Structural characteristics of biochar.
\\n\\n
IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\\n\\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\\n\\nLaunching 2021
\\n\\nArtificial Intelligence, ISSN 2633-1403
\\n\\nVeterinary Medicine and Science, ISSN 2632-0517
\\n\\nBiochemistry, ISSN 2632-0983
\\n\\nBiomedical Engineering, ISSN 2631-5343
\\n\\nInfectious Diseases, ISSN 2631-6188
\\n\\nPhysiology (Coming Soon)
\\n\\nDentistry (Coming Soon)
\\n\\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\\n\\nNote: Edited in October 2021
\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/132"}},components:[{type:"htmlEditorComponent",content:'With the desire to make book publishing more relevant for the digital age and offer innovative Open Access publishing options, we are thrilled to announce the launch of our new publishing format: IntechOpen Book Series.
\n\nDesigned to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
\n\nAfter a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
\n\nOur innovative Book Series format brings you:
\n\nIntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\n\nLaunching 2021
\n\nArtificial Intelligence, ISSN 2633-1403
\n\nVeterinary Medicine and Science, ISSN 2632-0517
\n\nBiochemistry, ISSN 2632-0983
\n\nBiomedical Engineering, ISSN 2631-5343
\n\nInfectious Diseases, ISSN 2631-6188
\n\nPhysiology (Coming Soon)
\n\nDentistry (Coming Soon)
\n\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\n\nNote: Edited in October 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:"10343",leadTitle:null,fullTitle:"Ocular Hypertension - The Knowns and Unknowns",title:"Ocular Hypertension",subtitle:"The Knowns and Unknowns",reviewType:"peer-reviewed",abstract:"This book provides useful information to physicians for managing ocular hypertension, which is one of the more controversial ocular conditions. It examines the social aspects of the disease and the new technologies available for treating it. The information presented will help physicians better diagnose and manage this condition.",isbn:"978-1-83969-338-0",printIsbn:"978-1-83969-337-3",pdfIsbn:"978-1-83969-339-7",doi:"10.5772/intechopen.91529",price:119,priceEur:129,priceUsd:155,slug:"ocular-hypertension-the-knowns-and-unknowns",numberOfPages:126,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"0ff71cc7e0d9f394f41162c0c825588a",bookSignature:"Michele Lanza",publishedDate:"October 13th 2021",coverURL:"https://cdn.intechopen.com/books/images_new/10343.jpg",numberOfDownloads:1320,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:0,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 17th 2020",dateEndSecondStepPublish:"February 23rd 2021",dateEndThirdStepPublish:"April 24th 2021",dateEndFourthStepPublish:"July 13th 2021",dateEndFifthStepPublish:"September 11th 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"240088",title:"Prof.",name:"Michele",middleName:null,surname:"Lanza",slug:"michele-lanza",fullName:"Michele Lanza",profilePictureURL:"https://mts.intechopen.com/storage/users/240088/images/system/240088.png",biography:"Michele Lanza is Associate Professor of Ophthalmology at Università della Campania, Luigi Vanvitelli, Napoli, Italy. His fields of interest are anterior segment disease, keratoconus, glaucoma, corneal dystrophies, and cataracts. His research topics include\nintraocular lens power calculation, eye modification induced by refractive surgery, glaucoma progression, and validation of new diagnostic devices in ophthalmology. \nHe has published more than 100 papers in international and Italian scientific journals, more than 60 in journals with impact factors, and chapters in international and Italian books. He has also edited two international books and authored more than 150 communications or posters for the most important international and Italian ophthalmology conferences.",institutionString:'University of Campania "Luigi Vanvitelli"',position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:'University of Campania "Luigi Vanvitelli"',institutionURL:null,country:{name:"Italy"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"191",title:"Ophthalmology",slug:"medicine-ophthalmology"}],chapters:[{id:"75503",title:"Ocular Hypertension in Blacks",doi:"10.5772/intechopen.96606",slug:"ocular-hypertension-in-blacks",totalDownloads:206,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Ocular hypertension occurs when intraocular pressure (IOP) is greater than the normal range with no evidence of vision loss or damage to the optic nerve. Individuals with ocular hypertension have an increased risk for glaucoma. The mean normal IOP is 15 mmHg and the mean IOP of untreated glaucoma is 18 mmHg. Elevated IOP commonly occurs in patients over the age of 50 and is often due to enlargement of the lens, narrowing of the angle, iridolenticular apposition, and pigment liberation that obstructs the trabecular meshwork. Cataract surgery and lensectomy can lower IOP and reduce the risk of glaucoma. The global wealth inequality of Blacks has created health inequities that have led to decreased access to surgical care contributing to higher rates of blindness from glaucoma. Greater education on the benefits of early cataract surgery and trabecular bypass for higher risk patients, as well as addressing wealth and health inequities, can help to bend the curve of blindness from glaucoma.",signatures:"Daniel Laroche and Kara Rickford",downloadPdfUrl:"/chapter/pdf-download/75503",previewPdfUrl:"/chapter/pdf-preview/75503",authors:[{id:"344431",title:"M.D.",name:"Daniel Laroche",surname:"Laroche",slug:"daniel-laroche-laroche",fullName:"Daniel Laroche Laroche"},{id:"346110",title:"M.Sc.",name:"Kara",surname:"Rickford",slug:"kara-rickford",fullName:"Kara Rickford"}],corrections:null},{id:"77263",title:"Retinal Vascular Implications of Ocular Hypertension",doi:"10.5772/intechopen.98310",slug:"retinal-vascular-implications-of-ocular-hypertension",totalDownloads:113,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In this chapter, we review the basics of retinal vascular anatomy and discuss the physiologic process of retinal blood flow regulation. We then aim to explore the relationship between intraocular pressure and retinal circulation, taking into account factors that affect retinal hemodynamics. Specifically, we discuss the concepts of ocular perfusion pressure, baro-damage to the endothelium and transmural pressure in relation to the intraocular pressure. Finally, we demonstrate the inter-relationships of these factors and concepts in the pathogenesis of some retinal vascular conditions; more particularly, through examples of two common clinical pathologies of diabetic retinopathy and central retinal vein occlusion.",signatures:"Fidan Jmor and John C. Chen",downloadPdfUrl:"/chapter/pdf-download/77263",previewPdfUrl:"/chapter/pdf-preview/77263",authors:[{id:"349068",title:"Associate Prof.",name:"John",surname:"Chen",slug:"john-chen",fullName:"John Chen"},{id:"349086",title:"Dr.",name:"Fidan",surname:"Jmor",slug:"fidan-jmor",fullName:"Fidan Jmor"}],corrections:null},{id:"77484",title:"Progression from Ocular Hypertension into Glaucoma",doi:"10.5772/intechopen.98886",slug:"progression-from-ocular-hypertension-into-glaucoma",totalDownloads:156,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Ocular hypertension (OHT) is characterized by raised intraocular pressure (IOP) >21 mmHg without any visual field (functional) or optic nerve (structural) defect featuring glaucoma. Raised IOP is a major risk factor of glaucoma and a proportion of eyes with OHT progresses into primary open angle glaucoma. Glaucoma is a debilitating disease with potential for blindness if left untreated and associated reduction in the quality of life of the affected individual. It is challenging for the clinicians to decide whether an OHT will progress into glaucoma or not based on the risk factor model of the Ocular hypertension treatment study. Moreover, the question whether only IOP or a myriad of factors like central corneal thickness, baseline IOP, visual field, family history of glaucoma, ocular biomechanics are all important in determining the progression is yet to be answered. The rate of progression is also important and needs analysis for further discussion. Summarizing the landmark studies on ocular hypertension and glaucoma to date are imperative in this regard. This chapter presents the overview of OHT and its possible etiology and pathophysiology, risk factors, clinical tests evaluating OHT eyes and elaborates on the progression of OHT to glaucoma over time in relation to the treatment.",signatures:"Sayantan Biswas",downloadPdfUrl:"/chapter/pdf-download/77484",previewPdfUrl:"/chapter/pdf-preview/77484",authors:[{id:"296088",title:"Ph.D.",name:"Sayantan",surname:"Biswas",slug:"sayantan-biswas",fullName:"Sayantan Biswas"}],corrections:null},{id:"75044",title:"Neuropathology in Hypertensive Glaucoma",doi:"10.5772/intechopen.96034",slug:"neuropathology-in-hypertensive-glaucoma",totalDownloads:179,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Hypertensive glaucoma is still defined as a disease where, at high intraocular pressure, retinal ganglion cell axons are impaired with excavation at the optic disc and changes in the visual field. In single cases, the study highlights the importance of knowledge of neuropathology not only at the level of the retina but the entire visual pathway, including the visual centres in the brain. It uses the issue of neurotransmission in the visual analyser and its pathology, but mainly the results of electrophysiological examinations and functional imaging of the brain using Positron Emission Tomography and Functional Magnetic Resonance. It does not overlook the imaging methods of the eye (nerve fibre layer, vessel density). On the basis of this information, therapy is recommended as well.",signatures:"Jan Lestak and Martin Fůs",downloadPdfUrl:"/chapter/pdf-download/75044",previewPdfUrl:"/chapter/pdf-preview/75044",authors:[{id:"343607",title:"Prof.",name:"Jan",surname:"Lestak",slug:"jan-lestak",fullName:"Jan Lestak"},{id:"345891",title:"Mr.",name:"Martin",surname:"Fůs",slug:"martin-fus",fullName:"Martin Fůs"}],corrections:null},{id:"76382",title:"Psychosocial Aspects of Glaucoma",doi:"10.5772/intechopen.97399",slug:"psychosocial-aspects-of-glaucoma",totalDownloads:213,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Glaucoma, not only leads to irreversible visual impairment, but also has a negative impact on Quality of Life of the patients. Visual disability, lifelong medical and surgical treatments and even the mere knowledge of having an irreversible potentially blinding condition tend to cause severe psychological stress in patients, leading to negative emotions such as anxiety or depression. The goal of glaucoma treatment should not be limited to preserving the vision, but also address the psychological aspects and preservation of patient wellbeing. Patient counselling, right from at the time of diagnosis, periodic psychological assessment and creating awareness in the society as a whole should be implemented as a part of holistic approach to glaucoma. Utilisation of Patient- reported quality of life tools would help clinicians in more closely understanding the problems and would, in turn, aid in providing comprehensive customised treatment option for each patient.",signatures:"Ashutosh Dayal",downloadPdfUrl:"/chapter/pdf-download/76382",previewPdfUrl:"/chapter/pdf-preview/76382",authors:[{id:"342532",title:"Dr.",name:"Ashutosh",surname:"Dayal",slug:"ashutosh-dayal",fullName:"Ashutosh Dayal"}],corrections:null},{id:"77068",title:"Physiological Bases of Electric Stimulation as a New Approach to Glaucoma IOP Control",doi:"10.5772/intechopen.98297",slug:"physiological-bases-of-electric-stimulation-as-a-new-approach-to-glaucoma-iop-control",totalDownloads:145,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This Chapter focuses in the electrophysiological bases to support Trans Palpebral Electrical Stimulation TPES as a new alternative to control Intraocular Pressure IOP. Primary open Angle Glaucoma POAG is described in our approach as a dysfunction of the membrane potential of TM cells due to the dysfunction of the Maxi potassium depended Calcium Channels BKCa2+ of the Trabecular Mesh TM. We review through the paper the main contributions about Trabecular mesh dysfunction related with Voltage dependent ionic channels. We also present in this paper new results in controlling intra ocular pressure IOP during one year of trans palpebral Electric stimulation in patients with Primary open-angle glaucoma (POAG).",signatures:"Luis Nino-de-Rivera, Diego Cervera and Paola Castillo-Juarez",downloadPdfUrl:"/chapter/pdf-download/77068",previewPdfUrl:"/chapter/pdf-preview/77068",authors:[{id:"187604",title:"Dr.",name:"Luis",surname:"Nino-de-Rivera",slug:"luis-nino-de-rivera",fullName:"Luis Nino-de-Rivera"},{id:"348304",title:"Dr.",name:"Diego",surname:"Cervera",slug:"diego-cervera",fullName:"Diego Cervera"},{id:"348305",title:"Dr.",name:"Paola",surname:"Castillo-Juarez",slug:"paola-castillo-juarez",fullName:"Paola Castillo-Juarez"}],corrections:null},{id:"75840",title:"Glaucoma Related to Ocular and Orbital Tumors",doi:"10.5772/intechopen.96907",slug:"glaucoma-related-to-ocular-and-orbital-tumors",totalDownloads:308,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Secondary glaucoma due to ocular and orbital tumors can be a diagnostic challenge. It is an essential differential to consider in eyes with a known tumor as well as with unilateral, atypical, asymmetrical, or refractory glaucoma. Various intraocular neoplasms including iris and ciliary body tumors (melanoma, metastasis, lymphoma), choroidal tumors (melanoma, metastasis), vitreo-retinal tumors (retinoblastoma, medulloepithelioma, vitreoretinal lymphoma) and orbital tumors (extra-scleral extension of choroidal melanoma or retinoblastoma, primary orbital tumors) etc. can lead to raised intraocular pressure. The mechanisms for glaucoma include direct (tumor invasion or infiltration related outflow obstruction, trabecular meshwork seeding) or indirect (angle closure from neovascularization or anterior displacement or compression of iris) or elevated episcleral venous pressure secondary to orbital tumors. These forms of glaucoma need unique diagnostic techniques and customized treatment considerations as they often pose therapeutic dilemmas. This chapter will review and discuss the mechanisms, clinical presentations and management of glaucoma related to ocular and orbital tumors.",signatures:"Sonal P. Yadav",downloadPdfUrl:"/chapter/pdf-download/75840",previewPdfUrl:"/chapter/pdf-preview/75840",authors:[{id:"342776",title:"Dr.",name:"Sonal P.",surname:"Yadav",slug:"sonal-p.-yadav",fullName:"Sonal P. Yadav"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"7858",title:"A Practical Guide to Clinical Application of OCT in Ophthalmology",subtitle:null,isOpenForSubmission:!1,hash:"8e2d479cc9258dee430f8ba4c353c468",slug:"a-practical-guide-to-clinical-application-of-oct-in-ophthalmology",bookSignature:"Michele Lanza",coverURL:"https://cdn.intechopen.com/books/images_new/7858.jpg",editedByType:"Edited by",editors:[{id:"240088",title:"Prof.",name:"Michele",surname:"Lanza",slug:"michele-lanza",fullName:"Michele Lanza"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7218",title:"OCT",subtitle:"Applications in Ophthalmology",isOpenForSubmission:!1,hash:"e3a3430cdfd6999caccac933e4613885",slug:"oct-applications-in-ophthalmology",bookSignature:"Michele Lanza",coverURL:"https://cdn.intechopen.com/books/images_new/7218.jpg",editedByType:"Edited by",editors:[{id:"240088",title:"Prof.",name:"Michele",surname:"Lanza",slug:"michele-lanza",fullName:"Michele Lanza"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8855",title:"Retinoblastoma",subtitle:"Past, Present and Future",isOpenForSubmission:!1,hash:"1686b2f1d697de9d4bc2005a5fa9b998",slug:"retinoblastoma-past-present-and-future",bookSignature:"Hind Manaa Alkatan",coverURL:"https://cdn.intechopen.com/books/images_new/8855.jpg",editedByType:"Edited by",editors:[{id:"223782",title:"Dr.",name:"Hind",surname:"Alkatan",slug:"hind-alkatan",fullName:"Hind Alkatan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6372",title:"Early Events in Diabetic Retinopathy and Intervention Strategies",subtitle:null,isOpenForSubmission:!1,hash:"46ff48bdb1bac8a69372566fff0e2f6d",slug:"early-events-in-diabetic-retinopathy-and-intervention-strategies",bookSignature:"Andrew T.C. 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This branch of geochemistry has dealt with numerous practical theoretical issues, such as the mechanism to transmit elements that make up non-soluble compounds in water, the system of the arrangements and their causes, and the numerous laws regulating the distribution of useful ore deposits.
\r\n\r\n\tGeochemistry of the elements is the study in metals, rocks, and earth covers of the distributing of chemical elements and their forms of presence. This section has found numerous facts concerning the distribution of chemical components. Light elements with atomic weights of less than 29 are the most prevalent elements on the earth's crust. The oxygen, hydrogen, silicon, and aluminum elements are the most common and most important elements in the formation of Earth crust and earth coverings. The first is roughly 50% of the Earth's composition and its life significance and the first and the second constitute water, and the combined elements consist of rocks which are more than half of the sedimentary rocks and are more widespread than other elements, with their numbers and weights of atomic material. There are however many questions that need to be solved, such as the high variability in chemical elements' concentrations and the presence of scarcity elements in the case of dispersion among other metals, such as rubidium.
