Relative amounts of compound families in essential oils of various
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"17",leadTitle:null,fullTitle:"Herbicides and Environment",title:"Herbicides and Environment",subtitle:null,reviewType:"peer-reviewed",abstract:"Herbicides are much more than just weed killers. They may exhibit beneficial or adverse effects on other organisms. Given their toxicological, environmental but also agricultural relevance, herbicides are an interesting field of activity not only for scientists working in the field of agriculture. It seems that the investigation of herbicide-induced effects on weeds, crop plants, ecosystems, microorganisms, and higher organism requires a multidisciplinary approach. Some important aspects regarding the multisided impacts of herbicides on the living world are highlighted in this book. I am sure that the readers will find a lot of helpful information, even if they are only slightly interested in the topic.",isbn:null,printIsbn:"978-953-307-476-4",pdfIsbn:"978-953-51-4531-8",doi:"10.5772/550",price:159,priceEur:175,priceUsd:205,slug:"herbicides-and-environment",numberOfPages:762,isOpenForSubmission:!1,isInWos:1,isInBkci:!0,hash:null,bookSignature:"Andreas Kortekamp",publishedDate:"January 8th 2011",coverURL:"https://cdn.intechopen.com/books/images_new/17.jpg",numberOfDownloads:132280,numberOfWosCitations:255,numberOfCrossrefCitations:48,numberOfCrossrefCitationsByBook:11,numberOfDimensionsCitations:253,numberOfDimensionsCitationsByBook:16,hasAltmetrics:1,numberOfTotalCitations:556,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 7th 2010",dateEndSecondStepPublish:"May 5th 2010",dateEndThirdStepPublish:"September 9th 2010",dateEndFourthStepPublish:"October 9th 2010",dateEndFifthStepPublish:"December 8th 2010",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,8",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"14108",title:"Dr.",name:"Andreas",middleName:null,surname:"Kortekamp",slug:"andreas-kortekamp",fullName:"Andreas Kortekamp",profilePictureURL:"https://mts.intechopen.com/storage/users/14108/images/2370_n.jpg",biography:"Curriculum vitae\n\nAndreas Kortekamp, PhD, was born in 1970 in Germany. After the first education steps and civilian service, he studied biology at the University of Karlsruhe and got his PhD in natural sciences in 2001. He has worked as a visiting scientist at the University of Kaiserslautern, University of Halle, and at the Federal Centre for Breeding Research on Cultivated plants (now Julius-Kühn-Institute) during his postdoctoral studies, and as assistant professor at the University of Hohenheim. \nSince 2009 Dr. Kortekamp is the head of the mycology and bacteriology department at the State Service Center Rheinpfalz for Research, Teaching and Consulting in Viticulture, Horticulture and Rural Development. He has served on the editorial board and as a reviewer of several international journals and is a member in several national and international scientific societies. Dr. Kortekamp teaches biochemistry, plant pathology, and viticulture at the graduate level. He is mainly interested in plant diseases, especially diseases of grapevine, mycology, microbiology, plant physiology, and in the effect of agrochemicals on crop plants.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Dienstleistungszentrum Ländlicher Raum",institutionURL:null,country:{name:"Germany"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"842",title:"Biodiversity",slug:"biodiversity"}],chapters:[{id:"12580",title:"Herbicides: the Face and the Reverse of the Coin. 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\r\n\tGustatory receptor cells housed in taste organs are responsible for processing and coding taste stimuli. These cells constitute a sensory filter for environmental taste signals and transfer information about taste stimuli directly to taste centers in the brain. These cells form the first layer of a decision-making process that ultimately determines whether a food is accepted or rejected by the animal. Similarly, olfactory stimuli play an important role in the orientation of many animals in their environment, including insects. Both invertebrates and vertebrates can detect and discriminate among many odorants that differ in size, shape, and complexity. In many animals, olfaction is the principal sensory modality by which it locates its food sources, mates, and egg-laying sites. For foraging purposes, animals must be able to detect food-related odorants, which may then influence odor-mediated orientation behavior and the discrimination and processing of these odorants in the animal’s brain. This book focuses on the morphology and physiology of both gustatory and olfactory systems in animals, with respect to peripheral chemosensory receptors and their organization, as well as neural circuits and pathways. In addition, clinical and industrial gustatory and olfactory applications and perspectives are discussed.
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Shields, Ph.D., is Associate Dean, Fisher College of Science and Mathematics and a full professor in the Biological Sciences Department, Towson University, Towson, Maryland, USA. Dr. Shields’ research explores gustatory, olfactory, and visual cues in insects.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"82613",title:"Dr.",name:"Vonnie D.C.",middleName:null,surname:"Shields",slug:"vonnie-d.c.-shields",fullName:"Vonnie D.C. Shields",profilePictureURL:"https://mts.intechopen.com/storage/users/82613/images/system/82613.png",biography:"Vonnie D.C. Shields, Ph.D., is Associate Dean, Fisher College of Science and Mathematics and a full professor in the Biological Sciences Department, Towson University, Towson, Maryland, USA. Dr. Shields’ research explores gustatory, olfactory, and visual cues in insects. Her laboratory employs morphological, behavioral, and electrophysiological techniques to better understand sensory mechanisms by which larval and adult insects find host plants and detect plant-associated volatiles. Dr. Shields received a BS and Ph.D. from the University of Regina, Regina, Saskatchewan, Canada. A portion of her Ph.D. studies was carried out at the University of Alberta, Edmonton, Alberta, Canada. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"68005",title:"Study of Essential Oils Obtained from Tropical Plants Grown in Colombia",doi:"10.5772/intechopen.87199",slug:"study-of-essential-oils-obtained-from-tropical-plants-grown-in-colombia",body:'Colombia, located at South America’s northwest, has coasts on the Caribbean and the Pacific Ocean, extensive prairies and mountains with many forests, wild pastures and cultivated land, rivers, and lakes. The country is rich in many natural resources and water. Contrasting landscapes and varied climatic conditions have made it after Brazil, the second most biodiverse country. This biodiversity includes medicinal and aromatic plants; most native aromatic plants remain unexamined. The aromatic herbs and spices commonly used in everyday life were brought to Colombia by the Spanish conquerors five centuries ago (basil, chamomile, mint, parsley, oregano, rosemary, sage, thyme, etc.); some (citronella, lemongrass, clove, ginger, cinnamon) were introduced later, in the last two centuries.
