List of hits from the EZbiocloud 16S database.
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Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"11021",leadTitle:null,fullTitle:"B-Complex Vitamins - Sources, Intakes and Novel Applications",title:"B-Complex Vitamins",subtitle:"Sources, Intakes and Novel Applications",reviewType:"peer-reviewed",abstract:"This book provides the most current information on the effects of vitamin B deficiency as well as the roles of niacin (vitamin B3), pyridoxine (vitamin B6), folate (vitamin B9), and vitamin B12 in numerous disorders. Chapters discuss novel applications of B-complex vitamins, such as thiamin in patients with critical conditions, dietary supplements in the prevention of renal stones, and treatment of COVID-19. Throughout, the authors discuss the effects of vitamin B deficiency from retrospective, perspective, and prospective points of view.",isbn:"978-1-83969-798-2",printIsbn:"978-1-83969-797-5",pdfIsbn:"978-1-83969-799-9",doi:"10.5772/intechopen.95718",price:119,priceEur:129,priceUsd:155,slug:"b-complex-vitamins-sources-intakes-and-novel-applications",numberOfPages:254,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"ad50bc292cda8d24f11aef2f5ef88f51",bookSignature:"Jean Guy LeBlanc",publishedDate:"February 23rd 2022",coverURL:"https://cdn.intechopen.com/books/images_new/11021.jpg",numberOfDownloads:1504,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:2,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:2,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 16th 2021",dateEndSecondStepPublish:"June 21st 2021",dateEndThirdStepPublish:"August 20th 2021",dateEndFourthStepPublish:"November 8th 2021",dateEndFifthStepPublish:"January 7th 2022",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"67023",title:"Dr.",name:"Jean Guy",middleName:null,surname:"LeBlanc",slug:"jean-guy-leblanc",fullName:"Jean Guy LeBlanc",profilePictureURL:"https://mts.intechopen.com/storage/users/67023/images/system/67023.jpeg",biography:"Dr. Jean Guy LeBlanc has an MSc and BSc in Biochemistry from the Université de Moncton, Canada, and a Ph.D. in Biochemistry from the National University of Tucuman, Argentina, where he is also a post-graduate teacher in the Faculty of Biochemistry, Chemistry and Pharmacy. He is also a Principal Researcher for CERELA-CONICET, Argentina. His main areas of study include the use of lactic acid bacteria to increase bioactive compounds (vitamins, digestive enzymes, antioxidants, etc.) for the fermentation of foods or as biopharmaceuticals to treat and prevent vitamin deficiencies, inflammatory diseases, and some types of cancer. Dr. LeBlanc has published 110 peer-reviewed articles and 33 book chapters and edited 8 books. He has also participated in 143 works in scientific meetings.",institutionString:"CERELA-CONICET",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Universidade Federal de Minas Gerais",institutionURL:null,country:{name:"Brazil"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"379",title:"Vitaminology",slug:"alimentology-vitaminology"}],chapters:[{id:"78520",title:"Poverty and Pellagra’s Penumbras",doi:"10.5772/intechopen.100001",slug:"poverty-and-pellagra-s-penumbras",totalDownloads:133,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Pellagra has largely been forgotten. This is unfortunate as important lessons are to be learnt about the diseases and social and economic consequences of poverty – and for the root cause of poverty (and of affluence) – that involve dietary nicotinamide and nicotinamide adenine dinucleotide (NAD) homeostasis. NAD disruption can occur not only from poor diet but from increased consumption from genotoxic, infectious and metabolic stresses. NAD deficiency is closely linked to poor physical and intellectual development, premature ageing and diseases of ageing. Acute infections, many with NAD-consuming toxins, that may differentially affect the NAD-depleted, now include COVID-19. Some Covid manifestations, such as myoclonic encephalopathy and “Long Covid,” resemble pellagra clinically and biochemically as both have disturbed nicotinic and tryptophan metabolism. Symbionts that supply nicotinic acid, such as TB and some gut micro-organisms, can become dysbiotic if the diet is very deficient in milk and meat, as it is for 1–2 billion or more. High doses of nicotinamide lead to inhibition of NAD-consuming enzymes and excessive induction of nicotinamide-n-methyl transferase (NNMT) with consequent effects on the methylome: this gives a mechanism for an unrecognised hypervitaminosis-B3 with adverse effects of nicotinamide overload for consumers on a high meat diet with “fortified” foods and “high energy” drinks. Methods of measuring NAD metabolism routinely for screening the populations at risk of deficiency and in metabolically ill or infectious disease patients should be developed urgently. Successful intervention should improve human capital and prevent many aspects of poverty, reduce discrimination and even the drive to emigrate.",signatures:"Adrian C. Williams and Lisa J. Hill",downloadPdfUrl:"/chapter/pdf-download/78520",previewPdfUrl:"/chapter/pdf-preview/78520",authors:[{id:"331134",title:"Assistant Prof.",name:"Lisa J.",surname:"Hill",slug:"lisa-j.-hill",fullName:"Lisa J. Hill"},{id:"331135",title:"Prof.",name:"Adrian C.",surname:"Williams",slug:"adrian-c.-williams",fullName:"Adrian C. Williams"}],corrections:null},{id:"80214",title:"Folates: An Introduction",doi:"10.5772/intechopen.102349",slug:"folates-an-introduction",totalDownloads:118,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Folate is a naturally occurring essential nutrient which is vital for DNA replication and a necessary substrate in various enzymatic reactions which are involved in synthesis of amino acids and vitamin metabolism. The synthetic and oxidized form of folate is folic acid, it is mainly incorporated into fortified foods and dietary supplements for preventive measures against folate deficiency. Folate deficiency has been linked with several abnormalities in both mother (anemia, peripheral neuropathy) and fetus (congenital abnormalities). Folic acid supplementation taken around the time of conception has been known to alleviate the risk of neural tube defects in the off springs. Optimal intake and absorption of folates is required for the maintenance of the human body’s normal functioning and keeping the genomic integrity intact.",signatures:"Abbas Shams",downloadPdfUrl:"/chapter/pdf-download/80214",previewPdfUrl:"/chapter/pdf-preview/80214",authors:[{id:"417035",title:"Ph.D. Student",name:"Abbas",surname:"Shams",slug:"abbas-shams",fullName:"Abbas Shams"}],corrections:null},{id:"78947",title:"Vitamin B9 in Dark Green Vegetables: Deficiency Disorders, Bio-Availability, and Fortification Issues",doi:"10.5772/intechopen.100318",slug:"vitamin-b9-in-dark-green-vegetables-deficiency-disorders-bio-availability-and-fortification-issues",totalDownloads:111,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Folic acid is a B complex water-soluble vitamin that is essential to humans, and its deficiency can cause problems including neural tube defects as well as heart-related diseases. An important feature of such vitamins is that they are generally not synthesized by mammalian cells and therefore must be supplied in sufficient amounts in the diet. Folate is a generic term for compounds, possessing vitamin activity similar to that of pteroylglutamic acid, and is the form of the vitamin, which is naturally present in foods. The main dietary sources of folic acid are dark green and leafy vegetables such as spinach, asparagus, romaine lettuce, broccoli, bok choy, turnip green, beet, dried or fresh beans, and peas. The amount of folate that is absorbed and utilized physiologically varies among different food sources and different chemical forms of the vitamin. About 85% of folic acid is estimated to be bioavailable; however, the bioavailability of food folate is estimated at about 50% of folic acid. Several national health authorities have introduced mandatory food fortification with synthetic folic acid, which is considered a convenient fortificant, being cost efficient in production, more stable than natural food folate, and superior in terms of bioavailability and bio-efficacy. Presently, many countries affected by diseases associated with a lack of folic acid have made it mandatory to supplement foods with the vitamin. Considering the need, several analytical procedures were standardized to determine the presence of folic acid in different food matrices. The reported methods are simple, selective, robust, and reproducible and can be used in routine analyses.",signatures:"Jagdish Singh",downloadPdfUrl:"/chapter/pdf-download/78947",previewPdfUrl:"/chapter/pdf-preview/78947",authors:[{id:"233561",title:"Dr.",name:"Jagdish",surname:"Singh",slug:"jagdish-singh",fullName:"Jagdish Singh"}],corrections:null},{id:"78671",title:"Meat and Vitamin B3: Getting a Grip on Engel’s Curve",doi:"10.5772/intechopen.100056",slug:"meat-and-vitamin-b3-getting-a-grip-on-engel-s-curve",totalDownloads:79,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"We evolved from herbivores to a meat eating “commons” in hunter-gatherer days and then to a non-egalitarian meat power struggle between classes and countries. Egalitarian-ism, trans-egalitarianism and extremes of inequality and hierarchy revolve around the fair-unfair distribution of meat surpluses and ownership of the means of meat production. Poor people on poor diets with too few micronutrients may explain many inequalities of human capital, height and health and divergent development of individuals and nations. Learning from past successes and collapses from switching trophic levels the lesson is that meat moderation toward the top of Engel’s curves, not calorie-centrism, is the best recipe for countries and classes. Improved health with longer lives and higher crystallised intelligence comes with an ample supply of micronutrients from animal products namely iron, zinc, vitamin A, vitamin B12 and other methyl-donors (such as choline), and nicotinamide (vitamin B3). We concentrate on nicotinamide whose deficits cause the degenerative condition pellagra that manifests as poor emotional and degenerative cognitive states with stunted lives and complex antisocial and dysbiotic effects caused by and causing poverty.",signatures:"Adrian C. Williams and Lisa J. Hill",downloadPdfUrl:"/chapter/pdf-download/78671",previewPdfUrl:"/chapter/pdf-preview/78671",authors:[{id:"331134",title:"Assistant Prof.",name:"Lisa J.",surname:"Hill",slug:"lisa-j.