",isbn:"978-1-80355-775-5",printIsbn:"978-1-80355-774-8",pdfIsbn:"978-1-80355-776-2",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"928cebbdce21d9b3f081267b24f12dfb",bookSignature:"Prof. Hosam M. 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He has been selected among the top 2 percent of scientists in the world, according to the Stanford University report for 2020.",coeditorOneBiosketch:"Prof. Ibrahim participated in a lot of research to find solutions to some chronic disease problems,\r\nand she supervised some masters and doctoral theses. She is a Referee and publisher\r\nmember in several international scientific journals, also a Member of Publication Integrity and Ethics (PIE) in London.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"144691",title:"Prof.",name:"Hosam M.",middleName:null,surname:"Saleh",slug:"hosam-m.-saleh",fullName:"Hosam M. Saleh",profilePictureURL:"https://mts.intechopen.com/storage/users/144691/images/system/144691.png",biography:"Hosam Saleh is a Professor of Radioactive Waste Management at the Radioisotope Department, Atomic Energy Authority, Egypt. He was awarded an MSc and Ph.D. in Physical Chemistry from Cairo University. Saleh has more than 25 years of experience in hazardous waste management with an emphasis on treatment and developing new matrixes for the immobilization of these wastes. He is also interested in studying innovative economic and environment-friendly techniques for the management of hazardous and radioactive wastes. He authored many peer-reviewed scientific papers and chapters and served as an editor of several books. 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She is a Referee and publisher\r\nmember in several international scientific journals.\r\nMember of Publication Integrity and Ethics (PIE) in London.\r\nShe obtained a Certificate of Excellence in the field of international scientific research\r\nreviewers from Publons.\r\nShe was selected in the global encyclopedia (Who's Who Edition 31 for 2014, 32 for\r\n2015, and 33 for 2016.",institutionString:"Egyptian Atomic Energy Authority",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Egyptian Atomic Energy Authority",institutionURL:null,country:{name:"Egypt"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"10",title:"Earth and Planetary Sciences",slug:"earth-and-planetary-sciences"}],chapters:[{id:"82515",title:"A Review on Elemental and Isotopic Geochemistry",slug:"a-review-on-elemental-and-isotopic-geochemistry",totalDownloads:0,totalCrossrefCites:null,authors:[{id:"144691",title:"Prof.",name:"Hosam M.",surname:"Saleh",slug:"hosam-m.-saleh",fullName:"Hosam M. 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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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Saleh and Martin Koller",coverURL:"https://cdn.intechopen.com/books/images_new/6847.jpg",editedByType:"Edited by",editors:[{id:"144691",title:"Prof.",name:"Hosam M.",surname:"Saleh",slug:"hosam-m.-saleh",fullName:"Hosam M. Saleh"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10060",title:"Cement Industry",subtitle:"Optimization, Characterization and Sustainable Application",isOpenForSubmission:!1,hash:"9a1e79b25dad63378b81fdb16909cd09",slug:"cement-industry-optimization-characterization-and-sustainable-application",bookSignature:"Hosam El-Din Mostafa Saleh",coverURL:"https://cdn.intechopen.com/books/images_new/10060.jpg",editedByType:"Edited by",editors:[{id:"144691",title:"Prof.",name:"Hosam M.",surname:"Saleh",slug:"hosam-m.-saleh",fullName:"Hosam M. Saleh"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"65085",title:"Application of Biochar to Enzyme Carrier for Stress Tolerance of Enzymes",doi:"10.5772/intechopen.82094",slug:"application-of-biochar-to-enzyme-carrier-for-stress-tolerance-of-enzymes",body:'\nAn enormous amount of greenhouse gas such as CO2 has recently been emitted from industries and thereby has caused serious global warming problems [1, 2]. Accordingly, the application of biomass materials, which are carbon neutral, to energies and functional materials, is crucial to reduce greenhouse gas emissions [3, 4]. However, most of biomass materials such as forestry residues have hardly been utilized in the field of functional materials. Accordingly, the development in the high value-added application of biomass materials has been desired to provide the multiple effective utilization system of biomass materials.
\nEnzymes are biocatalysts, which exhibit their outstanding biological activity under mild conditions, and have widely been used in pharmacy, biotechnology, and chemical industry [5, 6, 7]. Typical applications of enzymes are biotransformation, biosensor, biofuel cell, and so on. Enzymes are generally stable in a cell. However, they are gradually denatured and inactivated under various physical and chemical stresses such as heat, organic solvents, and so on [8]. In order to enhance the stability of enzymes used in vitro, enzyme immobilization, where enzyme molecules are attached to solid carriers, has widely been used [9, 10, 11]. The main required features of enzyme carriers are chemical stability, thermal stability, insolubility under reaction conditions, high affinity to enzymes, biocompatibility, the presence of reactive functional groups, availability, low price, regeneration, reusability, and so on. When enzymes are immobilized on carriers through adsorption, the catalytic activity, specificity, and stability of enzymes are influenced by the nature of carriers. Accordingly, the performance of enzymes can be enhanced by selecting an appropriate carrier.
\nA large quantity of the world’s oldest biochar was excavated from the cave of Kara Iwatani of Hijikawacho, Ozu-shi, Ehime, Japan, with a beast bone and the human bone piece 300,000 years ago. Since the ancient period, the biochar has been used not only as a fuel but also as a soil conditioner to support human life for a long time in the world [12]. Consequently, as the biocompatibility of biochar can be expected, we have examined the application of biochar to enzyme carriers. As a result, we have found that enzymes are effectively adsorbed on biochar [13, 14], and biochar-adsorbed enzymes exhibit the high thermal stability in water [15, 16, 17, 18]. Moreover, we have reported that the adsorption of enzymes on biochar sufficiently improves the enzyme activity in organic solvents [19, 20, 21].
\nIn the chapter, the characterization of biochar, the adsorption of enzyme on biochar, the high temperature-tolerant property of biochar-adsorbed enzymes, and the organic solvent-tolerant property of biochar-adsorbed enzymes are discussed.
\nBiochar has been prepared by pyrolyzing plant biomass waste such as bamboo waste at low temperatures under nitrogen atmosphere to produce functional groups, which were used as a binding site for the adsorption of enzymes (Figure 1) [13, 14]. The emission of carbon dioxide was reduced since plant biomass waste was not burned through the preparation of biochar. Moreover, the energy cost of the present preparation of biochar was suppressed, compared to that of the conventional preparation of charcoal. Consequently, the present preparation of biochar was a low-cost and environmentally benign process.
\nPreparation process of biochar.
In order to observe the surface of biochar, we have examined SEM images [14]. As seen in Figure 2, the morphology of biochar was strongly dependent upon the kind of raw materials. The roughness of biochar was remarkably low, and any pores were not observed at the magnification measured in the present work. The surface of bamboo charcoal was smoother than that of any other charcoal. Moreover, Raman spectra of biochar showed that the structure of biochar was amorphous [13].
\nSEM images of (a) adzuki bean charcoal, (b) bamboo charcoal, and (c) wood charcoal.
Table 1 shows the textural parameters of biochar obtained from low-temperature (−196°C) nitrogen adsorption isotherms, which allow the calculation of specific surface area, specific pore volume, and pore diameter peak [14]. In the table, the specific area of adzuki bean charcoal depicted the value obtained from the CO2 isotherm. The specific surface area and specific pore volume of biochar showed much small, compared with that of conventional activated carbon. The carbonizing temperature affects the surface property of charcoal [22]. The specific pore volume increases with an increase in carbonizing temperature. Consequently, the pore of biochar was not formed enough at low temperatures.
\nBiochar | \nSpecific surface area [m2/g] | \nPore volume [cm3/g] | \nPore diameter peak [nm] | \n
---|---|---|---|
Adzuki bean charcoal | \n204a | \n— | \n— | \n
Bamboo charcoal | \n294 | \n0.041 | \nLess than 2.6 | \n
Wood charcoal | \n117 | \n0.025 | \nLess than 2.6 | \n
Structural characteristics of biochar.
Specific area of adzuki bean charcoal was obtained from the CO2 isotherm.
Figure 3 shows CP/MAS 13C-NMR spectra of biochar [13]. Aromatic carbon (140–141, 131 ppm) was mainly detected, and C=O (200 ppm), COOH, CHO (175–190 ppm), and aromatic oxygen (150–153, 145–146 ppm) were also detected. Moreover, in order to assess the chemical property of the surface of biochar, the measurement on X-ray photoelectron spectroscopy (XPS) was carried out [19]. Figure 4 shows the elemental ratio of the surface of biochar detected by XPS. The main element was carbon atom, and oxygen and nitrogen atoms also existed on the surface of biochar to some extent. The ratios of oxygen and nitrogen atoms in adzuki bean charcoal were greater than those in any other charcoal. Narrow scan spectra of XPS showed C▬C, C▬H, C▬O, O▬C▬O, C=O, COOH, and C▬N, as seen in Figure 5. Many radical species due to functional groups containing oxygen atoms, which are formed by thermal decomposition of cellulose and hemicelluloses, are detected in charcoals carbonized at 500°C by the measurement of electron spin resonance, and functional groups decrease with increasing carbonization temperature [22, 23].
\nCP/MAS 13C-NMR spectra of biochar.
The elemental ratio of the surface of biochar detected by XPS.
The chemical bond ratio of biochar obtained from narrow scan spectra of XPS.
Figure 6 shows the relationship of the ζ potential of biochar with the solution pH [15]. The ζ potential of adzuki bean charcoal drastically decreased with increasing the pH value, exhibiting a negative value above pH 4, drops till pH 7, and was almost constant in the alkaline region. The pH dependence of the ζ potential of bamboo charcoal exhibited the same tendency to the case of adzuki bean charcoal.
\nEffect of solution pH on ζ potential of biochar.
Figure 7 shows the time course of the amount of lysozyme adsorbed on adzuki bean charcoal at pH 7 and 25°C when hen egg white lysozyme was employed as a model enzyme [16]. The amount of lysozyme adsorbed on adzuki bean charcoal increased with an increase in adsorption time, reached a plateau around 24 h, and was 11 μmol/g (0.16 g/g). As overall concentration of adzuki bean charcoal was 3 g/L in an aqueous solution, overall lysozyme concentration in the aqueous solution corresponded to 33 μM (0.48 mg/mL). From this result, the adsorption of lysozyme on adzuki bean charcoal was carried out for 24 h.
\nTime dependence of amount of lysozyme adsorbed onto adzuki bean charcoal.
As seen in Table 2, the amount of enzymes adsorbed on biochar was strongly dependent on the kinds of enzymes and/or biochars [14, 15]. The amount of lysozyme adsorbed on biochar was almost the same among three different charcoals although the specific surface area of adzuki bean charcoal or bamboo charcoal was more than twice larger than wood charcoal, as seen in Table 1.
\nBiochar | \nAmount of enzymes adsorbed (μmol/g) | \n|
---|---|---|
Lysozyme | \nα-Chymotrypsin | \n|
Adzuki bean charcoal | \n11 | \n17 | \n
Bamboo charcoal | \n9 | \n9.8 | \n
Wood charcoal | \n12 | \n21 | \n
Amount of enzymes adsorbed on biochar.
Figure 8 shows the adsorption isotherms of lysozyme on biochar. These isotherms gradually increased [13]. The amount adsorbed on adzuki bean charcoal exhibited large, compared to the amount adsorbed on bamboo charcoal. The curves in the figure were the fitting lines with Freundlich adsorption isotherm equation (Eq. 1).
\nAdsorption isotherms of lysozyme onto biochar; adsorption was carried out by incubating buffer solution (pH 7) containing a certain amount of lysozyme and 3 g/L biochar at 120 rpm and 25°C for 24 h.
Here,
Figure 9 shows the relationship of the amount of lysozyme adsorbed on biochar with the pH value of aqueous solutions at 25°C [14]. The curve of the amount adsorbed on adzuki bean charcoal had the optimum value around neutral pH, similar to the case of bamboo charcoal. The net charge of protein molecules alters with the pH of aqueous solutions. Since the isoelectric point (pI) of lysozyme is 11, the net charge of lysozyme becomes more positive below pH 11. Concerning the ζ potential of biochar, the ζ potential of adzuki bean charcoal drastically decreased with increasing the pH value, exhibited a negative value above pH 4, dropped till pH 7, and was almost constant in the alkaline region, as shown in Figure 6. The pH dependence of the ζ potential of bamboo charcoal exhibited the same tendency to the case of adzuki bean charcoal. When the pH value was around the pI of lysozyme or the pH where the ζ potential of biochar approached 0 volts, a dramatic decrease in the amount of lysozyme adsorbed on biochar was observed. On the other hand, in the vicinity of neutral pH where lysozyme and the surface of biochar were charged positively and negatively, respectively, the high amount of adsorption tended to be obtained. Consequently, these results indicate that the electrostatic interaction between the positively charged lysozyme and the negatively charged surface of biochar mainly contributes to the adsorption.
\nEffect of pH on the amount of lysozyme adsorbed onto biochar; adsorption was carried out by incubating buffer solution (appropriate pH) containing 500 μM lysozyme and 3 g/L biochar at 120 rpm and 25°C for 24 h.
Modest heating causes enzymes dissolved in an aqueous solution to be denatured and inactivated by unfolding of enzyme molecules due to the disruption of weak interactions such as ionic bonds, hydrogen bonds, and hydrophobic interactions, which are prime determinants of enzyme tertiary structures [25]. In order to assess the heat stress tolerance of enzymes adsorbed on biochar, an aqueous solution containing lysozyme adsorbed on adzuki bean charcoal was incubated at high temperatures [15]. Figure 10 shows photographs of aqueous solutions containing free lysozyme, the mixture of lysozyme and adzuki bean charcoal, and lysozyme adsorbed on adzuki bean charcoal before and after heat treatment was carried out at 90°C for 30 min, while under such heat conditions, raw eggs become hard-boiled eggs. The solution of free lysozyme immediately became turbid since thermally denatured enzymes were drastically aggregated by heat, as shown in Figure 10(d). The enzyme aggregation is precipitated above 10 μM lysozyme [26]. The formation of enzyme aggregation was enhanced since the present concentration of lysozyme was 33 μM. Adzuki bean charcoal was easily dispersed in an aqueous solution due to the good wettability to water as seen in Figure 10(b). Likewise, the mixture of lysozyme and adzuki bean charcoal was immediately precipitated by heat treatment due to the aggregation of denatured enzymes, as shown in Figure 10(e). On the other hand, lysozyme adsorbed on adzuki bean charcoal was easily dispersed in an aqueous solution, as seen in Figure 10(c). After the heat treatment, lysozyme adsorbed on adzuki bean charcoal was sufficiently dispersed in the solution, and the white enzyme aggregation and the cohesion among adzuki bean charcoals adsorbing lysozyme were not observed in the solution, as shown in Figure 10(f). When enzymes dissolved in an aqueous solution are placed at high temperatures, most of enzymes are instantaneously unfolded by the disruption of weak interactions consisting of ionic bonds, hydrogen bonds, and hydrophobic interactions of enzymes [25, 27]. Additionally, unfolded enzymes are aggregated with each other, and the chemical deterioration reactions occur in unfolded enzymes. In particular, enzyme aggregation easily occurs upon the exposure of the hydrophobic surfaces of an enzyme, and this phenomenon becomes the major problem because of the fast irreversible inactivation. The adsorption of lysozyme on adzuki bean charcoal could inhibit the formation of enzyme aggregation.
\nPhotographs of lysozyme solutions before and after heat treatment at 90°C for 30 min: (a) an aqueous solution containing free lysozyme before heat treatment, (b) an aqueous solution containing free lysozyme solution and adzuki bean charcoal before heat treatment, (c) an aqueous solution containing lysozyme adsorbed on adzuki bean charcoal before heat treatment, (d) an aqueous solution containing free lysozyme after heat treatment, (e) an aqueous solution containing free lysozyme solution and adzuki bean charcoal after heat treatment, and (f) an aqueous solution containing lysozyme adsorbed on adzuki bean charcoal after heat treatment.
When the remaining activity is defined as the ratio of the activity of lysozyme after heat treatment to that before heat treatment, time courses of remaining activities of free lysozyme and lysozyme adsorbed on adzuki bean charcoal through the heat treatment at pH 7.0 and 90°C are shown in Figure 11 [16]. The remaining activities of free lysozyme and lysozyme adsorbed on adzuki bean charcoal decreased with an increase in time. As shown in Figure 11, the remaining activities of free and adsorbed lysozyme exhibited the correlation of first-order kinetics with heat treatment time. Table 3 shows inactivation rate constants and half-lives of free and adsorbed lysozymes obtained from the curve fitting in Figure 11. The half-life of adsorbed lysozyme was seven times greater than that of free lysozyme. The remaining activity of free lysozyme was almost lost after heat treatment for 30 min, and the remaining activity in the mixture of lysozyme and adzuki bean charcoal exhibited 2%, while the remaining activity of lysozyme adsorbed on adzuki bean charcoal showed around 50%. The robust thermal stability of adsorbed lysozyme may be attributable to the suitable interaction of lysozyme with the surface of adzuki bean charcoal.