The extension of land cultivated with medicinal and aromatic plants more than doubled between 2007 (1253 ha) and 2015 (2709 ha) [1]. These plantations are located mainly in the Andean region, some in the Eastern Plains of Colombia. The crop of medicinal and aromatic plants amounted to 16,188 tons in 2015. This vegetal material was used for many applications different from essential oil (EO) extraction, in over 100 companies and 2500 commercial establishments [1]. Aromatic plants are used in Colombia’s food industry for beverages, and a portion of the crop is exported in fresh (8288 tons in 2017) [2]. Colombia has currently no commercial enterprise dedicated to the cultivation of aromatic plants destined to produce essential oils for export or the national market. Brazil, India, China, Indonesia, and the United States are Colombia’s main essential oil suppliers. In 2017, the total cost of the country’s essential oil imports was 14.289 million dollars, while the country exported just 298 thousand dollars [2]. Since there is no essential oil production, the EO exported amounts corresponded to commercialization of previously imported oils.
The publication of Colombian scientific articles on EO research started in 1974 and grew slowly during the following 30 years (less than three articles per year). The transition point was marked by the creation in 2005 of a network of research groups that joined their expertise around the development of the EOs agroindustry. The Research Center of Excellence for the Agroindustrialization of Aromatic and Tropical Medicinal Species (CENIVAM), under technical and administrative coordination at the Industrial University of Santander (Bucaramanga), has been a leader in aromatic plants and EO studies in Colombia for more than a decade. Over 250 scientific articles comprise the results of its investigations, which have been focused on the multidisciplinary and systematic search of promising native plants and on introduced species such as ylang-ylang, palmarosa, turmeric, patchouli, mints, basils, citrus, geraniums, and others. Researchers from more than 10 universities have carried out their work in areas of botany and taxonomy, plant physiology, and ecology; on the study of secondary plant metabolites, crop and post-harvest improvement, EO distillation and its optimization, and design of rural stills; on the study of volatile fractions from plants and flowers, obtainment of extracts with solvents and supercritical fluids (SFE-CO2), and catalytic transformation of EOs or their main components; and on the study of their diverse biological properties (antioxidant, antimicrobial, insecticidal, antiviral, and others).
The primary metabolites (proteins, lipids, sugars, etc.) in plants are vital for the plant to grow, multiply, and live, while secondary metabolites are required by the plant to survive. For sure and with all the experimental details studied, the role played by secondary metabolites in plants is not completely known, because they fulfill several functions and operate through different mechanisms. Among many secondary metabolites isolated from plants, there are some very special, widely used in various branches of industry, medicine, and in many products of everyday life. This class of substances is called EOs, volatile oils, ethereal oils, or essences. Numerous substances are part of these oils; they are a complex mixture of volatile compounds with very diverse chemical nature. What most characterizes and highlights them is their smell, generally pleasant and intense, that evokes the fragrance of the plant or of the fruit or wood, from which these oils come. The essence can be remembered as the smell, for example, of a freshly cut grass or vanilla, sweet and cloying, among other aromatic tones that an EO has, formed by a complex range of volatile substances with different fragrant notes and different sensory thresholds for their perception.
Isolated from flowers (rose, orange blossom, lily, ylang-ylang), seeds (coriander, celery, carrot, anise, cardamom), leaves and stems (basil, thyme, mint, lavender, oregano), bark (cinnamon), wood (pine, sandalwood), roots (valerian, vetiver), and rhizomes (ginger, turmeric). EOs can be considered as the soul of the plants, their spirit, which characterizes, highlights, evokes, and makes them memorable in time; oils, generally, produce a pleasant sensation, especially when diluted. The EOs in the plants can be found in the different oil cells (ginger, turmeric, vanilla), in the secretory channels (pine, artemisia, anise, angelica), in the glands (citrus, eucalyptus), or in the trichomes (many plants of Labiatae, Asteraceae, Solanaceae, Geraniaceae families). The plant material (aromatic plant), when subjected to water vapor, releases a liquid odoriferous mixture (EO) of various volatile substances; this mixture can have from 50 to more than 300 chemical substances and is composed of terpene hydrocarbons, their oxygenated derivatives, alcohols, aldehydes, and ketones, as well as ethers, esters, phenolic compounds, phenylpropanoids, and other derivatives [3].
EOs can be obtained from plant material by three main methods (Figure 1). (1) Steam distillation. This process is carried out with a superheated dry steam, usually generated by a boiler or steam generator, which penetrates the plant material at higher than atmospheric pressure; the steam current breaks the cells or oil channels in the plant and drags the volatile mixture, which condenses after passing through a cooling system (heat exchanger). Generally, the oils are lighter than water and with very little soluble in it; therefore, they can be separated by decantation. The exception is the clove oil, which is heavier than water and is collected under it. The steam distillation method is used to extract oils from rhizomes, roots, seeds (vetiver, valerian, ginger, anise, cardamom, etc.), and dried or fermented leaves of some plants (
Main methods of essential oil isolation.
The EO industrial production involves field distillation, in order to avoid the high transportation costs of large vegetal material loads from which only about 1% is going to be obtained as EO. Steam generation is one of the main components of the operation costs. Current trends point toward the use of lignocellulosic waste as biofuel for the furnace. Still capacity is determined by the crop size. The goal is to maintain the still operating for at least 300 days of the year and to schedule the harvests to avoid long storage (more than a week) of the cut vegetal material waiting for its distillation. This is mainly to prevent mold formation. Patchouli and vetiver are two exceptions to this rule, because a curing period of several days or months (vetiver) recommended to enhance oil yield and organoleptic quality.
The reality is that a large part of Colombian small growers have low purchasing power, low economic performance and productivity, and not very sophisticated technology level in rural operations and processes. Traditional agricultural production faces a complex problem that includes low prices, low profitability, and the increasingly acute lack of rural labor, because young people migrate to the cities. The EO industry is a very important rural development alternative in which the harvested vegetal material is no longer the final product, but the start of an added-value product chain. Several pilot projects, financed by the Ministry of Agriculture and Rural Development and Colciencias (Colombia’s Science Funding Agency), have been carried out in the past 15 years by CENIVAM with the participation of small rural farmers associations. The common goal of these projects has been the development of the EO value chain. The economic, agronomic, and quality viability of EOs obtained in several productive units have been studied. Each unit has characteristics, as follows: 5–8 ha crop extension, 20–22 families of small growers involved in each project, 3 or 4 plant species cultivated per unit (palmarosa, citronella,
Rural production and distillation of essential oils in Colombia (Barbosa, Santander).
The analytical technique routinely used for the instrumental chemical analysis of EOs is gas chromatography (GC), because the constituents of oils are volatile (monoterpenoids, esters, etc.) or semi-volatile substances (sesquiterpenoids, phenolic derivatives, etc.), whose molecular masses and boiling points do not exceed 300 a.m.u. and 300°C, respectively. A chromatographic system comprises four fundamental blocks: (1) sample introduction system (injector), (2) separation system (column), (3) detection system for analytes eluted from the column (detector), and (4) data analysis and operation control system.
