more recently identified CD4 T cells subsets include Th17 cells that are characterised by production of IL-17 and IL-23, and have been linked to inflammatory diseases, and T regulatory (Treg) cells, which are important in maintaining homeostasis and tolerance of the immune system [41, 42, 43]. Tregs express the transcription factor FoxP3 which is essential for their development and function [44, 45, 46]. In humans, mutations in FOXP3 have been found to result in immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, providing evidence that anomalies of Tregs can cause autoimmune disease and allergy [47].
During production of the T cell receptor (TCR) on T cells and B cell receptor (BCR) on B cells, random genetic recombination events can lead to receptors being produced that are specific to autoantigens [48, 49]. To prevent reaction to self, cells undergo central and peripheral tolerance events through which autoreactive cells are apoptotically removed, first in the primary lymphoid organs of the thymus (T cell) and bone marrow (B cell), and if this fails, in the secondary lymphoid organs after cells migrate to the periphery [49]. Self-reactive antibodies account for 55–75% of all antibodies expressed by early immature B cells, including polyreactive and anti-nuclear specificities [49]. However, it is estimated that the majority of newly produced B cells do not reach maturity, and during central and peripheral tolerance most of the self-reactive B cells are removed. If both selection processes fail in T or B cells, this will result in T and B cells able to react with the body’s own cells and tissues. These events lead to autoimmune disease.
Inflammation as a response of the body to infection or cell injury is a well-known concept that dates back to the beginning of medicine. However, Metchnikoff pointed out that although normally a method of protection, inflammation that exceeds normal bounds can cause disease [27]. Even with this knowledge, it was not until the 1950s that inflammation was recognised as inducing an autoimmune reaction responsible for disease. Autoimmune disease is characterised by an excessive immune response against self, often resulting in inflammation and tissue destruction, in the absence of a threat to the organism [50, 51]. Aberrant immune responses have been associated with over 80 disorders, including multiple sclerosis, and affects 5–7% of the population [52]. Clinical observations over the past decade have suggested that the prevalence of all autoimmune disease, not just MS, is increasing, bringing the issue to the forefront of scientific interest [53, 54]. Successful treatment of autoimmune disease is also of great societal interest, as they are commonly characterised by chronic natures, ongoing health care costs, and debilitating issues resulting in loss of productivity.
Immunological self-tolerance is maintained in part by Tregs. Tregs are CD4 T cells that actively and dominantly supress lymphocytes, particularly self-reactive T cells in the normal periphery that exist despite the deletion mechanisms in the thymus [43]. Natural CD25+ CD4 Tregs utilise several modes of suppression, including cell contact dependent mechanisms, such as the killing of APCs or responder T cells by granzyme and perforin, and by mediation of soluble factors, such as the secretion of immunosuppressive cytokines like IL-10, TGF-β or IL-35, or deprivation of cytokines necessary for expansion and survival of responder T cells (reviewed in [55, 56]).
Optimal T cell function relies on a carefully maintained state of equilibrium. When one subpopulation of T helper cells is activated, others are modulated or inhibited to promote the most specific effector response to the threat [57]. The cellular development of Tregs shares a common cytokine with Th17 cells, TGF-β [41, 42]. Th17 cells are the opposing force to Tregs, serving as an effector lymphocyte population that plays a key role in autoimmunity [41, 42]. At homeostasis, Th17 cells promote gut barrier defence, granulopoiesis, granulocyte chemotaxis and immunity against extracellular pathogen [58]. IL-17 induces granulopoesis indirectly through the stimulation of fibroblasts, epithelial and endothelial cells to secrete GM-CSF, IL-6, IL-8 and MIP-2, with IL-8 and MIP-2 enhancing chemotaxis of neutrophils [59, 60]. While Th17 cell mediated immunity is crucial for maintaining mucosal and haematopoietic homeostasis, too strong a response can induce autoimmunity. The relationship between Tregs and effector Th17 must remain balanced to provide the optimal functional immunity and health of an organism.
