The comparison between ACE and ACE2 is given in Table 1 [22, 23, 24, 25, 26].
\\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:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{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"}]},book:{item:{type:"book",id:"5967",leadTitle:null,fullTitle:"Brewing Technology",title:"Brewing Technology",subtitle:null,reviewType:"peer-reviewed",abstract:"Many alcoholic beverages produced using various methods are consumed throughout the world. Alcoholic beverages made by brewing cereals, such as beer and Japanese sake, are extremely popular. Brewing them requires a complicated process by which the cereal must be saccharified using enzymes such as amylase. For example, with beer brewing, malt enzymes are used for saccharification. By germination, malt is made from barley to produce enzymes. Finally, wort is made by processing at higher temperatures using malt. The actual techniques require high-level skills. In this book, the discussion encompasses leading-edge brewing technology with fermentation using a non-Saccharomyces starter, healthy uses of spent grain from brewing processes, and an electronic nose for quality control, but it also includes descriptions of local traditional alcoholic beverages of Korea and Cameroon.",isbn:"978-953-51-3342-1",printIsbn:"978-953-51-3341-4",pdfIsbn:"978-953-51-4732-9",doi:"10.5772/66269",price:119,priceEur:129,priceUsd:155,slug:"brewing-technology",numberOfPages:210,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"033658c083403dadc895cf64dee8017a",bookSignature:"Makoto Kanauchi",publishedDate:"July 19th 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5967.jpg",numberOfDownloads:20110,numberOfWosCitations:64,numberOfCrossrefCitations:45,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:94,numberOfDimensionsCitationsByBook:2,hasAltmetrics:1,numberOfTotalCitations:203,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 10th 2016",dateEndSecondStepPublish:"December 1st 2016",dateEndThirdStepPublish:"February 27th 2017",dateEndFourthStepPublish:"May 28th 2017",dateEndFifthStepPublish:"July 27th 2017",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"85984",title:"Ph.D.",name:"Makoto",middleName:null,surname:"Kanauchi",slug:"makoto-kanauchi",fullName:"Makoto Kanauchi",profilePictureURL:"https://mts.intechopen.com/storage/users/85984/images/5858_n.jpg",biography:"Makoto Kanauchi is a professor in the Department of Food Management, Miyagi University. He has been in the Department of Food Management, Miyagi University, since April 2005. Earlier, he was employed at the Institute of Food Science in Fuji Oil Corporation in Moriya, Ibaraki, Japan, as a researcher (August 2003–March 2005). Dr. Kanauchi also worked in Prof. Charlie Bamforth’s Laboratory in Food Science and Technology, University of California, Davis, California (November 1999–May 2003). In March 1999, he received his PhD degree in Bio-regulation from Tokyo University of Agriculture. Dr. Kanauchi received his MS degree in Brewing and Fermentation Science in March 1996 and graduated from Tokyo University of Agriculture in Tokyo, Japan.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Miyagi University",institutionURL:null,country:{name:"Japan"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"804",title:"Process Engineering",slug:"industrial-engineering-and-management-process-engineering"}],chapters:[{id:"55288",title:"Narrow Leaf Mutants in the Grass Family",doi:"10.5772/intechopen.68794",slug:"narrow-leaf-mutants-in-the-grass-family",totalDownloads:1763,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Leaf morphology is critical for the survival of plant species. After a leaf primordium is initiated at the flank of shoot apical meristem (SAM), the development along the medial‐lateral direction enlarges the leaf‐blades, leading to the increase of photosynthetic activities. Thus, the revelation of mechanisms that control development across a leaf is quite important for plant breeding. A variety of narrow leaf mutants have been identified in the grass family, which includes particularly important crops in the world. Here, the molecular mechanisms underlying the leaf development in the medial‐lateral direction are discussed as we introduce the three major groups of narrow leaf mutants in the grass family: (1) auxin‐related mutants, (2) cellulose synthase‐like D (CSLD)‐related mutants, and (3) polarity‐related mutants. The results obtained from these analyses could be directly applied to the breeding of major cereal crops such as maize, rice, and barley; therefore, they could contribute to the increase of food production.",signatures:"Takanori Yoshikawa and Shin Taketa",downloadPdfUrl:"/chapter/pdf-download/55288",previewPdfUrl:"/chapter/pdf-preview/55288",authors:[{id:"202026",title:"Dr.",name:"Takanori",surname:"Yoshikawa",slug:"takanori-yoshikawa",fullName:"Takanori Yoshikawa"},{id:"205913",title:"Prof.",name:"Shin",surname:"Taketa",slug:"shin-taketa",fullName:"Shin Taketa"}],corrections:null},{id:"56077",title:"Oxidative Enzyme Effects in Malt for Brewing",doi:"10.5772/intechopen.69803",slug:"oxidative-enzyme-effects-in-malt-for-brewing",totalDownloads:1776,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Malted barley is an important beer‐brewing material that strongly affects brewing processes, the aroma, and the taste of beer. In addition to imparting a good aroma, malt not only generates substrates and enzymes, such as starches and some amylase, for alcohol production but also generates beer‐quality‐degrading substances and enzymes. Four oxidases are specifically addressed in this chapter. First, thiol oxidase in malt is described. The activity of thiol oxidase decreases during malt storage. Next, ascorbate peroxidase was investigated. It has been detected in the acrospires and aleurones of germinating barley. The enzyme has extremely high affinity for hydrogen peroxide. Also, ascorbic acid oxidase (AAO) was investigated. It is developed in the embryo tissues of barley during steeping and during the initial stages of germination. The addition of ascorbic acid to mash leads to the survival of higher levels of polyphenol and thiols into wort and a reduced color in that wort. Finally, oxalate oxidase in barley kernels is described. It is probably less important than other oxidases in scavenging oxygen from mashes, because the enzyme has low affinity for oxygen. Beer quality is expected to be improved by the regulation of oxidant enzymes, such as thiol oxidase or AAO, oxalate oxidase, or substrates, such as oxygen.",signatures:"Makoto Kanauchi",downloadPdfUrl:"/chapter/pdf-download/56077",previewPdfUrl:"/chapter/pdf-preview/56077",authors:[{id:"85984",title:"Ph.D.",name:"Makoto",surname:"Kanauchi",slug:"makoto-kanauchi",fullName:"Makoto Kanauchi"}],corrections:null},{id:"54903",title:"Barley (Hordeum vulgare L.) Improvement Past, Present and Future",doi:"10.5772/intechopen.68359",slug:"barley-hordeum-vulgare-l-improvement-past-present-and-future",totalDownloads:2012,totalCrossrefCites:4,totalDimensionsCites:7,hasAltmetrics:0,abstract:"Barley has been cultivated for more than 10,000 years. Barley improvement studies always have the privilege of the breeders and scientists. This review is expected to provide a resource for researchers interested in barley improvement research in terms of mutation breeding, tissue culture, gene transfers, gene editing, molecular markers, transposons, epigenetic, genomic studies and system biology. We aimed to discuss some important and/or recent studies and improvements about barley for understanding the factors responsible for converting barley plants into the superior cereals, which occurred through gene transfers, gene editing and molecular breeding, which is important and could help us enhance the current pool of cultivated barley species to provide enough material for the future.",signatures:"Nermin Gozukirmizi and Elif Karlik",downloadPdfUrl:"/chapter/pdf-download/54903",previewPdfUrl:"/chapter/pdf-preview/54903",authors:[{id:"185345",title:"Dr.",name:"Nermin",surname:"Gozukirmizi",slug:"nermin-gozukirmizi",fullName:"Nermin Gozukirmizi"},{id:"201910",title:"MSc.",name:"Elif",surname:"Karlik",slug:"elif-karlik",fullName:"Elif Karlik"}],corrections:null},{id:"55278",title:"Saccharomyces and Non-Saccharomyces Starter Yeasts",doi:"10.5772/intechopen.68792",slug:"saccharomyces-and-non-saccharomyces-starter-yeasts",totalDownloads:2368,totalCrossrefCites:9,totalDimensionsCites:18,hasAltmetrics:0,abstract:"This chapter describes the importance of yeast in beer fermentation. Initially, the differences between Saccharomyces cerevisiae and Saccharomyces pastorianus in the production of “ale” and “lager” beers are analyzed. Then, the relationships between beer nutrients and yeast growth are discussed, with special emphasis on the production of the flavor compounds. The impact of the wort composition on flocculation is also discussed. Furthermore, conventional approaches to starter yeast selection and the development of genetically modified microorganisms are analyzed. Recent discoveries relating to the use of S. cerevisiae strains isolated from different food matrices (i.e., bread and wine) and the potential for the use of non-Saccharomyces starter strains in beer production are discussed. A detailed review of the selection of starter strains for the production of specialty beers then follows, such as for gluten-free beers and biologically aged beers. Yeast recovery from top-cropping and bottom-cropping systems and the methodologies and issues in yeast propagation in the laboratory and brewery (i.e., re-pitching) are also analyzed. Finally, the available commercial preparations of starter yeast and the methods to evaluate yeast viability prior to inoculation of the must are analyzed.",signatures:"Marilena Budroni, Giacomo Zara, Maurizio Ciani and Francesca\nComitini",downloadPdfUrl:"/chapter/pdf-download/55278",previewPdfUrl:"/chapter/pdf-preview/55278",authors:[{id:"201812",title:"Prof.",name:"Marilena",surname:"Budroni",slug:"marilena-budroni",fullName:"Marilena Budroni"},{id:"202915",title:"Dr.",name:"Giacomo",surname:"Zara",slug:"giacomo-zara",fullName:"Giacomo Zara"},{id:"206674",title:"Prof.",name:"Maurizio",surname:"Ciani",slug:"maurizio-ciani",fullName:"Maurizio Ciani"},{id:"206675",title:"Prof.",name:"Francesca",surname:"Comitini",slug:"francesca-comitini",fullName:"Francesca Comitini"}],corrections:null},{id:"55582",title:"Use of Non-Saccharomyces Yeasts in Bottle Fermentation of Aged Beers",doi:"10.5772/intechopen.68793",slug:"use-of-non-saccharomyces-yeasts-in-bottle-fermentation-of-aged-beers",totalDownloads:2391,totalCrossrefCites:8,totalDimensionsCites:14,hasAltmetrics:1,abstract:"Bottle fermented and brewed beers are reaching more recognition in present days due to their high sensory complexity. These beers normally are produced by an initial tank fermentation to metabolize the sugars obtaining the typical alcoholic degree, and later the foam and CO2 pressure is produced by subsequent bottle fermentation. The sensory profile is improved by the formation of some fermentative volatiles, but also by the ageing on lees, because beers are brewed during several months with the yeast cells that performed the fermentation. The use of non-Saccharomyces yeast is a trending topic in many fermentative food industries (wines, beer, bread, etc.). They open new possibilities to modulate flavor and other sensory properties during fermentation and biological ageing. This chapter review the effect of some non-Saccharomyces yeasts such as Schizosaccharomyces pombe, Torulaspora delbrueckii, Lachancea thermotolerans, Saccharomycodes ludwigii, and Brettanomyces bruxellensis in the bottle fermentation and brewing of beers analyzing their metabolic specificities and sensory contribution on beer taste.",signatures:"María Jesús Callejo, Carmen González and Antonio Morata",downloadPdfUrl:"/chapter/pdf-download/55582",previewPdfUrl:"/chapter/pdf-preview/55582",authors:[{id:"180952",title:"Prof.",name:"Antonio",surname:"Morata",slug:"antonio-morata",fullName:"Antonio Morata"},{id:"201383",title:"Prof.",name:"María Jesús",surname:"Callejo",slug:"maria-jesus-callejo",fullName:"María Jesús Callejo"},{id:"201384",title:"Prof.",name:"Carmen",surname:"González",slug:"carmen-gonzalez",fullName:"Carmen González"}],corrections:null},{id:"56133",title:"Concept of Nuruk on Brewing Technology",doi:"10.5772/intechopen.69380",slug:"concept-of-nuruk-on-brewing-technology",totalDownloads:2094,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Nuruk is a traditional Korean fermentation starter that is used to produce starch-based alcoholic beverages using various cereals as raw material. As a determinant factor for flavor, taste, and color of alcoholic beverages, Nuruk is an indispensable ingredient for brewing alcoholic beverages in Korea. Nuruk shows significant variation in the shape, and in the brewing and fermentation methods, which are dependent on the unique climate in each area. Therefore, it is worthy to note that the characteristics of Korean traditional Nuruk are based on its diversity. Thus, this chapter is aimed to scientifically identify the characteristics of traditional Nuruk on brewing technology. In this chapter, the concept of Nuruk will be discussed in terms of its history, production, microorganism diversity, and enzymatic function.",signatures:"Jang-Eun Lee and Jae-Ho Kim",downloadPdfUrl:"/chapter/pdf-download/56133",previewPdfUrl:"/chapter/pdf-preview/56133",authors:[{id:"201205",title:"Dr.",name:"Jang Eun",surname:"Lee",slug:"jang-eun-lee",fullName:"Jang Eun Lee"},{id:"204620",title:"Dr.",name:"Jae-Ho",surname:"Kim",slug:"jae-ho-kim",fullName:"Jae-Ho Kim"}],corrections:null},{id:"55749",title:"Exploitation of Brewing Industry Wastes to Produce Functional Ingredients",doi:"10.5772/intechopen.69231",slug:"exploitation-of-brewing-industry-wastes-to-produce-functional-ingredients",totalDownloads:3824,totalCrossrefCites:16,totalDimensionsCites:34,hasAltmetrics:1,abstract:"Nowadays, the consumers’ global demand for healthier diets is steadily increasing, and the development of novel functional ingredients has become a focus of the food industry. On the other hand, the accumulation of huge amounts of food wastes every year has led to environmental degradation and especially to significant loss of valuable material that could otherwise be exploited as new health-promoting ingredients, fuels and a great variety of additives. In this respect, the biggest challenge of the current scientific world is to convert the underutilised by-products generated by the food and beverage industries into more profitable and marketable added value products which would also contribute significantly to meet the nowadays society needs. This chapter gives an overview regarding the possibility of exploiting the brewing industry wastes as sources of bioactive compounds in order to produce functional ingredients and products with added value.",signatures:"Anca Corina Fărcaş, Sonia Ancuța Socaci, Elena Mudura, Francisc\nVasile Dulf, Dan C. Vodnar, Maria Tofană and Liana Claudia Salanță",downloadPdfUrl:"/chapter/pdf-download/55749",previewPdfUrl:"/chapter/pdf-preview/55749",authors:[{id:"191241",title:"Ph.D.",name:"Sonia A.",surname:"Socaci",slug:"sonia-a.-socaci",fullName:"Sonia A. Socaci"},{id:"191607",title:"Ph.D.",name:"Anca C.",surname:"Fărcaş",slug:"anca-c.