The GC can have conventional,
Ylang-ylang essential oil obtained by hydro-distillation from flowers. GC-MS analysis. DB-WAX column (60 m). Injection modes:
Ylang-ylang essential oil obtained from flowers by hydro-distillation and analyzed by GC-MS on a polar column (DB-WAX, 60 m), using different temperature programs:
The detection system differentiates the analyte molecules from those of the mobile phase (carrier gas), to which the detector is transparent. The response of the detector is based on the measurement of one of the physical properties of the system,
The preliminary or presumptive (tentative) identification of the EO components may be obtained once the retention indices are determined. The analysis in modern equipment uses a program for the column temperature; in these cases, linear retention indexes are calculated, which are part of many databases and bibliographic references [5, 6]. The confirmatory identification of a compound in a complex mixture analyzed by GC needs to obtain its “fingerprint,” which is the mass spectrum (MS) represented by a unique combination of charged fragments (ions) generated during the breakup of the previously ionized molecule. The complementarity of the chromatographic analysis (screening) with confirmatory spectral data (mass spectra) is achieved using the combination of two techniques, GC and MS. The GC-MS coupling complements the quantitative analysis carried out by GC-FID and provides important additional information,
EOs contain both nonpolar (monoterpene and sesquiterpene hydrocarbons) and polar compounds (their oxygenated derivatives, aliphatic alcohols, ketones, oxides, phenolic compounds and their derivatives, phenylpropanoids, and rarely acids, among others). Their analysis is performed by GC-FID (quantitative analysis) and by GC-MS (qualitative analysis), in two columns, with polar and nonpolar stationary phases. In columns with the nonpolar stationary phase, poly(dimethylsiloxane), PDMS, or 5% phenyl-PDMS, the elution of components happens depending on their boiling temperatures (or volatilities), that is, the retention times, tR, increase with the decrease of the volatility and with the increase of the molecular masses and boiling points of the components (Figure 5). The compounds reach the end of the column in the increasing order of their boiling points. In the polar column, poly(ethylene glycol), the elution order of the components is more difficult to predict, because it is related to the intermolecular forces between the analyte and the stationary phase and depends both on the dipole moment of the molecule (the polarity) and on the possibility of hydrogen bond formation between the substance and the stationary phase.
GC-MS chromatogram of ylang-ylang essential oil isolated from flowers by hydro-distillation and analyzed by GC-MS on a polar column (DB-WAX, 60 m).
The elution order of some compounds in columns with different stationary phases may be reversed. This often helps, together with the mass spectra and the fragmentation pattern study, to differentiate, for example, terpene alcohols from their acetates, since the latter sometimes do not exhibit molecular ions, M+• in their mass spectra. When the chromatographic parameters (tR, tRR, or retention indices) and spectroscopic parameters,
Fragmentation pattern in mass spectra (electron impact, 70 eV) of some essential oil components.
The biggest challenge in EO analysis is the complete separation of its components (Figure 7) because their frequent coelution occurs due to their very close or equal distribution constants. Some conventional strategies,
Ylang-ylang essential oil chromatogram (GC-MS) fragment.
In comprehensive gas chromatography (GC x GC), two columns are used, linked together by means of a modulator. In contrast to conventional multidimensional gas chromatography, the GC x GC requires a single detector with high processing frequency; both columns can be in the same oven or in two separate ovens. There are different types of modulators,
Fragment of GCxGC-HRMS-TOF chromatogram of ylang-ylang essential oil contaminated with plasticizer (phthalate) traces. m/z 149 is a base peak in alkyl phthalates’ mass spectra.
Further technical details for EO chemical characterization and that of their components can be found elsewhere [12, 13]. In summary, EO characterization necessary for its quality control and the determination of authenticity, as part of a technical data sheet necessary for its commercialization, can be divided into four main stages or areas: (1) organoleptic properties, (2) physicochemical determinations, (3) qualitative and quantitative analysis of the components present in the oil (chemical composition), and, finally, (4) some other determinations,
CENIVAM has studied Colombian plants widely used in popular medicine or in culinary, for example, anise [14], oregano [15], rue [16, 17], and other species introduced from Asia, such as lemongrass, citronella, ginger, citrics [18, 19, 20], vetiver, and ylang-ylang [21, 22, 23], as well as several native species, among others,
Compound family | Relative amount, % | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Carvone | Citral | Citral + Carvone | Myrcenone | Thymol | Carvacrol | Phellandrene | ||||||
Monoterpene hydrocarbons | 31.5 | 4.1 | 24.6 | 12.6 | 14.7 | 31.0 | 45.7 | 15.4 | 44.9 | 19.1 | 12.2 | 0.3 |
Oxygenated monoterpenes | 61.4 | 62.4 | 52.7 | 71.6 | 2.1 | 2.0 | 7.4 | 49.7 | 2.8 | 1.6 | 2.0 | 5.6 |
Oxygenated compounds (phenylpropanoids) | — | 6.9 | 2.7 | 0.0 | 63.3 | 57.7 | 2.0 | 4.4 | 47.7 | 0.2 | 78.1 | 7..9 |
Sesquiterpene hydrocarbons | 4.9 | 11.9 | 16.2 | 6.6 | 5.3 | 3.9 | 29.1 | 11.0 | 3.2 | 52.3 | 5.3 | 54.0 |
Oxygenated sesquiterpenes | 0.3 | 5.1 | 1.1 | — | 0.4 | — | 5.2 | 12.8 | 0.5 | 10.7 | 0.2 | 19.1 |
Relative amounts of compound families in essential oils of various
EOs have been used in phytotherapy and folk medicine for their good odor and antibacterial, antifungal or insecticidal activities. Phenols, alcohols and aldehydes are EO components capable of crossing the cell wall, and in doing so, they alter its permeability and may cause leakage of macromolecules, loss of ions, structure disruption, and, eventually, cell death. This cytotoxicity enables EO applications against human pathogens or parasites and for the preservation of vegetal and marine products. Due to their large number of constituents, EOs affect several targets simultaneously, and this may be the reason for the lack of microorganism resistance development or adaptation. Besides cytotoxicity, the antioxidant properties of EOs are generally invoked as an indication of their potential benefits for human health. This is related to the notion that many diseases are due to high oxidative stress generated by diet, environmental contaminants, or work habits. However, the prooxidant properties of some EO components can play a protective role by promoting the removal of damaged cells. The mitochondria produce reactive oxygen species which can oxidize phenolic compounds (EO components) and give rise to reactive phenoxyl radicals which accelerate the general cell damage [72].