-hill",fullName:"Lisa J. Hill"},{id:"331135",title:"Prof.",name:"Adrian C.",surname:"Williams",slug:"adrian-c.-williams",fullName:"Adrian C. Williams"}],corrections:null},{id:"78374",title:"Deficiency of Vitamin B-Complex and Its Relation with Body Disorders",doi:"10.5772/intechopen.99456",slug:"deficiency-of-vitamin-b-complex-and-its-relation-with-body-disorders",totalDownloads:235,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Vitamins B denote to some diverse kinds of vitamins which collectively, are recognized as B-complex vitamin. At hand are eight types of vitamins in vitamin B complex; thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), biotin (B7), folate (B9) also known as folic acid and cobalamin (B12). B vitamins have a direct impact on body energy levels, brain function and cell metabolism. There is a roundup of four top causes of vitamin B deficiency; a non-balanced diet, excessive alcohol consumption, various medications and gut malabsorption conditions. Deficiencies in these B vitamins can lead to a number of different symptoms like paresthesias, peripheral neuropathy, psychosis and heart attack and stroke over time if the deficiency is not reversed. Vitamins are found in highest abundance in meat, eggs and dairy or milk products such as butter, yogurt and cheese produced from milk of mammals usually buffaloes, cattle, goats, sheep and camels. Most people can get many nutrients they need, including B vitamins, by eating a varied diet of lean meats, grains, fruits and vegetables. This chapter provides an affluent of the most common types of vitamins B, including why body needs these, their deficiency symptoms and which foods contain them.",signatures:"Muhammad Farhan Sarwar, Muhammad Haroon Sarwar and Muhammad Sarwar",downloadPdfUrl:"/chapter/pdf-download/78374",previewPdfUrl:"/chapter/pdf-preview/78374",authors:[{id:"272992",title:"Dr.",name:"Muhammad",surname:"Sarwar",slug:"muhammad-sarwar",fullName:"Muhammad Sarwar"},{id:"427673",title:"Dr.",name:"Muhammad Haroon",surname:"Sarwar",slug:"muhammad-haroon-sarwar",fullName:"Muhammad Haroon Sarwar"},{id:"427674",title:"Dr.",name:"Muhammad Farhan",surname:"Sarwar",slug:"muhammad-farhan-sarwar",fullName:"Muhammad Farhan Sarwar"}],corrections:null},{id:"77817",title:"Retrospective, Perspective and Prospective of B-Complex Vitamins: Encapsulation of Vitamins and Release from Vitamin-Loaded Polymers",doi:"10.5772/intechopen.99284",slug:"retrospective-perspective-and-prospective-of-b-complex-vitamins-encapsulation-of-vitamins-and-releas",totalDownloads:120,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Vitamins are regarded as vital nutrients because, when combined, they performed hundreds of functions in the body. They strengthen bones, heal wounds, and boost your immune system. In addition, they transform food into energy and heal cellular damage. In this regard, B-complex vitamins, such as thiamine, riboflavin, and niacin are soluble vitamins that serve as coenzymes in energy metabolism enzymatic activities which building blocks of a healthy body. However, B-complex vitamins are sensitive to light, pH conditions, and temperature. Consequently, they must be encapsulated before they may be used in pharmaceuticals. Recently, it is mainly focused on reducing drug degradation or loss, increase drug bioavailability, limit adverse effects, and improve drug accumulation in the targeted location. To maintain optimum bioavailability during a defined term of therapy, the fraction of drug dosage released from a controlled release product must be significant enough to adjust for the quantity of active drug metabolized and/or eliminated from the body over the same period. Drug release systems also aim to increase the effectiveness of the drug and treat the damaged area. In this chapter, it is aimed to study the production of the vitamin-loaded polymer systems in various forms, such as micro/nanoparticles, micelle, hydrogel, liposome, and nanofiber, as well as release studies in pharmaceutical and biomedical applications.",signatures:"Fatma Nur Parin",downloadPdfUrl:"/chapter/pdf-download/77817",previewPdfUrl:"/chapter/pdf-preview/77817",authors:[{id:"419815",title:"Dr.",name:"Fatma Nur",surname:"Parın",slug:"fatma-nur-parin",fullName:"Fatma Nur Parın"}],corrections:null},{id:"78424",title:"Vitamin B6 and Related Inborn Errors of Metabolism",doi:"10.5772/intechopen.99751",slug:"vitamin-b6-and-related-inborn-errors-of-metabolism",totalDownloads:172,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Vitamin B6 (vitB6) is a generic term that comprises six interconvertible pyridine compounds. These vitB6 compounds (also called vitamers) are pyridoxine (PN), pyridoxamine (PM), pyridoxal (PL) and their 5′-phosphorylated forms pyridoxine 5′-phosphate (PNP), pyridoxamine 5′-phosphate (PMP) and pyridoxal 5′-phosphate (PLP). VitB6 is an essential nutrient for all living organisms, but only microorganisms and plants can carry out de novo synthesis of this vitamin. Other organisms obtain vitB6 from dietary sources and interconvert its different forms according to their needs via a biochemical pathway known as the salvage pathway. PLP is the biologically active form of vitB6 which is important for maintaining the biochemical homeostasis of the body. In the human body, PLP serves as a cofactor for more than 140 enzymatic reactions, mainly associated with synthesis, degradation and interconversion of amino acids and neurotransmitter metabolism. PLP-dependent enzymes are also involved in various physiological processes, including biologically active amine biosynthesis, lipid metabolism, heme synthesis, nucleic acid synthesis, protein and polyamine synthesis and several other metabolic pathways. PLP is an important vitamer for normal brain function since it is required as a coenzyme for the synthesis of several neurotransmitters including D-serine, D-aspartate, L-glutamate, glycine, γ-aminobutyric acid (GABA), serotonin, epinephrine, norepinephrine, histamine and dopamine. Intracellular levels of PLP are tightly regulated and conditions that disrupt this homeostatic regulation can cause disease. In humans, genetic and dietary (intake of high doses of vitB6) conditions leading to increase in PLP levels is known to cause motor and sensory neuropathies. Deficiency of PLP in the cell is also implicated in several diseases, the most notable example of which are the vitB6-dependent epileptic encephalopathies. VitB6-dependent epileptic encephalopathies (B6EEs) are a clinically and genetically heterogeneous group of rare inherited metabolic disorders. These debilitating conditions are characterized by recurrent seizures in the prenatal, neonatal, or postnatal period, which are typically resistant to conventional anticonvulsant treatment but are well-controlled by the administration of PN or PLP. In addition to seizures, children affected with B6EEs may also suffer from developmental and/or intellectual disabilities, along with structural brain abnormalities. Five main types of B6EEs are known to date, these are: PN-dependent epilepsy due to ALDH7A1 (antiquitin) deficiency (PDE-ALDH7A1) (MIM: 266100), hyperprolinemia type 2 (MIM: 239500), PLP-dependent epilepsy due to PNPO deficiency (MIM: 610090), hypophosphatasia (MIM: 241500) and PLPBP deficiency (MIM: 617290). This chapter provides a review of vitB6 and its different vitamers, their absorption and metabolic pathways in the human body, the diverse physiological roles of vitB6, PLP homeostasis and its importance for human health. Finally, the chapter reviews the inherited neurological disorders affecting PLP homeostasis with a special focus on vitB6-dependent epileptic encephalopathies (B6EEs), their different subtypes, the pathophysiological mechanism underlying each type, clinical and biochemical features and current treatment strategies.",signatures:"Hilal H. Al-Shekaili, Clara van Karnebeek and Blair R. Leavitt",downloadPdfUrl:"/chapter/pdf-download/78424",previewPdfUrl:"/chapter/pdf-preview/78424",authors:[{id:"418849",title:"Dr.",name:"Hilal",surname:"H. Al-Shekaili",slug:"hilal-h.-al-shekaili",fullName:"Hilal H. Al-Shekaili"},{id:"418866",title:"Prof.",name:"Clara",surname:"van Karnebeek",slug:"clara-van-karnebeek",fullName:"Clara van Karnebeek"},{id:"418867",title:"Prof.",name:"Blair",surname:"R. Leavitt",slug:"blair-r.