Another theory of immune regulation is the hypothesis of homeostasis between Th1 and Th2 cells. The subpopulations can be distinguished by the cytokines they produce and the expression of difference cell surface molecules. Th1 cells are responsible for cell mediated immunity, phagocyte dependent protective responses, B cell activation and production of opsonising antibodies such as IgG1, whereas Th2 cells produce cytokines that are responsible for strong antibody production, eosinophil activation and inhibition of several macrophage functions, thus providing phagocyte independent protective responses [61]. Th2 cells are also responsible for the general activation of B cells. When the Th1/Th2 paradigm is thrown out of balance by failure of central or peripheral tolerance, immunological disorders can occur due to uncontrolled responses [61].
MS arises when there is an imbalance in the body’s immune response, shifting it from a beneficial immune process that fights infection and disease towards a self-aggressive immune attack on the cells within the CNS (Figure 1). Genetic and environmental factor interaction may facilitate movement of autoreactive T cells, macrophages and NK cells and demyelinating antibodies from the periphery to the CNS. In the periphery self-antigens can be presented on MHC II molecules by APCs to TCRs on T cells, thereby activating proinflammatory T cells [48]. The activated T cells can then migrate through the blood brain barrier to the brain and spinal cord [2]. Once in the CNS the T cells can be reactivated by CNS antigens presented on MHC II by other APCs, primarily microglial cells [62]. Secretion of proinflammatory Th1 cytokines by the reactivated T cells can induce CNS inflammation by activating macrophages, B cells and other T cells [63]. The antibodies can also initiate a complement cascade resulting in assembly of the membrane attack complex, forming pores in the myelin membranes.
Multiple sclerosis pathogenesis. Autoreactive T cells, macrophages and NK cells, and demyelinating antibodies, may migrate across a compromised blood brain barrier. T cells are reactivated in the central nervous system by antigen presenting cells (APC). Anti-inflammatory cytokines released by Th2 cells can stimulate B cells to differentiate into plasma cells that secrete demyelinating antibodies. Alternatively, the release of proinflammatory cytokines by Th1 cells can enhance immune response, via activation of other immune cells such as CD8 T cells and macrophages to attack the myelin sheath and oligodendrocytes causing demyelination and the development of clinical symptoms of MS (created with
While inflammation and neurodegeneration are correlated in active lesions, research suggests that neurodegeneration may become independent from inflammation in progressive disease [64]. There are many MS therapeutics that suppress proinflammatory cytokines or their effector functions, but not all treatments show equal efficacy and can cause unintended effects. Currently, there is no cure. It is thus becoming clear that there is a need to elucidate the different populations important in initiating and progressing disease, and by studying their interactive networks, identify possible areas for targeted intervention.
While there is overwhelming evidence of a role for T cells in the pathogenesis of MS, further studies in humans and in the mouse model of disease, experimental autoimmune encephalomyelitis (EAE), provides compelling evidence that other cell types play major roles. Linkage to the Human Leukocyte antigen (HLA) locus, including MHC I and II genes, was the first genetic locus identified, and still provides today the strongest linkage to MS. Further studies have identified an extended HLA haplotype, HLA-DRB1*15:01, DQA1*0102, DQB1*0602, within the MHC class II region [65]. As MHC II molecules specifically present peptide antigens to activate CD4 T cells, this suggests that CD4 T cells are important in initiation and progression of MS.
Th1 cells are a lineage of CD4 effector T cells that promote cell mediated immune responses and are necessary for defence against intracellular viral and bacterial pathogens. They were originally believed to be the main pathogenic T cells in MS, not only because susceptibility genes were linked to MHC II molecules, but also because immune surveillance of a healthy brain to scan for infection, showed favouring towards infiltration by Th1 cells, and therapeutic strategies designed to induce a shift from Th1 to Th2 immune response resulted in beneficial outcomes in MS patients [66, 67, 68].
The development of Th1 cells is coupled to the involvement of cell-extrinsic and cell-intrinsic factors, including signal transducer activator 1 (STAT1), the transcription factor Tbx21, IL-21 and STAT4 [69]. The CD4-Th1 model for MS was further supported by a trial performed in 1987, which found that administering IFN-γ to RRMS patients exacerbated disease. An accompanying increase in circulating monocytes bearing class II (HLA-DR) surface antigens suggested that the attacks induced by the treatment were immunologically mediated [70].