\nTime course of remaining activity of free lysozyme and lysozyme adsorbed on adzuki bean charcoal through the heat treatment at pH 7.0 and 90°C.
Samples | \nRate constant (min−1) | \nHalf life (min) | \n
---|---|---|
Free lysozyme | \n0.168 | \n4 | \n
Lysozyme adsorbed on adzuki bean charcoal | \n0.027 | \n28 | \n
Rate constants and half lives of inactivation of lysozyme at 90°C.
To extend our study, the remaining activities of lysozyme adsorbed on biochar obtained from several kinds of plant biomass wastes have been measured after heat treatment at 90°C for 30 min. Lysozyme adsorbed on bamboo charcoal or wood charcoal exhibited the high thermal stability, similar to the case of lysozyme-adsorbed adzuki bean charcoal, as shown in Figure 12. On the other hand, the mixture of lysozyme and bamboo charcoal or wood charcoal showed several percent of remaining activity.
\nEffect of kind of biochar on remaining activity of lysozyme adsorbed on biochar after heat treatment at 90°C for 30 min.
The solution pH generally affects the activity and stability of enzymes in aqueous solutions [5]. Figure 13 shows the remaining activity of lysozyme adsorbed on bamboo charcoal against the solution pH of adsorption medium. The remaining activity of bamboo charcoal-adsorbed lysozyme was markedly influenced by the pH of adsorption medium and showed the maximum value at pH 5.
\nEffect of pH of adsorption medium on the remaining activity of lysozyme adsorbed on bamboo charcoal after the heat treatment at 90°C for 30 min.
Three-dimensional structures of enzymes consist of secondary structures such as α-helix and β-sheet [28]. To elucidate the influence of adsorption on the structure of lysozyme, bamboo charcoal-adsorbed lysozyme has been measured by Fourier-transform infrared (FTIR) spectroscopy. Figure 14 shows the FTIR spectra of native lysozyme and lysozyme adsorbed on bamboo at different pH. The most sensitive spectral region to enzyme secondary structural components is amide I (1700–1600 cm−1), which is due almost entirely to the C〓O stretch vibrations of peptide linkages [28]. The spectral pattern of bamboo charcoal-adsorbed lysozyme was influenced by the pH of adsorption medium. To evaluate the change in the secondary structure of bamboo-adsorbed lysozyme, the ratio of the absorbance at 1681 cm−1 to the absorbance at 1647 cm−1 (ABS1681/ABS1647) has been assessed since the band located at ca. 1681 cm−1 is assigned to intramolecular β-sheet and the band located at ca. 1647 cm−1 is assigned to α-helix. The ABS1681/ABS1647 ratio at pH 5 (0.86), where the remaining activity showed the maximum value, was similar to that of native lysozyme (0.88). Likewise, the ABS1681/ABS1647 ratio at pH 4 (0.92) was near that of native lysozyme. On the other hand, the ABS1681/ABS1647 ratios at pH 7 (0.69) and 9 (0.61) were different from that of native lysozyme. The effect of solution pH of adsorption medium on the thermal stability of bamboo charcoal-adsorbed lysozyme has been summarized as follows. The structure of bamboo charcoal-adsorbed lysozyme was nearly the native structure of lysozyme when lysozyme was adsorbed on bamboo charcoal at pH 4, but the electrostatic interaction between lysozyme and bamboo charcoal could not sufficiently contribute to the thermal stability. The electrostatic interaction between lysozyme and bamboo charcoal could strongly retain the structure of lysozyme at high temperatures when lysozyme was adsorbed on bamboo charcoal at pH 5, where the native structure of lysozyme was maintained. The structure of lysozyme was partially destroyed since the electrostatic interaction was too strong to maintain the native structure of lysozyme, and the thermal stability of bamboo charcoal-adsorbed lysozyme dropped when lysozyme was adsorbed on bamboo charcoal at pH 7 and 9. Therefore, these results indicate that biochar-adsorbed enzymes exhibit the excellent thermal stability when the native structure of enzymes is kept after the adsorption and the adsorption force is strong enough to retain the structure of enzymes against the heat stress.
\n(A) FTIR spectrum of native lysozyme. (B) FTIR spectrum of lysozyme adsorbed on bamboo charcoal at pH 4. (C) FTIR spectrum of lysozyme adsorbed on bamboo charcoal at pH 5. (D) FTIR spectrum of lysozyme adsorbed on bamboo charcoal at pH 7. (E) FTIR spectrum of lysozyme adsorbed on bamboo charcoal at pH 9.
Biotransformation catalyzed by an enzyme in nonaqueous media has been applied to numerous synthetic processes because of the following benefits [29]: (1) The solubility of nonpolar reactants and products is improved. (2) Synthetic reactions can take place by the use of a conventional hydrolase without an expensive energy substance such as adenosine triphosphate (ATP). (3) The stereoselectivity of enzymes is markedly altered. (4) The thermal stability of enzymes is highly improved. (5) Enzymes can easily be recycled by the filtration or the centrifugation. (6) The product can easily be recovered by the evaporation when the volatile organic solvent is used as a reaction medium. (7) The contamination such as the growth of microorganisms can be inhibited by using organic solvents. However, the enzyme tends to show the low activity in organic solvents, compared to that in water since an organic solvent in general works as a denaturant of enzymes [30].
\nFigure 15 shows the scheme of reaction catalyzed by α-chymotrypsin (α-CT) [30, 31]. When
α-CT-catalyzed transesterification of
In order to evaluate the catalytic activity of enzymes adsorbed on biochar in an organic solvent, the transesterification catalyzed by α-CT adsorbed on the different kind of biochar in acetonitrile has been examined [19]. Figure 16 shows the initial rates of
Dependence of kind of biochar on biochar-adsorbed α-CT-catalyzed transesterification. Free or biochar-adsorbed α-CT was placed in acetonitrile containing 5% (v/v) water, 10 mM
In order to elucidate the influence of a kind of biochar on the secondary structure of α-CT, the FTIR spectra of free and biochar-adsorbed α-CT were measured. Table 4 shows the ratio of the absorbance at 1650 cm−1 to the absorbance at 1630 cm−1 (ABS1650/ABS1630) of free α-CT and α-CT adsorbed onto biochar. As mentioned above, the band located at ca. 1650 cm−1 is assignable to α-helix, and the band located at ca. 1630 cm−1 is assignable to intramolecular β-sheet. The order of the ABS1650/ABS1630 ratio was bamboo charcoal-adsorbed α-CT > adzuki bean charcoal-adsorbed α-CT = wood charcoal-adsorbed α-CT > free α-CT. The order of the ABS1650/ABS1630 ratio was similar to that of the initial rate of transesterification as shown in Figure 16. The α-helical structure of α-CT molecule is more changeable than β-sheet, since the β-sheet structure is the main backbone of α-CT molecule [33]. Thus, the results indicate that at the higher initial rate, the transesterification is catalyzed by α-CT molecules having the secondary structure kept more highly. Moreover, it is suggested that the content of functional groups in bamboo charcoal is suitable to keep the secondary structure of α-CT in acetonitrile since functional groups contribute to the adsorption of α-CT on biochar.
\nSample | \nABS1650/ABS1630 (−) | \n
---|---|
Free α-CT | \n1.1 | \n
Adzuki bean charcoal-adsorbed α-CT | \n1.3 | \n
Bamboo charcoal-adsorbed α-CT | \n1.5 | \n
Wood charcoal-adsorbed α-CT | \n1.3 | \n
Ratio of the absorbance at 1650 cm−1 to the absorbance at 1630 cm−1 (ABS1650/ABS1630) of α-CT provided by the FTIR measurement.
Figure 17 shows time course of remaining activities of free α-CT and bamboo charcoal-adsorbed α-CT through the heat treatment at 50°C [20]. The state of free α-CT in acetonitrile, where α-CT was dispersed as the solid state, was unchanged during the heat treatment, although enzymes dissolved in an aqueous solution immediately form the aggregation of thermally denatured enzymes [15]. Likewise, the enzyme aggregation and the cohesion among bamboo charcoal-adsorbed α-CT were not observed in acetonitrile during the heat treatment. However, the remaining activities of free α-CT and BCP-adsorbed α-CT gradually dropped with an increase in heat time. The relation between the remaining activity of free α-CT and heat time could be correlated by first-order kinetics, while the relation between bamboo charcoal-adsorbed α-CT and heat time could be correlated by second-order kinetics. When the curve fitting was carried out in the figure, the half-life of inactivation of free α-CT was 33 min, and the half-life of inactivation of bamboo charcoal-adsorbed α-CT was 125 min. Therefore, the half-life of bamboo charcoal-adsorbed α-CT showed 3.8-fold, compared with that of α-CT. On the other hand, the half-life of inactivation of bamboo charcoal-adsorbed α-CT is 15 min in aqueous solutions at 45°C [17]. Consequently, the thermal stability of bamboo charcoal-adsorbed α-CT in acetonitrile was greater than that in water. As a result, the electrostatic interaction between α-CT and bamboo charcoal, which mainly contributes to the adsorption of α-CT on bamboo charcoal, is strengthened in acetonitrile as the dielectric constant of acetonitrile is much smaller than that of water [34].
\nTime course of remaining activities of free α-CT and bamboo charcoal-adsorbed α-CT through the heat treatment at 50°C.
In moist air, the catalytic activity of solid enzymes is markedly dependent on the thermodynamic water activity (aw), which is defined as the ratio of the water partial pressure to the vapor pressure of pure water [35]. Similarly, the catalytic activity of biochar-adsorbed enzymes might be influenced in hydrophilic organic solvents containing low water content. Figure 18 shows the relationship of the initial transesterification rate (Ve) and the initial hydrolysis rate (Vh) with the water activity in acetonitrile at 25°C [20]. Low water activity inhibited the inherent enzymatic hydrolysis of
Effect of water activity on the transesterification rate (Ve) and hydrolysis rate (Vh) of free α-CT and bamboo charcoal (BC)-adsorbed α-CT in acetonitrile.
Table 5 shows the absorbance ratio at 1650 and 1630 cm−1 (ABS1650/ABS1630) of bamboo charcoal-adsorbed α-CT [20]. The higher the absorbance ratio, the higher the secondary structure. The water activity did not affect the absorbance ratio (ABS1650/ABS1630) of bamboo charcoal-adsorbed α-CT, indicating that the secondary structure of bamboo charcoal-adsorbed α-CT does not depend on the water activity. Accordingly, the adsorption firmly makes the conformation of bamboo charcoal-adsorbed α-CT maintained. The absorbance ratio (ABS1650/ABS1630) of bamboo charcoal-adsorbed α-CT is higher than that of free α-CT, as seen in Table 4. The results illustrate that the water activity effectively affects the catalytic activity of bamboo charcoal-adsorbed α-CT having a native structure, compared to that of free α-CT.
\nWater activity (−) | \nABS1650/ABS1630 (−) | \n
---|---|
0.03 | \n1.3 | \n
0.28 | \n1.3 | \n
0.55 | \n1.3 | \n
0.73 | \n1.3 | \n
Ratio of the absorbance at 1650 cm−1 to the absorbance at 1630 cm−1 (ABS1650/ABS1630) of bamboo charcoal-adsorbed α-CT provided by the FTIR measurement.
The catalysis of free α-CT and bamboo charcoal-adsorbed α-CT was markedly dependent upon the nature of organic solvents as shown in Figure 19. The catalytic activity of bamboo charcoal-adsorbed α-CT was much superior to that of free α-CT in organic solvents. The initial transesterification rate of free α-CT in
Solvent dependence o of transesterification catalyzed by free α-CT (A) and BCP-adsorbed α-CT (B).
There have been some reports that the native conformation of enzymes may be altered when enzymes are immersed in organic solvents [37, 38]. Table 6 shows the ratio of the absorbance at 1650 cm−1 to the absorbance at 1630 cm−1 (ABS1650/ABS1630) of free α-CT and bamboo charcoal-adsorbed α-CT after they were immersed in organic solvents for 24 h. The absorbance ratio (ABS1650/ABS1630) of bamboo charcoal-adsorbed α-CT after the solvent immersion was similar to that before the solvent immersion. On the other hand, the absorbance ratio (ABS1650/ABS1630) of free α-CT was altered by the immersion in octane. Those results indicate that the conformation of bamboo charcoal-adsorbed α-CT is hardly influenced by the nature of solvents, compared to the case of free α-CT.
\nSolvent | \nABS1650/ABS1630 (−) | \n|
---|---|---|
Free α-CT | \nBamboo charcoal-adsorbed α-CT | \n|
None | \n1.14 | \n1.47 | \n
Acetonitrile | \n1.15 | \n1.51 | \n
1.20 | \n1.53 | \n
Ratio of the absorbance at 1650 cm−1 to the absorbance at 1630 cm−1 (ABS1650/ABS1630) of free α-CT and bamboo charcoal-adsorbed α-CT provided by the FTIR measurement after the solvent immersion.
Figure 20 shows the relation between the catalytic activity and the hydrophobicity defined as log P where P is a partition coefficient for a given solvent between
Relationship of log P of solvents with transesterification rate (A) or hydrolysis rate (B) of free α-CT and bamboo charcoal (BC)-adsorbed α-CT.
This chapter has introduced the study on the application of the biochar to enzyme carriers to develop the high value-added application of biomass materials. Biochar was thermal stable, chemical stable, insoluble under reaction conditions, available, low cost, regeneration, and reusable. Moreover, as biochar had functional groups for the interaction of enzymes and a high affinity to enzymes, enzymes were firmly adsorbed on biochar. On the other hand, the original weakness of enzymes due to the heat and organic solvent stresses could be much improved by adsorbing enzymes onto the biochar. Moreover, enzymes are strictly influenced not only by heat and organic solvents but also by ultraviolet, X-ray, sound wave, shake, freeze, pressure, shearing force, extreme ionic strength, urea, surfactant metal ion, reductant, and so on. It would be expected that suitable carriers having the high tolerance against those stresses are developed for an enzyme carrier by selecting a kind of biochar as well because there are a great variety of biomass in the earth.
\nThis work was mainly supported by a Grant-in-Aid for Scientific Research (C) from Japan Society for the Promotion of Science (No. 24561013) and a Grant-in-Aid for Scientific Research from Japan Science and Technology Agency (No. AS2111014D).
\nThe craniofacial growth and its harmonization with the dental apparatus take place according to a genetic program that acts in a coordinated manner, in both embryo foetal and postnatal stages. In addition to the structural pattern of development, the genetic program also ensures the control of each stage of ontogenesis, both in space and time, which eliminates the risk of developmental errors. During odontogenesis intricate genetic, molecular and cellular regulations establish accurate tooth number and precise location, size, morphology, and composition of each tooth.
However, deviations from usual structure, or function are possible. Any deviation, qualitative and/or quantitative, from usual pattern of development may be called developmental abnormality or anomaly. Developmental anomalies are also known as congenital anomalies or birth defects. Congenital anomalies are defined by the World Health Organization (WHO)“as structural or functional anomalies”. They can occur during antenatal life and can be detected”prenatally, at birth, or later in infancy” [1].
Development failure of one or more teeth is a result of specific disturbances (failure in the initiation of tooth formation, reduced odontogenic potential of the dental lamina, or premature arrest of tooth development) during the early stages (tooth initiation or morphogenesis stage) of odontogenesis affecting reciprocal interactions between the dental epithelium and mesenchyme and leading to absence of tooth germ [2]. Therefore, the usual number of deciduous and permanent dentitions, in both jaws, decrease and the condition is known as tooth agenesis. Family, twin, adoption and tooth development at molecular levels studies provide evidence-based interpretation of genetics as the predominant factors in the etiology of tooth agenesis. Frequently association of tooth agenesis with inherited monogenic syndromes supports the role of genetics in the etiology of missing teeth.
Absence of tooth developmental has direct clinical implications causing physical appearance, emotional, and functional impact on the affected individual. Most affected individuals lack only one or two permanent teeth, but patients who experience agenesis of more teeth are frequently encountered in dental practice as well. Severe forms of missing teeth lead to greater oral impairments. The lack of teeth, especially anterior teeth, malocclusion, drifting of teeth, diastemas between present teeth have negative impact on the oral health-related quality of life of the patients. Tooth agenesis poses medical problems due to ddysmorphic features that may only require cosmetic concern, or major anomalies that require clinical or cosmetic attention. Multidisciplinary teams1 will manage therapeutic options, such as retaining the primary tooth, orthodontic treatment to close the edentulous spaces, dental surgical implants, and fixed or removable dental prosthetic appliances. The proper treatment may be tailored to the individual. It not only improves speech and masticatory function but also psychosocial distress that may help to restore self-confidence.