-leavitt",fullName:"Blair R. Leavitt"}],corrections:null},{id:"78912",title:"Several Dosage Forms Containing Vitamin B and Their Use in Therapy",doi:"10.5772/intechopen.99645",slug:"several-dosage-forms-containing-vitamin-b-and-their-use-in-therapy",totalDownloads:110,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Vitamin B plays a critical role in the synthesis of DNA and maintaining the normal functioning of tissues. Therefore, its deficiency may lead to mental problems such as depression, schizophrenia, dementia, and systemic problems such as megaloblastic anemia and peripheral neuropathy. Vitamin B deficiency may be based on nutrition, as well as the use of some drugs such as metformin and omeprazole suppress the absorption of B vitamins, which may lead to deficiency. Since B vitamin is water soluble, it cannot be stored in the body. For this reason, it should be taken continuously with food. However, in cases where the vitamin B taken with food is not sufficient for the body, it should be reinforced with drugs or dietary supplements from outside. Studies have shown that the absorption of Vitamin B is 50% higher in food supplements than in foods. It can also be used as a targeting agent in tumor therapy, due to its overexpression in some tumor cells. Due to these properties of Vitamin B, various dosage forms are being developed. In this chapter, vitamin B-containing dosage forms, their production techniques, and their use in therapy will be mentioned.",signatures:"Özlem Çoban",downloadPdfUrl:"/chapter/pdf-download/78912",previewPdfUrl:"/chapter/pdf-preview/78912",authors:[{id:"418185",title:"Assistant Prof.",name:"Özlem",surname:"Çoban",slug:"ozlem-coban",fullName:"Özlem Çoban"}],corrections:null},{id:"78604",title:"Vitamins D and B12, Altered Synaptic Plasticity and Extracellular Matrix",doi:"10.5772/intechopen.100055",slug:"vitamins-d-and-b-sub-12-sub-altered-synaptic-plasticity-and-extracellular-matrix",totalDownloads:163,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Brain plasticity is regulated through dynamic interactions between perineuronal nets, matrix metalloproteases (MMPs) and the extracellular matrix (ECM). Several studies have identified a crucial role for vitamins D and B12 in brain development and a deficiency in these vitamins may contribute to the emergence of cognitive deficits, as well as the onset of both autism spectrum disorder and schizophrenia. However, the mechanisms underlying the interplay between ECM, MMPs, vitamins and these neuropsychiatric conditions are poorly understood. In this chapter, we seek to understand how the risk of neurodegeneration in vulnerable individuals and the aetiology of specific neuropsychiatric disorders are affected by vitamin D and B12 deficiency, in conjunction with low levels of the antioxidant glutathione, impaired GABAergic inhibition, and alterations in the permanent ECM.",signatures:"Marcela Bermudez Echeverry, Silvia Honda Takada, Bruna Petrucelli Arruda, Debora Sterzeck Cardoso, Pamela Pinheiro Martins, Juliane Midori Ikebara, Aline V. Sousa-Santos and Victor R.C. Torres da Silva",downloadPdfUrl:"/chapter/pdf-download/78604",previewPdfUrl:"/chapter/pdf-preview/78604",authors:[{id:"303364",title:"Prof.",name:"Marcela",surname:"Bermudez Echeverry",slug:"marcela-bermudez-echeverry",fullName:"Marcela Bermudez Echeverry"},{id:"429447",title:"Prof.",name:"Silvia",surname:"Honda Takada",slug:"silvia-honda-takada",fullName:"Silvia Honda Takada"},{id:"429448",title:"MSc.",name:"Bruna",surname:"Petrucelli Arruda",slug:"bruna-petrucelli-arruda",fullName:"Bruna Petrucelli Arruda"},{id:"429449",title:"MSc.",name:"Debora",surname:"Sterzeck Cardoso",slug:"debora-sterzeck-cardoso",fullName:"Debora Sterzeck Cardoso"},{id:"429450",title:"MSc.",name:"Pamela",surname:"Pinheiro Martins",slug:"pamela-pinheiro-martins",fullName:"Pamela Pinheiro Martins"},{id:"429451",title:"MSc.",name:"Juliane",surname:"Midori Ikebara",slug:"juliane-midori-ikebara",fullName:"Juliane Midori Ikebara"},{id:"429452",title:"MSc.",name:"Aline V.",surname:"Sousa-Santos",slug:"aline-v.-sousa-santos",fullName:"Aline V. Sousa-Santos"},{id:"429453",title:"MSc.",name:"Victor R.C.",surname:"Torres da Silva",slug:"victor-r.c.-torres-da-silva",fullName:"Victor R.C. Torres da Silva"}],corrections:null},{id:"78117",title:"Thiamin (B1) and Its Application in Patients with Critical Condition",doi:"10.5772/intechopen.99626",slug:"thiamin-b1-and-its-application-in-patients-with-critical-condition",totalDownloads:67,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Thiamin is an essential water-soluble nutrient that is naturally available in some foods and available as a supplement. This nutrient plays a vital role in metabolism, cell growth and development. The recommended daily intake of thiamin for adults is around 1.1–1.2 mg/day. Several studies have described that thiamin deficiency is commonly seen in critically ill patients, mainly sepsis. Thiamin deficiency reduces pyruvate access to the Krebs cycle, therefore, increases the production of lactate. The administration of thiamin in critically ill patients has been linked to better outcomes and depletion of mortality rate.",signatures:"Bastian Lubis, Putri Amelia, Aznan Lelo, Muhammad Akil and Vincent Viandy",downloadPdfUrl:"/chapter/pdf-download/78117",previewPdfUrl:"/chapter/pdf-preview/78117",authors:[{id:"416492",title:"M.D.",name:"Bastian",surname:"lubis",slug:"bastian-lubis",fullName:"Bastian lubis"},{id:"426756",title:"Dr.",name:"Putri",surname:"Amelia",slug:"putri-amelia",fullName:"Putri Amelia"},{id:"426757",title:"Dr.",name:"Muhammad",surname:"Akil",slug:"muhammad-akil",fullName:"Muhammad Akil"},{id:"426758",title:"Dr.",name:"Vincent",surname:"Viandy",slug:"vincent-viandy",fullName:"Vincent Viandy"},{id:"426759",title:"Prof.",name:"Aznan",surname:"Lelo",slug:"aznan-lelo",fullName:"Aznan Lelo"}],corrections:null},{id:"79851",title:"Role of Dietary Supplements in Prevention of Renal Stones: An Update",doi:"10.5772/intechopen.101661",slug:"role-of-dietary-supplements-in-prevention-of-renal-stones-an-update",totalDownloads:100,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Kidney stone disease is an oldest known and widespread medical condition characterised by its high prevalence in all over the world. Literature suggests that around 9–12% of population in industrialised countries have kidney stone disease in their lives with the 30–50% of reoccurrence rate. Because of high prevalence, recurrent and unpredictable nature of stone formation and its predominance mainly in adults contributes to the substantial impact on society, individual and health care system. In light of these trends, it’s imperative to use optimum preventive strategies to reduce the burden of kidney stone disease on individual and society. The aetiology of kidney stone disease is a multifactorial and it’s related to diet, environmental factors, genetics, metabolic syndromes and various life style factors. Its noteworthy that dietary and life style modification are the major contributors in the prevention of kidney stone reoccurrence. Dietary interventions aim to reduce the urinary abnormalities known to promote lithogenesis. Therefore, modification in the dietary factors is appealing way to patients and physicians in the treatment and prevention of stone recurrence as it is relatively inexpensive and safe. So, the present chapter is focusing on the role of dietary supplements in prevention of renal stones.",signatures:"Akshata Sangolli, Shridhar C. Ghagane and Rajendra B. Nerli",downloadPdfUrl:"/chapter/pdf-download/79851",previewPdfUrl:"/chapter/pdf-preview/79851",authors:[{id:"227286",title:"Dr.",name:"Shridhar C.",surname:"Ghagane",slug:"shridhar-c.-ghagane",fullName:"Shridhar C. Ghagane"},{id:"227446",title:"Prof.",name:"Rajendra B.",surname:"Nerli",slug:"rajendra-b.-nerli",fullName:"Rajendra B. 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Thus, a complete and nutritious diet must be followed before approved drugs and potential good vaccine research results are available to boost the normal functioning of the immune system. In order to activate adaptive and inborn immune responses, reduce cytokine levels such as proinflammatory cytokines, decrease oxidative stress, preserve endothelial homogeneity, improving pulmonary function, prevents hypercoagulable conditions and shortening the length of hospital stay; B-Complex vitamins play a significant role. 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From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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This mechanism is regulated by antioxidant system. With age, genetic, and environmental risk factors, this system becomes imbalanced and oxidative stress (OS) follows through increased levels of reactive oxygen and nitrogen species (ROS/RNS). The accumulation of oxidative damage induces modifications of lipids, proteins, and DNA/RNA, a common feature of many neurodegenerative diseases, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). Although it is difficult to impose one if oxidative stress is a cause or epiphenomenon of neuronal death, the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway is a primary sensor of oxidative stress and regulates the expression of several genes encoding antioxidant proteins and detoxifying. The Nrf2-ARE pathway activation, in animal models of neurodegeneration, has produced positive effects; these data support the need for studies aimed to develop drugs able to activate Nrf2-ARE pathway in the central and peripheral nervous system. This chapter sums up the role of oxidative damage in neurodegenerative disorders and the protective functions of the Nrf2-ARE pathway.