-farcas",fullName:"Anca C. Fărcaş"},{id:"192098",title:"Prof.",name:"Maria",surname:"Tofana",slug:"maria-tofana",fullName:"Maria Tofana"},{id:"192177",title:"Dr.",name:"Dan Cristian",surname:"Vodnar",slug:"dan-cristian-vodnar",fullName:"Dan Cristian Vodnar"},{id:"194168",title:"Dr.",name:"Francisc Vasile",surname:"Dulf",slug:"francisc-vasile-dulf",fullName:"Francisc Vasile Dulf"},{id:"203096",title:"Dr.",name:"Elena",surname:"Mudura",slug:"elena-mudura",fullName:"Elena Mudura"},{id:"203097",title:"Dr.",name:"Liana Claudia",surname:"Salanta",slug:"liana-claudia-salanta",fullName:"Liana Claudia Salanta"}],corrections:null},{id:"56040",title:"Traditional Processing and Quality Control of the “Red Kapsiki”: A Local Sorghum Beer from Northern Cameroon",doi:"10.5772/intechopen.69595",slug:"traditional-processing-and-quality-control-of-the-red-kapsiki-a-local-sorghum-beer-from-northern-cam",totalDownloads:1608,totalCrossrefCites:1,totalDimensionsCites:5,hasAltmetrics:0,abstract:"This study was propose to elucidate the traditional process production, biochemical, and microbiological parameters of the “red kapsiki” beer locally called “Te.” Direct interviews are conducted on the basis of questionnaires in four localities of the Far‐North region of Cameroon. At each site, beer samples are collected, labeled, and undergo physicochemical and microbiological analyses using standardized methods. The results show that the traditional “red kapsiki” beer process incorporates a malting step, a large brewing stage, and a final fermentation step which requires a starter. The biochemical parameters of the beer samples show a pH value ranging from 2.40 ± 0.19 to 3.26 ± 0.03 (pH < 4.5), an alcohol content between 3.85 ± 0.58 and 4.28 ± 0.78% (v/v), a soluble extract which varies from 6.30 ± 1.09 to 7.29 ± 0.26 °P, a total sugar content which fluctuates between 41.8 ± 0.39 and 72.9 ± 0.40 g/L. In addition, the “red kapsiki” beer shows a total polyphenol content between 843 ± 27 and 1150 ± 27 mg/L and a flavonol level fluctuating between 750 ± 23 and 1300 ± 27 mg/L. Microbial analyses show a poor hygienic quality according to Cameroon standards referenced on the French Agency Norms.",signatures:"Bayoï James Ronald and Djoulde Darman Roger",downloadPdfUrl:"/chapter/pdf-download/56040",previewPdfUrl:"/chapter/pdf-preview/56040",authors:[{id:"151333",title:"Dr.",name:"Djoulde Darman",surname:"Roger",slug:"djoulde-darman-roger",fullName:"Djoulde Darman Roger"},{id:"205707",title:"Dr.",name:"Bayoï",surname:"James Ronald",slug:"bayoi-james-ronald",fullName:"Bayoï James Ronald"}],corrections:null},{id:"55333",title:"Electronic Noses Applications in Beer Technology",doi:"10.5772/intechopen.68822",slug:"electronic-noses-applications-in-beer-technology",totalDownloads:2278,totalCrossrefCites:6,totalDimensionsCites:14,hasAltmetrics:0,abstract:"This chapter describes and explains in detail the electronic noses (e-noses) as devices composed of an array of sensors that measure chemical volatile compounds and apply classification or regression algorithms. Then, it reviews the most significant applications of such devices in beer technology, with examples about defect detection, hop classification, or beer classification, among others. After the review, the chapter illustrates two applications from the authors, one about beer classification and another about beer defect detection. Finally, after a comparison with other analytical techniques, the chapter ends with a summary, conclusions, and the compelling future of the e-noses applied to beer technology.",signatures:"José Pedro Santos, Jesús Lozano and Manuel Aleixandre",downloadPdfUrl:"/chapter/pdf-download/55333",previewPdfUrl:"/chapter/pdf-preview/55333",authors:[{id:"202750",title:"Dr.",name:"José Pedro",surname:"Santos",slug:"jose-pedro-santos",fullName:"José Pedro Santos"},{id:"202993",title:"Dr.",name:"Jesús",surname:"Lozano",slug:"jesus-lozano",fullName:"Jesús Lozano"},{id:"202994",title:"Dr.",name:"Manuel",surname:"Aleixandre",slug:"manuel-aleixandre",fullName:"Manuel Aleixandre"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"3205",title:"Design of Experiments",subtitle:"Applications",isOpenForSubmission:!1,hash:"e6e565e76cb1acf4a86290f16c750331",slug:"design-of-experiments-applications",bookSignature:"Messias Borges Silva",coverURL:"https://cdn.intechopen.com/books/images_new/3205.jpg",editedByType:"Edited by",editors:[{id:"136723",title:"Dr.",name:"Messias",surname:"Borges Silva",slug:"messias-borges-silva",fullName:"Messias Borges Silva"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. 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Mesothelioma is known for strong association with asbestos exposure, difficult surgical treatment and dismal prognosis. However, recent years have yielded significant discoveries, e.g., on germline mutations in BAP1 gene coding BRCA1-associated protein 1, pathogenetic role of inflammation, and innovative treatment approaches like immune checkpoint blockers and PARP inhibitors. The current book intends to summarise the classic concepts and innovations in the diagnostics, treatment and scientific studies of mesothelioma, resulting in a comprehensive reference for clinicians as well as a source of ideas for relevant clinical and basic research. We welcome high-quality original studies, meta-analyses and literature reviews. Case reports are encouraged as an attractive form of scientific article, preferably supplemented by a scientifically sound literature review ensuring a representative insight in the given pathology.
\r\n\r\n\tThe topics broadly include but are not limited to:
\r\n\r\n\t1) Epidemiology and legal aspects of mesothelioma: global and regional incidence and mortality, epidemiological time trends and geographic variations, local experience, limitations and bias affecting diagnostics and coding of mesothelioma, asbestos-related legislation, historical use of asbestos.
\r\n\t2) Causes of mesothelioma: asbestos, asbestiform fibres, non-asbestos causes, germline mutations of BAP1, mismatch repair genes, TP53, BRCA2 and other genes, gene-environment interaction in mesothelioma.
\r\n\t3) Pathogenesis of mesothelioma: asbestos-induced cytotoxicity, role of local inflammation, including M2 macrophages and/or reactive oxygen species among other mechanisms, markers of systemic inflammation (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, Glasgow Prognostic Score etc.), BAP1-related molecular pathways, other genetic and epigenetic alterations, miRNAs, stemness, tumour microenvironment and hypoxia.
\r\n\t4) Radiology in diagnostics and staging of mesothelioma: computed tomography, positron emission tomography and magnetic resonance imaging.
\r\n\t5) Tissue-based diagnostics of mesothelioma: cytology, histology and immunohistochemistry, informativity and limitations of the relevant methods, markers for differential diagnosis between benign versus malignant mesothelial cells and primary versus metastatic neoplasms in pleura or peritoneum, diagnostic protocols and algorithms, future developments via digital pathology, machine-based learning etc.
\r\n\t6) Clinical and histological features of BAP1-associated mesothelioma.
\r\n\t7) Liquid biopsy in mesothelioma: proteins, miRNAs, CTC, ctDNA etc.
\r\n\t8) Staging and prognosis of mesothelioma: state of the art, techniques and limitations of current staging systems, survival and prognostic factors, long-term survival.
\r\n\t9) Surgical management of mesothelioma: benefits and controversies of extrapleural pneumonectomy, pleurectomy/decortication (P/D) and extended P/D.
\r\n\t10) Systemic chemotherapy, immune checkpoint inhibitors, BAP1-pathway-targeting agents, PARP inhibitors and other innovations, mechanisms of chemoresistance in mesothelioma.
\r\n\t11) Radiotherapy.
\r\n\t12) Intracavitary chemo- and/or photodynamic therapy.
\r\n\t13) Peritoneal mesothelioma (PM): cytoreductive surgery, hyperthermic intraperitoneal chemotherapy and early postoperative intraperitoneal chemotherapy.
\r\n\t14) Rare locations and histological types: pericardiac mesothelioma, multicystic mesothelioma etc.
\r\n\t15) Mesothelioma in wild and domestic animals.
\r\n\t16) Communication and support: communicating diagnosis to the patient, palliative treatment, nutritional maintenance and psychological support.
Globalization is about the interconnectedness of people and businesses across the world that eventually leads to global cultural, political and economic integration. It is the ability to move and communicate easily with others all over the world in order to conduct business internationally. The word, globalization, is relatively new, coined in the late 1970’s. The airplane, the telephone, and the Internet are just three inventions, which are attributable to the spread of globalization. Due to the increased demand in the high tech industry around the world, business and industry have potential for huge profits working globally. So in today’s world, globalization is an important concept for students in higher education to understand and appreciate because of the demand in business and industry to hire people who can work with people of other nations and cultures and if need be can travel independently internationally to promote their business or industry. In addition, the world faces global challenges that will take interdisciplinary groups to solve these challenges; providing access to clean water for everyone on this planet and making clean renewable energy affordable just to name a few. These global challenges will need to be solved through the gathering and sharing of knowledge across disciplines, institutions, and other entities institutions on a global scale. Creating meaningful relationships that work globally is in itself challenging. In this chapter, we will look at global challenges, the makeup of model collaborative international teams; the importance of teaching globalization in higher education, how to best teach globalization, and discuss best practices in this area.
How did our world become so global? In a book titled,
11/9/89 -The New Age of Creativity: When the Walls Came Down and the Windows Went Up
8/9/95 The New Age of Connectivity: When the Web Went Around and Netscape Went Public
Work Flow Software
Uploading: Harnessing the Power of Communities
Outsourcing and Y2K
Offshoring: Running with Gazelles, Eating with Lions
Supply Chaining --Eating Sushi in Arkansas
Insourcing --What the Guys in the Funny Brown Shorts Are Really Doing
In-Forming --Google, Yahoo, MSN Web Search
The Steroids—Digital, Mobile, Personal and Virtual.
The first force to flatten the world was on 11/9/89, the fall of the Berlin Wall. Freidman calls this, The New Age of Creativity: When the Walls Came Down and the Windows Went Up. While the fall of the Wall liberated the Soviet citizens, it changed the balance of power towards democratic, free market government from authoritarian rule with central planned economies. In addition, there were ripple effects felt all over the world from the fall of the Wall one of those places was India. In 1991, India abolished trade controls after years of being almost bankrupt and then it started to prosper and grow all because of the fall of the Wall. Around the same time, May 22, 1990, IBM shipped Windows 3.0, a breakthrough version that made PCs easier to use. This version allowed millions of people for the first time to be authors of their own content in digital form, and share their content with others. As the Berlin Wall went down, Window went up. Freidman say, “The fall of the Berlin Wall didn’t just help flatten the alternatives to free-market capitalism and unlock enormous pent-up energies for hundreds of millions of people in places like India, Brazil, China, and former Soviet Empire. It allowed us to think about the world differently—to see it as more of a seamless whole. Because the Berlin Wall was not only blocking our way; it was blocking our sight—our ability to think about the world differently—to see it more as a seamless whole” (Freidman, 2007, pg. 54).
The second flattener of the world according to Freidman was 8/9/95 The New Age of Connectivity: When the Web Went Around and Netscape Went Public. The Internet was developed by Tim Berners-Lee in 1991, a British Computer Scientist. However, the Internet alone was not enough to manage the second flattening. The Internet coupled with Netscape, which went public in 1995, was the second flattener. Netscape made the Internet accessible to almost everyone. Fifteen days after Netscape was released, Windows 95 was released as the first operating system with a built-in Internet support system (Freidman, 2007).
The third world flattener was Work Flow Software as demonstrated by a company named Wild Brain, which makes animated movies. This company has been taking advantage of the flattened world by making animated films through a global supply chain. To see how this works, look at an example of one show called,
Uploading: Harnessing the Power of Communities was Freidman’s fourth world flattener. Apache is an open-source web tool that allows a single server machine to host thousands of different virtual websites—music, data, text or anything. Apache proved to be an excellent product that was developed by a group of computer geeks who gave it away for free. IBM couldn’t design anything better so it decided to join the group. IBM made a deal to help form a legal structure for Apache so there would be no copyright issues in using other products developed to be used with Apache. IBM’s buy-in also indicated to the computer community that this new way of building software that was trustworthy and valuable. In another example, a 19 year old from Stanford and a 24 year old from New Zealand developed Firefox 1.0 as an open-source community software for free in 2004 (Freidman, 2007). Freidman said, “…. the reason, I think community-developed software is also here to stay is that while it may not be sustainable without an economic incentive at some point, as a sheer tool for making breakthroughs and spreading those breakthroughs virally, it has proved to be very powerful” (2007, pg.111).
Freidman’s fifth world flatteners are Outsourcing and Y2K. By the late 1990’s, good things started happening in India; first the fiber optic cable linking India and the United States was exploding and the Y2K was on the horizon for January 1, 2000. The Y2K centered on a bug in computers and their internal clocks. When computers were first built to save memory space, internal clocks had two digits for the month, two digits for the day, and two digits for the year. So the issue with Y2K was that these internal clocks would mess up the entire computer because it could not go forward to the year 2000. America and India started having a relationship in a sense that started the huge flattener because with the fiber optic cable and the Internet this created a collaborative value added sources, so that businesses could source globally to the cheapest and smartest location, thus the relationship between India and America strengthened. The Y2K computer problem was fixed by low cost Indian labor and thus also a relationship between American business and Indian IT companies had been established. Therefore, the cheaper very good Indian IT companies prospered from these two events, the fiber optic networks and Y2K. Freidman said, “ …I believe that Y2K should be a national holiday in India, a second Indian Independence Day, in addition to August 15. …. because it was India’s ability to collaborate with Western companies, thanks to the interdependence created by fiber-optic networks, that really vaulted it forward and gave more Indians than ever some real freedom of choice in how, for whom and where they worked’’ (2007, pg.136).
Freidman’s sixth flattener of the world was Offshoring: Running with Gazelles, Eating with Lions. China joined the World Trade Organization (WTO) on December 11, 2001. They agreed to follow the same global rules governing imports, exports and foreign investments that other WTO countries in the world were following. This opened China up for a huge influx of companies working inside of China. Offshoring is when a company takes a whole factory and relocates it to another country (offshore). An example of offshoring is when, a whole factory moves from Fargo, North Dakota to Canton, China where it would produce the exact same product in the same way only much cheaper. Outsourcing is unlike offshoring, which is taking just one part of a business; for example, accounts receivable and having another company perform the exact same functions for a much cheaper cost, which the original company was doing in-house and reintegrating their work back into the original company’s operation. By China joining the WTO, China ultimately became a challenge to the whole world with its mass of low-wage unskilled and semi-skilled workers. Other poor countries like Malaysia, Thailand, Ireland, Mexico, Brazil and Vietnam have to compete for better tax breaks, subsidies, and other factors to encourage offshoring to their shores. Another problem that exists is workplace standards, lax labor laws, and low wages just to name a few. In talking about offshoring, Freidman tells a story about a friend of his who is an American-trained Chinese manager of a fuel pump factory in Beijing. Shortly after China joined the WTO, his friend posted the following proverb from Africa translated into Mandarin on the factory floor:
When the sun comes up, you better start running (Freidman, 2007).