There are several terms used to describe tooth agenesis: congenital absence of teeth, congenitally missing teeth, lack of teeth, or aplasia of teeth. Some suggest that the term” congenitally missing” teeth could be misleading because teeth are not visible at birth in the oral cavity and tooth development is completed after birth, or teeth may be lost by dental disease, or trauma, or extracted on clinical grounds. In the case of teeth, the development and differentiation continue long after birth, and instead of congenital many anomalies could rather be called developmental anomalies [3]. For the purpose of this chapter the term tooth agenesis will be used throughout. In the literature are used, most commonly, other descriptive terms mainly defined according to the number of missing teeth:
Hypodontia is the lack of one to six teeth missing (excluding the third molars) with mild to moderate levels of severity.
Oligodontia is the failure of development of more than six teeth missing (excluding the third molars) with severe level of severity.
Anodontia means the lack of all teeth without any associated abnormalities causing an extremely severe dental phenotype.
The terms hypodontia and oligodontia are sometimes used interchangeably being considered as a unique clinical entity. As stated by Nieminen [3] and Vastardis [4], this classification of tooth agenesis may not properly reflect the severity of the phenotype as the third molars are excluded. Wherefore tooth agenesis based on dental phenotype severity may be partial or selective, or hypodontia (mild forms of agenesis), severe forms of agenesis or oligodontia, and very rare cases of agenesis of whole the dentition or anodontia. According to OMIM [5], selective tooth agenesis (STHAG) with no other associated systemic features or isolated tooth agenesis has been separated into two entities. The first entity refers to oligodontia characterized by the developmental absence of six or more permanent teeth. The second one refers to hypodontia characterized by the developmental failure of fewer than six teeth. The number of missing teeth in both cases excludes agenesis of third molars, commonly called wisdom teeth.
Incisor-premolar hypodontia (IPH) is a term also used in the literature based on the high frequency of incisors and premolars missing teeth [6]. For the purpose of this chapter the term tooth agenesis will be used throughout.
Prevalence of tooth agenesis is an important information to be of use not only for the clinician and patients but also for policy makers, given the implication for treatment protocols. Many published studies reported large variation in the prevalence of tooth agenesis across the world due to differences between methods of sampling, sample size, age of subjects, orthodontic or non-orthodontic enrolled subjects, number of males and females, the third molars included or excluded, or ethnic population groups. Moreover, it has been claimed that agenesis of permanent teeth has increased over the years. Mattheeuws et al. [7] considered that the period of time was too short and the available data too limited to describe a possible trend in the human dentition. Their meta-analysis seems to confirm that tooth agenesis has been diagnosed more often in recent studies.
Both the primary and permanent dentitions may be affected by variations in the number of teeth, but the prevalence is different. A prevalence of less than 1% in the primary dentition has been reported in the European population ranging from 0.4 to 0.9%, and it has been reported to be 2.4% in Japanese population. [6, 8, 9]
Prevalence of permanent dentition has been studied extensively because it is no doubt more affected than primary dentition. Prevalence of tooth agenesis in permanent dentition also differs among studies of orthodontic/non-orthodontic subjects. Non-orthodontic population prevalence across the world varies between 1.6 and 9.6 per cent (most often-cited) [10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21] and calculated overall prevalence of tooth agenesis was estimated to be 6.53% ± 3.3% [22]. So far, some systematic reviews compare and evaluate prevalence studies on non-syndromic permanent teeth agenesis in various populations showing the prevalence varying from 0.3% in Indian population [16] to 15.7% in Hungarian population [17]. Polder et al. [11] reported the prevalence of non-syndromic agenesis in permanent teeth of European population (third molars excluded) varying between 3.4% in Switzerland to 10.1% in Norway. The wide range of prevalence values observed in population studies has suggested geographic differences. Published data reviewed by Pemberton et al. [23] reported that people of Scandinavian descent are the most susceptible to tooth agenesis in the permanent dentition whilst those of Asian or Arabic descent are the most susceptible in the primary dentition.
Gender predominance in tooth agenesis has been reported (Table 1) suggesting gender as a risk factor. Tooth agenesis show prevalence rates higher in females compared to males [11, 12, 24]. However, other studies reported no significant difference between the prevalence of tooth agenesis in males and females [19, 20].
Type of dentition | Prevalence % | Prevalence % | ||
---|---|---|---|---|
Minimum | Maximum | Male | Females | |
Primary | 0.4 | 0.9 | No significant differences | |
Permanent | 3.4 | 10.1 | 4.6 | 6.3 |
The prevalence of non-syndromic agenesis in permanent teeth (third molars excluded) in European population (summarized data).
In most patients, dental agenesis involved only one (47.8%) (Figure 1) or two teeth (35.1%) (Figure 2) [11]. Absence of one or two permanent teeth was reported in 83% - 87.9% of the subjects with tooth agenesis [11, 19, 20]. Thus, most of the affected individuals suffer only a mild form of tooth agenesis.
Female patient, 22 years old with non-syndromic tooth agenesis. (1,2,3) intraoral photos showing the missing upper right lateral incisor and the microdontia of the contralateral tooth. (4) panoramic radiograph confirming the agenesis of the maxillary right lateral incisor. * position of the missing tooth.
A 28-year-old female patient with trisomy 21 presenting lower second premolars agenesis. Several dental anomalies are observed on the intraoral photos (1,2,3): Upper diastema, maxillary lateral incisors microdontia, ectopic canines and spaced lower teeth. (4) panoramic radiograph shows the absence of the lower second premolars and an agenesis diagnosis can be confirmed. * position of the missing tooth.
Although tooth agenesis is a common development anomaly, the prevalence becomes progressively smaller as the number of missing teeth increases. For example, isolated agenesis of at least six teeth is relatively rare, affecting 0.08% of the Dutch population [25] and 0.16% of the Danish population. [26] Polder et al. [11] reported an overall prevalence of 0.14% in affected patients with six or more teeth. In addition, lack of all teeth without associated abnormalities is extremely rare, and prevalence is unknown. [19]
Apparently, any tooth in the arch can be missing, but tooth agenesis tends to affect distinct tooth classes differentially. Some tooth types were more often missing than other ones. Thus, the frequency of the individual teeth involved varies [11].
In the deciduous dentition, the upper lateral incisors account for more than 50% and together with lower incisors for 90% of all affected teeth [27]. Nieminen highlighted that there is an obvious association between the agenesis of the temporary teeth and the permanent teeth; a temporary tooth affected by agenesis is almost every time followed by missing of the corresponding permanent tooth [3, 27].
The third molars are the most prevalent missing teeth in all reports. Up to 70% of the population experience problems with their third molars, whether it is failure of proper eruption (impaction) or not erupting at all (agenesis). Up to 25% of the population may lose at least one third molar [10] and therefore, usually, third molar is excluded from the classification. The lowest prevalence of third molar agenesis reported so far was 10.1% for African American population [28] and the highest prevalence was 41% for the Korean population. [30] Excluding the third molars, in European population, the most frequently missing tooth is mandibular second premolar (2.91%–3.22%), followed by maxillary lateral incisor (1.55%–1.78%) or second premolar (1.39%–1.61%), as reviewed by Gracco et al. [19].
Other data support the conclusion that the most commonly missing tooth was the maxillary lateral incisor, followed by mandibular and maxillary second premolars [22]. Figure 3 illustrates the bilateral absence of second lower premolars. Agenesis of lower central incisors is common in Asian populations in both primary and permanent dentitions [9].
Female patient aged 7 years old with confirmed trisomy 21 presenting all four second premolars agenesis. Intraoral photos (1,2,3) emphasize a mixed dentition with lack of space for the alignment of the permanent teeth. (4) panoramic radiograph shows the congenital absence of the second premolars in both dental arches. * position of the missing tooth.
Less commonly affected teeth are, in order, lower incisors, maxillary first premolars, mandibular first premolars, maxillary canines and mandibular second molars (Figure 4). Patients who experience agenesis of these teeth (e.g., canine or maxillary central incisor) more often present with many missing teeth [11].
Tooth agenesis in a non-syndromic 21-year-old female patient. Intraoral photos (1,2,3) emphasizing a generalized microdontia and as a result, teeth are spaced with larger gaps in the lower arch. (4) Anamnesis and the examination of the panoramic x-ray reveal the congenital absence of the lower second molars, both in the right and in the left quadrant. * position of the missing teeth.
The most stable teeth are maxillary central incisors (prevalence of agenesis 0.016%) and mandibular first molars and canines (prevalence of agenesis about 0.03%) [3]. Recently, Eshgian et al. [21] concluded that hypodontia affected specific type of teeth. In their study, the most commonly missing teeth were maxillary premolars, lateral incisors and mandibular premolars. Comparing their results with other data from previous studies, they explained the differences in patterns and prevalence of tooth agenesis between different population groups by ethnic diversity in the distributions of mutant genes. The explanation was supported by the prevalence of people with missing permanent teeth which was significantly lower in blacks than in whites in U.S.A. [28], and different type of affected tooth, mandibular incisor in Hong Kong children population [29] and mandibular second premolars among Italians. [19] Polder et al. [11] considered that difference in the ethnic groups is not the explanation of differences in prevalence between populations due to the small number of reported hypodontia cases and the difficulty of detecting the anomaly without appropriate evidence.
Distinct patterns of permanent teeth agenesis have been reported but, as a general rule, if only one or a few teeth are missing, the absent tooth will be the most distal tooth of any given morphological class [3, 15, 24, 31].
It is known that upper lateral incisors, second premolars, and third molars are the last forming teeth in their tooth family, are in the embryonic fusion of the maxilla and the medial nasal processes and erupt in the critical terminal area of the dental lamina. For these reasons, the last forming teeth are more vulnerable to the critical actions of both genetic and environmental factors during odontogenesis and fail to develop. This can explain why tooth agenesis most frequently affects premolars, lateral incisors, and molars. (Figure 5) The anomaly was called ‘end-of-series. [31, 32] In 2017, it has been assumed by Juuri and Balic that tooth agenesis most frequently affects the last tooth to develop within the tooth family due to a gradual decrease of the odontogenic potential of the dental lamina. [33]
A 13-year-old male with confirmed Down syndrome presenting different dental anomalies. Intraoral photos (1–3) show mixed dentition with delayed eruption of permanent teeth, remarking the absence of the upper left lateral incisor. (4) Examination of the panoramic radiograph reveals the absence of the upper second premolars and of the maxillary left lateral incisor. * position of the missing teeth.
Tooth agenesis may be either bilateral or unilateral. Pinho et al. [32] hypothesized that if the etiology of hypodontia is primarily genetic, then bilateral missing teeth phenotype would be expected to be more commonly observed. Unilateral hypodontia might be a variation in severity of a genetic trait showing a microdont or peg-shaped contralateral tooth.
Most studies reported predominance of bilateral missing teeth, as reviewed by Rakhshan [15]. Goya et al. [34] found that symmetry of congenitally missing teeth was predominant (74.6%), Kirzioglu et al. [35] observed that bilaterally missing teeth was 73.2%, and Endo et al. [36] reported that 89% of the patients presented bilaterally missing teeth. Other researchers have found unilateral tooth agenesis more common. [37] Polder et al. [11] compared (based on nine studies) the occurrence of bilateral and unilateral agenesis for the most four affected teeth showing that only for maxillary lateral incisors prevalence of unilateral agenesis was lower than bilateral agenesis.
Bilateral agenesis of maxillary lateral incisors occurred more often.
Unilateral agenesis involving mandibular second premolars occurred more common.
Unilateral agenesis affecting maxillary second premolars was more frequently.
Unilateral agenesis of mandibular central incisors occurred more often.
Medina [38] stated that while symmetrical dental missing affects the maxilla (Figure 6), the mandible shows mostly unilateral agenesis. In the opinion of other researchers, the most common symmetric missing tooth could be the mandibular second premolar agenesis, followed by the absence of the maxillary second premolar or maxillary lateral incisor, as reviewed by Rakhshan [15].
Non-syndromic tooth agenesis in a 26-year-old female patient. Clinical intraoral appearance (1,2,3) emphasizing multiple dental problems, accentuated by the bilateral absence of the upper lateral incisors and of the second premolars. (4) panoramic radiograph confirming the agenesis of the four upper teeth. * position of the missing teeth.
No overall difference in tooth agenesis has been reported between maxilla and mandible for permanent dentition [11]. However, Gomes et al. [20] found maxillary hypodontia in 59.2% of patients and in the mandible of 40.8% with an overall ratio of 1.45:1 in orthodontic patients. Several reports mentioned a small but not always significant predominance of missing teeth in the maxilla [19, 20, 24] whilst other reported more missing teeth in the mandible than in the maxilla [36].
For the primary teeth, agenesis is more common in the maxilla [27].
No significant difference between left and right sides of the jaw has been reported. Nevertheless, predominance of tooth agenesis on the left side has been reported in some Scandinavian studies, as reviewed by Arte S. [18] and Fekonja A. [24] have found the missing teeth were more commonly absent on the right side.
No clear difference in tooth agenesis has been found between the anterior and posterior regions. Most studies showed higher prevalence in the anterior segment [15] and the few remaining analyses found no significant differences [36]. Endo et al. [36] suggested that in mild cases of tooth agenesis, the anterior segment might be more involved while the posterior segment might be predominant in severe cases.
Polder et al. considered the age of detectability as an important issue. A meta-analysis study made by Polder et al. revealed that the visibility of tooth germs by X-ray examination hangs on their degree of mineralization. Subjects at the same chronological age can show significant differences in mineralization stages and dental age. The major differences in mineralization can be found especially in mandibular second premolar buds or third molar buds which present a late onset of mineralization. Therefore, radiographic examination may show a false-positive result and a misdiagnosis of tooth agenesis. [11]
All primary teeth have erupted by the age of three and all permanent teeth except the third molars between the age of 12 and 14. Therefore, three to four years of age children are suitable for diagnosis of missing primary teeth by clinical examination, and 12 to 14-year-old children (the precise determination of teeth mineralization stages), for diagnosis of permanent teeth [22, 39]. While some studies reported age of detectability after eight years of age for the permanent dentition, and failure for the third molar to form is detectable by age 11.
Investigations so far show that several heterogenous factors may be involved in tooth agenesis. Tooth development is a complex process which involves a combination of genetic, epigenetic, and environmental factors. Thus, there is no single etiology of tooth agenesis. Family, twin, and adoption studies2 are the primary exploration by which the genetic basis of a condition may be established. In addition, observed prevalence differences between populations, and association with heritable syndromes supplied evidence for strong genetic influences on tooth agenesis [8]. These findings provided the reasoning for recent efforts to identify the relevant susceptibility genes and the molecular mechanisms by which they interact with environmental influences, and to correlate tooth agenesis phenotypes with their causative factors. Furthermore, genetic studies on mouse models with dental agenesis have identified a few transcription factors and signaling molecules, such as WNTs (wingless-related integration site), BMPs (bone morphogenetic proteins), FGFs (fibroblast growth factor), and NF–κB (nuclear factor kappa B) as candidate genes in human isolated and syndromic agenesis [40].
More than 300 genes are expressed and control odontogenesis and, apparently, any of these gene mutations may cause tooth agenesis. Among these genes, PAX9 (paired box gene 9), MSX1 (muscle segment homeobox 1), EDA (ectodysplasin A), WNT10A (wingless-type MMTV integration site family, member 10A), and AXIN2 (axis inhibitor 2) are the most frequently reported mutations associated with non-syndromic tooth agenesis (hypodontia/oligodontia), as reviewed by Al-Ani et al. [41] and Liu et al. [42]. (Table 2) These all genes have roles in both signaling pathways and in mediating the signal transduction cascades.
Normal expression of these genes is important for the tooth development. MSX1 is a transcription factors active in regions of condensing ectomesenchyme in the tooth germ. PAX9 is a transcription factor as well, it is expressed in the tooth mesenchyme, playing a significant role during odontogenesis in the progressive and reciprocal signal transduction pathways that normally occur in epithelial–mesenchymal cells. Both Msx1 and Pax9 are involved in the Bmp and Fgf pathways and interact during the tooth-bud-to-cap transition. Their expression profiles during early tooth development are largely overlapping, and Pax9 is known to activate transcription of
Studying 34 unrelated patients with isolated tooth agenesis, van den Boogaard et al. [43] reported that 19 patients, representing 56% of them, had mutations in the WNT10A gene. Of 34 patients, 3% presented mutations in the MSX1 gene, 9% and 3% had mutations in the PAX9 and AXIN2 genes, respectively. It was concluded that WNT10A is a significant gene in the etiology of isolated hypodontia.
Frameshift and nonsense mutations are highly likely all causative because they involve profound alteration of the protein primary structure, but missense mutations in these genes are found to cause tooth agenesis phenotypes characteristic in terms of severity and affected teeth as well [44].
As a rule, homozygous (identical mutation on both alleles of a specific gene) or compound heterozygous (both alleles of a gene are mutant, but the mutations are different) carriers of gene mutations exhibit more severe phenotype of tooth agenesis than heterozygous carriers (two different alleles, but only one is mutant).