\nOriginally, the primordial eukaryotic cells were unable to use oxygen for metabolic purposes. More than one billion years ago, according to endosymbiosis theory, these eukaryotic cells were colonized by aerobic bacteria, which can change with the host cells, and intracellular organelles became those we now call mitochondria. This alliance has facilitated bacteria to the availability of metabolic substrates, now assigned to the host cell, and at the same time has made a new kind of metabolism, much more efficient, eukaryotes: aerobic or oxidative metabolism [1]. Mitochondria are cytoplasmic organelles ranging from 1 to 10 μ and are often described as “electrical control units of the cell” because they generate most cell supply of adenosine triphosphate (ATP), used precisely as a chemical energy source from cell. Mitochondria not only perform this function but are also involved in other processes, such as signaling, cell differentiation, death, and also in the cell cycle control and cell growth [2]. The number of mitochondria in a cell varies according to the type of tissue and the body; there are cells with a single mitochondrion and cells with many thousands of mitochondria; these organelles are able to move freely in the cytoplasm and tend to thicken in the points where there is a greater demand for energy. The mitochondria, by means of the mitochondrial respiratory chain (OXPHOS), and through the process of oxidative phosphorylation, fulfill the requirements of ATP and therefore of energy of the cell [3]. The respiratory chain consists of a series of electron carriers (complexes), most of which are integral proteins of the inner membrane, containing prosthetic groups associated to proteins able to accept and donate one or two electrons [3]. The electron carrier complexes are four types: complexes I, II, III, and IV, in which two mobile electron carriers are to be added: cytochrome c and coenzyme Q. The respiratory chain is a very efficient mechanism, but during the step of transporting electrons, it may happen that a small percentage of electrons may prematurely reduce oxygen, forming reactive oxygen species (ROS), which are potentially harmful and dangerous for the cell. ROS are ions or very small molecules that include oxygen ions, free radicals and peroxides, organic and inorganic; they are highly reactive due to the presence of unpaired electrons in the orbital outside and are formed as a natural byproduct of oxygen metabolism and play an important role in cell signaling. The main source of ROS in vivo is aerobic respiration precisely, although they are also produced by the fatty acids beta-oxidation, by the xenobiotic components metabolism, after the activation of phagocytosis by pathogens. During periods of environmental stress, the ROS levels can increase dramatically, causing significant damage to cell structures. This increase is identified with the term of oxidative stress (OS) [4]. OS is usually defined as the altered balance between the production of ROS and their removal by cellular antioxidant mechanisms, such us enzymatic scavengers and low-molecular-weight reductants. Mitochondria use most of available oxygen (85–90%) to produce ATP, but, at the same time, are the major producers of ROS, such as superoxide (O−2) and hydrogen peroxide (H2O2) principally originate by loss of electrons from OXPHOS during oxidative phosphorylation with the consequent incomplete reduction of molecular oxygen [5, 6]. Superoxide itself is not greatly dangerous; nevertheless, it can rapidly react with the mild oxidant nitric oxide (NO to generate peroxynitrite (ONOO−) [7, 8]. Similarly, H2O2 is a slight oxidant but bit by bit it decomposes to generate the hydroxyl radical
Several lines of evidence in the literature suggest that the reactive chemical species and electrophilic substances can have an important role in inducing different causative mechanisms of various pathologies such as tumorigenesis, diseases affecting the cardiovascular system, central nervous system, and peripheral nervous system [21, 22]. The human body, in order to neutralize these toxic substances, has developed a plethora of defense mechanisms [23]. Between the several mechanisms, the Nrf2-ARE pathway is now considered the most regulator of cellular defense mechanisms against oxidative stress [24].
\nNrf2 be up to the Cap‘n’collar (Cnc) transcription factor family and is considered the leader of the antioxidant response since it regulates the expression of several defensive genes [25, 26]. Nrf2 is a very unstable protein, typically present in association with its negative regulator Kelch-like ECH-associated protein 1 (Keap1), which acts as a molecular sensor of cellular oxidative stress. Under basal condition, Keap1 restrains Nrf2 in the cytoplasm leading to its degradation. Particularly, Keap1 acts as a connection protein between Nrf2 and the Cul3-based E3-ubiquitin ligase complex, promoting Nrf2 ubiquitination and consequent degradation by the 26S proteasome [27, 28]. Activation of Nrf2 involves its cytosolic stabilization; specific cysteine residues (Cys 151, Cys 273, and Cys 288) have been identified as direct sensors for electrophiles and oxidants; chemical modifications in these sensor residues cause a conformational change that produce the dissociation of Nrf2 from Keap1. Nrf2, detached from his repressors, translocates to the nucleus and binds its partner, small Maf protein. The heterodimer Nrf2-sMAF ultimately binds antioxidant response element (ARE) sequences leading to the expression of cytoprotective genes thus allowing cell to efficiently cope with endogenous stress and exogenous toxicants [29]. Nrf2 also is able to modulate the transcription of genes involved in mitochondrial biogenesis [30] (Figure 1).
Regulation of Nrf2 by Keap1. In basal conditions, Nrf2 is sequestered in the cytoplasm by a Keap1 homodimer that facilitates ubiquitination and degradation of Nrf2 in the proteasome. In the presence of inducers that react with specific cysteine residues of Keap1, you get the release of Nrf2 and its nuclear translocation. In the nucleus, Nrf2 heterodimerizes with small Maf proteins and binds the antioxidant response element (ARE), by activating the expression of a battery of cytoprotective genes.
Abnormalities of Nrf2-ARE pathway were observed in several models of disease-aging dependent and in degenerative disorders; changes of Nrf2-ARE pathway cause ROS accumulation and therefore increase of oxidative damage to biological macromolecules. Several evidences in literature have showed that Nrf2 activation is induced in dopaminergic neurons in PD cases, but is decreased in hippocampus of AD patients [31]. In the motor cortex and spinal cord of ALS patients,
Pluripotent stem cells (iPSC)-derived neurons, which are generated from PD patients with PARK2 mutations, show an altered redox balance, mitochondrial dysfunction, and increased activity of the Nrf2 pathway [43]. Another study shows a significant alteration of the Nrf2-ARE pathway in neurospheres derived from the olfactory mucosa of PD patients [44]. Similar fluctuations are seen in two transgenic animal models of PD: αSyn-mutant A53T hαSynA53T [45] and MPTP mouse model [46]. In particular, Nrf2 downstream genes related to glutathione synthesis increase at the early stage and decrease at the late-stage disease with corresponding change in the total glutathione levels. Nrf2-regulated genes involved in glutathione synthesis, metabolism and transportation and detoxification of hydrogen peroxide/quinones increase in the SN and striatum of 1-month-old αSyn mice [47]. The Nrf2-ARE system is activated in cell culture systems as well in response to paraquat and maneb [48], and 6-hydroxydopamine [48, 49]. Apparently, the endogenous activation of the Nrf2-ARE pathway seems insufficient to neutralize the accumulation of oxidative damage. Thus, the research is focused in identifying an exogenous substance able to maintain long endogenous Nrf2-ARE activation to help the brain defend itself from oxidative damage [45, 50–53].
\nParkinson’s disease affects more than 1% of the population over 60 years of age and is the second most common neurodegenerative disorder after AD [54]. The 90% of cases are sporadic, whereas about 10% show a family background [55].
\nPD is caused by the degeneration of dopaminergic neurons within the substantia nigra pars compacta (SNc) and it is known that PD neurons are more susceptible to OS [56]. The selective vulnerability of SNc dopaminergic neurons can be caused by several pathogenic mechanisms that include exposure to genetic and environmental risk factors, alterated proteolytic systems, and mitochondrial dysfunctions [57]. In particular, mitochondrial defects lead to impaired energy and ROS production and therefore to altered bioenergetic and redox balance.
\nConsistent evidence shows that disrupted mitochondrial integrity and OS play a pivotal role in PD pathogenesis and disease progression.