Genus
Some tropical aromatic plants of
More than 30 botanical outings were organized by CENIVAM to various Colombian regions in the Andes, the Eastern Plains, the Caribbean, and the Pacific coasts. Over 1100 accessions of medicinal and aromatic plants were collected and taxonomically identified, under the due permit of access to the genetic resource. Hydro-distillation and steam distillation of these samples produced close to 1000 different EOs that were subjected to chemical characterization using GC techniques provided with FID and MS systems. Tests for antioxidant, antimicrobial, antiviral, antiparasitic, immunomodulatory, photoprotective, and antigenotoxic activities of the EOs revealed that more than 45% of these oils were highly active in one or two assays. The following sections highlight just a few of the interesting findings obtained in the search for natural ingredients with biological properties that may enable the development of products for the pharmaceutical, cosmetics, hygiene, or food industries.
Following the recognition of cytotoxicity and antioxidant capacity as main determinants of EO potential pharmaceutical applications, Olivero and co-workers [64] used the brine shrimp assay and the measurement of thiobarbituric acid induced in rat liver microsomes by a Fenton reagent to evaluate 13 EOs from Colombian plants for cytotoxicity and antioxidant capacity, respectively. Mean effective concentrations (EC50) below 100 μg/mL were registered for the
A study of cytotoxic activity of EOs from the Verbenaceae and Asteraceae families included 36 species of various origins. These oils were tested on Jurkat, HeLa, HepG2, and Vero cell lines [75]. None of the tested EOs was cytotoxic, except that from
A study of 12 EOs of 7
Essential oil (chemotype) or standard compound | Essay (± s, n = 3) | |||
---|---|---|---|---|
Main compounds | Yield, % w/w | ORAC (μmol Trolox®/g compound) | ABTS (μmol Trolox®/g compound) | |
6-Methyl-5-hepten-2-one (4.9%), α-terpinene (3.0%), thymol (64 6%), carvacrol (12 2%), | 1.2 | 3990 ± 58 | 5410 ± 48 | |
Limonene (10.7%), 1,8-cineole (5.0%), neral (15.6%), geranial (18.9%), spathulenol (4.7%) | 0.1 | 3630 ± 40 | 41 ± 2 | |
4.4 | 3400 ± 120 | 5200 ± 109 | ||
γ-Terpinene (5.0%), thymol (54.5%), thymyl acetate (4.8%) | 3.1 | 2840 ± 72 | 5090 ± 42 | |
1.5 | 1820 ± 82 | 310 ± 2 | ||
1.0 | 2050 ± 78 | 2750 ± 80 | ||
Geranial (27%), neral (21%), geraniol (6.0%) | 0.9 | 2000 ± 77 | 24.8 ± 0.4 | |
Limonene (30.2%), carvone (50.3%) | 0.8 | 1340 ± 54 | 126.4 ± 0.7 | |
Sabinene (7.4%), | 0.5 | 1200 ± 27 | 239 ± 4 | |
Carvacrol | 3410 ± 50 | 4609 ± 6 | ||
Thymol | 3000 ± 103 | 5700 ± 125 | ||
2800 ± 109 | N.D. | |||
γ-Terpinene | 1766 ± 8 | N.D. | ||
α-Phellandrene | 1040 ± 18 | 136 ± 3 | ||
α-Tocopherol | 550 ± 13 | 2429 ± 7 | ||
BHT | 457 ± 9 | 4760 ± 23 | ||
1,8-Cineole | 299 ± 5 | N.D. | ||
219 ± 2 | N.D. |
Main constituents and antioxidant capacity of Lippia essential oils.
EOs from plants of the Labiatae and Verbenaceae families are considered very useful in folk medicine, as antibacterials, antivirals, antifungals, antioxidants, and insecticides. The antiviral activity of 40 EOs of the Labiatae and Verbenaceae families and some monoterpenes were evaluated on human herpes virus types 1 and 2 using the end point titration technique [78]. Samples that showed reduction factor of viral titer in comparison to control without treatment (
The
Since plants are exposed daily to the sun radiation, they have evolved mechanisms that protect them from the effects of overexposure, such as damages to the DNA. When DNA suffers a damage, the cell responds with a set of actions that was discovered in 1975 by Miroslav Radman [80], who assigned the name of SOS response. The Pasteur Institute developed a colorimetric assay to detect carcinogens, based on this response in which the exposition to UV causes the DNA damage whose extent is associated with the intensity of light absorbance by a chromophore [81]. This SOS chromotest is highly sensitive to UV. A modified version has been used by Fuentes and collaborators [82] to identify plants of Colombian flora that may be a source of genoprotective compounds. Their application of the SOS chromotest in a survey of 50 extracts obtained with supercritical CO2 from aromatic plants grown in Colombia permitted to identify those that significantly reduced UV-induced genotoxicity depending on their concentration, as follows:
Synthetic insecticides are the most frequent pest control method in crop production and storage. However, their application has negative effects on environmental resources, elimination of beneficial insects, and toxicity for susceptible species and humans, who represent the last link in the food chain. EOs have attracted attention in recent years as potential pest control agents due to their insecticidal, repellent, and/or antifeedant properties. Stored products of insect pest control are important in managing post-harvest grains, food products and processed goods.
Weevils that consume flour (
Several tropical diseases for which there is no vaccine yet (yellow fever, Zika fever, chikungunya, dengue) are transmitted by
Colombia’s geographic and botanical conditions favor the development of its EOs agroindustry to convert this country into an important provider to the ever-growing EO world market. The initial offer will consist of EOs from aromatic plants of European and Asian origins, which are well-known and commonly traded in the international market. However, the results from the very small survey of Colombia’s biodiversity indicate that there are many promising alternatives for future market expansion. The evaluation of biological activities of EOs obtained from plants growing in Colombia points toward many opportunities to develop a wide range of products that employ them as active ingredients.
Financial support from
The authors declare that they do not have conflict of interest.
Humans are persistently exposed to various chemical and physical agents that have the potential to damage genomic DNA, such as, irradiation (IR), ultraviolet (UV) light, reactive oxygen species (ROS), et cetera [1]. The integrity and survival of a cell is critically dependent on genome stability and mammalian cells have established multiple pathways to repair different types of target DNA lesions to safeguard the genome from deleterious consequences of various kinds of stresses [2]. The significance of the DNA repair in the protection of genomic stability is highlighted by the fact that many proteins/factors involved have been preserved through evolution [3].