Th1 cells are also known to drive EAE. However, it was found that transgenic mice that lacked Th1 cells developed more severe EAE, thereby contradicting the Th1 cell theory for MS [71]. This conundrum was partially resolved following further investigation involving IL-23, a heterodimer cytokine composed of a unique p19 subunit and a common p40 subunit shared with IL-12. IL-23 promotes development of Th17 cells as opposed to Th1 cells [72]. Early studies on Th17 cells therefore dismissed a role for the previously favoured Th1 cells, but more recent research suggests that both cell types may play distinct roles in pathology [73]. It was suggested that Th1 cells accessed the CNS initially and subsequently facilitated the recruitment of Th17 cells [73].
Analysis of CNS tissue revealed distinct histopathological features and immune profiles depending on cytokine modulated T cells. IL-12p70 driven disease was characterised by macrophage-rich infiltrates, however in IL-23 driven lesions it was found that neutrophils and the growth factor, granulocyte colony stimulating factor (CSF), were the most prominent [74]. Research has shown that while IL-23 is commonly associated with the expansion of Th17 cells or the stabilisation of the Th17 phenotype, a similar course of EAE has been reported following the transfer of MOG-specific T cells into either wild type or IL-23 knockout mice [75]. This suggests that once encephalitogenic cells have been generated, EAE can develop in the absence of IL-23. IL-23 may therefore only be necessary for disease induction and not the effector phase of disease.
While MHC II molecules were found to be the strongest associated with MS in genetic studies, the MHC I HLA-A*0301 allele, independent of the HLA II haplotype DRB1*15,DQB1*06, was found to be increased in MS patients [65]. There was also a negative association with the MHC I HLA-A*0201 and disease [76]. As MHC I molecules are recognised by CD8 T cells, this suggests that CD8 T cells play a role in MS.
In one of the first studies that shifted from a CD4 T cell focus, CD8 T cells outnumbered the CD4 T cell subset in all parenchyma samples from MS patients, regardless of the MS type, duration or speed of disease progression [77]. Research has also shown that APCs, including dendritic cells (DCs), interact with T cells and proliferating lymphocytes, predominately CD8 T cells, at the margins of chronic active MS lesions [78]. CD8 T cells have also been found within active lesions of RRMS patients [77]. These T cells, and to a lesser extent, compartmentally differentially distributed B cells, have been shown to correlate with disease progression and damage.
CD8 T cells are an important subpopulation of MHC I restricted T cells, and are mediators of adaptive immunity. Cytotoxic T cells specialise in direct killing of cells that are infected, particularly with viruses, or are cancerous or damaged in other ways. Cytotoxic cells rely on two mechanisms for lytic activity: granule-dependent cytotoxicity (reviewed in [79]) and death receptor dependent cytotoxicity (reviewed in [80]). The principle mechanism used is granule-dependent cytotoxicity. In lesion prone areas of the CNS, T lymphocytes, including CD8 cytotoxic T lymphocytes (CTLs), are recruited to the affected tissue and brain cells are stimulated to present antigens to the T lymphocytes via de novo expression of MHC molecules. Although levels of MHC I and MHC II are very low in normal CNS parenchyma, neural injury leads to a massive increase in activated and phagocytotic microglial, which can serve as competent APCs [81]. To develop into functioning CD8 T cells, the TCR must recognise the MHC-peptide combination along with the costimulatory signal from APCs. While classical MHC I molecules necessary for CD8 T cell activation are not usually expressed on neural cells, they are induced in most inflammatory and degenerative CNS diseases [82].
Oligodendrocytes lack expression of costimulatory molecules and are thus unable to trigger the full effector of T cells, however they have been known to express MHC I in vitro [83]. Therefore, despite the lack of complete activation of the T cells, oligodendrocytes may still be targets of primed CTLs. MHC I expressing oligodendrocytes are susceptible to lysis by blood donor derived CD8 CTLs [83]. IFN-γ treated human oligodendrocytes also express Fas/CD95, and are therefore susceptible to death receptor dependent cytotoxicity [84]. Another component of the CNS, the neurons, were found to be capable of expressing MHC I when treated with IFN-γ [85, 86]. Medana and colleagues in 2000 discovered that hippocampal neurons were highly susceptible to direct application of cytotoxic granules, but showed no signs of perforin mediated lysis or membrane damage following attack by CTLs [87]. This effect was not observed in any other cell type.