\nMutations in several genes, such as PARK2, PARK6, and PARK7, are associated with early-onset familial forms of PD and with mitochondrial alterations leading to neuronal death [58]. Several studies show that some substances, such as MPTP and rotenone, are able to inhibit mitochondrial complex I and increase ROS production with possible loss of dopaminergic neurons in the SNc [59]. Furthermore, peripheral and central markers of oxidative damage are altered in PD patients, indicating that OS is a crucial player in PD pathogenesis [60–62]. PD has also been associated with alterations in the expression of antioxidant molecules such as glutathione and antioxidant enzymes. It was shown that oxidized glutathione is significantly higher, while other antioxidant molecules and catalase activity are decreased in blood cells from PD patients [63]. Furthermore, several studies have shown that the activation of antioxidant genes expression, in particular those under the control of the Nrf2/ARE system, has neuroprotective effects in different models of PD [64, 65].
\nActivation of the Nrf2-ARE pathway is able to protect against the toxic forms of αSyn. In SK-N-SH neuroblastoma cells, ferrous iron promotes αSyn aggregation through inhibiting Nrf2 pathway [66]. In a PD animal model, it was observed that the transgenic activation of Nrf2 and knockdown of Keap1 could delay the αSyn-mediated dopaminergic neuron loss and motor dysfunction [67]. Conversely, genetic deletion of Nrf2 increases αSyn toxicity and exaggerates αSyn/p-αSyn accumulation in dopaminergic neurites and gliosis. Nrf2 deficiency enhances the inflammatory response and lowers the capability of phagocytosis in primary microglial cells [68].
\nRecently, studies have identified the importance of astrocytic Nrf2-regulating αSyn proteostasis. Astrocytic overexpression of Nrf2 (GFAP-Nrf2) can reduce αSyn aggregates in the central nervous system of a PD mouse model with neuronal overexpression of human αSyn-mutant A53T [45]. The accumulation of hαSynA53T in the Triton-soluble fraction from the spinal cord decreases 60% in symptomatic mice. This is accompanied by a significant increase in hαSynA53T in the Triton-insoluble/SDS-soluble fraction. This movement of αSynA53T into Triton-insoluble/SDS-soluble aggregates is completely reversed by the overexpression of Nrf2 in astrocytes.
\nSimilar changes are observed for phosphorylated (Ser129) αSynA53T (p-hαSynA53T) in Triton-soluble and Triton-insoluble/SDS-soluble fractions. Fluorescent staining of hαSynA53T also shows a dramatic increase in hαSynA53T aggregates that colocalized with phαSynA53T. Again, these changes are completely reversed by GFAP-Nrf2.
\nThe autophagy-lysosome pathway (ALP) is a protein degradation system responsible for the turnover of proteins, aggregate proteins, and damaged organelles. Dysfunctions of autophagic mechanism result in the accumulation of cytoplasmic aggregates composed of misfolded proteins and deformed organelles, leading to neurodegeneration and other diseases [69–71]. A significant dysfunction of autophagic machinery is observed in the αSynA53T mice model [45, 72–74]. Nrf2 prevents chaperone-mediated autophagy dysfunction and increases lifespan, delays onset, and reduces aggregation in αSynA53T mice [45].
\nAlzheimer’s disease (AD) is the most common neurodegenerative disease, accounting for 60–70% of cases of dementia, and although its etiology is still unclear, it is characterized by the presence of brain amyloid plaques and neurofibrillary tangles whose accumulation ultimately leads to extensive neuronal loss and progressive decline of cognitive function [75–77]. They are aggregates of proteins distributed in the entorhinal cortex, hippocampus, and temporal, frontal, and inferior parietal lobes. Amyloid plaques are composed of aggregates of β-amyloid (Aβ) and of other protein aggregates such as hyperphosphorylated Tau, ubiquitin, and presenilins 1 and 2; amyloid plaques are sticky buildup which accumulates outside nerve cells. Neurofibrillary tangles are abnormal collections of twisted protein threads found inside nerve cells; the tangles are aggregates of hyperphosphorylated Tau protein [78]. Some of the major risk factors for AD are unhealthy aging in sporadic AD cases, the presence of ApoE-4 alleles in both sporadic and familial AD [79], and genetic factors, such as mutation in amyloid precursor protein (APP) and presenilin-1 (PS1) in familial AD [80] among others. AD brain is characterized by mitochondrial dysfunction, reactive gliosis, and oxidative damage to lipids and proteins [81–85].
\nSeveral studies demonstrate that the AD brain is under oxidative stress attack. A significantly increased HO-1 expression was reported in postmortem AD temporal cortex and hippocampus [82]. Additionally, an increased Nqo1 activity and expression were found in astrocytes and neurons of AD brain [86, 87] and Nrf2 was localized in cytoplasm in AD hippocampal neurons [31]. Furthermore, there is increased protein oxidation [88, 89] and lipid peroxidation [90–92] in AD brain. Recent studies in aged APP/PS1 AD mouse models showed Nrf2 protein levels [93].
\nSeveral evidences in literature have shown that Nrf2-ARE pathway is able to mitigate the toxicity mediated by Aβ. These studies have confirmed the neuroprotective role of Nrf2 against ROS generation and cell death induced by Aβ in vitro [94–97]. Tert-butylhydroquinone (tBHQ), a prototypical Nrf2 activator, has been reported to reduce Aβ1-42 secretion in the NT2N cell line with increased cell viability [98]. The sulforaphane, Nrf2 activator, is able to preserve cognitive function in an AD animal model [99]. Strikingly, overexpression of mitochondria catalase in APP (Tg2576) transgenic mice dramatically reduces full-length APP and its c-terminal fragment 99, lowers soluble and insoluble Aβ levels, extends lifespan, and improves working memory [100]. A genetic study has demonstrated that overexpression of Nrf2 in the hippocampus causes increase in mTOR activity; these data suggest that Nrf2 could mediate autophagy and alter processing/clearance of APP and/or Aβ.
\nALS is a progressive disease with fatal outcome, in which the motor cortex and spinal cord motor neurons are selectively affected. The disease in 90% of cases occur sporadically (SALS) while in 10% of cases there is a clear familiarity (FALS) [101]. The etiology and pathogenesis of ALS are currently largely unknown. ALS is considered a degenerative multifactorial disease in which cell death is a consequence of a complex interaction between genetic risk factors and environmental factors. To explain the neuronal death, several hypotheses have been proposed, among which the most accredited implicates oxidative stress [102–106]. In fact, levels of oxidative stress biomarkers were observed to be altered in SALS patients; these data indicate that most likely a redox imbalance is relevant in the pathogenesis of disease [107–112]. Elevated levels of HNE have been detected also in cerebrospinal fluid (CSF) from ALS patients [113, 114]. Additionally, mitochondrial alterations have been observed in motor neuron of ALS patients [115–118]. These dysfunctions are tightly interrelated with OS cascades, activating overlapping molecular pathways in a vicious cycle of harmful events. Specifically, alterations in mitochondrial morphology and biochemistry have been extensively detected in postmortem tissues [119] and in lymphocytes [120] from SALS patients, in SOD1 transgenic mice, and cellular models [52]. Dynamic and morphological abnormalities, along with metabolic deficits in the activities of the OXPHOS proteins, have also been described in both SALS and FALS patients [121]. Furthermore, impairment in antioxidant mechanisms has also been shown in ALS, including downregulation of members of glutathione S-transferase family [122, 123], peroxiredoxins [124], and Nrf2 [125–129].
\nThe first causative gene associated with genetic ALS form was the Cu-Zn superoxide dismutase 1. In FALS patients with SOD1 gene mutations and in G85R animal model, cytoplasmic inclusions containing modified SOD1 proteins have been observed [130]. In the last decade, genome-wide association (GWA) studies identified two genes associated with sporadic and non-SOD1 familial ALS: RNA/DNA-binding proteins, 43-kDa transactive response (TAR) DNA-binding protein (TDP-43), and fused in sarcoma/translocated in liposarcoma (FUS/TLS) [131–135]. Both TDP-43 and FUS are predominantly nuclear proteins involved in RNA metabolism; however, both are observed as aggregates in the cytosol of ALS neurons [136].
\nNrf2 activators have been shown to protect against oxidative stress and cell death induced by SOD1-mutant protein [137, 138]. The Nrf2 overexpression in glial cells directly increases the resistance to oxidative stress and helps indirectly, through the increate secretion of glutathione, the ability of the motor neurons to neutralize the toxic effects caused by SOD1-mutant protein [139]. Also Nrf2 and Keap1 expression analysis showed a reduction of Nrf2 protein in patients than in controls; conversely, there have been no significant differences in the expression of Keap1 levels between patients and controls [140–142].
\nRecently, NSC34 motor neuronal cell lines expressing TDP-43 mutants exhibit shortened neurites, alteration of oxidative stress markers levels. These effects are reversed by the UPS inhibitor MG132, but not by the Nrf2 activator sulforaphane [143, 144]. This is attributed to an increase in HO-1 following MG132 treatment that appeared to be independent of Nrf2 activation. While the role of Nrf2 in protection against SOD1-mutant neuronal toxicity is clear, its effect on other ALS-associated gene mutations particularly TDP43 and FUS needs to be clarified by future studies.