DNA damage, induced by endogenous and exogenous agents, is a common event and must undergo a variety of DNA damage repair in order to ensure the faithful transfer of genetic information during cell division [3]. Four main DNA polymerases are involved with nuclear DNA replication: DNA polymerase α, β, δ and ε [1] (Figure 1). DNA repair pathways, which are also recognized as guardians of the genome, protect cells from numerous damages leading to DNA breaks [4]. Failure to restore DNA lesions or inappropriate repair of DNA damage give rise to genomic instability, which is a hallmark of cancer. Remarkably, mild and massive DNA damage are differentially integrated into the cellular signaling networks and, in consequence, provoke different cell fate decisions. After mild damage, the cellular response is cell cycle arrest, DNA repair, and cell survival, whereas severe damage, drives the cell death response. The inability of the DNA damage response (DDR) to repair following endogenous and exogenous insults can lead to (i) an accumulation of errors in genomic DNA, (ii) subsequent malignant transformation, (iii) cancer progression and (iv) further impairment of the DNA repair capacity. DNA repair mechanisms comprise the detection and deletion (excision) of the lesion, the rejoining of DNA ends and the restoration of the complementary sequence based on a DNA template.
Sub-cellular localization of eukaryotic and retroviral DNA polymerases.
Since cancer cells typically have many mutations compared to a non-cancer cell, it was proposed that one of the earliest changes in the development of a cancer cell is a mutation that increases the spontaneous mutation rate [5]. The presence of a “mutator phenotype” could increase the acquisition of alterations that could lead to enhanced drug resistance limiting the effectiveness of anti-cancer drug treatment.
Viral infection is characterized by the high genetic variability found in virus populations [6]. This phenomenon is attributed to the inaccuracy of the replication machinery that is unique to the viral life cycle. Virulence, pathogenesis and the ability to develop effective antiretroviral drugs and vaccines are largely dependent on genetic diversity in viruses [7]. Retroviruses are RNA viruses that replicate through a DNA intermediate in a process catalyzed by the viral reverse transcriptase (RT) in cytoplasm (Figure 1) [7]. Human immunodeficiency virus type 1 (HIV-1), the etiological agent of AIDS, exhibits exceptionally high mutation frequencies [8]. The accepted explanations for the inaccuracy of HIV-1 RT are the relatively low fidelity of the enzyme during DNA synthesis and the deficiency of intrinsic proofreading activity. A strong mutator phenotype is also observed for herpes viral DNA polymerase mutants with reduced intrinsic 3′ → 5′ exonuclease activity [9].
Mitochondrial DNA (mtDNA) alterations have been associated with various human diseases with impaired mitochondrial function [10]. Mitochondrial DNA polymerase γ (pol γ) is responsible for replication of mtDNA and is implicated in all repair processes (Figure 1) [11]. Mitochondrial DNA is prone to mutations, since it is localized near the inner mitochondrial membrane in which reactive oxygen species are generated. Additionally, mtDNA lacks histone protection and the highly efficient DNA repair mechanisms [12]. The mutation rate of mtDNA is estimated to be about 20–100-fold higher than that of nuclear DNA [13]. The mutagenic mechanisms were shown to be replication errors caused by mis insertion (as a result of a dNTP excess), or decreased proofreading efficiency [14, 15].
Thus, in various compartments of the cell, enhanced DNA replication fidelity is a vital activity for the preservation of genomic stability for many organisms.
Genomic integrity of the cell is crucial for the successful transmission of genetic information to the offspring and its survival [16]. DNA is constantly being damaged. Essentially, DNA lesions can occur in two major ways, affecting either a single-stranded break (SSB) or double-stranded (DSB) or mono-adducts and inter-strand crosslinks, respectively. To combat this, eukaryotes have developed complex DNA damage repair (DDR) pathways (Figure 2). The active pathways for DNA repair are base excision repair (BER), nucleotide excision repair (NER), and mismatch repair MMR for SSB repair, whereas homologous recombination (HR) and non-homologous end-joining (NHEJ) for DSB repair [16]. Nucleotide excision repair (NER) removes a variety of helix-distorting lesions such as typically induced by UV irradiation, whereas base excision repair (BER) targets oxidative base modifications. Mismatch repair (MMR) scans for nucleotides that have been erroneously inserted during replication. The most deleterious types of damage in DNA are DSBs that are typically induced by IR and resolved either by NHEJ or by HR, whereas RECQ helicases assume various roles in genome maintenance during recombination repair and replication.
DNA damage and repair mechanisms. Various DNA damaging agents cause a range of DNA lesions with different outcomes at both the genomic and cellular levels. Each are corrected by a specific DNA repair mechanism, namely, base-excision repair (BER), nucleotide excision repair (NER), homologous recombination (HR)/non-homologous end-joining (NHEJ) or mismatch repair (MMR).
A low fidelity of DNA synthesis in various compartments of the cell by main replicative DNA polymerases leads to genomic instability (mutator phenotype) [17]. The errors produced during DNA synthesis could result from three fidelity determining processes: a) nucleotide misinsertion into the nascent DNA, b) lack of exonucleolytic proofreading activity, that is, the mechanism to identify and excise incorrect nucleotide incorporated during DNA synthesis, and c) extension of mismatched 3′-termini of DNA (Table 1) [18].
Biochemical properties of cellular DNA polymerases | |||
---|---|---|---|
Function | 3′ → 5′ exonuclease | Proofreading | |
Nuclear DNA polymerases | |||
α | primase | no | no |
β | repair | no | no |
δ | Lagging DNA synthesis, repair | yes | yes |
ε | Leading DNA synthesis, repair | yes | yes |
Mitochondrial DNA polymerase | |||
γ | DNA synthesis | yes | yes |
Retroviral DNA polymerase | |||
HIV-1 RT | DNA synthesis | no | no |
Biochemical properties of eukaryotic and retroviral DNA polymerases.
Incorrectly repaired DNA lesions can lead to mutations, genomic instability, changes in the regulation of cellular functions, progression of cancer and premature aging. Cells can repair the large variety of DNA lesions through a variety of sophisticated DNA-repair machineries, recognizing and activating battery of proteins/factors for the repair of damaged DNA. DNA replication is a complex process influenced by numerous proteins/factors. The most important part of the DNA damage response is the activation of tumor repressor p53 protein [18].