Research to date indicates that all cellular elements of the CNS may act as targets to CTLs but that susceptibility and cytotoxic pathways involved vary dependent on the cell type and the immune activations during the course of the inflammatory process.
Historically, B cells have not been recognised as major players in regulatory function in the development of autoimmune diseases, although the identification of autoantibodies produced by autoreactive plasma cells and their pathogenic consequences are widely accepted [88]. B cells are considered effector cells as well as cells with immunoregulatory potential. B cells in MS patients express increased levels of costimulatory molecules, increasing the stimulation of antigen-reactive T cells [89]. It has been reported that MS patients have increased levels of IL-6 and GM-CSF, correlating with increased Th17 cells [90, 91]. B cell targeted therapies utilise B cell depleting monoclonal antibodies against the B cell marker CD20. These antibodies trigger B cell lysis through antibody dependent cellular cytotoxicity, complement dependent cytotoxicity or apoptosis induction [92].
Administration of daclizumab, an alpha subunit of IL-2 receptor blocking monoclonal antibody, to MS patients was found to strongly reduce brain inflammation. This therapy, while being associated with a decline in circulating CD4 and CD8 T cells, also correlated with a significant expansion of CD56bright NK cells in vivo. This provided supporting evidence of NK cell-mediated negative immunoregulation of T cells during daclizumab treatment [93], and the identification of NK cells in association with MS, where positive outcome was possibly due to the treatment’s effect of increasing the NK cell numbers [94, 95].
For decades, NK cells have been classified as a component of the innate immune system. However, evidence suggests that, like B and T cells, NK cells are educated during development, possess antigen-specific receptors, undergo clonal expansion and generate memory cells (reviewed in [96]). Research originally suggested that NK cells developed and underwent differentiation within the bone marrow, however more recent extensive ex vivo characterisation of haematopoietic precursor cells (HPCs) and downstream NK cell development intermediates (NKDIs) reveals that they are enriched in secondary lymphoid tissues (STLs), including the tonsils, spleen and lymph nodes [97, 98, 99, 100]. This suggests that NK cells in humans can differentiate in the SLTs, and may do so preferentially.
Human NK cells are phenotypically defined by expression of CD56 and the lack of CD3 expression [101]. CD56 is the 140-kDa isoform of neural cell adhesion molecule (NCAM) found on NK cells and a minority of T cells [102]. NK cells are categorised into two distinct populations depending on the cell surface density of CD56. The majority of human NK cells, approximately 90%, express low levels of CD56 (CD56dim) and high levels of FCyRIII (CD16), while the minority express higher levels of CD56 (CD56bright) [103]. CD56bright NK cells have long being associated with an immunoregulatory role, due to increased production of NK-derived immunoregulatory cytokines, including IFN-γ, TNF-β, IL-10, IL-13 and GM-CSF, and reduced cytotoxicity compared to CD56dim NK cells [104]. CD56bright NK cells express receptors for cytokines such as IL-12, IL-15 and IL-18, produced by APCs, which can trigger proliferation of CD56bright NK cells and their production of molecules, including IFN-γ, IL-10 and IL-13 [104]. It has been demonstrated that DCs are a key source of cytokines for the activation of CD56bright NK cells [105]. Modulation and proliferation of CD56bright NK cells can also occur due to DC-derived IL-27 [105]. Activated NK cells can modulate the function of APCs by stimulating monocytes to produce TNF-α and kill immature DCs by a perforin-dependent process referred to as DC editing [106, 107].
However, more recent research has challenged this commonly accepted concept of CD56bright as the primary source of immunoregulatory cytokines. Studies have shown that CD56dim NK cells are also a major source of proinflammatory cytokines and chemokines that are induced rapidly after target cell recognition [108, 109].