Friedman concludes by saying, “…. if Americans and Europeans want to benefit from the flattening of the world and the interconnecting of all the markets and knowledge centers, they will all have to run at least as fast as the fastest lion—and I suspect that lion will be China, and I suspect that will be pretty darn fast” (2007, pgs.150-151).
Freidman’s seventh flattener was Supply-Chaining – Eating Sushi in Arkansas. Wal-Mart is undoubtedly the largest retail company in the world and it does not manufacture a single product it sells. At Wal-Mart’s headquarters in Bentonville, Arkansas they have a 1.2 million square foot distribution center that has a sophisticated global supply chain. This supply chain moves 2.3 million general merchandise cartons a year down its supply chain and into its stores. As one box gets transported through the supply chain, the engineering system keeps track of it coming in, where it is needed, if it needs to be supplied again, and if it does it sends the order in all automatically. Supply chaining allows suppliers, retailers, and customers to create value by collaborating horizontally. Supply chaining also forces common standards between companies so that every process can interface with the next. These types of global supply chains have become important all over the world, the challenges are global optimization and coordination disruption prone supply with hard to predict demand. Wal-Mart is very good at redirecting its products when there is a change in demand. If demand is low in Texas then products can be redirected midstream to Indiana. What does sushi in Arkansas have to do with supply chaining? With its role as one of the ten forces that flattened the world, Wal-Mart in Bentonville, Arkansas was one of those places Thomas Friedman needed to see for himself. Freidman said, “I was thinking, Boy I would really like some sushi tonight. But where am I going to find sushi in northwest Arkansas? And even if I found it, would I want to eat it? Could you really trust eel in Arkansas? When I arrived at the Hilton near Wal-Mart’s headquarters, I was stunned to see, like a mirage, a huge Japanese steak house-sushi restaurant right next door (2007, pg156). As it turned out there were three new Japanese restaurants opening soon in Bentonville. The demand for sushi in Arkansas was not an accident, it had to do with the fact that all of the suppliers of Wal-Mart had also opened up shop in Bentonville, which is now referred to as “Vendorville” (Freidman, 2007).
Freidman’s eighth flattener was Insourcing- What the Guys in Funny Brown Short Are Really Doing. It seems that UPS and FedEx both are synchronizing global supply chains for small and large companies. UPS headquarters is located in Atlanta but the UPS Worldport distributions hub is located next to the Louisville International Airport, which at night is taken over by the UPS fleet of cargo jets (270 aircraft) as packages are flown all over the world, sorted, and flown back out again a few hours later. However, UPS is much more than just a delivery company of packages. It does much more, for example, when you send your Toshiba laptop to be fixed via UPS what actually happens is that UPS is fixing the computers at its hub in Louisville in a special clean room where UPS employees are wearing blue smocks and replacing broken motherboards in Toshiba computers and shipping them out again. They are doing the same kinds of services for other companies like Papa John’s Pizza. UPS employees are driving Papa John’s Pizza trucks delivering supplies to various stores. UPS does work for Nike, Jockey and HP by having warehouses of products where they can fill the orders and the orders can be shipped via UPS. This type of business started around 1996, when UPS created a whole new global business opportunity. The term “Insourcing” fits the best for this work because UPS engineers go inside a business, analyze its manufacturing, packaging, and delivery processes; and then designs, redesigns, and manages the whole global supply chain. If a company needs it, UPS will finance part of the business. Freidman says, “UPS is creating enabling platforms for anyone to take his or her business global or to vastly improve the efficiency of his or her global supply chain” (2007, pg 175).
The ninth flattener was In-Forming- Google, Yahoo, MSN Web Search. According to Freidman, In-Forming is the individual or personal analog to uploading, outsourcing, insourcing, supply-chaining, and offshoring (2007). Whether it is Google, Yahoo, or MSN Web Search, when these search engines were new, people would react with eureka moments when they found the something in a search that was really good. Now people presume they will find the data they are looking for when they are doing a search. It is staggering the amount of information that is out to be mined. In-forming also involves searching for friends, allies, and collaborators. Search engines are businesses too. Freidman said, “Everyone can now be Googled—but everyone now can also Google. Google also equalizes access to information – it has no class boundaries, few education boundaries, few linguistic boundaries, and virtually no money boundaries” (2007, pgs.184-185).
The tenth and final flattener of the world was The Steroids- Digital, Mobile, Personal, and Virtual. In this flattener there are six steroids. The first steroid has to do with computing and the computational capacities, storage capacity, and input/output capacity of computers. In 1971, the Intel 404 processor produced only 60,000 instructions per seconds. Today’s processor does over 20 billion instructions per second. Not only are the chips faster they are also smaller. The second steroid is the breakthroughs in instant messaging and file sharing. The third steroid is the ability to make phone calls over the Internet. The fourth steroid is videoconferencing. The fifth steroid is the advances in computer graphics driven by computer games. The sixth steroid is the most impressive; it’s the wireless technology and all the devices. Freidman said, “As a result of these steroids, engines can now talk to computers, people can talk to computers, and people can talk to computers farther, faster, more cheaply, and more easily than ever before. And as that has happened, more people from more places have started asking one another the same two questions: Can you hear me now? Can we work together now?”(2007, pg. 198-199).
Over the last century, amazing inventions and innovations have transformed many lives around the world, they include: the airplane; automobile; radio and television; electrification; water supply and distribution; electronics; telephony; air condition and refrigeration; highways; spacecrafts; computers; Internet; imaging; household appliances; health technologies; petroleum and petroleum technologies; laser and fiber optics; nuclear technologies; and high performance materials (Constable & Somerville, 2003). None of these inventions would have been possible without mathematicians, scientists, engineers, and technologists working together. The world needs all of these professions to collaborate globally on global challenges and create the inventions that will make our lives better in the 21st century.
Many groups have weighed in on the global challenges Scientist, Engineers, Futurist, etc. Scientist in the InterAcademy Panel, a global network of the world’s science academies, a group of 70 scientist from various academies around the world, were recently polled at a conference hosted by the Royal Society in London, they listed the following in order as the global challenges for the world in 2020:
Climate Change
Food Security
Loss of Biodiversity
Water Shortages
Global Population
Education
Nuclear Issues
Pandemics
Ageing
Poverty
Terrorism (Highfield & Lawton, 2010).
Engineers in the United States (U.S.) through a panel convened by the U. S. National Academy of Engineering (NAE) on the other hand have another list of Global Challenges. These are their challenges:
Make solar energy economical
Provide energy from fusion
Develop carbon sequestration methods
Manage the nitrogen cycle
Provide access to clean water
Restore and improve urban infrastructure
Advance health informatics
Engineer better medicines
Reverse-engineer the brain
Prevent nuclear terror
Secure cyberspace
Enhance virtual reality
Advance personalized learning
Engineer the tools of scientific discovery (Grand Challenges for Engineering Committee, 2008).
The Millennium Project, which is a global think tank, founded in 1996. This think tank connects international experts in universities, corporations, NGOs, UN agencies and governments all around the world. The Millennium project has list of 15 Global Challenges. Their Global Challenges, which are more extensive than the other groups, are as follows:
How can sustainable development be achieved for all while addressing global climate change?
How can everyone have sufficient clean water without conflict?
How can population growth and resources be brought into balance?
How can genuine democracy emerge from authorization regimes?
How can policymaking be made more sensitive to global long-term perspectives?
How can the global convergence of information and communication technologies work for everyone?
How can ethical market economies be encouraged to help reduce the gap between rich and poor?
How can the threat of new and reemerging diseases and immune micro-organisms be reduced?
How can the capacity to decide be improved as the nature of work and institutions change?
How can shared values and new security strategies reduce ethnic conflicts, terrorism, and the use of weapons of mass destruction?
How can the changing status of women help improve the human condition?
How can transnational organized crime networks be stopped from becoming more powerful and sophisticated global enterprises?
How can growing energy demands be met safely and effectively?
How can scientific and technological breakthrough be accelerated to improve the human condition?
How can ethical considerations become more routinely incorporated into global decisions? (Glenn, Gordon & Florescu, 2010)
If you look at all three of these global challenging lists, many of them are similar which tells us that these truly are important global challenges and they have been thought out by a number of different groups. The question is how do we solve these challenges? That is the billion dollar question.
One way to solve global challenges would be for mathematicians, scientists, engineers, and technologist all over the world to work on these global challenges together, some of that is happening now, but not to the extent that it could or should be happening. Unfortunately, in the U.S. higher education institutions are focused on becoming the best research institutions. The university’s traditional rewards for faculty engaged in research are for individual accomplishments. While lip service is given to rewarding faculty who collaborate in research, collaborating doesn’t get a faculty member promoted or tenured at research universities. There has been a call to change the way university’s reward faculty, however, there has been no change in the way faculty are tenured and promoted. It probably will take a world crisis for America’s best and brightest to realize the potential for working with others globally in a range of fields to solve the world’s greatest challenges.
What would it take to educate our college students today to feel comfortable in working with any group of individuals around the world on a project? Are our university students being prepared for this type of work? The answer today would be no for a majority of undergraduate students, however, in order to accomplish this, some skills for the future need to be entrenched into higher education institutions. As an example, a recent report from the Center for the Advancement of Engineering Education (CAEE) stated that undergraduate engineering education students reported a considerable increase in intellectual growth, but reported lower personal growth and fewer opportunities to study abroad than other college students (Atman et.al, 2010).
In preparing for a global career, students in their undergraduate studies should try to acquire global competencies and multicultural skills. Included in the global competencies would be workable knowledge of global leadership skills which are essential to succeed in a globalized world. If you intend to be a global leader, you should know the answers to the following questions. These questions were provided by working professionals at the IBM Corporation:
What skills are required in a global environment?
What to do and what not to do when leading in a global environment?
How to identify & tackle problems in a global team?
How to think outside the box and use innovative & creative ideas in a global team?
How to leverage the assets within a global team? (Gandhi, 2009)
IBM, described as world’s top provider of computer products and services, defines six competencies that global leaders should possess when managing global teams:
The ability to leverage global assets or managing global resources effectively and efficiently.
The ability to serve distinct global markets and seek new client opportunities.
The ability to address with the team; who has control to make decisions, how are risks, successes, and accountabilities shared within the team.
The ability to build collaboration within your global team through traditional methods or new collaborative tools.
The ability to understand and manage the different specialization in the team, utilize and componentized the skills as needed.
The ability to identify the key skills in the global team and utilize them in such a way that you get the most value from the project (Gandhi, 2009).
Gandhi goes on to indicate global team barriers that can hamper a team’s development, they are: cultural differences; differences in expertise levels; geographic time zones differences; trust issues; language and communication differences; and work style differences. These are all further explained below:
Cultural differences - There are differences in countries, educational systems, religious backgrounds, environments, and cultures. Just in the cultural differences there are differences in individual verses collective orientation which come into play too. The best way to handle this is to build a cultural awareness, and acceptance in the team.
Differences in expertise level – The differences in expertise in a team can lead to ego issues. This is a challenge for the leader because ego problems can cause distrust issues. It is the leader’s role to understand the expertise of each of the team members.
Geographic time zones differences – The lead must consider a common time but also take into consideration cultural considerations. Allow flexible work schedules to accommodate individuals. And if needed allow for a share the pain approach so that everyone suffers equally. Always clearly communicate the acceptable time range to host a meeting. Perhaps it is not necessary for all to participate in all the meetings, make sure the right people are included in the right meetings.
Trust issues - Leaders must build the trust in the team. The leader should have at least one face to face meeting so that everyone can meet. Introduce a break the ice type scenario so that individuals can meet and learn about each other in a relaxed atmosphere before the team starts on the project. Clearly communicate team objectives, team responsibilities, team member accountabilities, project timelines, risks, etc to all team members. To build trust, communication is extremely important.
Language and communication differences- English words have different meaning in different languages so this is an area that can be extremely difficult. The use of colloquials can be very complicated in conversations. Encourage clarifications, and use a lot of pauses in communications to make sure everyone to clear.
Work style differences- Each member of the team will have different work styles and this will reflect their culture. Even a local team of individuals will have different work styles. As long as individuals can work independently and they are aware of the project deadline, goals, risks and accountability then they can still succeed (Gandhi, 2009).
Building collaborative teams in the university setting can be simulated to some extent. Some of the tools available today that can be used to accomplish this are: WIKIs; Chat Rooms, Forums, Discussion Boards, Lotus Notes; Instant Messaging; Video Chats or Web Video Conferences; and Virtual Workspace Tools. These tools can be used to connect with one member of the global team or have a whole global team meeting. They can also be used for informal get together or so called global team coffee breaks for non work related talk or to celebrate team events (i.e., team member birthday, etc.).
Today international corporations and industries are looking for individuals who can work in a global world. International organizations have offices all over the world or may work with other organizations in order to get innovative products or services to market at the fastest possible speed. These individuals will need to know how to work successfully in international, multicultural, and interdisciplinary teams. For example, most engineering institutions produce one-disciplined technically successful skilled engineers; however, they don’t all produce engineers that are capable of working outside their discipline let alone working in a global world.
Engineering can be used as an example of one of these professions where industry has emphasized the need for more soft skills from the engineering graduate, who usually graduates with a multitude of technical skills in their related field of study and very little in the way of teamwork, communication, flexibility, multidisciplinary team work, leadership, and hardly any thoughts to multicultural and global awareness.
One example of teaching multidisciplinary team skills to engineering students was conducted in Europe with a group of six European university institutions from five European countries; Denmark, Czech Republic, Poland, Portugal, and The Netherlands. This group of universities working with an industry partner in Denmark developed a summer school for engineering students, which was specifically designed to include innovation, as well as the following:
Team- oriented Activities- Students worked collaboratively in teams to develop and engineer a product.
Multidisciplinary Approach- Teams were composed of students with different discipline backgrounds, but whose skills, knowledge, and experiences were important to achieve the project’s goal.
Multicultural Approach –Teams were composed of students from different countries.
Problem-based Learning –Learning was centered on students, using open assignments with several solutions possible and professors served as tutors.
Intensive Schedule –Students worked solely on the project because of the short three week summer term.
Industry-oriented – Summer school takes place in an industrial setting and the assignments given to the students are closely aligned with the industry requirements (Larsen et al., 2009).