The p53 represents a major factor for the maintenance of genome stability and for the suppression of cancer [19, 20]. The p53 protein is commonly referred to as the “
Under normal conditions within the cell, p53 is maintained at low levels by the E3 Ubiquitin ligase MDM2, mediating p53 proteasomal degradation [23]. In response to exposure to various endogenous and exogenous stress signals (such as DNA damage, oncogene activation, hypoxia, and nutrient depletion), the protein is stabilized and functionally activated by a series of post-translational modifications (
In response to various endogenous and exogenous stress signals, the activated p53 arrests the cell cycle until the DNA damage is repaired thereby preventing the cancer. If the DNA damage cannot be repaired apoptosis occurs for eliminating cells that contained excessive and irreparable damaged DNA.
p53 exhibits the functional heterogeneity in its basal (non-induced) state and under various p53 inducible circumstances [20]. Increasing evidences suggest various “non-transcriptional functions” of p53, that can contribute to tumor suppressor activity [25]. p53 may modulate DNA repair through processes, which are independent of its transactivation function. p53 is actively transported between the nucleus and cytoplasm. Furthermore, p53 translocate to mitochondria [26]. p53 can directly interact with DNA repair related cellular factors [27]. The origin, duration, intensity of the stress signals, the interaction with other cellular or viral proteins, and stress-mediated subcellular localization of p53 determines the outcome of the p53 response, namely, its pro- or anti-survival functions [28]. p53 protein executes multi-compartmental functions in the cell by either numerous p53-regulated proteins or by its intrinsic biochemical activities [28].
The functioning of the eukaryotic genome relies on effective and accurate DNA replication and repair [2]. DNA replication in the nucleus of eukaryotic cells employs DNA polymerases (pols) α, β, δ, and ϵ, that are the key enzymes required to maintain the integrity of the genome under all these circumstances [1, 3]. However, the maintenance of genomic integrity is complicated by the fact that the genome is persistently challenged by a variety of endogenous and exogenous DNA-damaging factors [4]. DNA lesion can block DNA replication, which can lead to double-strand breaks (DSB) or alter base coding potential, leading to mutations. The accumulation of damage in DNA can affect gene expression leading to the malfunction of many cellular processes [4]. Various DNA repair systems operate in cells to remove DNA lesions, and several proteins are known to be the key components of these repair systems.
The presence of p53 was demonstrated in different nuclear compartments and suggested that the p53 population not engaged in transcriptional regulation could exert functions other than induction of growth arrest or apoptosis and directly participate in processes of repair [25]. p53 mediating various activities are correlated with the levels of the p53 protein in the cells [27, 29]. The non-genotoxic stress may include a long-lasting, moderate accumulation of p53 in nucleus. Conversely, acute genotoxic stress may induce rapid and transient accumulation of very high levels of p53 with preferential activation of target genes involved in apoptosis [29]. There is a possibility that both transcriptional and transcription-independent pathways act in synergy thereby amplifying the potency of involvement of p53 in DNA repair.
p53 localized in cell nuclei in response to replication stress actively participate in various processes of DNA repair and DNA recombination via its ability to interact with components of the repair and recombination machinery and by its various biochemical activities [30, 31]. Both
The C-terminal 30 amino acids of p53 were shown to recognize several DNA damage-related structures.
In addition, full range of various intrinsic biochemical features of the p53 protein support its possible roles in DNA repair. After DNA damage: (a) p53 is able to recognize and bind sites of DNA damage, such as ssDNA and dsDNA ends [33, 34], (b) p53 catalyzes DNA and RNA strand transfer and promotes the annealing of complementary DNA and RNA single-strands [35, 36], (c) p53 binds insertion/deletion mismatches and bulges [37], (d) p53 binds to three-stranded heteroduplex joints and four-stranded Holliday junction DNA structures with localization specifically at the junction, suggesting that p53 directly participates in recombination repair [38], (e) it can bind DNA in a non-sequence-specific manner [39], (f) p53 exhibits a Mg2+ dependent 3′ → 5′ exonuclease activity [40, 41, 42, 43].
Noticeably, the same central region within p53, where tumorigenic mutations are clustered, recognizes DNA sequence specifically, is required for junction-specific binding of heteroduplex joints and is necessary and sufficient for the 3′ → 5′ exonuclease activity on DNA [28]. In addition to p53’s biochemical activities, numerous reports on physical and functional protein interactions further strengthened the proposal of a direct role of p53 in BER, NER, and DSB repair.
Oxidative DNA damage is largely repaired by the BER pathway. p53 might directly facilitate BER mainly via association with BER components. Wtp53 directly enhanced BER activity measured both
The cellular response depends on the dose of genotoxic agent introduced to the cells. Increasing doses of genotoxic agents cause the accumulation of activated p53 that determines the onset of BER or apoptosis. Low doses of DNA damaging agent resulted in the enhancement of p53-dependent BER activity whereas high levels induced different p53 post-translational modifications that down regulate BER pathway and instead provoked an apoptotic response [29]. The quantitative changes in p53 protein level were associated with qualitative changes in p53 phosphorylation status. In all, this may indicate that increasing doses of genotoxic agents cause the accumulation of activated p53 that determines the onset of BER or apoptosis.
NER is an important DNA repair process that detects and eliminates lesions including both chemical alteration and structural distortion of the DNA helix (
Pathogenic mutations in the GG components XPC and DDB2 (XPE) result in xeroderma pigmentosum (XP) a disease characterized by increased UV-sensitivity and skin cancer incidence [46]. Conversely, mutation in TC genes result in Cockayne’s syndrome that is characterized by neurological abnormalities but no increase in skin cancer incidence. Some NER proteins, particularly the GG damage recognition proteins, can decide a cell’s fate by triggering the initiation of the repair pathway or by signaling apoptosis [46]. Therefore, if the GG pathway is defective, neither DNA repair nor apoptosis occurs, resulting in a cancer cell containing high levels of UV-induced mutations that does not undergo apoptosis. How this non-transcriptional function of p53 contributes to tumor suppression is unclear.
DNA mismatch repair (MMR) is an important DNA repair pathway, which facilitates removal of incorrect nucleotides incorporated during replication. p53 facilitates excision of incorrect nucleotides produced from the error prone nature of DNA polymerases and misincorporation of the incorrect base [25]. Mismatched bases can be either a G/T or A/C pair. To initiate MMR a nick in the DNA either 5′ or 3′ to the mismatch must occur. Proteins that bind the mismatch in humans are
Mutator phenotypes (with the potential for cancer progression) have been reported for cells that lack a proofreading 3′ → 5′ exonuclease activity associated with the DNA polymerase [54]. Excision of incorrectly polymerized nucleotides by exonucleases is an imperious mechanism diminishing the errors during DNA polymerization [55]. Certain organisms with a deficiency of exonucleolytic proofreading, have an increased susceptibility to cancer, especially under conditions of stress. Because the misincorporation of non-complementary dNTPs during DNA replication represents a chief mechanism of gene mutation [56], the removal of the wrong nucleotides from DNA is critical for genomic stability. The intrinsic limited accuracy of DNA polymerases and the imbalance of intracellular dNTP pools are the two most important factors responsible for DNA replication errors [57, 58]. The proofreading for such replication errors by the 3′ → 5′ exonuclease activity associated with the DNA replication machinery is extremely important in reduction of the occurrence of mutations. Interestingly, the mammalian DNA pol α, an enzyme considered to be responsible for the lagging strand replication [59], lacks the 3′ → 5′ exonuclease proof-reading activity and is prone to making replication errors [60].