The absence of MHC class I molecules, as indicated by virally infected cells or cancerous cells with MHC I downregulated, is not always sufficient to induce NK cell mediated death, suggesting that there must be activating receptors on NK cells whose affinity for target cell ligands dominates over the inhibitory signals of the NK cell. Some activating receptors identified include NKG2D, the NCR, and NKp80 [110, 111, 112]. NKG2D is the best characterised of these activating NK cell receptors. It is a c-type lectin-like receptor expressed on the surface of all human NK cells and recognises at least six ligands, each with a MHC class I homology [113]. Following receptor-ligand interaction, NKG2D phosphorylates an adaptor protein that recruits and activates phosphatidylinositol-3 (PI-3) kinase, which results in perforin-dependent cytotoxicity [114, 115]. Gunesh et al. found that the deletion of CD56 on the NK92 cell line lead to impaired cytotoxic function. The knockout CD56 cells failed to polarise during immunological synapse formation and had severely impaired exocytosis of lytic granules [116].
Treatment of MS patients with IFN-β caused an expansion of CD56bright NK cells, and resulted in the population of CD56dim cells being diminished [117]. The study also found that the proportion of CD56bright NK cells was significantly higher in the secondary lymphoid tissues compared to the peripheral blood for the control group [117]. This suggested that CD56bright NK cells may preferably locate within secondary lymphoid tissues, where they are able to interact with T cells and contribute to control of disease activity in MS [117].
There is an ongoing debate as to whether NK cells have a predominately beneficial or detrimental role in EAE, made even more complex by the lack of CD56 expression on murine NK cells. Studies have shown that enhancing the regulatory features of NK cells ameliorates the disease course of EAE. When the interaction between NKG2A and its ligand Qa-1 (the murine equivalent to the human HLA-E) expressed on target cells were blocked by antibodies specific for either antigen, it was found that NKG2A-expressing NK cells in particular decreased CNS inflammation by killing microglial and T cells [118, 119].
Enrichment of NK cells through treatment with IL-2 coupled with a monoclonal antibody specific for IL-2 (IL-2 mAb) was also found to ameliorate EAE [120]. The IL-2 mAb supplements the proliferation of NK and CD8 T cells in mice by increasing the biological activity of the pre-existing IL-2 by formation of immune complexes [121]. Increased levels of IL-2 was also found to expand Tregs while preventing the induction of Th17 during EAE development [122]. However, NK cells have different effects during the early stages of EAE, and possibly MS, compared to the late stages. In the early stages NK cells were found to protect the CNS whereas NK cells were found to kill neural stem cells (NSCs) during the late stages of EAE, as a result of reduced expression of Qa-1 on NSCs [120, 123].
NKT cells are unique T lymphocytes that express NK cell lineage markers, and act as a bridge between the innate and adaptive immune system. NKT cells account for a small percentage of lymphocytes, but have profound immunomodulatory roles in a variety of diseases [124]. There are two categories of NKT cells, type I and type II. Type I NKT cells, also known as invariant NKT cells (iNKT cells), express a semi-invariant Vα24-Jα18 (Vα14-Jα18 in mice), paired with a restricted range of β chains, that recognises α-galactosylceramide (α-GalCer) presented by CD1d [125, 126]. Type II NKT cells use TCRα and β chains that are reactive to a broad range of antigens, but do not recognise α-Galcer [127].
Nonobese diabetic (NOD) mice are susceptible to MOG-induced EAE. However, if NKT cells are increased either by transgenesis or adoptive transfer, the mice show protection from disease [128]. EAE protection has been correlated with inhibition of Ag-specific IFN-γ production in the spleen, modulating the encephalitogenic Th1 response [128]. There is conflicting evidence as to the effects of deletion of NKT cells on EAE. Some studies resulted in no effect on disease[129], with other studies showing disease exacerbation in CD1d-deficient and Jα18-deficient mice [130, 131]. Activation of type I NKT cells by α-GalCer has been shown to improve EAE outcome. These improvements arise by indirectly enhancing Th2 response and reducing the Th1 response, or potentiating the differential of immunosuppressive myeloid cells [131, 132, 133, 134]. However conflicting studies showed that high doses of α-GalCer could worsen EAE by directly enhancing Th17 and Th1 differentiation through phosphorylation of STAT3 and activation of NK-κB [135].