Besides the single-gene mutations, Michon [45] reported the functional role of miRNAs in proliferation and differentiation of cells and tissues during odontogenesis and possible dental defects development. His results support the view of complex genetic etiology of tooth agenesis.
Attention should be turned to the expression of a mutation in a family. In families with a probable dominant or recessive Mendelian inheritance, there seems to be a variable missing teeth phenotype. In other words, tooth agenesis patterns are different in expressivity among the affected members within a family having the same molecular cause. Vastardis studied incisor agenesis in families with dominant pattern of inheritance. Autosomal dominant disorders express variability in clinical manifestation caused by reduced penetrance and variable expressivity of mutant gene. Consequently, individuals in the same family who carry an identical mutation can vary in the severity of their incisor agenesis. Variable expressivity determines developmental alteration of lateral incisor shape (peg-shaped) or rudimentary third molars and unilateral agenesis may be the result of incomplete penetrance. [46]
Mostowska et al. described a three-generation family with severe autosomal dominant oligodontia. Those affected lacked all permanent molars, second premolars, and mandibular central incisors. The authors found a novel mutation of MSX1. Mutation occurs in exon 2, at nucleotide 581 a cytosine is changed to a thymine (c.581C → T transition), and disrupts the homeobox domain, which is highly conserved. The new mutation causes non-syndromic oligodontia (absence of 14 permanent teeth) in their proband. Two healthy members from the proband’s family carry the same missense mutation. [47] To date, many studies provide evidence for great intra- and inter-familial clinical variability in families with isolated tooth agenesis. [3, 13, 41]
There are several possible genetic mechanisms to explain these major differences in expressivity of the phenotype with the same molecular cause. One of them lies in the concepts of penetrance and expressivity. Reduced (incomplete) penetrance and variable expressivity are factors that influence the effects of particular genetic changes and are commonly seen with Mendelian dominant traits. Tooth agenesis shows incomplete penetrance, since pedigree studies demonstrate individuals who must carry the mutation but who do not appear to be affected themselves. Reduced penetrance probably occurs when final effect of a gene mutation can be indirectly influenced by modifier genes, epigenetic factors, or miRNAs. Potential modifier genes may act in the same or in different development pathways altering (exacerbate or attenuate the effect of the gene mutation) the clinical phenotype.
Epigenetic factors do not change the gene sequence. Epigenetic alterations may be induced spontaneously, in response to environmental factors, or may be part of a person’s make up (allele dosage, copy number variants, allele variants). Identical twins are ideal subjects for studying the effects of epigenetic modifications. Monozygotic co-twins sharing sex, age, and identical genomes display discordant phenotypes for missing teeth which may be explained by epigenetic differences. In their twin study, Townsend et al. supported the view that, even though there is a relatively strong genetic basis to missing teeth, the number or position of affected teeth can be influenced by epigenetic factors. Epigenetic alteration activities, such as DNA methylation and histone modification, at each stage, at the local level during the odontogenesis process, may account for distinct phenotypic differences in the final appearance of teeth of the identical twins. During tooth development, odontogenetic cells reply differently to epigenetic variation in spatiotemporal expression of local signaling molecules passing between cells. [48]
miRNAs play an important role in controlling gene activity by regulating translation during tooth development. Changes in miRNAs levels have been linked to several dental defects [45]. Thus, in a population, the missing teeth phenotype might not occur so often as the abnormal genotype. On the other hand, individuals with the same genetic condition may have more missing teeth than another having only one missing tooth. Thus, expressivity describes individual variability. Variable expressivity is probably caused by a combination of genetic, environmental, and lifestyle factors, most of which have not been identified.
Dreesen et al. analyzed hypo−/oligodontia phenotype variations in nine families at individual, intrafamilial and interfamilial levels aiming to evaluate whether the different agenesis patterns in the pedigrees are predictive of mutations in specific genes based on reported genotype–phenotype associations. Familial aggregation was noted but the tooth agenesis patterns were variable between family members, in terms of number of missing teeth. Therefore, tooth agenesis is not (always) a simple monogenic disorder. The authors proposed a multifactorial aetiological model with many genes and environmental factors modulating the clinical expression. [49]
Genetic heterogeneity describes different gene mutations or genetic mechanisms that produce the same or similar clinical phenotype. Heterogeneity can be recognized by subtle differences in clinical phenotype or evidence of different patterns of inheritance. Genetic testing can confirm the gene mutation responsible for a certain clinical phenotype. Usually, genetic heterogeneity complicates the risk estimation in genetic counseling and genetic prognoses.
Two types of genetic heterogeneity are recognized: locus heterogeneity (clinical phenotype is caused by mutations at two or more different loci), and allelic heterogeneity (clinical phenotype is caused by more than one mutation within the same gene, same locus).
Locus heterogeneity is well documented in selective tooth agenesis (STHAG).
There are ten loci associated with STHAG. Nine of them are autosomal loci (STHAG1 to STHAG9) and one STHAGX1 is sex-linked locus as it follows the X-linked dominant pattern of inheritance. The corresponding gene located at
In 1998, Ahmad et al. [50] reported an autosomal recessive form of hypodontia in a large consanguineous Pakistani family. This was the first report of hypodontia associated with other dental anomalies, such as enamel hypoplasia and failure of teeth eruption, leading to the edentulous state prematurely. The locus was named
In 2000, Wang et al. [51] described a rare, heritable, form of agenesis of permanent teeth. The tooth number anomaly was named He-Zhao deficiency. The only clinical feature of affected individuals was oligodontia. It was transmitted in an autosomal dominant manner with reduced penetrance in a large six successive generation family coming from a small village in China. The number of missing teeth ranged from “a few teeth to the entire set of teeth”. Some of the patients were more likely to have first and second molars. This distinct form of permanent tooth agenesis is associated with
In 2015, Huckert et al. [52] reported mutations in LTBP3 (latent transforming growth factor-beta-binding protein 3) gene causing different dental phenotypes and brachyolmia (short trunk, mild short stature with platyspondyly and scoliosis). The association of oligodontia with hypoplastic amelogenesis imperfecta, taurodontic molars and short stature has been designed as a distinct entity named DASS (dental anomalies and short stature) (OMIM 601216). So, STHAG6 was incorporated into DASS.
Another example of locus heterogeneity is provided by mutations in EDA, EDAR and EDARADD genes which express the similar phenotype of hypohidrotic ectodermal dysplasia. (Table 3).
Gene symbol/locus | Gene name | Cytogenetic location | Gene /locus OMIM number | Description of tooth agenesis clinical features | Inheritance | Phenotype OMIM Number |
---|---|---|---|---|---|---|
AXIN2 | axis inhibitor 2 | 17q24.1 | 604025 | Oligodontia – severe permanent teeth agenesis | Autosomal DOMINANT | 608615 |
EDA | ectodysplasin A | Xq13.1 | 300451 | Tooth agenesis, selective, X-linked 1 (STHAGX1) | X-linked DOMINANT | 313500 |
GREM2 | GREMLIN-2 homolog, cystine knot superfamily gene | 1q43 | 608832 | Tooth agenesis, selective,9 (STHAG9) | Autosomal DOMINANT | 617275 |
LRP6 | low density lipoprotein receptor-related protein-6 | 12p13.2 | 603507 | Tooth agenesis, selective,7 (STHAG7) | Autosomal DOMINANT | 616724 |
MSX1 | muscle segment homeobox 1 | 4p16.2 | 142983 | Tooth agenesis, selective,1, with or without orofacial cleft (STHAG1) | Autosomal DOMINANT | 106600 |
PAX9 | paired box gene 9 | 14q13.3 | 167416 | Tooth agenesis,selective,3 (STHAG3) Hypodontia/Oligodontia 3 | Autosomal DOMINANT | 604625 |
STHAG2 | 16q12.1* (*the disorder was placed on the map by statistical methods) | 602639 | Tooth agenesis, selective, (STHAG2) | Autosomal recessive | 602639 | |
STHAG5 | 10q11.2-q21* (*the disorder was placed on the map by statistical methods) | 610926 | Tooth agenesis, selective,5 (STHAG5) Hypodontia/Oligodontia 5 (He-Zhao deficiency) | 610926 | ||
WNT10A | wingless-type MMTV integration site family, member 10A | 2q35 | 606268 | Tooth agenesis, selective,4 (STHAG4) with or without ectodermal dysplasia | Autosomal DOMINANT or recessive | 150400 |
WNT10B | wingless-type MMTV integration site family, member-10B | 12q13.12 | 601906 | Tooth agenesis, selective,8 (STHAG8) | Autosomal DOMINANT | 617073 |
Gene mutations involved in NON-SYNDROMIC tooth agenesis are passed on to the next generation following different Mendelian patterns of inheritance (according to OMIM database).
Online Mendelian Inheritance in Man (OMIM™) is a comprehensive, authoritative and timely knowledgebase of human genes and genetic phenotype compiled to support research and education in human genomics and the practice of clinical genetics. It is freely available and updated daily.
Gene symbol | Gene name | Cytogenetic location | Gene/locus OMIM number | Name of disorder associated with tooth agenesis | Inheritance | Phenotype OMIM Number |
---|---|---|---|---|---|---|
AXIN2 | axis inhibitor 2 | 17q24.1 | 604025 | Oligodontia-colorectal cancer syndrome | Autosomal DOMINANT | 608615 |
EDA | ectodysplasin A | Xq13.1 | 300451 | Hypohidrotic ectodermal dysplasia 1 (HED) | X-linked reccessive | 305100 |
EDAR | ectodysplasin A receptor | 2q13 | 604095 | Ectodermal dysplasia 10A, hypohidrotic/hair/nail type Ectodermal dysplasia 10B, hypohidrotic/hair/nail type | Autosomal DOMINANT Autosomal recessive | 129490 224900 |
EDARADD | edar-associated death domain | 1q42-q43 | 606603 | Ectodermal dysplasia 11A, hypohidrotic/hair/tooth type Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type | Autosomal DOMINANT Autosomal recessive | 614940 614941 |
LTBP3 | latent transforming growth factor-beta-binding protein 3 | 11q13.1 | 602090 | Dental anomalies and short stature | Autosomal recessive | 601216 |
MSX1 | muscle segment homeobox 1 | 4p16.2 | 142983 | Ectodermal dysplasia 3, Witkop type Orofacial cleft 5 Wolf-Hirschhorn syndrome* (*a contiguous gene deletion syndrome in which multiple genes are involved) | Autosomal DOMINANT Autosomal DOMINANT Isolated cases | 189500 608874 194190 |
NEMO (IKBKG) | inhibitor of nuclear factor kappa-b kinase, regulatory subunit gamma | xq28 | 300248 | Incontinentia pigmenti | X-linked DOMINANT | 308300 |
PITX2 | paired-like homeodomain transcription factor 2 | 4q25 | 601542 | Axenfeld-Rieger syndrome, type 1 | Autosomal DOMINANT | 180500 |
WNT10A | wingless-type MMTV integration site family, member 10A | 2q35 | 606268 | Schopf-Schulz-Passarge syndrome Odontoonychodermal dysplasia | Autosomal recessive Autosomal recessive | 224750 257980 |
Gene mutations frequently associated with SYNDROMIC tooth agenesis.
Allelic heterogeneity is illustrated by the different mutations in the MSX1 and PAX9 genes. For example, MSX1 mutations show overlapping and non-overlapping phenotypes. Almost all mutations are responsible for autosomal dominant STHAG1 involving second premolars, first molars and third molars. Few MSX1 mutations are associated with combinations of tooth agenesis with oral clefting (cleft palate only and cleft lip and cleft palate) and nail abnormalities (Witkop syndrome). [49] (Table 3)
Genotype–phenotype correlations refer to the association between specific germline mutations, meaning genotype, and the resulting spectrum of disease expression of that mutation in the affected individual, meaning phenotype. Usually, such correlations are made for monogenic disorders which follow Mendelian inheritance patterns. Moreover, the correlations can clarify which characteristics of a mutation affect the severity of dental anomaly with a genetic background. On the other hand, the pattern of tooth agenesis provides useful information about how gene mutation might affect an individual and other member of the family. Tooth agenesis runs in families and hypodontia/oligodontia patients have one or more affected family members. [48] So, the family members can be appropriately counseled by a geneticist, and predictive/pre-symptomatic genetic testing should be considered for early diagnosis and early intervention, especially for children.
Research studies have linked non-syndromic hypodontia/oligodontia phenotype with specific gene mutations. For example, among identified mutations, MSX1 and PAX9 genes can cause variation in clinical phenotype of tooth agenesis. Kim et al. [53] studied the pattern of missing teeth in families with certain MSX1 and PAX9 mutations. The missing teeth pattern associated with MSX1 mutants was different from that associated with mutations in PAX9. MSX1-associated tooth agenesis involved bilaterally symmetrical absence of maxillary and mandibular second premolars and maxillary first premolars. PAX9-associated tooth agenesis involved also bilaterally symmetrical missing teeth, usually maxillary and mandibular second molars were affected. Yu et al. [54] stated that WNTB10B-associated oligodontia affected most lateral incisors. In contrast, genotype–phenotype analysis of oligodontia pattern associated with WNT10A mutations revealed that premolars were the most frequently missing teeth.
Mutations in nine genes (MSX1, PAX9, AXIN2, WNT10A, EDA, EDAR, EDARADD, NEMO and KRT17) have been associated with non-syndromic oligodontia, as reviewed by Liu et al. [42] Oligodontia phenotype is caused by haploinsufficiency. Mutations produce a reduction in functional gene product below a threshold required for normal dental development [8].
Apparently, reduced quantities of a gene product should equally affect the formation of all teeth. Oligodontia caused by defects in MSX1 and PAX9 yields typical, although variable and overlapping patterns of tooth agenesis [8]. Mutations of MSX1 result in the absence of all permanent third molars, all second premolars, maxillary first premolars and variably other teeth, whereas defects in PAX9 cause mainly agenesis of molars, typically of all permanent maxillary and the second and third mandibular molars as well as variably of other teeth. [55] Regarding AXIN2 gene, five mutations were reported to be associated with non-syndromic tooth agenesis: four missense and one frameshift mutations. The phenotype is variable in expression and involved at least seven teeth. One study reported that a mutation in EDARADD gene led to non-syndromic oligodontia. [41]
Not all of the tooth agenesis forms can be linked to precis genetic mutations, at a single gene locus. Tooth agenesis is a common developmental anomaly and has a definite familial tendency. However, the proportion of affected near relatives is less than what expected for a monogenic trait. One way to recognize a complex trait is through unpredictable inheritance patterns in successive generations. Tooth agenesis is probably caused by several independent defective genes, acting alone or in combination with other genes, and interacting with environmental factors, leading to a specific clinical phenotypic pattern. Being produced by multiple genes, a multifactorial trait seems to be more susceptible to environmental/stochastic or nongenetic factors.
Incomplete penetrance, genetic background, and variable expression levels did not explain all major differences in the expressivity of the phenotype with the same molecular cause. For these reasons, some authors based on evidence from genetic studies, animal models, and environmental correlates suggested an oligogenic or polygenic inheritance of tooth agenesis. [42, 45, 46, 47, 48]
For instance, Vastardis [45] stated that tooth development is a very complex process and involves many” players”. Thus, third molar agenesis cannot be explained in most cases with a simple model of autosomal dominant transmission. Fekonja et al. [24] suggested that genes could be the dominant factor for the agenesis in the anterior region, while the posterior teeth could be missing sporadically. Townsend et al. [56] proposed a multifactorial aetiological model, with possibly many genes, and also environmental and epigenetic factors contributing to tooth development based on lack of complete concordance for missing teeth in monozygotic twins.
It has been documented by various statistical analyses using single locus and polygenic patterns that both approaches are possible. From genetical point of view, multifactorial inheritance of tooth agenesis is troublesome to analyze. It is difficult to state whether hypodontia is a result of a polygenic or single gene defect. It arrives at a diagnosis of multifactorial inheritance for tooth agenesis only after the monogenic forms of inheritance have been considered and found unlikely.
Molecular basis or locus of isolated anodontia (OMIM 206780) are unknown. Gorlin et al. [57] described complete absence of the permanent dentition with the entire primary dentition present and erupted at a normal time. Anodontia presented evidence of autosomal recessive inheritance, including multiple affected sibs and consanguineous parents. Based on three family studies, it was documented that anodontia of permanent teeth is a homozygous state of the gene responsible for pegged or missing maxillary lateral incisors. [5]
Pseudoanodontia should not be confused with anodontia. Pseudoanodontia or false anodontia occurs, when teeth are absent clinically because of impaction, delayed eruption, exfoliation or extraction. In GAPO syndrome (GAPO syndrome is the acronymic designation for a complex of growth retardation, alopecia, pseudoanodontia, and progressive optic atrophy - OMIM 230740) is described pseudoanodontia, failure of tooth eruption. The syndrome is caused by mutations of ANTXR1 gene (anthrax toxin receptor 1) located on 2p13.3, and the pattern of inheritance is autosomal recessive [58].