The students, who participated in the multidisciplinary, multicultural project, summer school were pleased with the course. The industry partner was very impressed with the quality of the innovative ideas, the animations and the prototypes. The faculty involved planned to improve the technical analysis from industry partners and plan to add more multidisciplinary activities in cost and marketing analysis. The most valuable outcomes of the summer school was the new ideas, recruitment potential, and inspiration that the young students’ received out of the experience. There was no doubt that it was a very successful summer school (Larsen, et al., 2009).
Another model program named, International Networked Teams for Engineering Design (INTEnD) program involves Michigan State University (MSU) and the University of Texas Pan American is meeting the challenges of globalization by offering collaborative, multidisciplinary, and innovative engineering education programs. The research and education program was started in 1998 by a multidisciplinary team of educators from MSU and other engineering educators from a variety of universities around the world; Technical University Deft, University of Utrecht, Eindhoven University, Kaiserslautern University, Tsinghua University, Catholic University of Leuven, St. Petersburg Technical University, Carlos III University, and Monterrey Institute of Technology and Higher Education (ITESM) (Mariasingan et al, 2007).
In addition, the University of Michigan has also added an Engineering Global Leadership Program, Global Product Development Course, and a partnership with a Chinese university, Shanghai Jiao Tong University in order to prepare their engineering students for a global career. Other engineering school’s such as Purdue University created a Global engineering program in 2005, which focuses on preparing students for a global world. The University of Wisconsin- Madison has a certificate in International Engineering (Mariasingan et al, 2007). All of these changes in engineering education show that the faculty and administration in these universities are at the forefront of educating a global workforce.
Brigham Young University received a National Science Foundation (NSF) grant to implement a global virtual team’s course taught concurrently with an international capstone experience in an engineering school. This course provided students with an opportunity to be in a productive cross-cultural experience in an effective manner. This course was not meant to replace face to face interaction in different cultures (study abroad opportunities) but was meant to supplement students practice in international virtual teams and to successfully use their engineering skills. The global virtual team’s course increased the understanding of other cultures (Zaugg et al, 2010).
In 2010 a global study entitled Attributes of a Global Engineer was performed by the American Society for Engineering Education (ASEE) and the International Federation of Engineering Education Societies (IFEES) to determine the skills and experiences that today’s engineering student need to develop in school and throughout their career to successfully compete in a global workplace. ASEE’s Board of Directors established the ASEE Corporate Member Council (CMC) to convey the ideas and views of corporations to ASEE. With over 120 corporate and non-academic institutional members, the CMC\'s mission is to foster, encourage, and cultivate the dialogue between industry and engineering educators. Its strategic goals are:
Diversity in engineering education
Enhancing the K-12 educational pipeline/future workforce
Reforming engineering education
Collaborating on engineering research and intellectual property
Liaison with engineering, technology, and the Society
CMC has several Special Interest Groups (SIGs), which exist to share information and advance key priorities of the CMC. The International Engineering Education SIG is the CMC sponsor of the Attributes of a Global Engineer Survey Project.
The Attributes of a Global Engineer Survey Project grew out of an expressed need by CMC members to identify and validate specific knowledge, skills, abilities, and perspectives that would be required of an engineer living and working in an increasingly global context. Specifically, the goal was to refine a list of attributes that would be applicable to engineers regardless of specialty, location, or background.
The process began in early-2008, led by the International Engineering Education SIG, and involved CMC members developing a list of competencies derived from representative job descriptions, literature reviews, and other reports. This initial list was consolidated through a series of SIG meetings and events throughout 2008 and 2009; thus, here are the attributes that emerged through this process (Hundley et al, 2011):
Engineering Science Fundamentals
Mathematics (including statistics)
Physical and Life Sciences
Political and Socio-economic Sciences
Information Technology - Digital Competency
Engineering
Understanding of Design and Product Processes
Understanding of Product Life Cycle Development
Effective Teamwork/Common Goals
Possess a Multi-Disciplinary, Systems Perspective
Maintain Focus with Multiple Project Assignments
Context in which Engineering is practiced
Economics/Finances of Projects
Basic Supplier Management Principles
Customer and Societal Emotions and Needs
Cultures, Languages, and Business Norms
Societal, Economic, and Environmental Impacts of Engineering Decisions
An International/Global Perspective
Communication
Written (Memos, reports, email, letters, etc.)
Verbal (Technical & non-technical presentations plus an effective “elevator” speech)
Foreign Language (Technically fluent in at least two languages acknowledging English is considered a key global language)
Graphic (Design drawings, charts & graphs, presentation, and basic brochure design)
Digital Competency
Competent at Internet Collaboration and Communication Tools (Web-based meeting tools, team rooms, teleconferencing; file sharing, E-mail, etc.)
Listening
Teamwork
Active and Effective Participation in Team Efforts
A Willingness to Respect the Opinions of Others and Support Team Decisions
Leadership
An Acceptable Personal Image and a Positive Personal Attitude
Treating People with Fairness, Trust, and Respect
Respect for Diversity
Courtesy and Respect
An Eagerness to Help Others
Flexibility
Self-Confidence to Adapt to Rapid/Continuous/Major Change
Thinking Both Critically and Creatively - Independently and Cooperatively
Curiosity and Desire to Learn - For Life (Show initiative, Inquire & Learn)
Seeking Advice and Forming Daily Questions to Discover New Insights.
Commitment to Quality, Timeliness, and Continuous Improvement
Understanding Basic Project and Risk Management and Continuous Improvement Concepts (like LEAN+)
Ethical Standards and Professionalism
Operate in Accordance With Acceptable Business, Societal, and Professional Norms
Maintain the Highest Level of Integrity, Ethical Behavior, and Professional Competence
Understand and Applies Good Personal Judgment
At the ASEE Annual Conference in 2010, SIG stakeholders attempted to translate the attributes into specific competencies that could be identified by levels of importance and proficiency at certain intervals of an individual’s education and professional development. The initial list totaled 48; however, through in-person meetings at the Conference, and through bi-weekly telephone conference calls and other electronic communication, the list was ultimately synthesized and consolidated. After further review and validation from CMC members, a total of 20 competencies associated with the attributes of a global engineer emerged (Hundley et al., 2011). These are:
Demonstrates an understanding of engineering, science, and mathematics fundamentals
Demonstrates an understanding of political, social, and economic perspectives
Demonstrates an understanding of information technology, digital competency, and information literacy
Demonstrates an understanding of stages/phases of product lifecycle (design, prototyping, testing, production, distribution channels, supplier management, etc.)
Demonstrates an understanding of project planning, management, and the impacts of projects on various stakeholder groups (project team members, project sponsor, project client, end-users, etc.)
Demonstrates an understanding of the ethical and business norms and applies norms effectively in a given context (organization, industry, country, etc.)
Communicates effectively in a variety of different ways, methods, and media (written, verbal/oral, graphic, listening, electronically, etc.)
Communicates effectively to both technical and non-technical audiences
Possesses an international/global perspective
Possesses fluency in at least two languages
Possesses the ability to think both critically and creatively
Possesses the ability to think both individually and cooperatively
Functions effectively on a team (understands team goals, contributes effectively to team work, supports team decisions, respects team members, etc.)
Maintains a positive self-image and possesses positive self-confidence
Maintains a high-level of professional competence
Embraces a commitment to quality principles/standards and continuous improvement
Embraces an interdisciplinary/multidisciplinary perspective
Applies personal and professional judgment in effectively making decisions and managing risks
Mentors or helps others accomplish goals/tasks
Shows initiative and demonstrates a willingness to learn
The Attributes of a Global Engineer study indicated that a majority of the respondents, 52.5%, indicated that it was important, that an engineer functions effectively upon graduation from Tertiary/College/University on a team (understands team goals, contributes effectively to team work, supports team decisions, respects team members). As well, the same study indicated that, 48.4%, indicated that it was important, that engineers possess an international/global perspective upon graduation from Tertiary/College/University. In addition, the study indicates that a majority, 53.8%, indicated that it was important, that an engineer embraces an interdisciplinary/multidisciplinary perspective. This international study indicates that it is important for engineers to develop global skills while they attend Tertiary/College/University (Hundley et al, 2011).
A study by the National Academy of Engineering, The Engineer of 2020, calls for future engineers in the U.S to have complex social, global and professional skills to be successful in the future. There are a number of underlying guiding principles that lead the authors of this study to their conclusions, they are: (1) the continued pace of accelerating technological innovation; (2) the fact that technology deployed will continue to be intensely globally interconnected; (3)those affected or involved with technology will be increasingly diverse and multidisciplinary; (4) technological innovation will be shaped and affected by social, cultural, political, and economic forces; and (5) technology in everyday lives will be more seemingly transparent and more significant than it is today. Given those underlying principles the authors of the study suggested strongly that engineers of the future should have the following team skills in a global context: collaborate in a multidisciplinary and multicultural team of experts across multiple fields; have excellent communication skills with both technical and non-technical individuals; be able to communicate with technology, have an understanding for complex global markets and social context, be flexible, be receptiveness to change, and have mutual respect for everyone (Committee on the Engineer of 2020, 2004). In the past, the engineering profession use to respond as technology and society changes, but today technology is changing very rapidly and society is continually changing. We need to know how to work in a faster more global society.
To best teach globalization, students need to experience it, so it goes without saying that university students must take advantage of studying abroad, international internships, or research opportunities abroad. Another best practice opportunity for students is to be proficient in at least one foreign language, while it is common to be proficient in several languages in Europe this is not widely practiced in the U.S. During a graduate program, students should take advantages of enrolling in foreign universities and pursuing a dual degree, especially one that has an agreement with the university you are attending. Faculty should create sustainable networks with a foreign university in education or research in order to provide their students with these options. The institution should have a formal process or framework for globalization. It might include a discussion on how will the curriculum be restructured to include globalization, what teaching methods will be best used, and/or should international interdisciplinary research centers be established. Global competencies need to be a part of every undergraduate’s education and all barriers should be removed so that more work can be done on global research (Widdig & Lohmann, 2007).
The Wharton School of Business is changing its curriculum to better prepare its graduates for a fast changing global business environment. Changes to their curriculum include several focused short term courses in the U.K., India, Brazil, China, Israel and South Africa. For example, the course in Brazil is about the environment, the one in Israel is about technology, etc. Wharton has also added courses to their curriculum in global finance, management and an increased focus in soft skills like writing, leadership and multicultural understanding (Korn, 2011). These types of curriculum changes are happening in other elite business schools as well.
In Finland, globalization is integrated in the curriculum to promote internationalization of higher education. However, specialization and depth is more important in engineering education in the United States than internationalization. In Finland, internationalization is defined through three areas: mobility, multiculturalism, and networking. The key areas for internationalization in the engineering education in Finland are through:
student, teacher, and researcher mobility;
international R&D projects;
development of joint and double degrees with other institutions in other countries;
increase in foreign students and researchers in Finland;
measures in supporting the integration of foreign students and personnel in Finland;
development of the exportation competencies;
enhanced study opportunities for non-native speakers and those with immigrant backgrounds; and
more efficient use of the international organizations and cooperation arrangements (Tossavainen, 2009, p.528).
All of these key areas cover mobility, multiculturalism and networking.
Another excellent example of best practices of readying students to work in the global world has been practiced in The Georgia Institute of Technology since the late 1990’s when Georgia Tech’s President, Dr. G. Wayne Clough, took office in 1994. President Clough realized fast that there were a number of talented students on campus who were multi-dimensional. These students were good in music, sports or some other area and in addition these students also were interested in engineering. These students were not the best engineering students, these students were able to communicate, they were more socialized, they asked for help when needed, they thought horizontally, and most of all these students were able to tie things together from different disciplines and fields. These students made great engineering students because of these other qualities. Since that finding in the late 1990’s, Georgia Institute of Technology started targeting a unique group of freshmen, till 50% of the entering freshman in engineering played musical instruments, or participated in a musical group. This was so prevalent that President Clough had to build more recital and concert areas on campus. President G. Wayne Clough created a different kind of graduate. The students that graduate from the Georgia Institute of Technology in engineering are adaptable and can think across the disciplines and therefore are ready for a global flat world (Freidman, 2007).
Thomas Friedman said in his book, The World is Flat, that the one ability students should have when leaving college is the ability to, “learn how to learn – and to constantly absorb, and teach yourself, new ways of doing old things or new ways of doing new things” (2007, pg 309). Friedman goes on to say that what you know today will soon be out of date. Thus, university students need to be aware that lifelong learning is a skill that they will need to incorporate throughout their life whether it is exploring globalization or broader aspects of a specific discipline.
Recently, there has been a call in engineering education to supplement the current curriculum with globalization, team work and multi-culture learning. However, there is also a call to bring back the excitement that an engineering profession use to enjoy, especially in a world where society needs sustainable supplies of energy, water, food, and healthcare with trends toward globalization (Turner, 2010). Turner goes on to say, “The curriculum must incorporate active, engaging and relevant learning, teaching and assessment strategies to develop, self-aware, well-motivated, enterprising and independent learners” (2010, pg 36.).
Some university students learn the lessons of globalization by studying internationally. Some 3 million international students study abroad. Meaning they study at universities outside their home countries. Newly created or expanded universities in China, India, and Saudi Arabia are competing with the same students, faculty and research pre-eminence of that of Harvard and Oxford. A good example of this would be the President of King Abdullah University Science and Technology (KAUST), a brand new graduate school in Saudi Arabia. The President, who is originally from Singapore but who had a global trotting career path through Canada, United States and back to Singapore before taking the President’s position in Saudi Arabia. The renowned international business school INSEAD, has campuses, in France, Singapore, Israel, and Abu Dhabi. Students study on several campuses. (Wildavsky, 2010).
Finally, there are some pragmatic strategies to facilitate, encourage, and sustain global-oriented teaching in higher education—approaches that are adaptable to a variety of disciplines and institutional contexts. These include:
Increasing the size of the international student body population
Increasing the size of foreign-born faculty members
Developing or expanding partnerships with international institutions
Providing for robust study abroad experiences of varying lengths and contexts
Engaging students in classroom, co-curricular, and other educational activities that heighten their awareness of internationalization
Fostering service learning, undergraduate research, and experiential education that includes an international component
Leveraging the partnerships of other stakeholders (e.g., alumni, business/industry organizations, professional associations and societies, community members) to provide a platform for students to participate in international learning opportunities.
By 2025, internationalization will have sharpened the hierarchy in world higher education, with a handful of university “transnational corporations” in the highest tier alongside private firms and local community college-style institutions in the lowest. This is one of the predictions made by Felix Maringe, Senior Lecturer in education at the University of Southhampton and Nick Foskett, Vice Chancellor of Keele University in a book they edited titled, Globalization and Internationalization in Higher Education. So while there is a concern of just how to teach globalization in higher education, there is also a big push for universities to go global (Morgan, 2010). Vice Chancellor Foskett says that the key theme of the book is the failure of universities to understand higher education internationalization in the context of the globalization of the world economy, rather than as a simple recruitment of international students. The book indicates that internationalization will be innate for universities at the top of the tier through cross-cultural programs, overseas campuses or distance learning (Morgan, 2010). This is only one small solution for globalizing students.