\nThe manipulation of the Nrf2-ARE pathway at the genetic level is being studied through the use of siRNA or antisense oligonucleotides against Keap1 to activate/overexpress Nrf2. Antisense drugs are being researched to study neurodegenerative disorders, cancer, metabolic disorders, and disorders with inflammatory components among others. Antisense drug fomivirsen, marketed as Vitravene, has been approved by the US Food and Drug Administration (FDA) for the treatment of cytomegalovirus retinitis. Since then, numerous antisense therapies have been tested but have not produced significant clinical result. This has not diminished the potential of gene therapies. Antisense oligonucleotide can bind to the target RNA and disrupt RNA splicing, transcription, translation, and replication, thereby modulating gene expression. Several studies showed that siRNA-mediated knockdown of Keap1-activated Nrf2-ARE pathway in mouse cortical astrocytes and provided partial protection against MPTP-mediated toxicity in mouse, in vivo [65, 145]. The overexpression of target gene can also be achieved by viral-mediated gene transduction but it is too early to conclude on efficacy of viral-mediated gene therapy in human neurodegenerative disorder cases. Nrf2 modulation in various neurodegenerative disorders has been previously described in this chapter. Hence, using the antisense oligonucleotide against Keap1, lentiviral-mediated Nrf2 overexpression or siRNA against Keap1-mediated overexpression of Nrf2 treatment can prove beneficial in neurodegenerative disorders.
\nAmong recent patents, Curna, Inc. filed patent for the use of antisense for the treatment of Nrf2-related disorders. The initial study published under International Application for the Patent Cooperation Treaty (PCT) showed that antisense CUR-0330 and CUR 0332 showed two- to threefold increase in Nrf2 mRNA expression compared to control (PCT/US2010/027394). The invention is targeted at the inhibition of natural antisense transcript to Nrf2 as a strategy toward modulation of Nrf2 expression in disease models [145].
\nThe modulation of Nrf2 expression by using several other pharmacological interventions to inhibit Keap1 and Nrf2 interaction is under investigation.
\nThe Nrf2/ARE pathway can be pharmacologically activated also by molecules of both natural derivation (nutraceuticals) and chemical synthesis. Between Nrf2/ARE activators of natural origin, sulforaphane, polyphenols, and curcumin have been included; between chemical synthesis substances, chemical Nrf2/ARE activators include triterpenoids and N-(4-(2-pyridyl)(1,3-thiazol-2-yl))-2-(2,4,6-trimethylphenoxy) acetamide (CPN-9).
\nSFN, derived from cruciferous vegetables such as broccoli, activates Nrf2 through the modification of reactive cysteine residues of Keap1 [146, 147], and SFN is able to overstep the blood-brain barrier, induce the transcription of Nrf2-dependent gene expression in the basal ganglia, and protect dopaminergic neurons from cell death MPTP induced [64, 148]. Other Nrf2/ARE pathway natural inducers are EGCG and resveratrol, belonging to the family of polyphenols that, for their antioxidant qualities, are considered to be important nutraceuticals. EGCG, a flavonoid polyphenol, for example, showed antioxidant and neuroprotective functions in cultured motoneuron-neuroblastoma hybrid cell line transfected with mutSOD1 [149] and in PC12 cells exposed to paraquat [150]. Furthermore, EGCG was shown to be neuroprotective in mice model of ALS: oral administration to mice expressing mutSOD1 delayed symptoms onset [151–154].
\nResveratrol, a polyphenolic compound present in red wine, demonstrated protective effects against hypoxic injury in rat spinal cord dorsal column by activating Nrf2 pathway [155, 156].
\nCurcumin, a member of the curcuminoid family isolated from plant
Furthermore, several synthetic Nrf2/ARE activators were recently developed. Recently, triterpenoids emerged as a potent class of Nrf2/ARE inducers. Triterpenoids are very powerful inducer of Nrf2 pathway: they are able to protect dopaminergic neurodegeneration in MPTP mouse model of PD [165], and increase the lifespan in ALS mouse models [166]. Another chemical activator of Nrf2/ARE pathway is CPN-9 which selectively suppresses cell death triggered by OS in a cell-type-independent manner. SH-SY5Y cells pretreated with CPN-9 were more resistant to cytokine-induced apoptosis. CPN-9 is able to decrease the ROS levels through the induction of several antioxidant genes [137]. Finally, we know that that some drugs such as bromocriptine [167] and azathioprine [168] were capable to induce the Nrf2/ARE pathway, therefore providing insight into a possible development of new synthetic molecules Nrf2 activators.
\nOxidative stress and misfolded proteins are two mechanisms that act together to the pathogenesis of several inflammatory and degenerative diseases. The detailed mechanism by which Nrf2-ARE pathway carries out its action is still unclear. Current data suggest that Nrf2 affects both primary protein degradation pathways, the UPS and ALP, which are both altered in neurodegenerative diseases.
\nDespite the progress made in understanding the importance of Nrf2/ARE pathway, it remains to clarify the exact mechanism by which it exerts its function so that it may lead to discovery of new targets for the treatment of neurodegenerative diseases. In the past decade, Nrf2-ARE pathway activation has shown promising results for the treatment of many disorders including neurodegenerative disease. Several of these Nrf2 activators or their brain accessible synthetically modified compounds have passed phase II and III clinical trials. BG-12, an oral formulation of DMF (Biogen Idec, Inc.), is in phase III clinical trials for the treatment of multiple sclerosis (MS). Bardoxolone methyl, an oral formulation of CDDO-MA (Reata Pharmaceuticals, Inc.), is currently in phase III clinical trials for chronic kidney disease in type II diabetes mellitus patients, but there are no existing clinical trials in the pipeline for neurodegenerative disorders. EGCG, resveratrol, and curcumin are in various phases of clinical trial for treatment and efficacy in neurodegenerative disorders such as AD, PD, and ALS. The knowledge gained from these studies will further help in identifying clinically relevant approaches for the activation of Nrf2 in CNS and potentially lead to finding treatments for these devastating neurological disorders.
\nThis chapter was supported by the CariLucca Foundation grant (539999_2014_Siciliano_SLAFCARILUCCA).
\nMegadiverse countries constitute exceptional areas on Earth where most of the planetary biodiversity is present. The complexity of these areas is huge, but in most of the cases, two major points are key: (1) the geographical location, and (2) the abiotic and biotic elements present. Mexico is one of the top five megadiverse countries in the world and its macrodiversity and endemism are well represented by amphibians, mammals, plants, and reptiles [1]. However, the knowledge of microscopic organisms such as archaea, bacteria, protozoa, microscopic algae, and microscopic fungi, that inhabit aquatic, atmospheric, marine, and soil ecosystems is neither poorly known, studied nor understood.
The vision of this chapter is to contribute to the knowledge, research, and study of microscopic life in different Mexican ecosystems, as they are often ignored or poorly mentioned in federal texts or even in biotic inventories. Our examples are some members of the class actinobacteria [2], and we aim to demonstrate why it is so important to study these bacteria in such detail to fully explore and untap the unknown actinobacterial diversity with potential in biology. Using a dynamic isolation strategy on air, soil, and marine sediments and sponges collected from yet unexplored sites of the Mexican territory, we have been able to cultivate novel actinobacteria. Our findings showed that expertise, patience, and talent of the techniques applied are keys in the hunt for new potential microbes.
The isolation of microorganisms, including actinobacteria, is not new but a dynamic strategy that is continuously changing, and the developed to date is a powerful tool. For more than two centuries, researchers from Japan, the UK, and USA have shown that beneficial microorganisms isolated from the soil are important to Biology. In recent years the isolation of the first genus of actinobacteria from the marine origin [3] and novel marine species [4] have shown the importance of exploring the marine environment. Extreme or unexplored sites have also shown the isolation of actinobacteria including putative novel actinobacteria [5].
Our research studying actinobacteria started in 1999 [6, 7], but until 2009 we properly started the exploration of the Mexican (marine) ecosystems [8] as an independent group. We followed bioprospecting, diversity, and systematic approach but designing a selective isolation strategy was the first step for a complete full project or protocol [9].
Actinobacteria is a complex group of bacteria, they present forms such as rods or bacilli, many differentiate in vegetative mycelium, aerial hyphae, and chain of spores, and in a few genera fragmentation of the hyphae is present. In general, the Gram reaction is positive and the content of guanine plus cytosine is above 69%mol. The morphological characteristics within the class showed how complex this group is. Actinobacteria are considered saprophytes or beneficial microbes, but a small number of species have been shown to be either pathogenic [10] or opportunistic [11]. This microbial group has been isolated or cultivated using classical methods from almost every sample taken on Earth and they are always detected when using molecular methods to study this group in a given environmental sample.