NKT cells from MS patients have been reported to have an increased production of cytokines. IL-4 production was increased by CD4 NKT cell clones in RRMS compared to other MS progression types, causing significant Th2 bias [136]. However, NKT cells in progressive MS patients displayed proinflammatory profiles [137]. It has also been suggested that the current available drugs for MS treatment may function through NKT cell targeting. A large reduction of type I NKT cells in peripheral blood was associated with remission of MS [136]. Type 1 interferon-β (T1IFN-β), a popular disease modifying therapy (DMT) for RRMS treatment, has been noted to promote expansion and functionality of type I NKT cells in vitro and to prevent disease in in vivo models of MS [138]. Research indicates a diverse role for NKT cells in MS pathology due to cytokine production.
Besides imbalances in cytokine levels in the CNS and cerebrospinal fluid (CSF), immune imbalances also occur in the blood of MS patients, as reflected by altered levels of cytokines and cytokine producing cells (reviewed in [139]). The cause of these imbalances are thought to be due to circulating monocytes, with monocytes and macrophages influencing early MS, mediating both pro and anti-inflammatory responses [140, 141].
Surface expression of CD14 and CD16 are used to distinguish three distinct monocyte subsets: classical (CD14++CD16−), intermediate (CD14++CD16+) and nonclassical (CD14+ CD16++) [142]. Monocytes and macrophages perform the key functions of antigen presentation and co-stimulation vital to the body’s immune response, with important roles in T and B cell activation and differentiation via the CD40-CD154 interaction (reviewed in [143]). Macrophages are primarily derived from blood borne monocytes, are present at sites of active demyelination in MS, and are assumed to be a part of the demyelinating process [144]. These inflammatory cells produce a range of toxic oxygen metabolites which mediate host tissue destruction. During MS progression, there is a significant expansion of the CD16+ monocyte population, which can primarily be attributed to nonclassical monocytes [145]. Depletion of these nonclassical monocytes may be an alternative to T and B cell depletion with the advantage of leaving the major classical monocyte population untouched. Selective subset depletion of monocytes may also supplement existing therapies to increase efficacy [145].
Multiple sclerosis is a complex autoimmune disease. Due to the many cell types involved in pathogenesis of the disease, therapeutics and treatments are often broad ranged and relatively inefficient. Further studies are necessary to uncover the genetic and environmental triggers leading to aberrant cellular toxicity and its role in MS pathogenesis. Discovering these and the related pathways will potentially lead to more targeted therapeutics and the elimination of not only MS but other autoimmune and neurological diseases in the future.
AMLW is supported by an Australian Government Research Training Program Stipend and MAJ was supported by an MS Research Australia/NHMRC Research Betty Cuthbert Fellowship. Project funds were obtained from Multiple Sclerosis Research Australia (MSRA), Lions’ club, Australia, and Australian Health Research Alliance-Women’s Health Research Translation Network (WHRTN).
The authors declare no conflict of interest.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. 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Costa",authors:null},{id:"399",doi:"10.5772/5035",title:"Cable-based Robot Manipulators with Translational Degrees of Freedom",slug:"cable-based_robot_manipulators_with_translational_degrees_of_freedom",totalDownloads:3763,totalCrossrefCites:14,totalDimensionsCites:21,abstract:null,book:{id:"6110",slug:"industrial_robotics_theory_modelling_and_control",title:"Industrial Robotics",fullTitle:"Industrial Robotics: Theory, Modelling and Control"},signatures:"Saeed Behzadipour and Amir Khajepour",authors:null},{id:"26941",doi:"10.5772/32809",title:"The Role of Haptics in Games",slug:"-the-role-of-haptics-in-gaming-experience-",totalDownloads:4729,totalCrossrefCites:16,totalDimensionsCites:21,abstract:null,book:{id:"624",slug:"haptics-rendering-and-applications",title:"Haptics Rendering and Applications",fullTitle:"Haptics Rendering and Applications"},signatures:"Mauricio Orozco, Juan Silva, Abdulmotaleb El Saddik and Emil Petriu",authors:[{id:"65724",title:"Dr.",name:"Abdulmotaleb",middleName:null,surname:"El Saddik",slug:"abdulmotaleb-el-saddik",fullName:"Abdulmotaleb El