Tooth agenesis is usually isolated, but gene mutations have been identified that either cause tooth agenesis as a sole isolated agenesis, or tooth agenesis in association with a wide variety of multiorgan malformation syndromes. (Table 3
Thus, tooth agenesis is a primary feature of many single-gene Mendelian syndromes that affect not only teeth but also several other ectodermal derivatives indicating that the development of teeth and certain tissues/organs are under the control of the same gene molecular functions and common molecular mechanisms are responsible for tooth and other organ development. A pleiotropic mutation may influence several, apparently unrelated, traits simultaneously, due to the gene coding for a product used by a myriad of cells or different targets that have the same signaling function. For instance, two AXIN2 nonsense mutations caused syndromic tooth agenesis, such as oligodontia and predispose to colorectal cancer, or oligodontia and variable other findings, including colonic polyposis, gastric polyps, a mild ectodermal dysplasia phenotype with sparse hair and eyebrows, and early onset colorectal and breast cancers [42].
Adventitious chromosomal abnormalities cause tooth agenesis in association with other clinical features and recognizable patterns of malformations known as chromosomal syndromes.
Down syndrome and tooth agenesis (OMIM 190685)
Down syndrome (DS), a common and well-known syndrome, is caused by an autosomal aneuploid defect called trisomy involving the human chromosome 21 (Ts21). The extra chromosome 21 or part of its long arm (including many genes) may come in distinct genetic ways, such as full trisomy 21, mosaic trisomy 21 or unbalanced translocation trisomy 21 causing DS distinctive facial features. The difference between DS people could be made by chromosome analysis because craniofacial features are similar. So, cytogenetic analysis is not relevant for predicting the severity of oro-dental features in DS [59].
Missing teeth were reported in 23–47% of cases (Figure 7). Third molars, second premolars, and lateral incisors are most frequently absent in the permanent dentition. Peg-shaped maxillary lateral incisors have been observed in 10%. In 12–17% of cases, deciduous lateral incisors are missing. Extreme hypodontia and anodontia have been noted occasionally. [60] There is a higher incidence of dental anomalies, such as taurodontism, fusion of deciduous lower lateral incisor with a canine, morphologic crown alterations, enamel hypoplasia and hypocalcification. Irregular alignment is common as well. Tooth eruption of both deciduous and permanent teeth is delayed in 75% of cases and irregular sequence of eruption is common. [60] DS children with missing teeth have a more obvious tendency in developing a Class III relationship of the jaws than DS children without tooth agenesis. This must be taken into account when treating a DS patient [61].
Wolf-Hirschhorn syndrome and missing teeth (OMIM 194190)
The deletion of the distal short arm of human chromosome 4 causes del(4p) syndrome known as Wolf-Hirschhorn syndrome. The critical region is 4p16.3 (WHSCR) and lies approximately 2 Mb from the telomere, so that multiple genes are deleted. Most important genes, playing a major role in early development, are NDS2 (nuclear receptor binding SET domain protein 2), LETM1 (leucine zipper and EF-hand containing transmembrane protein 1), and MSX1 (muscle segment homeo box homolog 1) cause the typical signs and symptoms of this disorder, such as characteristic facial appearance (microcephaly, high forehead, prominent glabella,” Greek warrior helmet” facies, broad and/or beaked nose, hypertelorism, short philtrum, micrognathia, downturned corners of the mouth, short upper lip, dysplastic ears, preauricular tags), delayed growth and development, intellectual disability, and seizures. Agenesis of many permanent teeth has been reported. [60]
About 10% of the patients have cleft lip and palate, 25% present cleft palate, and 50% with micrognathia and high arched palate.
Although, MSX1 gene is outside the WHSCR, in people with Wolf-Hirschhorn syndrome it is frequently deleted. Previous studies reported the critical role of MSX1 in dental, lip, and palate development. [62, 63] Some people with Wolf-Hirschhorn syndrome present mutations of MSX1 gene. It is expected that deletion of MSX1 gene might disrupt the formation of oral structures in early development, causing missing teeth and other dental abnormalities associated with an opening in the roof of the mouth (cleft palate) and/or a split in the upper lip (cleft lip). Nieminen et al. considered that haploinsufficiency of MSX1 gene is a possible mechanism for selective tooth agenesis 1 but a single copy of the gene is not sufficient to produce the oral cleft phenotype. [64]
Multiple tooth agenesis in a 14-year-old female patient with trisomy 21. (1–3) intraoral photos reveal a mixed dentition. It is important to note that the prolonged retention of several primary teeth, either due to the congenital absence of the permanent successor tooth (which is the case of the missing maxillary right lateral incisor) or the deviation in the eruptive path of the permanent successor which determinate the concomitant presence of both the deciduous and the permanent teeth on the arch (in the figures, the deciduous teeth are marked with red arrows while the permanent ones are labeled by blue arrows). The degree of complexity involved in this case is increased not only by the agenesis of the upper right lateral incisor, but its association with another three missing incisors in the lower arch. (4) based on the anamnesis and the examination of the panoramic radiograph, it was confirmed the agenesis of the upper right lateral incisor, lower lateral incisors, and the lower right central incisor. Moreover, left second molars in both arches present an elongated pulp chamber and apically displaced furcations, which are specific for the diagnosis of taurodontism. * position of the missing teeth.
Tooth agenesis cases are either familial or sporadic. Sporadic cases are commonly considered to be nonhereditary, with low risk for relatives or offspring.
By definition, a sporadic disorder arises in the absence of evidence for a heritable or environmental etiology. Affected individuals occur occasionally in families with no reported medical history of tooth agenesis. Consequently, apparently sporadic tooth agenesis may be not inherited from parents but may arise from different aetiologies. Fisher et al. considered that apparently sporadic disorders imply genetic or environmental factors. Sporadic cases can arise from new mutations in germs cells or somatic cells, as well as disorders with an environmental cause. [65].
Usually, environmental factors may cause arrested tooth development. Different kinds of trauma in the dental region, such as fractures, surgical procedures on the jaw, and extraction of the preceding primary tooth are mentioned in the literature, as reviewed by Arte. [18] Furthermore, Vastardis H. [46] reported that dental agenesis in association with other developmental abnormalities may occur because of syphilis, scarlet fever, rickets or nutritional disorders during pregnancy or childhood that act in the early stages of a developmental process. Besides, the authors emphasized the effects of cranial irradiation on endocrine function and tooth development.
Tooth agenesis is diagnosed by intraoral examination (teeth did not erupt), radiographic assessment of oral cavity (no visible mineralization), and a detailed dental history to rule out extractions and trauma. Unusual spacing in a child’s dentition should lead the parent or dentist to suspect tooth agenesis. Occasionally, tooth agenesis could be a clinical sign of a possible underlying syndrome and not only an isolated disease. Referrals to genetic specialists should be considered if a dentist suspects a patient is affected with tooth agenesis.
Using genetic testing, it is possible to screen or diagnose a patient and make a precise etiological diagnosis. Tooth agenesis may occur without a family history, although it is often familial. Monogenic forms of tooth agenesis have a strong genetic component and genetic testing has usually a confirmatory role. The known mutations in some genes can be screened for early signs of developing problems and identification of the individuals at risk.
The analysis is available for genes involved in both syndromic and non-syndromic forms of tooth agenesis, but the test is expensive, and it is not always covered by health insurance.
Known genotype–phenotype correlations can be used for mutation detection. Clinical features in tooth agenesis might be predictive of underlying genotype. For example, if specific teeth are missing, such as maxillary first premolars associated with MSX1 mutations or lateral incisors associated with WNT10B mutations, tooth agenesis pattern gives clue to the most appropriate genetic tests to follow. Genetic testing panel for selective tooth agenesis analyses changes in nine genes at once. Looking for tooth agenesis-associated gene mutations, MSX1, PAX9, WNT10A, LRP6, EDA, WNT10B cause non-syndromic selective tooth agenesis, AXIN2 causes oligodontia-colorectal cancer syndrome, LTBP3 causes dental anomalies and short stature, and PTH1R causes primary failure of tooth eruption.
http://ctgt.net/panel/oligodontia-selective-tooth-agenesis-ngs-panel
Combining the clinical features with genetic data is possible to increase precision in diagnosis, assess prognosis, and prediction of treatment response, provide information for healthcare management and family planning. Genetic counseling is indicated if an individual has a positive family history. For example, Boogaard et al. [43] consider that by including WNTA10A in the DNA diagnostics of isolated tooth agenesis, the yield of molecular testing in this condition was significantly increased from 15% to 71%.
Several dental anomalies have been reported in association with congenitally missing teeth. Tooth number reduction is frequently associated with a reduction in tooth size of (microdontia), altered crown morphology (molars with fewer cusps), short-rooted teeth, and enlarged tooth body and pulp chamber (taurodontic molar). The fusion of primary teeth is often followed by hypodontia in the permanent successors.
Clefting, or an aberrant space between normally fused tissues, usually occurs as either cleft lip with or without cleft palate (CL/P) or cleft palate only (CPO). Whether cases of clefts with dental anomalies should be considered isolated or syndromic cleft can be debated. However, the co-occurrence of cleft lip/palate and tooth agenesis is sometimes described as CL/P-hypodontia syndrome. Arte [18] described hypodontia as a very common anomaly in patients with oral and facial clefts. More studies analyzed tooth agenesis patterns in unilateral/bilateral, complete/incomplete, CL, CL/P or CPO, inside or outside the cleft region.
Published data show that tooth agenesis is more frequently observed in patients with cleft lip and palate (CLP) or their unaffected sisters and brother than in the general population because of close relationship between tooth and cleft formation with respect to the critical time of development and anatomical position. [66, 67, 68, 69] Bartzela et al. reported a higher prevalence of dental anomalies in people with cleft lip and palate than in the non-cleft population, even outside of the cleft region. They studied tooth agenesia patterns in human unilateral and bilateral cleft lip and palate and identified more than 50 different patterns of missing teeth. The most common pattern involved maxillary lateral incisors, and maxillary and mandibular second premolars. The frequency of tooth anomalies seems to be related to the severity of the cleft type. The prevalence of missing teeth reaches 100% in patients with the most severe type of isolated cleft, such as complete bilateral mixed clefting phenotype.
The prevalence of tooth agenesis in people complete unilateral cleft lip and palate has been reported within a range of 48.8% to 75.9% inside the cleft area. The prevalence outside the cleft region was found to be between 27.2% and 48.8%. [66] when compared with the prevalence of tooth agenesis in general population, which ranges between 3.2% to 7.6%, the prevalence of tooth agenesis in non-affected siblings of cleft lip and palate patients was found to be 11.1% outside the cleft area. [11, 70]
The high prevalence of missing teeth outside of cleft region suggests the common genetic background for both tooth agenesis and clefts. So, odontogenesis and palate formation are developmentally related events, and one gene or few genes, might be involved in both processes, in common genetic pathways. Other studies reported no absence of permanent teeth in the maxillary arch outside the cleft (distal to the canines) in unoperated patients with cleft, suggesting that the surgical procedure done to close palatal clefts disrupts the formation of the developing tooth buds, as reviewed by Slayton et al. [68]
Slayton et al. provided an overview of published data related to similar genetic component for non-syndromic simultaneous presence of both orofacial clefts and hypodontia. The combined phenotype of tooth agenesis with orofacial clefts outside the cleft region was described in both humans and animal models and provide evidence to support a common genetic etiology. Mouse knockout models for deficiency of MSX1 and PAX9 failed to form teeth and had cleft palate. [68]
Few monogenic disorders, such as Van der Woude syndrome (caused by mutation in the IRF6 gene - interferon regulatory factor 6), ectrodactyly-ectodermal dysplasia-clefting syndrome 3 (caused by mutation in the TP63 gene - tumor protein p63), and Kallmann’s syndrome (caused by mutation in the FGFR1 gene - fibroblast growth factor receptor 1) have both clefting and hypodontia as typical phenotypic findings. (Table A1) It should be pointed out that the same gene, IRF6 (interferon regulatory factor 6) may cause a disease as rare as Van der Woude syndrome and also to contribute to much more common defects, such as isolated cleft with or without cleft palate. [71]
Primary failure of tooth eruption (OMIM 125350) was reported in association with hypodontia. The most affected teeth are first, and second molars and involvement can be unilateral or bilateral. Based on family studies, the reported pattern of inheritance was consistent with autosomal dominant ones and molecular cause involved mutation of PTHR1 gene (parathyroid hormone 1 receptor) located on 3p21.31 [72]. Regarding permanent dentition, delayed development of posterior permanent teeth in association with the third molar agenesis was reported in the literature, as reviewed by Nieminen [3]. An average delay of two years was observed, with great variation, in a group of 85 patients with agenesis of on the average seven permanent teeth. It was also reported excessive retardation of development of teeth contralateral to missing teeth. Schalk-van der Weide [25] reported a tendency of early developing teeth of males to be retarded in association with severe agenesis, and in females with severe agenesis second mandibular molars to be significantly delayed in development (only mandibular teeth were studied). The delay correlated with the extent of agenesis was most prominent in positions next to the teeth that had failed to develop.
In population studies the relationship of tooth agenesis and microdontia has been shown to be statistically significant. Microdont teeth is small enough to be outside the usual limit of variation and along with the reduction in size, these teeth often exhibit a change in shape. Microdont teeth may be either usual form or with tapering (peg or conical) crowns (Figure 8). The most common form of microdontia is localized type, affecting maxillary incisors. Peg maxillary lateral incisors are seen in 1.2 to 3.2% of general population. This is a genetic trait which is manifest as either peg or missing maxillary lateral incisors. The microdont teeth show an autosomal dominant inheritance pattern and variable expressivity. Some studies reported families in which both genitors have pegged permanent maxillary lateral incisors. Their children had severe tooth agenesis involving primarily agenesis of succedaneous permanent teeth. It was suggested that children expressed the gene mutation in homozygous status. Some studies reported a 2:1 preference for the left side. In addition, reduced tooth sizes have also been observed within the healthy relatives of patients with severe tooth agenesis [3]. Baccetti [73] reported a significant reciprocal association between agenesis of second premolars and reduced upper lateral incisors. Third molar agenesis was associated with reduction in the cusp number of the molars, as reviewed by Arte. [18] The association of microdontia and tooth agenesis is frequently observed in Down syndrome and various types of ectodermal dysplasia. Generalized microdontia of all teeth is extremely rare in people without some sort of syndrome.
Tooth agenesis in a down syndrome male patient, aged 8 years old. (1–3) intraoral evaluation shows the absence of the right lateral incisors both in the upper and lower arches. (4) the panoramic radiograph confirms the agenesis of maxillary right lateral incisor which is associated to a peg-shaped in the contralateral quadrant. Moreover, agenesis of the lower right lateral incisor is also revealed together with a hypotaurodontism in all four first molars. * position of the missing teeth.
Abnormal positions, or ectopic placement, of teeth (OMIM 189490) are believed to result from a disturbance of the tooth developmental structure. Various forms of the position or eruption disturbance of teeth tend to be associated with tooth agenesis. Differences in frequencies of the abnormal trait between population groups have been observed, as well as differences in the pattern of associations among displaced maxillary canines (a typical type of malposition of canines) and tooth agenesis.
Pirinen et al. [74] studied the palatal displacement of the canine in regard to congenital absence of permanent teeth in 106 Finnish probands and their first- and second-degree relatives. All the probands had had surgical and orthodontic treatment for displaced maxillary canines. Incisor-premolar hypodontia and peg-shaped incisors were found to be strongly associated with palatally displaced canines. The authors concluded that palatally displaced canine belongs to a spectrum of dental anomalies related to incisor-premolar hypodontia.
Peck et al. reported a strong association of displaced maxillary canines with third molar agenesis and second premolar agenesis, whereas upper lateral incisor agenesis was not significantly interrelated [75]. Garib et al. reported an increased occurrence of displaced maxillary canines associated with second premolars agenesis [76]. Lagana et al. concluded that only the agenesis of maxillary lateral incisors should be considered directly connected with displaced maxillary canine. [77]
Taurodontism (OMIM 272700) is characterized by large pulp chambers, with changes usually most striking in the molars. The taurodont tooth lies deep in alveolar bone. Taurodont teeth are associated with missing teeth in chromosome aneuploydies, such as Down syndrome (Figure 9). It occurs also in other syndromes, especially those having an ectodermal defect, e.g., otodental dysplasia. A family having affected sibs with a combination of sparse hair, oligodontia, and taurodontism was reported in the literature. [78]
Multiple tooth agenesis in an 8-year-old male patient with down syndrome. (1,2,3) examination of the dental arches reveals a mixed dentition, with a delayed tooth eruption pattern. (4) panoramic radiograph showing the absence of both the lateral incisors in the maxillary arch and the agenesis of the lower right lateral incisor and the left central incisor. Moreover, the agenesis is associated with mesotaurodont first molars in both upper and lower arches * position of the missing teeth.