Three steps, base selection, exonucleolytic proofreading, and DNA elongation, ensure the high fidelity of DNA replication. wtp53 exhibits an intrinsic 3′ → 5′ exonuclease activity. wtp53, co-located with the DNA replication machinery [61], specifically interacts with pol α and has been shown to preferentially eliminate mismatched nucleotides from DNA with its 3′ → 5′ exonuclease activity, thereby enhancing the DNA replication fidelity of pol α
Hydroxyurea (HU), an inhibitor of ribonucleotide reductase involved in the
The functional interaction of DNA polymerase and exonuclease activity was observed with p53/pol-prim complex. p53-containing DNA pol-prim complex excised preferentially a 3′-mispaired primer end over a paired one and replaced it with a correctly paired nucleotide [63]. In contrast, a pol-prim complex containing the hot spot mutant p53R248H did not display exonuclease activity and did not elongate a mispaired 3′-end, representing that the p53 exonuclease from the p53/pol-prim complex was indispensable for the subsequent elongation of the primer by DNA polymerase. These findings support the view that p53 might fulfill a proofreading function for pol-prim and suggest that the defect in proofreading function of p53 may contribute to genetic instability associated with cancer development and progression [63].
DSBs are the most severe type of DNA damage, and these DSBs generated at the replication fork are repaired by two principal repair pathways: homology-based repair (HR) and non-homologous end-joining (NHEJ) [25, 31]. Furthermore, replication blocking lesions such as bulky adducts are subject to HR repair, thereby rescuing the replication fork. HR is considered the most error-free pathway, because sister chromatids are the preferred template, however, it can also produce genetic instability upon up- or down-regulation [25].
Depending on the type and quality of the DSB repair pathway involved, the repair process may end up with deletions, loss of heterozygosity, and chromosomal translocations which may accelerate the multistep process of tumorigenesis. p53 can control HR
p53 prevents the accumulation of DSBs at stalled-replication forks induced by UV or hydroxyurea (HU) treatment. When DNA replication is blocked, p53 becomes phosphorylated on serine 15 and associates with key enzymes of HR such as, Rad51, and Rad54 [68, 69]. Notably, during replication arrest p53 remains inactive in transcriptional transactivation, further supporting the direct involvement in HR regulatory functions unrelated to transcriptional transactivation activities.
p53 preferentially represses HR between certain mispaired DNA sequences. p53 specifically recognizes preformed heteroduplex joints structurally resembling early recombination intermediates, when comprising these mispairings [68]. p53 is able to attack DNA by 3′–5′ exonuclease activity principally during Rad51-mediated strand transfer and to display a DNA substrate preference for heteroduplex recombination intermediates with a further enhancement of the exonucleolytic activity for mispaired as compared to correctly paired heteroduplex DNA [38].
Highlighting the significance of p53 DNA interactions in the regulation of strand exchange events, p53 inhibits branch migration of Holliday junctions (HJs) [25, 31]. p53 recognizes this HJs -like structure and controls the generation and branch migration of the replication fork as well as its resolution, to prevent error-prone DSB repair and to cause replication pausing until the DNA lesion is repaired.
Mammalian cells repair the majority of double-strand breaks by NHEJ [69, 70] which is regarded as principally inaccurate process. The role of p53 in NHEJ remains unclear. p53 has an inhibitory effect on error-prone NHEJ but not error-free NHEJ [71], thereby suppressing genomic instability arising from low-fidelity repair. Remarkably, after the exposure to IR, DSB rejoining increases with loss of wtp53function. Inhibition of in vitro end-joining was observed with the oncogenic mutant p53(175H), whereas the phosphorylation-mimicking mutant p53(15D) failed to inhibit, thereby providing evidence for possible role of phosphorylated p53 in the regulation of NHEJ [72].
Various
Under normal conditions a basal pool of p53 is retained intra-cellular, with the distribution of p53 between the different subcellular compartments dependent on the cellular stress milieu [28]. Indeed, wtp53 occurs in cytoplasm in a subset of human tumor cells such as breast cancers, colon cancers and neuroblastoma [73, 74, 75]. Shuttling between nucleus and cytoplasm not only regulates protein localization, but also often impacts on protein function.
p53, localized in the cytoplasmic lysates of non-stressed p53-proficient cell lines [e.g. LCC2, HCT116 (p53+/+)] exerts an inherent 3′ → 5′ exonuclease activity displaying identical biochemical functions characteristic for recombinant wtp53 [76, 77]: 1) it removes 3′-terminal nucleotides from various nucleic acid substrates: ssDNA, dsDNA, and RNA/DNA template-primers, 2) it hydrolyzes ssDNA in preference to dsDNA substrate, 3) it shows a marked preference for excision of a mismatched vs. correctly paired 3′ terminus with RNA/DNA and DNA/DNA substrates, 4) it excises nucleotides from nucleic acid substrates independently from DNA polymerase, 6) it fulfills the requirements for proofreading function; acts coordinately with the exonuclease-deficient viral DNA polymerases.
Viruses exploits their cellular host for their successful replication, they utilize cell proteins for multiple purposes during their intracellular replication [78]. Since viral infection evokes cellular stress, the infected cells harbor stabilized activated p53 and manipulate p53’s guardian role. Interestingly, increased p53 levels have been noted following infection of cells with various viruses including retrovirus-human immunodeficiency virus [79], which exhibits exceptionally high genetic variability [6], due to the low fidelity of the replication apparatus that is exclusive to the retroviral life cycle.
Reverse transcriptase (RT) of HIV-1 is responsible for the conversion of the viral genomic ssRNA into the proviral DNA in the cytoplasm [7]. The lack of intrinsic 3′ → 5′ exonuclease activity, the formation of 3′-mispaired DNA and the subsequent extension of this DNA were shown to be determinants for the low fidelity of HIV-1 RT [80]. p53 can proofread for HIV-1 RT, increasing the fidelity of DNA synthesis by excising incorrectly polymerized nucleotides from RNA/DNA and DNA/DNA temple-primers in the direct exonuclease assay, when first binding to a 3′-terminus and during ongoing DNA synthesis
DNA polymerase (pol) γ is the sole DNA polymerase that is responsible for replication and repair of mtDNA [81]. It is well established that defects in mtDNA replication lead to mitochondrial dysfunction and disease [56, 60]. Mutations in mtDNA can arise from exogenous sources, from endogenous oxidative stress, or as spontaneous errors of replication during either DNA synthesis or repair events [82]. Mitochondrial DNA is replicated by DNA polymerase γ in concert with replisome accessory proteins such as the mitochondrial DNA helicase, single-stranded DNA binding protein, topoisomerase, the multifunctional mitochondrial transcription factor A (TFAM) with important roles in mtDNA replication and initiating factors.