In the world today, there are over 1 billion people who don’t have adequate supplies of clean water, countless who don’t have access to medical care, millions who live without enough to eat. We live in a world that is more interconnected and more vulnerable than ever before. Infectious diseases can be transmitted easily across countries because we are so mobile. The grand challenges, no matter what group they are hailed from, in this century are huge. The young people, who are in universities and colleges, are the ones that can work towards solving these grand challenges, but it is the responsibility of those teaching these students to make sure they are equipped with right set of skills to make sure they are able to work with multicultural multidisciplinary teams to solve the problems that face the world. In pursing the grand challenges of the century, the world is much smaller and more inclusive and more connected. The challenges of the century are not that of isolated locales but of the planet as a whole. Therefore, globalization of education must be a necessary part of higher education. Business and engineering schools alike in the United States have added or are considering globalization as an important addition to a student’s higher education package. Globalization is already an important part of European education. Globalization is not a passing phenomenon. It is here to stay. Universities and colleges throughout the world need to recognize that every student needs to have global skills.
The last two decades have seen epidemic outbreaks by novel viruses including SARS, MERS, and influenza which shared certain commonalities such as a likely zoonotic origin, high mortality rates, and less available therapeutic methods to counteract them. The COVID-19 pandemic shows no signs of slowing down with affecting 223 countries, with 224,811,910 cases, and 4,633,797 death tolls till date [1]. With what history on earlier pandemics has made us understand and with the rapidly mutating nature of the SARS-CoV-2 virus, it is not unreasonable to say that the pandemic is here to stay, and the world must learn to co-exist with it. The first reported case of COVID-19 was found in Wuhan, China in December 2019. By March 2020, the disease had spread across the globe and had become a public health emergency. The WHO declared a pandemic state to the disease spread on March 11, 2020 [2]. With more than a year since the declaration of the pandemic, the scientific community has yet not developed a definitive anti-viral drug to combat the disease spread. Even though the advent of vaccination has set the pace in favour of global health, we have a long way to go to eradicate if at all suppress the disease spread.
SARS-CoV-2 is highly virulent and highly contagious with the R0 value of 3.77 [3]. Though it predominantly affects the respiratory system, other organ systems like the gastrointestinal system, heart, kidney, and central nervous system are also targeted by the virus. Fever, chills, cough, shortness of breath or breathing difficulty, sore throat, nasal congestion, diarrhoea, nausea, vomiting, generalised body aches are some of the common symptoms noted in patients infected with COVID-19 [4].
Neurological manifestations of COVID-19 include non-specific symptoms like headache, dizziness, fatigue, and myopathy and more specific symptoms like anosmia, ageusia, impaired consciousness, stroke, meningitis, acute transverse myelitis, and Guillian-Barre syndrome [5, 6]. More than one third of the individuals with COVID-19 were found to present with neurological symptoms [7, 8]. The presence of viral RNA in cerebrospinal fluid and the brain was observed in COVID-19 patients [9]. Preliminary
Coronaviruses are the largest among RNA viruses. They have a crown-like spikes on their surface and hence the name. SARS-CoV-2 is the latest/seventh coronavirus to become pathogenic to humans. It belongs to the Coronaviridae family which includes four genera; α−, β−, γ−, and δ-CoV. Out of these human pathogens include HCoV- 229E, HCoV- NL63 [α − CoV] and OC43, and HKU1 [β − CoV] that in most cases cause mild self-limiting respiratory disease. γ − and δ-CoV strains mainly affect avian species [13]. SARS-CoV and MERS-CoV, causatives of SARS and MERS, are beta coronaviruses that caused up to 9.6% and 34.3% mortality rates which were responsible for earlier pandemics that resulted in a death toll of 812 and 866, respectively [14]. SARS-CoV-2 is more similar to SARS-CoV and MERS-CoV while being far more pathogenic and transmissible than the earlier known coronaviruses.
SARS-CoV-2 is a beta coronavirus that is positive-sense single-stranded RNA virus with 29–30 kb in size. It has four structural proteins and 16 non-structural proteins. Nucleocapsid protein [N], membrane protein [M], spike protein [S], and envelope protein [E] are the four structural proteins (Figure 1). The capsid of the genome is formed by N protein and the genome is further surrounded by an envelope that is made up of M, E, and S proteins. Like other coronaviruses, SARS-CoV-2 has enveloped with a crown-like spikes on its surface. It is the spike protein that is responsible for the variations in host specificity and tissue tropism of the different coronavirus. Spike protein is a type-I membrane glycoprotein and has two functional subunits S1 and S2 with different functional domains in the amino and carboxy terminal. S1 subunit contains the receptor-binding domain [RBD] and binds with the receptor in the host cells. S2 subunit fuses the membranes of the host cells and the virus. The entry of the virus into the host cell involves binding of the S protein [S1 subunit] to a specific cell receptor followed by priming of the S protein by proteases in the host cell. This leads to the fusion of the spike protein to the cell membrane which is mediated by the S2 subunit [15]. The specific cell receptor through which SARS-CoV-2 enters the host cell is the ACE2 receptor and the protease in the host cell that processes the spike protein to reveal the fusion peptide between S1 and S2 subunits facilitating its entry, is a TMPRSS2 serine protease, member of the hepsin/TMPRSS subfamily [16]. Another protein named furin or paired basic amino acid cleaving enzyme [PACE], a member of the subtilisin-like proprotein convertase family, mediates proteolytic cut of the S protein at S1-S2 boundary, is required for TMPRSS2 processing of S protein. Both TMPRSS2 and furin are essential for the entry of SARS-CoV-2 into the cell. The furin cleavage site in the S protein of SARS-CoV-2 is not found in SARS-CoV and other beta coronaviruses [17].
ACE2 is a cell surface protein, a metalloproteinase and an ectoenzyme which is an obligatory receptor for SARS-CoV and SARS-CoV-2. The affinity of SARS-CoV-2 to ACE2 is ten times higher than that of SARS-CoV which partly explains its higher pathogenicity [18]. It was discovered in 2000 by two independent groups of researchers while searching for human ACE homologues [19, 20]. The gene for ACE2 in humans is located in Xp22 and has 18 exons, a majority of which are similar to the exons of the ACE gene [21]. Despite ACE2 exhibiting 42% sequence identify and 61% sequence similarity with ACE, the two enzymes show enormous variations (Table 1) [27].
ACE | ACE2 | |
---|---|---|
Forms | Exists as a 2-domain somatic form and a one domain testicular form | Exists as a single form |
Structure | Transmembrane ectoenzyme with two active sites | Transmembrane ectoenzyme with one active site |
Enzymatic action | Removes C-terminal dipeptide – peptidyl-dipeptidase | Removes single amino acid from C-terminus – carboxypeptidase |
Substrate specificity | Converts Ang I to Ang II | Converts Ang I to Ang (1-9) |
Does not cleave Ang II | Converts Ang II to Ang (1-7) | |
Converts Ang (1-9) to Ang (1-7) | Does not cleave Ang (1-9) | |
Converts Ang (1-7) to Ang (1-5) | Does not cleave Ang (1-7) | |
Does not cleave Ang A | Converts Ang A to Alamandine | |
Hydrolyses bradykinin | Does not cleave bradykinin | |
Does not cleave des-Arg9-bradykinin | Hydrolyses des-Arg9-bradykinin | |
Action on amyloid protein | Hydrolyses Aβ-43 to Aβ41 | Hydrolyses Aβ43 to Aβ42 |
Hydrolyses Aβ-42 to Aβ40 | Does not cleave Aβ-42 | |
Localisation within cells | Equal distribution between apical and basolateral membranes | Localised on the apical membrane |
Transports intestinal amino acids | No | Transports intestinal neutral amino acids |
Shedding into plasma | Unidentified. May involve metalloproteinase and A Disintegrin | By A Disintegrin and Metalloprotease 17 (ADAM 17) |
Response to ACE inhibitor | Inhibited | Resistant, gets upregulated |
Acts as a receptor to virus | No | Receptor for SARS-CoV and SARS-CoV-2 |
Since the 20 years of its discovery, ACE2 was found to have a multitude of physiological and pathological functions based on its three fundamental actions viz. negative regulation of renin-angiotensin system [RAS], facilitation of amino acid transport in the intestine, and surface receptor for SARS-CoV and SARS-CoV-2. ACE2 is mainly expressed in the lungs, intestine, liver, heart, kidneys, testes, and brain. In the brain, it is expressed in neurons, astrocytes and oligodendrocytes, and in ventricles, substantia nigra, hypothalamus, hippocampus, middle temporal gyrus, posterior cingulate cortex, nuclei in pons—the nucleus of tractus solitarius and pre-Bötzinger complex and olfactory bulb [21, 28]. ACE2 expression is higher in astrocytes, astrocytic foot processes, pericytes, and endothelial cells which form the key components of the blood–brain barrier [29]. In the olfactory epithelium, its expression is higher in the supporting sustentacular cells than in olfactory sensory neurons [30]. The sites of ACE2 expression are given in Table 2 [31].
Vascular system | Endothelial cells, vascular smooth muscle cells, and migratory angiogenic cells |
Heart | Cardiomyocytes, endothelial cells, pericytes, and epicardial adipose cells, and cardiofibroblasts |
Skin | sebaceous gland cells and basal epidermal layer |
Kidneys | glomerular endothelial cells, proximal tubule epithelial cells, bladder urothelial cells, luminal surface of tubular epithelial cells, and podocytes |
Reproductive system | Ovary, oocyte, uterus, vagina, and placenta of the female reproductive system Adult Leydig cells and cells in the seminiferous ducts in the testis of the male reproductive system |
Liver | Perinuclear hepatocytes, cholangiocytes, epithelial cells of the bile duct |
Gut | Stratified epithelial cells of oesophagus, stomach, Intestinal epithelial cells, enterocytes of small intestine, absorptive enterocytes from the ileum, colon and rectum, and endothelial cells |
Pancreas | Acinar cells and duct cells of the exocrine gland and alpha, beta, delta, and PP cells of islets of Langerhans |
Thyroid | Glandular cells |
Oral cavity | Tongue, buccal mucosa, gingiva, leucocytes within the oral mucosa, non-keratinising squamous epithelium of the oral cavity – basal layer |
Upper airway | Ciliated epithelial cells, goblet cells |
Lungs | Pulmonary vasculature, type I and II alveolar epithelial cells, bronchiolar epithelial cells |
Eyes | Pigmented epithelial cells, photoreceptor cells, Müller glial cells |
Central nervous system | Neurons, astrocytes, and oligodendrocytes, and in ventricles, substantia nigra, hypothalamus, hippocampus, middle temporal gyrus, posterior cingulate cortex, nuclei in pons – nucleus of tractus solitarius and pre-Bötzinger complex and olfactory bulb and cerebral vasculature and components of blood–brain barrier (astrocytes, astrocytic foot processes, pericytes, and endothelial cells) |
Sites of ACE2 expression.
ACE2 is a type 1 integral membrane protein that includes a short cytoplasmic C-terminus, a transmembrane region, collectrin, and N-terminal ectodomain. Zinc-binding motifs, HEMGH forms the active site of the enzyme. N-terminal domain has a claw-shaped protease domain which is the binding site of receptor-binding domain [RBD] of SARS-CoV and SARS-CoV-2. N terminus is homologous to ACE and is a carboxypeptidase that metabolises peptides like angiotensin II, kinins, apelin-13, apelin-36, neurotensin 1–13, kinetensin, and morphins, and C terminus is homologous to collectrin which is involved in the trafficking of neutral amino acid transporter [B[o]AT1] in the intestinal epithelium [32].
Both ACE and ACE2 play a major role in maintaining renin-angiotensin system [RAS] homeostasis. ACE2 acts like a negative regulator of ACE in RAS. RAS involves a variety of proteins and enzymes. Angiotensinogen is an inactive precursor that gets cleaved by renin to form angiotensin I. ACE acts on angiotensin I to convert into angiotensin II [Ang II] while ACE2 converts Ang II to Ang [1-7]. Ang [1-7] then binds to Mas receptors and causes attenuation of the signal cascade that was activated by Ang II (Figure 2). Thus, ACE2 not only inactivates Ang II but also generates the antagonistic peptide Ang [1-7] [33]. Ang [1-7] can also be formed from Ang I by neutral endopeptidases and neprilysin, but the most effective pathway of Ang [1-7] generation is through ACE2 [34]. The conversion of Ang II to Ang [1-7] by ACE2 is 70 folds more efficient than the conversion of Ang I to Ang [1-9] by ACE2. Thus, under physiological conditions, ACE2 mainly forms Ang [1-7] than Ang [1-9] [34].
While Ang II, which acts via angiotensin 1/AT1 [primary mediator] and angiotensin 2/AT2 receptors is a potent vasoconstrictor, a pro-fibrotic, and a pro-inflammatory agent, Ang [1-7] acts via Mas receptors and has vasodilator, anti-apoptotic and anti-proliferative effect. Mas receptors are G protein-coupled receptors and in the brain, they are highly expressed in the dentate gyrus of the hippocampus, a site-specific for adult neurogenesis and in blood vessels [35]. The ACE2/Ang [1-7]/Mas receptor axis of the RAS is considered to be the protective arm of the renin-angiotensin system. A balance in ACE/ACE2 is critical which implies a balance between the pro-inflammatory pro-oxidative arm and the anti-inflammatory and anti-oxidative arm of RAS. An increase in ACE/ACE2 ratio was observed in many pathological conditions including cardiovascular pathology, renal dysfunction, pulmonary hypertension, in cigarette smokers, and Alzheimer’s disease [36, 37, 38, 39]. SARS-CoV-2 which enters the host cells via ACE2 also causes downregulation of ACE2 and the major targets of SARS-CoV-2 are those which express higher levels of ACE2 [26]. The fibrotic and inflammatory processes observed in various organs in COVID-19 patients could be attributed to the dysregulation of ACE2 and subsequently, RAS which is observed in endocrine, paracrine, and intracrine levels in several organs [40]. Dysregulation of RAS in the brain is associated with neuroinflammation and neurodegeneration [41].
The old dogma that the production of functional neurons does not occur in adult life was refuted when Altman and Das published evidence to support the continuation of neurogenesis in adult life in rodents [42]. Neurogenesis refers to the process of the generation of new neurons from neural stem cells. This process which plays a major role in brain development in embryonic life ceases to exist shortly after birth in the majority of brain areas except two. The subgranular zone [SGZ] of the dentate gyrus of the hippocampus and subventricular zone [SVZ], lining the lateral wall of the lateral ventricles are the two areas where neurogenesis persists well into adult life albeit declining slightly with ageing (Figure 3) [43, 44]. There is a complex microenvironment that nourishes and supports the neural progenitor cells and their progeny which is called the ‘neurogenic niche’. There are various trophic factors, blood vessels, supporting glial cells, and hormones in the neurogenic niche that help to control and enhance neurogenesis [45]. The newborn neurons mature and get integrated into neural circuits and are involved in a variety of functions including learning and memory like temporal and pattern separation, high-resolution memory, synaptic plasticity, fear conditioning and emotions, and olfaction [46]. Incidentally altered neurogenesis is implicated in several neuropsychiatric diseases like Alzheimer’s disease, Parkinson’s disease, depression, Huntington’s disease, and stroke, epilepsy, and demyelinating disease [46, 47].