Actinobacteria also have the innate ability to produce secondary metabolites with biological activity, to date, this class encompasses 80% of the microbes that produce the antibacterial compounds used in medicine. Complete Genome Sequencing of some genera of actinobacteria such as
The more we study and discover actinobacteria the more important they become in pass, present, and future assignments. Microorganisms and microbial biomass, including actinobacteria, represent the major resource for biotechnology and biological areas. We should continue exploring their role in nature in order to understand their biology, ecology, and bioprospecting potential [13, 14, 15, 16].
The Earth’s atmosphere is divided into six specific layers with completely different characteristics: (1) Troposphere, (2) Stratosphere, (3) Mesosphere, (4) Thermosphere, (5) Ionosphere, and (6) Exosphere. It has been established that the atmosphere plays an important role to transport microorganisms, place to place, continent to continent. The latter has been established using scientific tools in the last 200 years and in the last 15 years, NASA has monitored mineral dust particles from the Sahara desert with a robust precision using spaceborne satellites. These Saharan dust plumes contain microorganisms and enter mainland Mexico by the Yucatan Peninsula [17].
The atmosphere is a hostile environment for microorganisms though there are a significant number of them in the troposphere, with air as their main dispersion pathway. The abundance, diversity, survival, and transport of microorganisms, as passive drivers, and how they get stressed severely by the conditions presented in the atmosphere have fully been reported [18]. Most of the microorganisms in the atmosphere are present as spores, while others have adapted to resist desiccation or high/low temperatures [19]. Recent reports have also shown that some microorganisms (i.e., by using specific proteins) can act as ice nucleating particles [20] and that they may play an important role in cloud formation [21]. In general, bacteria (including actinobacteria) present in the atmosphere are attached to suspended particles [17], and their concentration change notably during the dry or wet seasons of each year [22].
As part of the African Dust and Biomass Burning Over Yucatan (ADABBOY) Project [23] in the city of Merida (N 21°02´75.4´´ W 89°65´44.8´´) a selective isolation strategy was carried out in order to cultivate/recovered putative actinobacteria in May 2017. Air samples were impacted using a Quick Take 30 Sample Pump® and a BioStage® SKC (Figure 1) in Petri dishes prepared with a slightly modified Glucose Yeast Malt extract agar (GYM medium; Appendix A; Medium 65: DSMZ; www.dsmz.de) supplemented with Rifampicin (5 μg/mL; Sigma-Aldrich, USA) and Nystatin (50 μg/mL; MICOSTATIN® Bristol Myers Squibb, Mexico).
The device used for the air particles.
Plates were incubated in two different laboratories and conditions. The first laboratory was in the city of Merida at the Universidad Autónoma de Yucatán, using an aerobic incubator set at 25°C and the plates were incubated for 24 hours. For the second procedure, the plates were transported to a laboratory in Mexico City where the incubation time continued aerobically at 30°C (IncuMax IC-320, Amerex USA) for 8 weeks with eye observation each week. One microorganism with the production of aerial hyphae, a gray mass of spores, and a very deep purple diffusible pigment (Figure 2) was selected from the isolation plates for further studies.
Morphology and purple diffusible pigment of an airborne streptomycete.
The selected isolate was coded C6-CCA-May-1. After a purification process using GYM medium and two different techniques (cross streak and serial dilutions), bacterial biomass and spores of the strain were ultra-preserved in 20% glycerol. Morphological characterization was carried out using a GYM medium (Figure 3) and a Gram staining procedure (Figure 4) was carried out following well-known universal protocols.
Aerial hyphae and spore mass of isolate C6-CCA-May-1.
Gram staining of the airborne streptomycete.
Molecular identification of strain C6-CCA-May-1 was carried out following protocols previously published [8, 24]. First, the DNA of strain C6-CCA-May-1 was extracted and used as a template for PCR amplification using the 16S rRNA gene (Appendix B). The sequence of the 16S rRNA gene PCR product confirmed that strain C6-CCA-May-1 belongs to the genus
Hit taxon name | Hit strain name | Accesion | Similarity | Hit taxonomy | Completeness (%) |
---|---|---|---|---|---|
NBRC 133559T | AB18350 | 99.51 | Bacteria;Actinobacteria;Actinobacteria_c;Streptomycetales;Streptomycetaceae;Streptomyces | 99.6 | |
NBRC 13404T | AB18381 | 98.88 | 99.9 | ||
KNN 35.1bT | LT621750 | 98.77 | 95.5 | ||
NBRC 13000T | AB184249 | 98.66 | 99.9 | ||
NBRC 15423T | AB184670 | 98.66 | 99.0 |
List of hits from the EZbiocloud 16S database.
A Bayesian phylogenetic tree was constructed in order to establish the taxonomic position of
Phylogenetic tree of the 16S rRNA gene of the airborne streptomycete.
Streptomycetes are an ecologically important group capable of producing diverse bioactive compounds. However, their taxonomy and diversity in air samples remain unknown. For almost two centuries the genus
Seventy percent of our planet is covered by the ocean but from one marine research project, there are 10 of terrestrial origin. Little is still known about marine biodiversity (including microorganisms) though their potential is extraordinary and needs to be fully studied and exploited. Mexico is surrounded by the Pacific Ocean, the Sea of Cortez (
In the present project, a total collection of 34 marine sediments or sponges were collected at RANP during two expeditions (December 2017 and January 2018). A selective isolation strategy using 11 of the marine sediments and two different media was developed following a previously reported study [24]. In order to isolate marine obligate and nonobligate actinobacteria, 1 g of wet sediments was transferred to tubes containing 9 mL of saline solution (0.9%; NaCl; Sigma-Aldrich, Mexico), four dilutions were prepared (10−1 to 10−4) and 100 μL (Gilson, France) of each dilution were spread onto marine GYM medium and 1:10 marine GYM medium (Appendix A); both media supplemented with Rifampicin [15, 25 and 50 μg/mL] and Nystatin (100 μg/mL). Plates were then aerobically incubated at 30°C (IncuMax IC-320, Amerex USA) for up to 16 weeks. Starting at week eight, the isolation plates were checked by eye looking for actinobacterial colonies. Once putative colonies were noticed each was then streaked in new GYM plates without antibiotics or antifungal compounds until an axenic culture was obtained. The conditions of incubation were as mentioned above. Because of the pressure set in the isolation strategy, not many microbes were able to grow but actinobacteria were successfully cultivated.
A preliminary test to quickly select marine obligate actinobacteria was carried out using marine GYM medium (Figure 6A and C) and GYM medium (Figure 6B and D). A positive result was considered when nonmicrobial biomass was observed growing on the surface of GYM medium after 4 weeks of incubation (Figure 6B). The ones that presented growth only in the marine GYM medium were considered those marine obligate actinobacteria (Figure 6A). It should be pointed out, however, that we were also able to isolate nonobligate actinobacteria that showed the typical characteristics of members of the family Micromonosporaceae [32] (Figure 6C and D). Up to date there is only one genus that is considered halophile within the Phylum Actinobacteria, and this is
Screening of obligate and nonobligate marine actinobacteria.
The molecular identification using the 16S rRNA gene of obligate and nonobligate marine actinobacteria confirmed that they belong to the genera
Code of microorganism | Identity (%) | Hit taxonomy | Accesion |
---|---|---|---|
C114 col. 1 | 99 | GD145235.1 | |
C60 b bca col. 1 | 100 | MH299440.1 | |
C60a col. 3 | 100 | KX394599.1 | |
C60 col. 4 | 99 | KX394598.1 | |
C72 col. 2 | 100 | AG506245.1 | |
C134 col. 4 | 99 | CF133005.1 |
Taxonomic identification of some of the obligate and nonobligate marine actinobacteria from RANP.
To isolate obligate and nonobligate marine actinobacteria from the sponge samples, five different species of
Strategy to isolate actinobacteria from six marine sponges.
Starting at week eight, the isolation plates were checked by eye looking for actinobacterial colonies (Figure 8). Once putative colonies were selected they were streaked in new GYM plates until axenic culture were obtained. The conditions of incubation were the same as mentioned before.
Morphology of the marine obligate actinobacteria.
The preliminary test to select marine obligate actinobacteria was carried out as mentioned previously. Obligate marine actinobacteria (Figure 9A) were isolated from
Morphology of obligate and nonobligate marine actinobacteria.
We isolated marine obligate actinobacteria that were preliminarily assigned to the genus
The microbial communities of marine obligate and nonobligate actinobacteria associated with marine sediments remain poorly characterized [34] and we must continue searching for these gifted microorganisms [35]. Culture-dependent methods captured approximately 3% of the total count of the microbes and in some reports around 39 genera have been only detected in culture. The latter shows the importance to carry out/improve, innovative and original selective isolation techniques since these may be more effective than previously recognized.