Saddik"},{id:"126984",title:"Prof.",name:"Emil",middleName:null,surname:"Petriu",slug:"emil-petriu",fullName:"Emil Petriu"},{id:"126985",title:"Dr.",name:"Mauricio",middleName:null,surname:"Orozco",slug:"mauricio-orozco",fullName:"Mauricio Orozco"},{id:"126986",title:"MSc.",name:"Juan",middleName:null,surname:"Silva",slug:"juan-silva",fullName:"Juan Silva"}]}],mostDownloadedChaptersLast30Days:[{id:"379",title:"Robot Kinematics: Forward and Inverse Kinematics",slug:"robot_kinematics__forward_and_inverse_kinematics",totalDownloads:51735,totalCrossrefCites:63,totalDimensionsCites:78,abstract:null,book:{id:"6110",slug:"industrial_robotics_theory_modelling_and_control",title:"Industrial Robotics",fullTitle:"Industrial Robotics: Theory, Modelling and Control"},signatures:"Serdar Kucuk and Zafer Bingul",authors:null},{id:"12134",title:"Anticipatory Mechanisms of Human Sensory-Motor Coordiantion Inspire Control of Adaptive Robots: a Brief Review",slug:"anticipatory-mechanisms-of-human-sensory-motor-coordination-inspire-control-of-adaptive-robots-a-bri",totalDownloads:3564,totalCrossrefCites:1,totalDimensionsCites:2,abstract:null,book:{id:"3658",slug:"robot-learning",title:"Robot Learning",fullTitle:"Robot Learning"},signatures:"Alejandra Barrera",authors:null},{id:"39423",title:"Output Tracking Control for Fuzzy Systems via Static-Output Feedback Design",slug:"output-tracking-control-for-fuzzy-systems-via-static-output-feedback-design",totalDownloads:2319,totalCrossrefCites:1,totalDimensionsCites:2,abstract:null,book:{id:"2229",slug:"fuzzy-controllers-recent-advances-in-theory-and-applications",title:"Fuzzy Controllers",fullTitle:"Fuzzy Controllers - Recent Advances in Theory and Applications"},signatures:"Meriem Nachidi and Ahmed El Hajjaji",authors:[{id:"25659",title:"Prof.",name:"Ahmed",middleName:null,surname:"El Hajjaji",slug:"ahmed-el-hajjaji",fullName:"Ahmed El Hajjaji"},{id:"141360",title:"Dr.",name:"Meriem",middleName:null,surname:"Nachidi",slug:"meriem-nachidi",fullName:"Meriem Nachidi"}]},{id:"51207",title:"Human Movement Control",slug:"human-movement-control",totalDownloads:2125,totalCrossrefCites:0,totalDimensionsCites:2,abstract:"Control theory is used to design automatic systems, which are able to maintain a desired behaviour despite of the disturbances. It is present in different machines we use every day; in fact, technical systems in our homes and all the industries are hard to imagine today without these concepts. Moreover, the same theories can be used for modelling life processes as a collection of inputs, outputs, plants and control loops. Feedback is one of the main concepts behind control; in particular, several examples of physiological control mechanisms for regulating life aspects can be found in the human anatomy, for example, blood pressure, cholesterol levels, body movements, the equilibrium, etc. Those processes can be damaged by the aging effects, diseases, accidents or when the mechanism has been broken and cannot be recovered naturally; consequently, it will be required external assistance. A relative new field in control theory is related with developing technology for helping with physiological and medicals problems. However, in comparison with machines, those physiological processes are highly nonlinear, with delays and slow responses. Another problem is when human becomes the operators using their capacities of decision making to close the control loop, as they are prone to errors and mistakes. For those reasons, the biomedical system needs to be carefully designed and several aspects have to be considered. This chapter gives a small review of some internal and external control processes within the human body and discusses how to interact with them for designing biomedical devices. Under this design scheme, a practical application of a smart electric wheelchair for assisting persons with strong disabilities is presented. These assistive robotic systems are in close contact with the user, and thus, it is determinant to have a user-friendly relation between the human and the interface. Therefore, intuitive interfaces were included in the design and an intelligent navigation assistant to guarantee a collision-free path.",book:{id:"5238",slug:"automation-and-control-trends",title:"Automation and Control Trends",fullTitle:"Automation and Control Trends"},signatures:"David Balderas and Mario Rojas",authors:[{id:"183076",title:"M.Sc.",name:"David",middleName:null,surname:"Balderas Silva",slug:"david-balderas-silva",fullName:"David Balderas