(a) Structure of ACE2 and SARS-CoV-2; (b) Interaction of spike protein and ACE2; (c) Shedding of ACE2 and entry of SARS-CoV-2 into the cell.
Renin-Angiotensin System.
Coronal section of the brain showing the sites of adult neurogenesis.
The process of adult neurogenesis occurs in stages viz. maintenance of neural stem/progenitor cells [NPC] and proliferation of NPC, fate specification/commitment, differentiation, maturation, survival of immature neurons, and integration into neural circuitry. The defining abilities of NPC are self-replication and multipotency, that is, the ability to differentiate into multiple lineages of cells and in this case neurons, astrocytes, and oligodendrocytes [48]. There are different types of neural progenitor cells in SGZ and SVZ. Type-1 cells in SGZ, B-cells in SVZ, and radial glia-like cells in SGZ and SVZ are largely quiescent cells, which are similar to radial glia cells found during embryonic development and have a morphology similar to mature astrocytes. Type-2 cells in SGZ and C-cells in SVZ are small roundish cells that are highly proliferative, and they give rise to type-3 cells in SGZ and A-cells in SVZ which represent committed neuroblasts. The type-1/B-cells are multipotent and have unlimited self-renewal capacity which get activated by various factors and multiply to form highly proliferative transient intermediate progenitor cells [TIP] in the SGZ. In SVZ, the transit-amplifying cells [TAC] [type-2/C-cells] has the ability to differentiate into neurons. These divide to form neuroblasts or immature neurons [type-3/A-cells] which proceed to neuronal differentiation and forms newborn neurons that mature and get integrated into neural circuitry in the brain. It is pertinent to know that many of the newborn neurons perish and only 15–30% of immature neurons survive the maturation process. There are various factors that regulate this step and thereby the process of adult neurogenesis [49, 50, 51].
In SGZ, the NPCs form granule cells which are the principal excitatory cells of the dentate gyrus. Their axons form the mossy fibres extending to the CA3 region and their dendrites are in the molecular layer which receives connections from the entorhinal cortex. Immature neurons that are less than a week-old start to have neurite outgrowth and by one- or two-weeks axons can be observed in the hilus, and dendrites start to extend to the molecular layer without spines which being developed by around the 16th day. By 17 days, functional connections are formed by the axons [mossy fibres] with the CA3 pyramidal neurons [52]. They release glutamate as the neurotransmitter. After around 1 week of birth, the newborn granule cells receive GABAergic inputs and after 2 weeks receive glutamatergic inputs [53]. These immature neurons exhibit enhanced excitability by virtue of high input resistance and subthreshold calcium ion conductance which enables them to develop action potential with less excitatory currents. They also have a low threshold for induction of LTP [long-term potentiation] [54, 55]. Between 3 weeks and 2 months, there occurs a gradual increase in spine formation, dendritic arborisation and connection, boutons on CA3 neurons, and maturation of mossy fibres. By less than 2 months, the newborn neurons become functionally indistinguishable from fully mature granule cells [52].
In SVZ, restricted neural progenitor cells migrate along scaffolds maintained by specialised astrocytes via the rostral migratory stream [RMS] to reach the olfactory bulb. By 15–30 days, they differentiate into two types of interneurons, GABAergic granule neurons [95%] and GABA or dopaminergic periglomerular neurons [5%]. The newborn GABAergic granule neurons can become cells with dendrites that do not cross beyond the mitral cell layer and those with non-spiny dendrites that extend till the external plexiform layer. These interneurons mature and get integrated into olfactory network and start responding to olfactory signals [52].
There are various factors that regulate neurogenesis. These include intrinsic niche-derived intrinsic mechanisms and extrinsic systemic factors. The intrinsic factors that regulate adult neurogenesis are given in Table 3. There are extrinsic environmental cues and systemic factors that can positively and negatively affect adult neurogenesis like physical exercise, dietary intake, olfactory/hippocampal-dependent learning, environmental enrichment, ageing, stress, alcohol abuse, and certain inflammatory conditions [46, 56, 57, 58, 59].
Intrinsic factors | Examples |
---|---|
Neurotrophic factors | brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), nerve growth factor (NGF), glia-derived nerve factor (GDNF), fibroblast growth factor 2 (FGF-2), epidermal growth factor (EGF) |
Morphogens | Notch, sonic hedgehog (Shh), wingless ligands (Wnts), and bone morphogenic proteins (BMPs). |
Inflammatory cytokines | tissue necrosis factors α (TNFα), interleukin-6 (IL-6) and IL-1β IL-4 and IL-10 |
Neurotransmitters | gamma-aminobutyric acid (GABA), glutamate, dopamine, serotonin, norepinephrine, acetylcholine |
Hormones | Glucocorticoids, sex hormones, leptin, incretin |
Epigenetic factors | methyl-CpG-binding domain protein 1 (Mbd1), MYST family histone acetyltransferase Querkopf (Qkf), mixed-lineage leukaemia 1 (Mll1), polycomb complex protein (Bmi-1), histone deacetylase 2 (HDAC2), and microRNAs (miR124, 137, 184, 185, and 491-3p) |
Transcriptional factors | sex-determining region Y-box 2 (Sox2), Orphan nuclear receptor TLX, forkhead box O proteins (FoxOs), prospero homeobox 1 (Prox1), neurogenic differentiation1 (NeuroD1), Kruppel-like factor 9, cyclic AMP response element-binding protein (CREB), paired box protein (Pax6), and neurogenin 2 (Neurog2) |
List of intrinsic factors that affect adult neurogenesis.
There are different ways that are the possible pathway for the entry of SARS-CoV-2 into the brain. Some of the ways include olfactory transmucosal invasion, hematogenous dissemination, and neuronal retrograde dissemination [5]. The olfactory sensory neurons of the olfactory mucosa are bipolar neurons. The axons of the olfactory sensory neurons along the apical side project into the nasal cavity while that on the basal side merge into filia and protrudes into the olfactory bulb through the cribriform plate. Thus, the olfactory sensory neurons are in direct contact with the cerebrospinal fluid [60]. In the olfactory mucosa, ACE2 receptors are mainly found in the non-neuronal cells, sustentacular cells while their expression in the olfactory sensory neurons is less [30]. The blood vessels lining the olfactory mucosa express both ACE2 and TMPRSS2 protease receptors which help in the invasion of the SARS-CoV-2 virus and facilitate binding, replication, and accumulation of the virus [61, 62]. Studies have found that SARS-CoV-2 enters CNS through this neural-mucosal interface by infection of the olfactory neurons or by diffusion through channels formed by olfactory ensheathing cells in the olfactory mucosa [60, 63]. Following the olfactory transmucosal invasion, the virus passes along the olfactory tract via axonal transport, trans-synaptic transport, or microfusion to different areas of the brain linked with the olfactory tract [60, 64].
Recent studies have observed that SARS-CoV-2 RNA was found in brain regions that are not directly connected to olfactory mucosa like the cerebellum which shows that other forms/routes of viral entry into the brain are at play. Neuronal retrograde dissemination is the one where the virus may breach peripheral nerve terminals and take a trans-synaptic route to reach CNS. For instance, SARS-CoV-2 may invade peripheral chemoreceptors and may reach the cardiorespiratory centre in the brain stem [65] or through the gut-brain axis where the virus may enter the brain through enteric nerves [66]. In case of hematogenous dissemination, the virus after infecting the airways may breach the epithelial barrier and enter the bloodstream. Through systemic circulation, the virus may reach the cerebral circulation and could infect endothelial cells of blood–brain barrier or epithelial cells of the blood CSF barrier to reach the brain or via circumventricular organs which lack the blood–brain barrier [5]. Trojan horse mechanism is another way by which SARS-CoV-2 could reach the brain parenchyma. It is the process in which the virus infects leucocytes which get activated and disseminate to other tissues and cross blood–brain barrier [67].
Once SARS-CoV-2 enters the brain, it enters and infects the neurons, glial cells, and endothelial cells through ACE2 and replicates which leads to cell death. It causes damage to the blood–brain barrier which will increase its permeability and cause oedema, intracerebral bleeding, and neuronal death. The infected neurons can release inflammatory mediators that can activate other immune cells like mast cells, neurons, microglia, astrocytes, endothelial cells, and pericytes [68, 69].
Earlier studies show that survivors of critical illness have higher risk of developing neuropsychiatric consequences after discharge from the hospital. The prevalence of symptoms of depression, anxiety, and post-traumatic stress was found to be 29% [28, 29, 30, 31, 32, 33, 34], 34% [30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42], and 34% [27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50] in survivors of critical illness, respectively [70, 71, 72]. Impairment in memory, attention, and concentration was observed in SARS survivors 1 year after recovery [73]. Based on the knowledge from earlier infections by coronaviruses, SARS, and MERS, an increased risk of neuropsychiatric disorders like depression, anxiety, post-traumatic stress disorder, are possible in a long-term follow-up of patients recovered from COVID-19 [12].
Neuropsychiatric disorders that display impaired adult neurogenesis include major depressive disorder, Alzheimer’s disease, Parkinson’s disease, schizophrenia, and post-traumatic stress disorder. All of these correlate well with the reduction in hippocampal volume, cognitive deficits, and mood dysregulation [74]. A recent 3-month prospective study by Yiping Lu et al. conducted in COVID-19 recovered patients found that there was grey matter enlargement in olfactory cortices and hippocampus bilaterally [75]. Yiping Lu et al. also found that the grey matter volume of the hippocampus was negatively related to loss of smell during the disease phase [75]. Anosmia over a course of time in upper respiratory tract infections was found to be associated with a decrease in the grey matter volume [GMV] of the central olfactory system due to loss of stimulation while enlargement of GMV is observed during recovery [76]. Functional compensation in the form of enlarged neurons and an increase in the dendritic spine and compensatory enhanced neurogenesis are believed to be the reason behind GMV enlargement during recovery [77]. Loss of memory that persisted 3 months after the active infection in COVID-19 recovered patients was found to be negatively related to hippocampal grey matter volume [75]. Memory acquisition depends on newborn neurons and impairment in the acquisition of memory occurs due to inhibition of adult neurogenesis in the hippocampus [78, 79].
Anosmia is regarded as the key feature of COVID-19 which either occurs as an only symptom or in association with other signs and symptoms [80, 81]. Earlier studies show that any impairment in olfactory neurogenesis is associated with anosmia since neurogenesis in the olfactory epithelium and olfactory bulb is essential for the sense of smell [82, 83]. Dysfunction or atrophy of the olfactory bulb was observed in COVID-19 patients by recent studies done using brain imaging reports [84, 85]. Pathogenic changes in COVID-19 seem to cause loss of dopaminergic neurons, defects in the dopamine system, and exacerbate the clinical features of Parkinson’s disease [PD] [86, 87]. Anosmia is an important premotor symptom of PD which is not directly related to the neurodegenerative process in substantia nigra but appears to be related to defective adult neurogenesis [88, 89].
Understanding the process of adult neurogenesis in COVID-19 may reveal a critical role of the regenerative capacity of NPCs in combating the neuropsychiatric consequence of COVID-19. There are no studies or evidence to link COVID-19 with adult neurogenesis yet. Based on the factors like the presentation of neuropsychiatric symptoms in COVID-19, the occurrence of symptoms like anosmia, memory and cognitive deficits in COVID-19, the neuro-invasive potential of SARS-CoV-2, ACE2 expression in sites of adult neurogenesis, increased levels of pro-inflammatory cytokines like IL-6, Il-1β which inhibit adult neurogenesis and impact of earlier coronavirus infections, it might not be far-fetched to say that COVID-19 could have a possible impact on adult neurogenesis. There is a severe scarcity in research analysing the effect of SARS-CoV-2 infection on adult neurogenesis. The current chapter, which is speculative and based on a thorough literature search, discusses the possible changes in adult neurogenesis in COVID-19 emphasising the role of ACE2. If proven to be true in the future, the findings in this article will help in achieving early intervention to address the neuropsychiatric long-term consequence of COVID-19.
SARS-CoV-2 entry into the cell through ACE2 is followed by the downregulation of ACE2. A decrease in ACE2 will lead to dysregulation of RAS and various other complications. A recent study has found that ACE2 is expressed in young neurons and in human-induced pluripotent stem cell-derived neural progenitor cells [90]. ACE2 is found to have various neuroprotective functions. It converts neurotoxic amyloid protein Aβ into neuroprotective one in transgenic mice [91]. ACE2 activator, diminazene increased CREB, BDNF, glutamate, and nicotinic receptor and decreased the levels of apoptotic and inflammatory proteins in the AD model of D-galactose-ovariectomized rats [92]. All these factors play a major role in adult neurogenesis. ACE2 deficiency in mice was found to be accompanied by significantly impaired learning and memory [93]. Exercise-induced neurogenesis in the dentate gyrus was abolished in ACE2 deficient mice. Ang II, Ang [1-7], and Mas receptors were not found to be responsible and hence the mediator of this effect is not identified yet [94].
ACE2 expression is stronger in the enterocytes of the small intestine and colon, which is even higher than in the lungs. Neural ganglia cells in the colon of the enteric nervous system also express ACE2 receptors. Intestinal ACE2 plays a major role in the transport of neutral amino acids via B0AT1, neutral amino acid transporter. ACE2/B0AT1 complex regulates the composition and function of gut microbiota. ACE2 knockout animals showed lower levels of serum neutral amino acid levels like tryptophan, and impaired gut microbiota composition along with reduced expression of small intestinal antimicrobial peptides [95]. Enteric infection is an important presentation of COVID-19. Faeces of COVID-19 patients were found to have Viral mRNA [96, 97]. SARS-CoV-2 entry via the enteric route into host cell leads to ACE2 shedding due to S priming which may lead to gut microbiota dysbiosis [98]. Depletion of gut microbiota by prolonged antibiotic treatment resulted in impairment in cognitive function and hippocampal neurogenesis in adult mice [99]. The existence of a strong link between gut microbiota and the development of mental disorders, depression, and anxiety which are associated with impaired adult neurogenesis has been explored in recent studies [100].