It has been documented by Baccetti T. [73] that rotation of premolars is significantly associated with missing upper lateral incisors. The author found a significant association between unilateral agenesis of upper lateral incisors and rotation of the lateral incisor on the other side of the dental arch, and between unilateral agenesia of premolars and rotation of premolars on the other side of the arch.
The finding that there is a significant association between enamel hypoplasia and hypodontia not involving systemic syndromes has been reported by Baccetti T. [73] and Lai et al. [79] It may indicate a common genetic origin for both dental anomalies. However, it also is possible that a single or concurrent environmental factor may have been responsible for the etiology of both defects. Some authors have noted that local infection, as well as radiation, may cause both hypodontia and enamel hypoplasia, as review by Lai et al. [79]
Concomitant hypo-hyperdontia (CHH) is a rare mixed numeric dental anomaly characterized by congenitally missing teeth and supernumerary teeth occurring in the same individual. These two conditions are considered as the opposite extremes in the development of the dentition. [80] The prevalence of CHH was found to range from 0.002 to 0.7%. Due to its rarity and sporadicity, the causes of CHH have been completely unknown. So far, only 80 cases have been reported in the literature. Wang et al. summarized prior research and concluded that more than two-thirds of cases had one supernumerary tooth, and the remaining, two or more teeth. The most commonly supernumerary tooth was mesiodens. Most frequently missing teeth were upper lateral incisors, lower incisors, and premolars. Only a few cases had canines and molars agenesis. Both jaws were affected, bimaxillary hypo-hyperdontia, in about three fourth of the cases. The remaining one-fourth presented maxillary hypo-hyperdontia, the only maxilla being involved. [81]. In most cases, CHH was diagnosed during a regular dental examination. Recently, Wang et al. [81] presented 21 cases of CHH, including 4 familial cases and a syndromic case, and scrutinized their dental phenotypes. Their study results indicated molar taurodontism as the most frequently (29%) observed concurrent dental anomaly of CHH. They also described the fusion of primary lower lateral incisors and canines followed by missing permanent lower laterals. More results described the central cusps of premolars identifiable from the panoramic radiograph of 3 cases. Only one case presented macrodontia of tooth number 9 (upper left central incisor), a premaxillary supernumerary toothand missing tooth number 10 (upper left lateral incisor). The authors concluded,” these concurrent dental aberrations suggested that molecular and cellular mechanisms regulating tooth number also play significant roles in tooth morphogenesis”.
Tooth agenesis has a high prevalence in human population. It was documented that missing tooth has a negative impact on daily quality of life causing significant complications, such as physical appearance problems, oral functional limitations, or psychosocial distress, and cost not only for the affected individual but also for the public health care system worldwide. Early diagnosis is still the best way to prevent complications of missing teeth but understanding the genetic make-up of affected individuals, the dentist must integrate the tools of genetics in the dental practice for prediction, prevention, and personalized dental therapy.
The authors declare no conflict of interest.
Syndrome name and prevalence | Tooth agenesis - levels of severity | Associated phenotypic features by region | Genetic cause | Inheritance | OMIM Orpha-code |
---|---|---|---|---|---|
ADULT syndrome <1/1,000,000 | associated dental anomalies: small teeth, dysplastic teeth, premature loss of secondary teeth (<25 years) | • Lacrimal duct obstruction • Conjunctivitis • Breast hypoplasia • Mammary gland hypoplasia • Widely spaced nipples • Absent nipples • Hypoplastic nipples • Ectrodactyly • Syndactyly • Ectodermal dysplasia • Atrophic skin • Thin skin • Dry skin • Freckling • Photosensitive skin • Dermatitis • Adermatoglyphia • Dysplastic nails • Nail pits • Blond hair • Thin scalp hair • Sparse axillary hair • Premature scalp hair loss (>30 years) | mutations of TP63 gene (tumor protein p63) 3q28 | AD | 103285 978 |
Axenfeld-Rieger syndrome, type 1 1/200,000 | • Maxillary hypoplasia • Short philtrum • Prominent supraorbital ridges • Iris dysplasia (goniodysgenesis) • Iris hypoplasia • Prominent Schwalbe line (posterior embryotoxon) • Glaucoma • Displaced pupils • Dyscoria • Polycoria • Aniridia • Microcornea • Megalocornea • Strabismus • Broad nasal bridge • Thin upper lip • Umbilical defect (redundant periumbilical skin) • Imperforate anus • Anal stenosis • Hypospadias • Growth hormone deficiency | mutations of PITX2 (paired-like homeodomain transcription factor 2) 4q25 | AD Genetic heterogeneity Variable expressivity | 180500 782 | |
Ectodermal dysplasia 3, Witkop type 1–2/10,000 | Normal to small primary teeth Partial to total absence of permanent teeth ( | • Normal facies • Lip eversion • Normal sweat glands • Thin, small friable nails • Koilonychia • Longitudinal ridging • Nail pits • Toenails often more affected than fingernails • Nail changes improve with age • Normal hair | mutations of MSX1 (muscle segment homeobox 1) 4p16.1 | AD | 189500 2228 |
Ectrodactyly, Ectodermal Dysplasia, and cleft lip/palate syndrome 3; EEC type 3 1–9/100.000 | Microdontia Caries | • Maxillary hypoplasia • Malar hypoplasia • Hearing loss • Small ears • Malformed auricles • Blue irides • Photophobia • Blepharophimosis • Blepharitis • Dacryocystitis • Lacrimal duct abnormalities • Flat nasal tip • Cleft lip • Cleft palate • Xerostomia • Absence of Stensen duct • Growth hormone deficiency • Hypogonadotropic hypogonadism • Central diabetes insipidus | mutations of TP63 3q28 | AD | 604292 1896 |
Hypohidrotic ectodermal dysplasia 1 (XHED) or Christ-Siemens-Touraine syndrome 1/15,000 (1/50,000 to 1/100,000 male births) | Microdontia Conical teeth Taurodontism | • Small cranial length • Frontal bossing • Hypoplastic maxilla • Small chin • Small facial height • Prominent supraorbital ridges • Periorbital wrinkles • Periorbital hyperpigmentation • Absent tears • Absent miebomian glands • Scant-absent eyebrows • Scant-absent eyelashes • Small nose • Hypoplastic alae nasi • Nasal mucosa atrophy • Ozena • Depressed nasal root and bridge (‘saddle nose’) • Decreased palatal depth • Prominent lips • Respiratory difficulties • Atrophic rhinitis • Atrophic pharyngeal mucosa • Hypoplastic or absent mucous glands which may lead to dried secretions and obstruction • Atrophic mucosa causing dysphonia • Hypoplastic-absent mammary glands • Hypoplastic-absent nipples • Hypohidrosis • Anhidrosis • Sweat pore aplasia • Soft, thin skin • Dry skin • Mild localized pigmentation abnormalities • Skin peeling/scaling (newborn) • Eczema • Periorbital wrinkling • Periorbital hyperpigmentation • Hypoplastic-absent sebaceous glands • Hypoplastic-absent eccrine sweat glands • Spoon-shaped nails • Hypotrichosis • Fine, brittle hair • Scanty hair • Absent or scanty eyelashes • Absent or scanty eyebrows • Blonde, fine scalp hair • Hoarse voice due to dry laryngeal mucosa • Intolerance to heat and fevers • Susceptible to hyperthermia | mutations of EDA (ectrodysplasin A) Xq13.1 | X-linked recessive Xq13.1 Heterozygous females show variable expressivity (mild to severe manifestations) including hypodontia, conical teeth, reduction in scalp/body hair, and difficulty nursing | 305100 238468 |
Kallmann syndrome 2 hypogonado-tropic hypogonadism 2 with or without anosmia; HH2 1/8,000 males and 1/40,000 females, but is probably underestimated. | (in some patients) | • Hearing loss, unilateral (rare) • Iris coloboma (rare) • Hyposmia/anosmia (in some patients) • Absence of nasal cartilage, unilateral (rare) • Cleft lip • Cleft palate • Osteopenia (in some patients) • Clinodactyly (rare) • Fusion of fourth and fifth metacarpal bones (rare) • Ectrodactyly (rare) • Ectrodactyly (rare) • Hypogonadotropic hypogonadism • Delayed or absent puberty • Low to undetectable gonadotropin levels • Low testosterone level • Low estradiol level • Micropenis • Cryptorchidism • Primary amenorrhea | mutation of FGFR1 (fibroblast growth factor receptor 1) 8p11.23 | AD | 147950 478 |
KBG syndrome unkown prevalence | Associated dental anomalies: macrodontia of the upper central incisors, wide upper central incisors, ridged teeth, fused incisors | • microcephaly • round face early in life • triangular face later in life • long philtrum • large prominent ears • hypertelorism • telecanthus • long palpebral fissures • broad bushy eyebrows • anteverted nares • hypoplastic alae nasi • cervical rib fusion • accessory cervical ribs • cryptorchidism • delayed bone maturation • vertebral body fusion • vertebral arch abnormalities • thoracic kyphosis • clinodactyly • decreased hand length • syndactyly • simian crease • broad bushy eyebrows • low anterior hairline • low posterior hairline • developmental delay • mental retardation • eeg anomalies (in some patients) • seizures (in some patients) | ankrd11 (ankyrin repeat-containing cofactor 1) 16q24.3 | AD | 148050 2332 |
1/50,000 – 1/250,000 | Dental caries Anomalous anterior teeth Enamel hypoplasia Supernumerary teeth | • Microcephaly • Frontal bossing • Facial asymmetry • Microretrognathia • Hypoplasia of the malar bones • Low-set ears • Hearing loss • Epicanthus • Hypertelorism • Telecanthus • Downslanting palpebral fissures • Broad nasal bridge • Hypoplastic alar cartilage • Hyperplastic oral frenuli • Buccal frenuli • Median cleft lip (in 45% of patients) • Pseudocleft of the upper lip • Lobulated tongue (30–45%) • Bifid tongue (30–45%) • Tongue nodule • Cleft palate • Tongue hamartoma (70%) • High-arched palate • Thickened alveolar ridges • Irregular margin of the lips • Cardiac anomalies • Fibrocystic liver (45%) • Dilatation and beading of the intrahepatic bile ducts • Hepatic fibrosis • Pancreatic cysts (29%) • Ovarian cysts • Adult onset polycystic kidney (50%) • Abnormalities of the fingers (45%) • Clinodactyly • Syndactyly • Brachydactyly • Polydactyly, preaxial or postaxial (rare) • X-ray shows irregular pattern of radiolucency and/or spicule-like formation in metacarpals and phalanges • Abnormalities of the toes (25%) • Duplication of the hallux • Polydactyly, preaxial or postaxial (rare) • Milia of upper face and ears (infancy) • Dry scalp • Dry, rough, sparse hair • Alopecia • Variable mental retardation (40%) • Central nervous system malformations (40%) • Abnormal gyrations • Absence of corpus callosum • Gray matter heterotopias • Myelomeningocele (rare) • Stenosis of the aqueduct of Sylvius (rare) • Hydrocephalus • Arachnoid cysts • Cerebellar abnormalities • Seizures • Hypothalamic hamartoma • Porencephaly • Major depression (rare) • Abnormal liver enzymes in those with hepatic cysts or fibrosis • Proteinuria in those with cystic kidneys | mutations of OFD1 gene Xp22.2 | X-linked DOMINANT Xp22.2 (usually lethal in males) | 311200 2750 |
Van der Woude syndrome 1 (VWS1) 1/35,000 – 1/100,000 | • Lower lip pits • Cleft lip • Cleft palate • Cleft uvula | mutations of IRF6 gene (interferon regulatory factor 6) 1q32.2 | AD | 119300 888 |
Tooth agenesis associated frequent in genetic syndromes based on OMIM database.
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\\n\\nSara Uhac was appointed Managing Director of IntechOpen at the beginning of 2014. She directs and controls the company’s operations. Sara joined IntechOpen in 2010 as Head of Journal Publishing, a new strategically underdeveloped department at that time. After obtaining a Master's degree in Media Management, she completed her Ph.D. at the University of Lugano, Switzerland. She holds a BA in Financial Market Management from the Bocconi University in Milan, Italy, where she started her career in the American publishing house Condé Nast and further collaborated with the UK-based publishing company Time Out. Sara was awarded a professional degree in Publishing from Yale University (2012). She is a member of the professional branch association of "Publishers, Designers and Graphic Artists" at the Croatian Chamber of Commerce.
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\\n\\nAdrian Assad De Marco joined the company as a Director in 2017. With his extensive experience in management, acquired while working for regional and global leaders, he took over direction and control of all the company's publishing processes. Adrian holds a degree in Economy and Management from the University of Zagreb, School of Economics, Croatia. A former sportsman, he continually strives to develop his skills through professional courses and specializations such as NLP (Neuro-linguistic programming).
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\n\nBut, one thing we have in common is -- we are all scientists at heart!
\n\nSara Uhac, COO
\n\nSara Uhac was appointed Managing Director of IntechOpen at the beginning of 2014. She directs and controls the company’s operations. Sara joined IntechOpen in 2010 as Head of Journal Publishing, a new strategically underdeveloped department at that time. After obtaining a Master's degree in Media Management, she completed her Ph.D. at the University of Lugano, Switzerland. She holds a BA in Financial Market Management from the Bocconi University in Milan, Italy, where she started her career in the American publishing house Condé Nast and further collaborated with the UK-based publishing company Time Out. Sara was awarded a professional degree in Publishing from Yale University (2012). She is a member of the professional branch association of "Publishers, Designers and Graphic Artists" at the Croatian Chamber of Commerce.
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\n\nDr Alex Lazinica
\n\nAlex Lazinica is co-founder and Board member of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his Ph.D. in Robotics at the Vienna University of Technology. There, he worked as a robotics researcher with the university's Intelligent Manufacturing Systems Group, as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and, most importantly, co-founded and built the International Journal of Advanced Robotic Systems, the world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career since it proved to be the pathway to the foundation of IntechOpen with its focus on addressing academic researchers’ needs. Alex personifies many of IntechOpen´s key values, including the commitment to developing mutual trust, openness, and a spirit of entrepreneurialism. Today, his focus is on defining the growth and development strategy for the company.