Silva"},{id:"184877",title:"MSc.",name:"Mario",middleName:null,surname:"Rojas",slug:"mario-rojas",fullName:"Mario Rojas"}]},{id:"51070",title:"Fuzzy PD Controller in NAO System's Platform",slug:"fuzzy-pd-controller-in-nao-system-s-platform",totalDownloads:1587,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Humanoid robotic platforms rarely achieve the desire trajectory because of the deviation generated during the robot walking. This problem is due to different circumstances such as robot manufacturing, wear and tear of mechanic parts, or variations of floor flatness. Currently, one of the humanoid robots on the market is the robotic platform developed by Aldebaran Robotics called NAO robot, and it is used for different purposes where the robot needs to navigate into controlled spaces. NAO presents the issue of deviation during walking; therefore, a Fuzzy PD Controller is developed and implemented for this platform to reduce the orientation error and to ensure reliability during navigation. Inertial sensors are used to get the orientation reference and for feedback of the closed-loop control. Consequently, a robust control was implemented and tested in different conditions of floor and velocity during the robot’s navigation such as robot races and maze resolution. Experimental results show that fuzzy controller achieves significant improvements in the trajectories of NAO.",book:{id:"5238",slug:"automation-and-control-trends",title:"Automation and Control Trends",fullTitle:"Automation and Control Trends"},signatures:"Edgar Omar López‐Caudana and César Daniel González Gutiérrez",authors:[{id:"26464",title:"Dr.",name:"Edgar",middleName:"Omar",surname:"Lopez-Caudana",slug:"edgar-lopez-caudana",fullName:"Edgar Lopez-Caudana"},{id:"185936",title:"Mr.",name:"César Daniel",middleName:null,surname:"González Gutiérrez",slug:"cesar-daniel-gonzalez-gutierrez",fullName:"César Daniel González Gutiérrez"}]}],onlineFirstChaptersFilter:{topicId:"257",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:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,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:106,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:3,numberOfUpcomingTopics:0,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:15,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. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"June 29th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:32,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:36,paginationItems:[{id:"82195",title:"Endoplasmic Reticulum: A Hub in Lipid Homeostasis",doi:"10.5772/intechopen.105450",signatures:"Raúl Ventura and María Isabel Hernández-Alvarez",slug:"endoplasmic-reticulum-a-hub-in-lipid-homeostasis",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"82409",title:"Purinergic Signaling in Covid-19 Disease",doi:"10.5772/intechopen.105008",signatures:"Hailian Shen",slug:"purinergic-signaling-in-covid-19-disease",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82374",title:"The Potential of the Purinergic System as a Therapeutic Target of Natural Compounds in Cutaneous Melanoma",doi:"10.5772/intechopen.105457",signatures:"Gilnei Bruno da Silva, Daiane Manica, Marcelo Moreno and Margarete Dulce Bagatini",slug:"the-potential-of-the-purinergic-system-as-a-therapeutic-target-of-natural-compounds-in-cutaneous-mel",totalDownloads:10,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82103",title:"The Role of Endoplasmic Reticulum Stress and Its Regulation in the Progression of Neurological and Infectious Diseases",doi:"10.5772/intechopen.105543",signatures:"Mary Dover, Michael Kishek, Miranda Eddins, Naneeta Desar, Ketema Paul and Milan Fiala",slug:"the-role-of-endoplasmic-reticulum-stress-and-its-regulation-in-the-progression-of-neurological-and-i",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}}]},overviewPagePublishedBooks:{paginationCount:32,paginationItems:[{type:"book",id:"7006",title:"Biochemistry and Health Benefits of Fatty Acids",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7006.jpg",slug:"biochemistry-and-health-benefits-of-fatty-acids",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Viduranga Waisundara",hash:"c93a00abd68b5eba67e5e719f67fd20b",volumeInSeries:1,fullTitle:"Biochemistry and Health Benefits of Fatty Acids",editors:[{id:"194281",title:"Dr.",name:"Viduranga Y.",middleName:null,surname:"Waisundara",slug:"viduranga-y.-waisundara",fullName:"Viduranga Y. 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Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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