Neuroinflammation directly impairs adult hippocampal neurogenesis. Pro-inflammatory cytokine IL-1β, IL-6, IFN-α causes a reduction in neural cell proliferation and suppresses adult hippocampal neurogenesis [101, 102, 103]. SARS-CoV-2 entry into the brain triggers an immune response by activating microglia, astrocytes, and other immune cells. This leads to increased production of cytokines in the brain. Cytokine storm which is a deadly hyperinflammatory response is considered to be a hallmark feature of COVID-19 pathogenesis [104]. Hypercytokinemia of IL-6, IL-10, and TNF-α was observed in COVID-19 patients. Increased levels of IL-6 correlate with mortality and the need for ventilator support [105, 106].
Thus, there are different possible mechanisms through which SARS-CoV-2 affects adult neurogenesis via ACE2. This chapter, however, will focus on the role of ACE2 in possible alterations in adult neurogenesis in COVID-19 via neurotransmitters.
Neurotransmitter signalling is found to play a major role in the formation of new neurons in addition to its clear and indisputable role in communication between neurons. Starting from embryogenesis, neurotransmitters are involved in neuronal proliferation. In adult neurogenesis, they influence various steps including proliferation, differentiation, and migration. In addition to the direct action of neurotransmitters on adult neurogenesis, they also influence other factors that regulate neurogenesis like neurotrophic factors and growth factors [107].
Serotonin is a crucial monoaminergic neurotransmitter that acts as a mood stabiliser and is associated with feelings of happiness, well-being, and contentedness. In the brain, it is synthesised by the Raphe nuclei neurons in the brain stem from tryptophan using neuron-specific tryptophan hydroxylase 2 enzymes. Vesicular monoamine transporter 2 [VMAT] packs the synthesised serotonin into vesicles. Serotonin transporters [SERT] re-uptake serotonin back to presynaptic neurons after its release, thereby regulating its extracellular levels [108]. The serotonergic fibres from raphe nuclei have projections throughout the brain and especially to the granule cells and interneurons of the dentate gyrus of the hippocampus. Serotonin is known to play a major regulatory role in adult hippocampal neurogenesis. Selective serotonin reuptake inhibitors [SRRI] are commonly used antidepressants that act by increasing serotonin levels in the brain causes clinical improvement associated with an increase in adult hippocampal neurogenesis characterised by increased neuronal proliferation and number of newborn neurons [109]. Malberg et al. in 2000 were the first to show that chronic treatment with fluoxetine improved adult hippocampal neurogenesis [109]. In the dentate gyrus, serotonin is known to promote neuronal development and its depletion was found to cause reduced dendritic spine density of granule cells [110, 111, 112, 113]. Chronic treatment with SSRI, fluoxetine was found to increase the survival of newborn neurons in the dentate gyrus [109, 114]. In stress models like inescapable stress, cold restraint stress in the animal model, fluoxetine administration was found to exhibit neurogenic and neuroprotective roles in the hippocampus [114, 115]. Accelerated synaptogenesis and increased long-term potentiation [LTP] in the hippocampus were also observed by long-term treatment by fluoxetine [116].
Recent studies have found that ACE2 plays a major role in the biosynthesis of serotonin [5HT]. The precursor for 5HT is an essential amino acid, tryptophan which can cross the blood–brain barrier and whose intestinal absorption was found to be reduced by 70% in case of ACE2 deficiency. Thus, ACE2 has an indirect modulatory role in 5HT synthesis in the brain [117]. There are recent studies that show that 5HT synthesis in the brain is dependent on ACE2, which acts by modulating 5HT metabolism and ACE2 deficiency leads to decreased serum tryptophan levels and decreased serotonin levels in the brain [94].
Dopamine is involved in executive functions, volition, motor control, motivation, pleasure/reward, and attention/concentration [118]. The role and mechanism of action of dopamine in adult neurogenesis are not elucidated fully. Dopamine was found to modulate cell proliferation in the embryonic brain [119]. Hippocampus and sub-ventricular zone [SVZ] which are the neurogenic niche containing neural stem cells receive dopaminergic projections from the substantia nigra and ventral tegmental area. Dopamine receptors are also widely expressed in these two areas and play a regulatory role in adult neurogenesis and neural plasticity [120, 121]. Earlier studies show that depletion of dopamine in the rat model reduces both proliferation and survival of neural precursor cells in the sub-granular zone [SGZ] of the dentate gyrus [122, 123]. Dopaminergic denervation in substantia nigra caused a significant reduction in the proliferation of neural stem cells in SGZ and SVZ which was reversed by D2 receptor stimulation in rodents [123]. In humans, post-mortem studies have revealed that the number of neural precursor cells in SGZ and SVZ was reduced in patients with Parkinson’s disease [124]. Dopamine was also found to increase the type 2A early progenitor cell in the hippocampus of rodents via D1 like receptors [118]. Dopamine receptor agonist pramipexole increases the proliferation and survival of newborn neurons in SVZ, olfactory bulb [119].
RAS plays a major role in dopaminergic vulnerability through AT1 receptors. Dysregulation of RAS due to the downregulation of ACE2 induced by SARS-CoV-2 may increase the vulnerability of dopaminergic neurons and subsequently dopamine levels [125]. Interactions between dopamine and angiotensin receptors that are counterregulatory in nature are observed in substantia nigra and striatum [125]. The gene for ACE2 was found to coexpress and coregulate with that of dopa decarboxylase [DDC] in non-neuronal cells, which is a major enzyme of dopamine, serotonin, and histamine biosynthesis. DDC converts L-3,4-dihydroxyphenylalanine [L-DOPA] into dopamine which subsequently forms norepinephrine and epinephrine and L-5-hydroxytryptophan into serotonin. This coexpression and coregulation link between the genes for ACE2 and DDC gives rise to the possibility of a functional link between the actions of ACE2 and DDC [i.e.,] in the synthesis of Ang [1-7] and dopamine and serotonin mediated by ACE2 and DDC, respectively [126]. Following the infusion of Ang [1-7] in the hypothalamus of rats, brain dopamine levels increased which emphasises the link between ACE2 and DDC. SARS-CoV-2 induced downregulation of ACE2 could cause the decreased synthesis of serotonin and dopamine [94, 127].
The SARS-CoV-2 infection has been found to cause loss of dopaminergic neurons and deficits in the dopamine system [86, 128]. ACE2 expression is high in dopaminergic neurons and the downregulation of ACE2 by SARS-CoV-2 may cause depletion of dopaminergic neurons and dopamine levels. This is evident from the worsening of symptoms observed in COVID-19 patients with Parkinson’s disease [PD], requiring increased dopamine replacement therapy [129]. ACE2 deletion in the knockout mouse model caused a significant reduction in dopamine D1 mRNA expression in substantia nigra [130].
Norepinephrine is an important catecholamine that is involved in alertness, arousal, sleep–wake cycle, memory storage, and emotions. It modulates various functions of the hippocampus like learning, memory, and mood. Noradrenergic axon terminals arising from the locus coeruleus densely innervate the neurogenic niche in the adult hippocampus [131]. Norepinephrine along with the other monoaminergic neurotransmitters plays a major role in adult neurogenesis. Norepinephrine was found to activate the stem cells and neural precursor cells via β3-adrenergic receptors where non-proliferating latent precursor cells develop the ability to respond to mitogens and generate neurospheres. It also increases the proliferation of early progenitor cells in the adult hippocampus via β2-adrenergic receptors [132, 133]. Depletion of norepinephrine significantly decreased the proliferation of progenitor cells of granule cells in the hippocampus [134]. Antidepressants that selectively increase norepinephrine were found to increase adult hippocampal neurogenesis [132].
Downregulation of ACE2 by SARS-CoV-2 may affect the activity of DDC due to the coexpression and coregulation between the genes for ACE2 and DDC. This could lead to a decrease in the biosynthesis of dopamine and subsequently norepinephrine [126].
Glutamate is the predominant excitatory neurotransmitter of the CNS. It plays a vital role in both embryonic brain development and adult neurogenesis. Its extracellular levels are especially higher in the neurogenic niche when compared to other areas of the brain [135, 136]. It has trophic effects on the developing neurons before synapse formation like proliferation, migration, and maturation. It causes an increase in the proliferation of neural progenitor cells [NPC]. The NPCs express NMDA metabotropic glutamate receptors, stimulation of which caused increased intracellular calcium and activation of NeuroD1, proneural gene [137]. Glutamate signalling plays a positive role in maintaining the proliferation of NPCs and the survival rates of newborn neurons [137, 138].
Gamma-aminobutyric acid [GABA] is a principal inhibitory neurotransmitter in the CNS. It is produced from glutamate by the action of the enzymes glutamate decarboxylase GAD65 and GAD67 [139]. Dysfunction in the GABAergic system is implicated in major depressive disorder and anxiety [140]. However, in the developing brain, GABA exerts an excitatory effect, that is, GABA is excitatory in immature neurons. Tonic discharge from GABAergic neurons is necessary for maintaining the quiescent state of NPCs. The absence of GABAergic excitability will cause impairment in neuronal maturation and synapse formation while an excess of it over newborn neurons will lead to seizures [141]. In SGZ, GABA mediates depolarisation of progenitor cells which is involved in the incorporation of AMPA receptors in immature granule cells, which is critical for learning and formation of memory [142]. It has a negative influence on neuroblasts. It inhibits the proliferation and migration of neuroblasts. It also inhibits the proliferation of NPCs [143, 144, 145]. It also promotes the differentiation of hippocampal NPCs. GABAA receptor agonist, phenobarbital caused a reduction in NPC proliferation and increase in differentiation which resulted in an increased number of newborn neurons [146]. Thus, it plays crucial role in different stages of adult neurogenesis. GABA and glutamate signalling play a major role in adult neurogenesis. Selective activation of the receptor subtypes of GABA and glutamate expressed in NPCs plays a pivotal role in self-replication and fate commitment of the developing neurons into a particular progeny [147].
A recent study has found ACE2 to be located mainly in excitatory neurons of the brain and to a lesser extent in inhibitory neurons like GABAergic neurons [148]. This indicates that SARS-CoV-2 once enters the brain has the potential to access the glutamatergic and GABAergic neurons. The consequence of this is not known however, viral entry may trigger apoptotic pathways and cause excitatory-inhibitory imbalance, and lead to neuronal death [149]. Cytokine release from infected neurons and other activated microglia and astrocytes may also cause a decrease in glutamate and GABA [150]. These effects are implicated along with impaired adult neurogenesis in neurodegenerative diseases like Parkinson’s disease and Alzheimer’s disease. Seizure is one of the neurological symptoms in COVID-19 patients, in which an increase in glutamate levels and decrease in GABA levels in the cerebral cortex and hippocampus is an implicated mechanism [151]. This further emphasises the possible impact of SARS-CoV-2 on glutamate and GABA.
Thus, SARS-CoV-2 induced downregulation of ACE2 in COVID-19 is potentially detrimental to adult neurogenesis. ACE2 deficiency affects the levels and actions of the neurotransmitters serotonin, dopamine, norepinephrine, GABA, and glutamate which play crucial roles in adult neurogenesis.
SARS-CoV-2 has been found to have a high affinity to ACE2 receptors. Such high affinity has been linked to affect neurogenesis through a variety of mechanisms. The present chapter has clearly postulated the link between this deadly virus and its effect on monoaminergic neurotransmitters as well as GABA and glutamate which play a major role in adult neurogenesis. As ACE2 receptors are expressed in the hippocampus, decreased neurogenesis in this region could be one of the major factors behind the neuropsychiatric disorders associated with patients affected with COVID-19. Awareness and early intervention to prevent and treat long-term psychiatric consequences of COVID-19 are crucial. We should be aware of the possibility that in the long term, COVID-19 may be associated with cognitive and psychiatric disorders in those who recovered. Despite having a mild course of disease in children and adolescents, immunological response to the infection in this population may affect synaptic pruning which may lead to various issues that may not be immediately apparent. Insights into the various machinations of adult neurogenesis in COVID-19 can be used to engineer the process to help with the pathological changes in the brain inflicted by the disease.
The authors would like to thank the Deanship of Scientific Research, Majmaah University for the support of this chapter.