Soil is one of the most complex ecosystems on Earth and its amount of organic matter, mineral composition, and diversity of microorganisms will determine its ecology. There are different kinds of soils but in general, those with less anthropogenic impact will be richer in microorganisms. Mexico encompasses 26 types of soil out of the 32 recognized in the world [36, 37] and this is due to several causes, namely: (1) the complexity of the topography originated from the volcanic activity in the Cenozoic Era, (2) the wide altitudinal gradient (from 0 to 5, 600 m.a.s.l.), (3) by the five main climates present according to the Köppen classification [38], (4) the enormous diversity of landscapes present and, finally (5) the different kind of rocks that the Mexican territory enclose. It is well recognized that actinobacteria are abundant in soils and that they play an important role in the degradation and recycling of organic matter. Soil microorganisms have a remarkable ability to produce compounds with biological activity such as antibiotics, and historically this has been exemplified by streptomycin which is produced by a streptomycete named
Mexico encompasses nearly 4, 000 insular regions of outstanding natural beauty, their biodiversity is remarked by high number of endemism (plants and animals) and most of these regions are federal protected. Revillagigedo Archipelago National Park (RANP) [39] encompasses four tropical volcanic Islands: (1) Socorro, (2) Clarion, (3) San Benedicto, and (4) Roca Partida. The RANP is considered as one of the best-preserved areas in the world.
In the present project, soil samples were collected at five different sites of Socorro Island (SI) (Figure 10) in 2016 and 2017, respectively (Table 3). A selective isolation strategy using five soil samples and three different media was developed in order to isolate actinobacteria. One gram of each soil was transferred to tubes containing 9 mL of saline solution (0.9%; NaCl; Sigma-Aldrich, Mexico). Modified Pikovskaya agar (Appendix A), GYM without antibiotics or antifungal compounds, and marine GYM supplemented with Rifampicin [5 μg/mL] and Nystatin (100 μg/mL) were used as isolation media. The dilutions used for modified Pikovskaya and marine GYM were 10−1 to 10−4 and for GYM 10−6 to 10−8. One hundred microliters (Gilson, France) of each dilution were spread in the media and then aerobically incubated at 30°C (IncuMax IC-320, Amerex USA) for up to 4 weeks.
Sites of sampling in Socorro Island.
Code of sampling site | Name of sampling site | Meter of above sea level (masl) | Date of sampling | ||
---|---|---|---|---|---|
S1 | Camping place | South of Socorro Island | 450 | 25 | December 2016 |
S2 | Cave | 550 | 28 | ||
S3 | North camping place | North of Socorro Island | 941 | 30 | |
S4 | Everman volcano | South East of Everman volcano | 850 | 3 | January 2017 |
S5 | Parrot camping place | 600 |
General information of the sampling sites.
The isolation plates were checked by eye looking for actinobacteria and selected colonies were streaked in new GYM media plates until axenic cultures were obtained (Figure 11). The conditions of incubation were the same as mentioned above. The cultivable actinobacteria diversity was remarkable but only 215 isolates were selected from the isolation plates. Eighty-six isolates presented morphological differentiation based on aerial hyphae and spore mass so that they were considered as streptomycetes (Figure 12).
Isolation plate (a), selected actinobacteria (b), and axenic culture (c).
Morphological diversity of actinobacteria from Socorro Island soils.
Molecular identification using the 16S rRNA gene of 10 selected strains morphologically resembling streptomycetes confirmed that they indeed belong to this extensive and important genus (Table 4). The phylogenetic tree constructed using five of sequences of the selected strains showed that they are different amongst them and from those more related
Code of microorganism | Hit taxonomy | Identity (%) |
---|---|---|
C1-S1-1 | 99 | |
C10-S2-14 | ||
C67-S2-1 | ||
C43-S3-1 | ||
C43-S3-2 | ||
C58-S5-2 | ||
C59-S5-1 | ||
C59-S5-2 | ||
C27-S4-3 | ||
C57-S5-1 |
Preliminary identification of selected streptomycetes from the different sites.
Phylogenetic tree of the 16S rRNA gene selected streptomycetes isolates.
Soil actinobacteria, particularly
More than two centuries of work to isolate actinobacteria from natural resources have ended in major discoveries, academic contributions, and important recognitions. Novel actinobacteria represent the entree of new natural compounds of significant importance. For more than 15 years our research group has developed and applied selective isolation strategies exploring distinct natural unexplored sites or less studied ecological niches in Mexico. To avoid the isolation of the “same bugs,” it is needed to use different selective isolation strategies, pre-treatments of the environmental sample, supplementation of the media with a specific concentration of antibiotics and antifungal compounds while carefully selecting the target organisms.
The results presented in this chapter support the proposal that the isolation of microorganisms is not “
Actinobacteria is one most of the diverse and complex groups of bacteria and produces more than 80% of the antibiotics used in medicine today. Their ability to produce novel natural compounds, such as antibiotics and novel cancer compounds is widely recognized. According to the World Health Organization (WHO) there is an urgent need to discover novel antibiotics for priority pathogenic bacteria and emerging pathogenic organisms [43] and the first step to respond and to contribute with this global initiative is to isolate novel actinobacteria. To our knowledge, our reports here are one of the few research projects in our country that are dedicated to study the ecological role and the genetic potential of novel actinobacteria from unexplored sites or less studied ecological niches in Mexico.
Our research was supported by Instituto Politécnico Nacional (IPN)—Secretaría de Investigación y Posgrado (SIP), Grants SIP 20170432, 20170434, 20170410, 20181167, 20181528, 20181803, 20196605, 20196630, 20196649, 20201026, 20201893, 20202083, 20210987, 20211209, and 20211740. L.C.-C. was supported by a Ph.D. Scholarship from Consejo Nacional de Ciencia y Tecnología (CONACyT, Mexico) no. 270230 and Beca de Estímulo Institucional de Formación de Investigadores Program (BEIFI-IPN). ETQ, CJHG and JCCD acknowledge Comisión de Operación y Fomento de Actividades Académicas del Instituto Politécnico Nacional (COFAA), Estímulo al Desempeño de los Investigadores (EDI) and Sistema Nacional de Investigadores (SNI-CONACYT) fellowships. A.A-V ackcnowledges a Mexican Postdoctoral Scholarship Program 3 and 4, Program 4, 2020–2021 and Program 1 and 2, Program 2, 2021–2022 (CONACyT, Mexico).
The authors declare no conflict of interest.
Glucose Yeast Malt Extract Agar -GYM medium- (DSM medium 65) | |
---|---|
Dextrose (Bacto™, BD) | 4 g |
Yeast extract (Bacto™, BD) | 4 g |
Malt extract (Bacto™, BD) | 10 g |
Calcium carbonate (SIGMA-ALDRICH) | 2 g |
Agar (Bacto™, BD) | 12 g |
Distilled water | 1000 mL |
pH 7.2 |
Marine media was prepared by replacing distilled water with artificial seawater (Ocean™). 1:10 marine GYM medium was prepared using an aliquot of marine GYM. All the media was sterilized at 121°C, 1.5 Lb. for 15 min.
Reagents | Volume |
---|---|
10× DNA polymerase buffer [50 mM stock solution] (Bioline, USA) | 5 μL |
MgCl2 [50 mM] (Bioline, USA) | 1.5 μL |
dNTPs [10 mM stock mixture] (Bioline, USA) | 1.25 μL |
Primer 27f [20 μM stock solution] (Invitrogen) | 0.5 μL |
Primer 1525r [20 μM stock solution] (Invitrogen) | 0.5 μL |
DNA [100 ng/μL] | 1 μL |
Taq polymerase [5 U] (Bioline, USA) | 1 Unit |
Ultra-pure Milli-Q water | Up to 50 μL |
Amplification was achieved using a Techno 512 gradient PCR machine.
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\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{},profiles:[{id:"396",title:"Dr.",name:"Vedran",middleName:null,surname:"Kordic",slug:"vedran-kordic",fullName:"Vedran Kordic",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/396/images/7281_n.png",biography:"After obtaining his Master's degree in Mechanical Engineering he continued his education at the Vienna University of Technology where he obtained his PhD degree in 2004. He worked as a researcher at the Automation and Control Institute, Faculty of Electrical Engineering, Vienna University of Technology until 2008. 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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. 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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. 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He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:null},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. 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He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. 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Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. 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He obtained his Master’s degree in the Department of Information and Communications from Gwangju Institute of Science and Technology (GIST) in 2003. In 2010, he received his Ph.D. degree in the School of Information and Mechatronics from GIST. In the meantime, he was an executed team leader at Culture Technology Institute, GIST, 2010-2012. In 2011, he worked at Lancaster University, the UK as a visiting scholar. In September 2012, he joined Daegu University, where he is currently an associate professor in the School of ICT Conver, Daegu University. Also, he served as the Board of Directors of KSIIS since 2019, and HCI Korea since 2016. From 2017~2019, he worked as a center director of the Mixed Reality Convergence Research Center at Daegu University. From 2015-2017, He worked as a director in the Enterprise Supporting Office of LINC Project Group, Daegu University. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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