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As the science gets more advanced and the information about these two points becomes clearer, the view of this information might modify our understanding to these processes. Then, some topics might be dropped, and others might be raised or become more obvious. However, the feeding of halophyte forages as per se has several drawbacks and therefore, they have to be fed in mixed rations, fortifying these rations with energy supplements.",book:{id:"5978",slug:"new-perspectives-in-forage-crops",title:"New Perspectives in Forage Crops",fullTitle:"New Perspectives in Forage Crops"},signatures:"Salah A. Attia-Ismail",authors:[{id:"204190",title:"Emeritus Prof.",name:"Salah",middleName:"Abdelaty",surname:"Attia-Ismail",slug:"salah-attia-ismail",fullName:"Salah Attia-Ismail"}]},{id:"72082",doi:"10.5772/intechopen.92303",title:"Revalorization of Coffee Waste",slug:"revalorization-of-coffee-waste",totalDownloads:1087,totalCrossrefCites:4,totalDimensionsCites:10,abstract:"One of the household methods most used to prepare the coffee beverage is the coffee dripping method, which generates millions of tons of coffee waste (CW). Its disposition without control causes environmental matters due to the high consumption of oxygen during its discomposing process. However, the high availability, low cost, and chemical composition of CW (cellulose, hemicelluloses, lignin, ashes, protein, aliphatic acids, fats, and water) make them useful material for obtaining added-value products and bioenergy. In this chapter, the state of the art of different sustainable alternatives to revalorize CW is shown. CW has been successfully applied as an adsorbent for removing pollutants from wastewater and gas, a precursor for obtaining activated carbon, and a feedstock for producing energy and valuable products using mono-process extraction and biorefinery.",book:{id:"8952",slug:"coffee-production-and-research",title:"Coffee",fullTitle:"Coffee - Production and Research"},signatures:"Felipe J. Cerino-Córdova, Nancy E. Dávila-Guzmán, Azucena M. García León, Jacob J. Salazar-Rabago and Eduardo Soto-Regalado",authors:null},{id:"56029",doi:"10.5772/intechopen.69614",title:"Production of Spineless Cactus in Brazilian Semiarid",slug:"production-of-spineless-cactus-in-brazilian-semiarid",totalDownloads:1889,totalCrossrefCites:4,totalDimensionsCites:8,abstract:"The term “spineless cactus” is used in Brazil to designate cultivars of Opuntia ficus indica Mill and Nopalea cochenillifera Salm Dyck. The spineless cactus was consolidated in Brazilian semiarid as a strategic fundamental food resource in several production livestock systems, constituting a plant with enormous productive potential. Thus, the spineless cactus has been widely cultivated and used for several decades, by enabling the animal feeding in critical periods of year because of its characteristics, morpho‐anatomical and physiological (CAM), which makes it tolerant to long droughts, being a crop that presents high productivity in droughts conditions, when compared to other forages. Nevertheless, the spineless cactus is a crop relatively picky about soil and climate characteristics of region, presenting greater growth in fertile soils, as well as in regions where nighttime temperatures are cool and the air humidity is relatively high. Although the crop be adapted to long droughts periods, many times it’s necessary to perform irrigation in its production system, mainly in regions of low rainfall, for to supply its water needs, thus ensuring productivity and survival of crop. Therefore, the knowledge of characteristics of plant, as well as of appropriate management techniques to crop, is essential for the good performance of spineless cactus.",book:{id:"5978",slug:"new-perspectives-in-forage-crops",title:"New Perspectives in Forage Crops",fullTitle:"New Perspectives in Forage Crops"},signatures:"Wilma Cristina Cavalcante dos Santos Sá, Edson Mauro Santos,\nJuliana Silva de Oliveira and Alexandre Fernandes Perazzo",authors:[{id:"139631",title:"Dr.",name:"Edson Mauro",middleName:null,surname:"Santos",slug:"edson-mauro-santos",fullName:"Edson Mauro Santos"},{id:"180036",title:"Dr.",name:"Juliana",middleName:null,surname:"Oliveira",slug:"juliana-oliveira",fullName:"Juliana Oliveira"},{id:"203022",title:"MSc.",name:"Wilma",middleName:null,surname:"Sá",slug:"wilma-sa",fullName:"Wilma Sá"},{id:"207265",title:"Dr.",name:"Alexandre",middleName:null,surname:"Perazzo",slug:"alexandre-perazzo",fullName:"Alexandre Perazzo"}]},{id:"70151",doi:"10.5772/intechopen.89224",title:"The Harvest and Post-Harvest Management Practices’ Impact on Coffee Quality",slug:"the-harvest-and-post-harvest-management-practices-impact-on-coffee-quality",totalDownloads:1802,totalCrossrefCites:3,totalDimensionsCites:7,abstract:"Coffee is one of the most important agricultural commodities in the world. The coffee quality is associated with pre-harvest and post-harvest management activities. Each step starting from selecting the best coffee variety for plantation until the final coffee drink preparation determines the cupping quality. The overall coffee quality influenced by the factors which involve in changes the physicochemical properties and sensorial attributes, including the post-harvest operations. The post-harvest processing activities contribute about 60% of the quality of green coffee beans. The post-harvest operations include pulping, processing, drying, hulling, cleaning, sorting, grading, storage, roasting, grinding, and cupping. This chapter comprises the harvest and post-harvest operations of coffee and their impacts on coffee quality.",book:{id:"8952",slug:"coffee-production-and-research",title:"Coffee",fullTitle:"Coffee - Production and Research"},signatures:"Mesfin Haile and Won Hee Kang",authors:null},{id:"69900",doi:"10.5772/intechopen.89508",title:"Coffee By-Products: Nowadays and Perspectives",slug:"coffee-by-products-nowadays-and-perspectives",totalDownloads:1148,totalCrossrefCites:3,totalDimensionsCites:6,abstract:"Coffee is one of the most consumed products around the world; 2.25 billions of coffee cup are consumed everyday in the world. For coffee crop production, different by-products are produced, such as coffee peel, coffee husk, parchment, and spent coffee grounds. These by-products have several problems associated at the final disposition. In this book chapter, we study the main coffee varieties produced in the world, the by-products produced, and its composition and finally assess the potential of supramolecular solvents (SUPRAS) and water as green solvents for high-added-value compound extractions. Bioactive compounds were extracted from fresh and dried coffee peel in an acceptable rate for industrial applications. SUPRAS offer advantages in terms of rapidity (5 min) and simplicity (stirring and centrifugation at room temperature), thus avoiding costly processes based on high pressure and temperature. Extractions carried out using water as solvent is another technique of extraction mixing temperature (above 60°C) and time (4.5 min) obtained a beverage or solution with presence a bioactive compounds how caffeine, chlorogenic acid and polyphenols.",book:{id:"8952",slug:"coffee-production-and-research",title:"Coffee",fullTitle:"Coffee - Production and Research"},signatures:"Laura Sofía Torres-Valenzuela, Johanna Andrea Serna-Jiménez and Katherine Martínez",authors:null}],mostDownloadedChaptersLast30Days:[{id:"71528",title:"A Detail Chemistry of Coffee and Its Analysis",slug:"a-detail-chemistry-of-coffee-and-its-analysis",totalDownloads:2331,totalCrossrefCites:5,totalDimensionsCites:6,abstract:"This review article highlights the detailed chemistry of coffee including its components; chemical constituents like carbohydrates, proteins, lipids, and caffeine; aromatic principles; oil and waxes; and minerals and acids. The high extent of caffeine can be found in the coffee plants; hence, in the second part of the study, various analytical methods are designed for the proper identification, separation, optimization, purification, and determination of caffeine present in coffee, tea, and marketed coffee. These analytical methods are appropriated for the separation and quantification of caffeine. The various analytical methods include spectroscopy methods like UV, IR, and NMR spectroscopy; chromatographic methods like paper, TLC, column, HPLC, and gas chromatography; and hyphenated techniques like LC–MS, GC–MS, and GC–MS/MS. This article compares and contrasts the amount of caffeine by various analytical methods.",book:{id:"8952",slug:"coffee-production-and-research",title:"Coffee",fullTitle:"Coffee - Production and Research"},signatures:"Hemraj Sharma",authors:null},{id:"70151",title:"The Harvest and Post-Harvest Management Practices’ Impact on Coffee Quality",slug:"the-harvest-and-post-harvest-management-practices-impact-on-coffee-quality",totalDownloads:1793,totalCrossrefCites:3,totalDimensionsCites:7,abstract:"Coffee is one of the most important agricultural commodities in the world. The coffee quality is associated with pre-harvest and post-harvest management activities. Each step starting from selecting the best coffee variety for plantation until the final coffee drink preparation determines the cupping quality. The overall coffee quality influenced by the factors which involve in changes the physicochemical properties and sensorial attributes, including the post-harvest operations. The post-harvest processing activities contribute about 60% of the quality of green coffee beans. The post-harvest operations include pulping, processing, drying, hulling, cleaning, sorting, grading, storage, roasting, grinding, and cupping. This chapter comprises the harvest and post-harvest operations of coffee and their impacts on coffee quality.",book:{id:"8952",slug:"coffee-production-and-research",title:"Coffee",fullTitle:"Coffee - Production and Research"},signatures:"Mesfin Haile and Won Hee Kang",authors:null},{id:"72400",title:"Factors Affecting Efficiency of Vegetable Production in Nigeria: A Review",slug:"factors-affecting-efficiency-of-vegetable-production-in-nigeria-a-review",totalDownloads:803,totalCrossrefCites:0,totalDimensionsCites:2,abstract:"Vegetables are important for maintenance of good health; their production and marketing are veritable sources of employment and livelihood. To promote vegetables’ contribution to the above, there is a need for sustainable and efficient production process. The paper reviewed production, socioeconomic factors, and constraint affecting efficiency of production of three important vegetables (tomato, pepper, and onion). The review showed that socioeconomic factors found to increase technical efficiency in vegetable production were educational level, extension contact, and household size. Influence of farmer age on technical efficiency was inconclusive due to varied opinions. Increase in farm size, quantity of seed, amount of fertilizer, and agrochemical were found to have positive influence on output. Majority of the literature reviewed opined that increase in quantity of labour raises productivity; however, it must be utilized efficiently. The mean technical efficiency of the vegetables varied from the southern to the northern part of the country. The cross cutting constraints in vegetables production are pest and diseases, inadequate storage facilities, and high cost of improved inputs. The study recommends increase awareness and sensitization on optimum levels of resource use for increased productivity and appropriate intervention to constraints in the value chain.",book:{id:"10142",slug:"agricultural-economics",title:"Agricultural Economics",fullTitle:"Agricultural Economics"},signatures:"Iyabo Bosede Adeoye",authors:[{id:"317695",title:"Dr.",name:"Iyabo Bosede",middleName:null,surname:"Adeoye",slug:"iyabo-bosede-adeoye",fullName:"Iyabo Bosede Adeoye"}]},{id:"65591",title:"Insect Pest Management in Organic Farming System",slug:"insect-pest-management-in-organic-farming-system",totalDownloads:2595,totalCrossrefCites:1,totalDimensionsCites:4,abstract:"Due to the regulations of organic farming, few options remain for organic farmers to manage pests and diseases in their crops compared to conventional farming. However, major pests could still be managed through manipulation of the agroecosystem processes in advantage of the crops and disadvantage of pests. The limited number of active plant protection substances authorized for use in organic farming can provide support to natural and biological control agents in suppression of pests and diseases. This chapter highlights the principles and strategies of crop protection in organic farming, the cultural practices adopted, the active substances allowed for use to suppress pests, and the impacts on faunal and floral biodiversity. A case study of organic date palm cultivation is discussed.",book:{id:"6988",slug:"multifunctionality-and-impacts-of-organic-and-conventional-agriculture",title:"Multifunctionality and Impacts of Organic and Conventional Agriculture",fullTitle:"Multifunctionality and Impacts of Organic and Conventional Agriculture"},signatures:"Hamadttu Abdel Farag El-Shafie",authors:[{id:"192142",title:"Dr.",name:"Hamadttu",middleName:null,surname:"El-Shafie",slug:"hamadttu-el-shafie",fullName:"Hamadttu El-Shafie"}]},{id:"69412",title:"Soil Management and Water-Use Efficiency in Brazilian Coffee Crops",slug:"soil-management-and-water-use-efficiency-in-brazilian-coffee-crops",totalDownloads:806,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Brazil is a world leader in coffee production. However, currently, it coexists with recurrent and severe droughts, accompanied by intense heat, strong insolation and low relative humidity. As the cultivation is carried out primarily in the rainy season, these world climate variations have affected crops yields and fruits quality, requiring innovative actions that promote efficient use of water stored in the soil. Among several soil management practices that promote a more rational use of water, deep tillage combined with liming, gypsum and fertilizer amendments lead to an increase in effective depth of coffee roots, therefore reducing water stress. Moreover, intercropping with Urochloa sp. is highly efficient in enhancing soil structure, water infiltration and plant available water capacity. Additionally, other innovative techniques and practices are also introduced in this chapter.",book:{id:"8952",slug:"coffee-production-and-research",title:"Coffee",fullTitle:"Coffee - Production and Research"},signatures:"Bruno Montoani Silva, Geraldo César de Oliveira, Milson Evaldo Serafim, Carla Eloize Carducci, Érika Andressa da Silva, Samara Martins Barbosa, Laura Beatriz Batista de Melo, Walbert Junior Reis dos Santos, Thiago Henrique Pereira Reis, César Henrique Caputo de Oliveira and Paulo Tácito Gontijo Guimarães",authors:null}],onlineFirstChaptersFilter:{topicId:"27",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:133,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"7",title:"Bioinformatics and Medical Informatics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",isOpenForSubmission:!0,editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",slug:"slawomir-wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",biography:"Professor Sławomir Wilczyński, Head of the Chair of Department of Basic Biomedical Sciences, Faculty of Pharmaceutical Sciences, Medical University of Silesia in Katowice, Poland. His research interests are focused on modern imaging methods used in medicine and pharmacy, including in particular hyperspectral imaging, dynamic thermovision analysis, high-resolution ultrasound, as well as other techniques such as EPR, NMR and hemispheric directional reflectance. Author of over 100 scientific works, patents and industrial designs. Expert of the Polish National Center for Research and Development, Member of the Investment Committee in the Bridge Alfa NCBiR program, expert of the Polish Ministry of Funds and Regional Policy, Polish Medical Research Agency. Editor-in-chief of the journal in the field of aesthetic medicine and dermatology - Aesthetica.",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},{id:"8",title:"Bioinspired Technology and Biomechanics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",isOpenForSubmission:!0,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. He received his MSc and PhD in Biomedical Engineering respectively from the Federal University of Uberlândia (UFU, Brazil) in 2000 and from the University of Reading (UK) in 2005. 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He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. 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In Southeast Asia, for example, Talaromyces marneffei is an important pathogenic thermally dimorphic fungus that causes systemic mycosis. Widespread fungal infections with complicated and variable clinical manifestations, such as Candida auris infection resistant to several antifungal medicines, Covid-19 associated with Trichoderma, and terbinafine resistant dermatophytosis in India, are among the most serious disorders. \r\nInappropriate local or systemic use of glucocorticoids, as well as their immunosuppressive effects, may lead to changes in fungal infection spectrum and clinical characteristics. Hematogenous candidiasis is a worrisome issue that affects people all over the world, particularly ICU patients. CARD9 deficiency and fungal infection have been major issues in recent years. Invasive aspergillosis is associated with a significant death rate. Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. It will provide significant opportunities and support for scientists, clinical doctors, mycologists, antifungal drug researchers, public health practitioners, and epidemiologists from all over the world to share new research, ideas and solutions to promote the development and progress of medical mycology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment"},{id:"5",title:"Parasitic Infectious Diseases",scope:"Parasitic diseases have evolved alongside their human hosts. In many cases, these diseases have adapted so well that they have developed efficient resilience methods in the human host and can live in the host for years. Others, particularly some blood parasites, can cause very acute diseases and are responsible for millions of deaths yearly. Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. In the current atmosphere of the Coronavirus pandemic, communities around the world, particularly those in different underdeveloped areas, are faced with the growing challenges of the high burden of parasitic diseases. At the same time, they are faced with the Covid-19 pandemic leading to what some authors have called potential syndemics that might worsen the outcome of such infections. Therefore, it is important to conduct studies that examine parasitic infections in the context of the coronavirus pandemic for the benefit of all communities to help foster more informed decisions for the betterment of human and animal health.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",keywords:"Blood Borne Parasites, Intestinal Parasites, Protozoa, Helminths, Arthropods, Water Born Parasites, Epidemiology, Molecular Biology, Systematics, Genomics, Proteomics, Ecology"},{id:"6",title:"Viral Infectious Diseases",scope:"The Viral Infectious Diseases Book Series aims to provide a comprehensive overview of recent research trends and discoveries in various viral infectious diseases emerging around the globe. The emergence of any viral disease is hard to anticipate, which often contributes to death. A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. This series will focus on various crucial factors related to emerging viral infectious diseases, including epidemiology, pathogenesis, host immune response, clinical manifestations, diagnosis, treatment, and clinical recommendations for managing viral infectious diseases, highlighting the recent issues with future directions for effective therapeutic strategies.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",keywords:"Novel Viruses, Virus Transmission, Virus Evolution, Molecular Virology, Control and Prevention, Virus-host Interaction"}],annualVolumeBook:{},thematicCollection:[{type:"book",id:"11672",title:"Chemokines Updates",subtitle:null,isOpenForSubmission:!0,hash:"c00855833476a514d37abf7c846e16e9",slug:null,bookSignature:"Prof. Murat Şentürk",coverURL:"https://cdn.intechopen.com/books/images_new/11672.jpg",editedByType:null,submissionDeadline:"May 6th 2022",editors:[{id:"14794",title:"Prof.",name:"Murat",middleName:null,surname:"Şentürk",slug:"murat-senturk",fullName:"Murat Şentürk",profilePictureURL:"https://mts.intechopen.com/storage/users/14794/images/system/14794.jpeg",biography:"Dr. Murat Şentürk obtained a baccalaureate degree in Chemistry in 2002, a master’s degree in Biochemistry in 2006, and a doctorate degree in Biochemistry in 2009 from Atatürk University, Turkey. Dr. Şentürk currently works as an professor of Biochemistry in the Department of Basic Pharmacy Sciences, Faculty of Pharmacy, Ağri Ibrahim Cecen University, Turkey. \nDr. Şentürk published over 120 scientific papers, reviews, and book chapters and presented several conferences to scientists. \nHis research interests span enzyme inhibitor or activator, protein expression, purification and characterization, drug design and synthesis, toxicology, and pharmacology. \nHis research work has focused on neurodegenerative diseases and cancer treatment. Dr. Şentürk serves as the editorial board member of several international journals.",institutionString:"Ağrı İbrahim Çeçen University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Ağrı İbrahim Çeçen University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}],selectedSeries:{title:"Infectious Diseases",id:"6"},selectedSubseries:null},seriesLanding:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"June 29th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:318,numberOfPublishedBooks:32,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",fullName:"Abdulsamed Kükürt",profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",institutionString:null,institution:{name:"Kafkas University",institutionURL:null,country:{name:"Turkey"}}},{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/118507",hash:"",query:{},params:{id:"118507"},fullPath:"/profiles/118507",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()