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Historically, species have been described and characterized on the basis of morphological criteria, which are closely linked by environmental conditions or which find their limits especially in groups where they are difficult to access, as is the case for many species of microorganisms. The need to understand the molecular mechanisms in species has made the PCR an indispensable tool for understanding the functioning of these biological systems. A number of markers are now available to detect nuclear DNA polymorphisms. In genetic diversity studies, the most frequently used markers are microsatellites. 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Local systems include local heating, local air-conditioning, local ventilation, and split systems.",book:{id:"6807",slug:"hvac-system",title:"HVAC System",fullTitle:"HVAC System"},signatures:"Shaimaa Seyam",authors:[{id:"247650",title:"M.Sc.",name:"Shaimaa",middleName:null,surname:"Seyam",slug:"shaimaa-seyam",fullName:"Shaimaa Seyam"},{id:"257733",title:"MSc.",name:"Shaimaa",middleName:null,surname:"Seyam",slug:"shaimaa-seyam",fullName:"Shaimaa Seyam"},{id:"395618",title:"Dr.",name:"Shaimaa",middleName:null,surname:"Seyam",slug:"shaimaa-seyam",fullName:"Shaimaa Seyam"}]},{id:"70315",title:"Some Basic and Key Issues of Switched-Reluctance Machine Systems",slug:"some-basic-and-key-issues-of-switched-reluctance-machine-systems",totalDownloads:1264,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Although switched-reluctance machine (SRM) possesses many structural advantages and application potential, it is rather difficult to successfully control with high performance being comparable to other machines. Many critical affairs must be properly treated to obtain the improved operating characteristics. This chapter presents the basic and key technologies of switched-reluctance machine in motor and generator operations. The contents in this chapter include: (1) structures and governing equations of SRM; (2) some commonly used SRM converters; (3) estimation of key parameters and performance evaluation of SRM drive; (4) commutation scheme, current control scheme, and speed control scheme of SRM drive; (5) some commonly used front-end converters and their operation controls for SRM drive; (6) reversible and regenerative braking operation controls for SRM drive; (7) some tuning issues for SRM drive; (8) operation control and some tuning issues of switched-reluctance generators; and (9) experimental application exploration for SRM systems—(a) wind generator and microgrid and (b) EV SRM drive.",book:{id:"8899",slug:"modelling-and-control-of-switched-reluctance-machines",title:"Modelling and Control of Switched Reluctance Machines",fullTitle:"Modelling and Control of Switched Reluctance Machines"},signatures:"Chang-Ming Liaw, Min-Ze Lu, Ping-Hong Jhou and Kuan-Yu Chou",authors:[{id:"37616",title:"Prof.",name:"Chang-Ming",middleName:null,surname:"Liaw",slug:"chang-ming-liaw",fullName:"Chang-Ming Liaw"},{id:"306461",title:"Mr.",name:"Min-Ze",middleName:null,surname:"Lu",slug:"min-ze-lu",fullName:"Min-Ze Lu"},{id:"306463",title:"Mr.",name:"Ping-Hong",middleName:null,surname:"Jhou",slug:"ping-hong-jhou",fullName:"Ping-Hong Jhou"},{id:"306464",title:"Mr.",name:"Kuan-Yu",middleName:null,surname:"Chou",slug:"kuan-yu-chou",fullName:"Kuan-Yu Chou"}]}],onlineFirstChaptersFilter:{topicId:"1",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"83092",title:"Novel Composites for Bone Tissue Engineering",slug:"novel-composites-for-bone-tissue-engineering",totalDownloads:0,totalDimensionsCites:0,doi:"10.5772/intechopen.106255",abstract:"Novel metal oxide-doped fluorophosphates nano-glass powders were synthesized by melt quenching method, and their non-toxicity is proved by MTT. Their efficacy in bone formation is confirmed by osteocalcin and ALP secretion. Composites were made using PLA, PDLLA, PPF, or 1,2-diol with fluorophosphates nano-glass powders (AgFp/MgFp/ZnFp). Their non-toxicity was assessed by cell adhesion and MTT. The ability of the composite for bioconversion was assessed by RT-PCR estimation for osteocalcin, Collagen II, RUNX2, Chondroitin sulfate, and ALP secretion accessed by ELISA method. The animal study in rabbit showed good callus formation by bioconduction and bioinduction. The bioconversion of the composite itself was proved by modified Tetrachrome staining. From the 12 different composites with different composition, the composite PPF+PDLLA+PPF+ZnFp showed the best results. These obtained results of the composites made from common biological molecules are better than the standards and so they do biomimic as bone substitutes. The composites can be made as strips or granules or cylinders and will be a boon to the operating surgeon. The composite meets nearly all the requirements for bone tissue engineering and nullifies the defect in the existing ceramic composites.",book:{id:"11453",title:"Biomimetics - Bridging the Gap",coverURL:"https://cdn.intechopen.com/books/images_new/11453.jpg"},signatures:"Pugalanthipandian Sankaralingam, Poornimadevi Sakthivel and Vijayakumar Chinnaswamy Thangavel"},{id:"82823",title:"The Metropolitan Transformation of Ioannina City from 1940 to 2015",slug:"the-metropolitan-transformation-of-ioannina-city-from-1940-to-2015",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.105884",abstract:"The chapter presents the urban and regional changes in the city of Ioannina, Greece. This city is located in the periphery of Epirus, which is in the western Balkans, Eastern Europe. The chapter examines, with the tools of aerial photos and QGIS software, the spatial transformation of Ioannina city from 1940 to 2015. Map science is a field through which the users could observe and compare maps from past to future. The plans and the planning were formed under the values, standards, and fundamentals of the mosaic of politics, good practices, urban rules, and citizen level. The urban space has already changed until nowadays. The chapter examines the reasons for urban politics and social–economic moments that became the epitome of these urban and regional changes. The results show the comparative spatial study from each historical period.",book:{id:"11488",title:"GIS and Spatial Analysis",coverURL:"https://cdn.intechopen.com/books/images_new/11488.jpg"},signatures:"Efthymios-Spyridon Georgiou"},{id:"83066",title:"Carbon Nanomaterials Based Supercapacitors: Recent Trends",slug:"carbon-nanomaterials-based-supercapacitors-recent-trends",totalDownloads:3,totalDimensionsCites:0,doi:"10.5772/intechopen.106730",abstract:"The increasing demand for renewable energy sources worldwide and the predicted depletion of current fossil fuel sources need continuous energy storage and conversion technology development. The use of supercapacitors (SC) as electrical energy storage devices in consumer electronics items and alternative power sources is an interesting and potentially lucrative area of application. Therefore, continuous developments are conducted to improve SC performance using different composites and nanocomposites. Carbon materials in SC are among the most important uses of this material. This chapter provides a short communication on recent progress in supercapacitor-based carbon materials. Various fundamental carbon allotropes were presented and debated, including fullerene, carbon nanotubes, and graphene-based supercapacitors.",book:{id:"11538",title:"Updates on Supercapacitors",coverURL:"https://cdn.intechopen.com/books/images_new/11538.jpg"},signatures:"Mohamed M. Atta and Rania M. Ahmed"},{id:"83080",title:"Boron Doping in Next-Generation Materials for Semiconductor Device",slug:"boron-doping-in-next-generation-materials-for-semiconductor-device",totalDownloads:0,totalDimensionsCites:0,doi:"10.5772/intechopen.106450",abstract:"The article surveys the most recent achievements starting with the boron doping mechanism, mainly focused on doping in semiconductor materials such as Si, Ge, graphene, carbon nanotube, or other 2D materials. Frequently used doping methodologies are discussed, including ion implantation and solid-phase doping, mainly focused on recent developing techniques of monolayer doping. These doped materials’ structural, electronic, and chemical properties are addressed to understand the boron doping effect better. Theoretical and experimental information and data are used to support such atomic-level effects. Therefore, this review can provide valuable suggestions and guidelines for materials’ properties manipulation by boron doping for further research exploration.",book:{id:"11762",title:"Characteristics and Applications of Boron",coverURL:"https://cdn.intechopen.com/books/images_new/11762.jpg"},signatures:"Linh Chi T. 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Although much of the research work has been done on modeling and predicting fouling, it is still a poorly understood phenomenon representing the complexity of its mechanism. The common fouling mitigation action after the onset of fouling is to optimize the operating condition, e.g., increase the bulk flow velocity or decrease surface temperature. However, many quantitative and semi-empirical models have been developed to predict the fouling rate for preventive actions and optimizing cleaning schedules.",book:{id:"11161",title:"Heat Transfer",coverURL:"https://cdn.intechopen.com/books/images_new/11161.jpg"},signatures:"Obaid ur Rehman, Nor Erniza Mohammad Rozali and Marappa Gounder Ramasamy"},{id:"83057",title:"Communication Technologies and Their Contribution to Sustainable Smart Cities",slug:"communication-technologies-and-their-contribution-to-sustainable-smart-cities",totalDownloads:3,totalDimensionsCites:0,doi:"10.5772/intechopen.106223",abstract:"Sustainable smart cities (SSC) are becoming a reality as many develop their unique model of smart cities based on vast communication infrastructure. New technologies led to innovative ecosystems where transportation, logistics, maintenance, etc., are automated and accessed remotely. Information and communication coordinate their overall activities. Sensors embedded in these devices sense the environment to provide the required input. Together with artificial intelligence, machine learning, and deep learning, it enables them to facilitate effective decision-making. This chapter discusses the role of integrating technologies in smart cities, focusing on the information and communication aspects, challenges, limitations, and mitigation strategies related to the infrastructure, implementations, and best practices for attaining SSC. We propose a four-layered model covering the main aspects of incorporating communication technology within sustainable smart cities. It covers the basic physical level, providing guidelines for designing a smart city that supports the requirements of a proper communications infrastructure. The level above is the network level where we describe current communication networks and technologies. The rest two upper layers represent the software with integrated and embedded communication components. 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Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. 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He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. 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Currently, he is a professor of Orthodontics. He holds a Certificate of Advanced Study type A in Technology of Biomaterials used in Dentistry (1995); Certificate of Advanced Study type B in Dento-Facial Orthopaedics (1997) from the Faculty of Dental Surgery, University Denis Diderot-Paris VII, France; Diploma of Advanced Study (DESA) in Biocompatibility of Biomaterials from the Faculty of Medicine and Pharmacy of Casablanca (2002); Certificate of Clinical Occlusodontics from the Faculty of Dentistry of Casablanca (2004); University Diploma of Biostatistics and Perceptual Health Measurement from the Faculty of Medicine and Pharmacy of Casablanca (2011); and a University Diploma of Pedagogy of Odontological Sciences from the Faculty of Dentistry of Casablanca (2013). 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She is now a lecturer at the University of Witwatersrand, South Africa, and a principal researcher at the Health Economics and Epidemiology Research Office (HE2RO), South Africa. Dr. Moolla holds a Ph.D. in Psychology with her research being focused on mental health and resilience. In her professional work capacity, her research has further expanded into the fields of early childhood development, mental health, the HIV and TB care cascades, as well as COVID. She is also a UNESCO-trained International Bioethics Facilitator.",institutionString:"University of the Witwatersrand",institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419588",title:"Ph.D.",name:"Sergio",middleName:"Alexandre",surname:"Gehrke",slug:"sergio-gehrke",fullName:"Sergio Gehrke",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038WgMKQA0/Profile_Picture_2022-06-02T11:44:20.jpg",biography:"Dr. Sergio Alexandre Gehrke is a doctorate holder in two fields. The first is a Ph.D. in Cellular and Molecular Biology from the Pontificia Catholic University, Porto Alegre, Brazil, in 2010 and the other is an International Ph.D. in Bioengineering from the Universidad Miguel Hernandez, Elche/Alicante, Spain, obtained in 2020. In 2018, he completed a postdoctoral fellowship in Materials Engineering in the NUCLEMAT of the Pontificia Catholic University, Porto Alegre, Brazil. He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. In addition, he is also a Collaborating Professor in several Postgraduate programs at different universities all over the world.",institutionString:null,institution:{name:"Universidad Católica San Antonio de Murcia",country:{name:"Spain"}}},{id:"342152",title:"Dr.",name:"Santo",middleName:null,surname:"Grace Umesh",slug:"santo-grace-umesh",fullName:"Santo Grace Umesh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/342152/images/16311_n.jpg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"333647",title:"Dr.",name:"Shreya",middleName:null,surname:"Kishore",slug:"shreya-kishore",fullName:"Shreya Kishore",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333647/images/14701_n.jpg",biography:"Dr. Shreya Kishore completed her Bachelor in Dental Surgery in Chettinad Dental College and Research Institute, Chennai, and her Master of Dental Surgery (Orthodontics) in Saveetha Dental College, Chennai. She is also Invisalign certified. She’s working as a Senior Lecturer in the Department of Orthodontics, SRM Dental College since November 2019. She is actively involved in teaching orthodontics to the undergraduates and the postgraduates. Her clinical research topics include new orthodontic brackets, fixed appliances and TADs. She’s published 4 articles in well renowned indexed journals and has a published patency of her own. Her private practice is currently limited to orthodontics and works as a consultant in various clinics.",institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"323731",title:"Prof.",name:"Deepak M.",middleName:"Macchindra",surname:"Vikhe",slug:"deepak-m.-vikhe",fullName:"Deepak M. Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. His research interests include root canal morphology, functionally graded concept, dental biomaterials, epidemiology and dental education, biomimetic restoration, finite element analysis and endodontic regeneration. Dr. Madfa has numerous international publications, full articles, two patents, a book and a book chapter. Furthermore, he won 14 international scientific awards. Furthermore, he is involved in many academic activities ranging from editorial board member, reviewer for many international journals and postgraduate students' supervisor. Besides, I deliver many courses and training workshops at various scientific events. Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\r\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\r\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Orthodontist, Assoc Prof in the Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. After graduating from TED Ankara College in 1986, she attended the Hacettepe University, Faculty of Dentistry in Ankara. \nIn 1993 she attended the Gazi University, Faculty of Dentistry, Department of Orthodontics for her PhD education. After finishing the PhD education, she worked as orthodontist in Ankara Dental Hospital under the Turkish Government, Ministry of Health and in a special Orthodontic Clinic till 2011. Between 2011 and 2016, Dr. Deniz Uzuner worked as a specialist in the Department of Orthodontics, Faculty of Dentistry, Gazi University in Ankara/Turkey. In 2016, she was appointed associate professor. Dr. Deniz Uzuner has authored 23 Journal Papers, 3 Book Chapters and has had 39 oral/poster presentations. She is a member of the Turkish Orthodontic Society. Her knowledge of English is at an advanced level.",institutionString:null,institution:null},{id:"332914",title:"Dr.",name:"Muhammad Saad",middleName:null,surname:"Shaikh",slug:"muhammad-saad-shaikh",fullName:"Muhammad Saad Shaikh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jinnah Sindh Medical University",country:{name:"Pakistan"}}},{id:"315775",title:"Dr.",name:"Feng",middleName:null,surname:"Luo",slug:"feng-luo",fullName:"Feng Luo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sichuan University",country:{name:"China"}}},{id:"344229",title:"Dr.",name:"Sankeshan",middleName:null,surname:"Padayachee",slug:"sankeshan-padayachee",fullName:"Sankeshan Padayachee",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"315727",title:"Ms.",name:"Kelebogile A.",middleName:null,surname:"Mothupi",slug:"kelebogile-a.-mothupi",fullName:"Kelebogile A. Mothupi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"423519",title:"Dr.",name:"Sizakele",middleName:null,surname:"Ngwenya",slug:"sizakele-ngwenya",fullName:"Sizakele Ngwenya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"337613",title:"Mrs.",name:"Tshakane",middleName:null,surname:"R.M.D. Ralephenya",slug:"tshakane-r.m.d.-ralephenya",fullName:"Tshakane R.M.D. Ralephenya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419270",title:"Dr.",name:"Ann",middleName:null,surname:"Chianchitlert",slug:"ann-chianchitlert",fullName:"Ann Chianchitlert",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419271",title:"Dr.",name:"Diane",middleName:null,surname:"Selvido",slug:"diane-selvido",fullName:"Diane Selvido",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419272",title:"Dr.",name:"Irin",middleName:null,surname:"Sirisoontorn",slug:"irin-sirisoontorn",fullName:"Irin Sirisoontorn",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}}]}},subseries:{item:{id:"18",type:"subseries",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. 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. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11414,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,series:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983"},editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",slug:"arli-aditya-parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",slug:"cesar-lopez-camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",slug:"shymaa-enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]},onlineFirstChapters:{paginationCount:1,paginationItems:[{id:"83092",title:"Novel Composites for Bone Tissue Engineering",doi:"10.5772/intechopen.106255",signatures:"Pugalanthipandian Sankaralingam, Poornimadevi Sakthivel and Vijayakumar Chinnaswamy Thangavel",slug:"novel-composites-for-bone-tissue-engineering",totalDownloads:0,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Biomimetics - Bridging the Gap",coverURL:"https://cdn.intechopen.com/books/images_new/11453.jpg",subseries:{id:"8",title:"Bioinspired Technology and Biomechanics"}}}]},publishedBooks:{paginationCount:1,paginationItems:[{type:"book",id:"10795",title:"Plant Stress Physiology",subtitle:"Perspectives in Agriculture",coverURL:"https://cdn.intechopen.com/books/images_new/10795.jpg",slug:"plant-stress-physiology-perspectives-in-agriculture",publishedDate:"April 28th 2022",editedByType:"Edited by",bookSignature:"Mirza Hasanuzzaman and Kamran Nahar",hash:"c5a7932b74fe612b256bf95d0709756e",volumeInSeries:11,fullTitle:"Plant Stress Physiology - Perspectives in Agriculture",editors:[{id:"76477",title:"Prof.",name:"Mirza",middleName:null,surname:"Hasanuzzaman",slug:"mirza-hasanuzzaman",fullName:"Mirza 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