A high frequency of mutations within mtDNA, resulting in mitochondrial dysfunctions, is an important source of various diseases including cancer and human aging [81, 82]. To verify mtDNA integrity, cells hold various DNA damage response pathway(s) comprising mtDNA replication/repair preservation programs that either preclude or repair damage [83]. The mutagenic mechanisms were shown to be replication errors formed by either pol γ during DNA synthesis by incorporation of incorrect nucleotide or produced due to the presence of unbalanced dNTP concentrations, or by diminished proofreading efficiency. MtDNA is not protected by histones and mtDNA repair is ineffective [81]. Furthermore, a potentially important source of replication infidelity is damage due to ROS. pol γ, was demonstrated to stably misincorporate highly mutagenic 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) opposite template adenine in a complete DNA synthesis reaction
Because of the susceptibility of mtDNA to oxidative damage and replication errors, it is vital to protect mtDNA genomic stability to preserve health. Mitochondrial localization of p53 was observed in non-stressed and stressed cells [26]. Mitochondrial p53 (mit-p53) levels are proportional to total p53 levels, and the majority of p53 was present inside the intra-mitochondrial compartment-matrix, in which mtDNA is located [85]. The mit-p53 physically and functionally interacts with both, mtDNA and pol γ [86].
Notably, with the exception of NER, components of these nuclear DNA repair pathways are also shared in mtDNA maintenance. Several studies illustrated the participation of p53 in mtDNA repair:
53 enhances mitochondrial BER (mtBER) through direct interaction with the repair complex in mouse liver and cancer cells [87]. p53 modulates mtBER through the stimulation of the nucleotide incorporation step.
p53 interacts physically with human mtSSB (HmtSSB)
Intra-mitochondrial p53 provides an error-repair proofreading function for pol γ by excision of misincorporated nucleotides [89]. The p53 in mitochondria may affect the accuracy of DNA synthesis by acting as an external proofreader, thus reducing the production of polymerization errors.
In addition to having a critical role in preservation of genome integrity, alterations in the expression, and function of DNA repair proteins are a major facilitator of tumor responses to chemo- and radiotherapy, commonly functioning by inducing DNA damage in tumor cells. Nucleoside analogs, clinically active in cancer chemotherapy (
The cytotoxic activity of gemcitabine (2′2’-difluorodeoxycitidine, dFdC) was strongly correlated with the amount of dFdCMP incorporated into cellular DNA [92]. The p53 protein recognizes dFdCMP-DNA in whole cells, as evidenced by the fact that p53 protein rapidly accumulated in the nuclei of the gemcitabine treated ML-1 cells [93]. Although, the excision of the dFdCMP from the 3′-end of the DNA was slower than the excision of mismatched nucleotides in whole cells with wtp53 (ML-1) and not detectable in CEM cells harboring mutant p53. ML-1 cells were more sensitive to the cytotoxic effect of the drugs compared to the p53-null or mutant cells. The recognition of the incorporated NAs in DNA by wtp53 did not confer resistance to gemcitabine, but may have facilitated the apoptotic cell death process. It was reported that treatment with gemcitabine resulted in an increased production of DNA-dependent protein kinase (DNA-PK) and p53 complex in nucleus, that interacts with the gemcitabine-containing DNA [93, 94]. DNA-PK and p53 sensor complex may serve as a mechanism to activate the pro-apoptosis function of p53. Apparently, the prolonged existence of the NA-stalled DNA end induced the kinase activity, which subsequently phosphorylated p53 and activated the downstream pathways leading to apoptosis.
Remarkably, p53 present in complex with DNA-PK exhibited 3′ → 5′ exonuclease activity with mismatched DNA, however the active p53 was unable of excising efficiently the incorporated drug from NA-DNA construct containing gemcitabine at the 3′-end [94]. Notably, the specific effects of gemcitabine exposure appeared to vary depending on the duration of treatment and upon the cell line.
It should be pointed out, that wtp53 in ML-1 cells removed the purine nucleoside analog fludarabine (F-ara-A) more efficiently than gemcitabine [93]. Further studies are needed to assess the role of p53 in cellular response to various anti-cancer purine and pyrimidine NA-induced DNA damage.
HIV-1 RT readily utilizes many NAs and the incorporation of nucleoside RT inhibitors (NRTIs) into the 3′-end of viral DNA leads to chain termination of viral DNA synthesis in cytoplasm [88, 95]. p53 protein in the cytoplasm excises the incorporated NAs during both RNA-dependent and DNA-dependent DNA polymerization reactions, although less efficiently than the mismatched nucleotides; longer incubation times were required for excision of the terminally incorporated analogs [96]. The data suggest that p53 in cytoplasm may act as an external proofreader for NA incorporation and confer cellular resistance mechanism to the anti-viral compounds.
Pol γ is unique among the cellular replicative DNA polymerases as it is sensitive to inhibition by nucleoside analogue reverse transcriptase inhibitors (NRTIs) used in the treatment of HIV, which can cause an induced mitochondrial toxicity [97]. Acquired mitochondrial toxicity occurs as a consequence of incorporation of NA into mtDNA or inhibition of mtDNA replication or both. A terminally incorporated NA may be removed by p53 in mitochondria [97]. The removal of the incorporated NA by p53 exonuclease, indicates that the presence of the cellular component-p53 in mitochondria may be important in defining the cytotoxicity of NAs toward mitochondrial replication, thus affecting risk–benefit approach (NA toxicity versus viral inhibition) [98, 99]. Apparently, the presence of p53 in mitochondria may be important, as the excision of the mispair and NA by p53 is favorable event for mitochondrial function.
p53 is a multifunctional protein with positive and negative effects. In general, drug resistance that occurs in cancer chemotherapy and antiviral therapy is a negative event that will decrease the efficacy of the treatment. The recognition and removal of NA from drug-containing DNAs by p53 exonuclease activity in various compartments of the cell may play a role in decreasing drug activity, leading to various biological outcomes: 1)the excision of the incorporated NA from DNA in nucleus may confer resistance to the drugs (negative effect) [93]; 2)the removal of the NA by p53 from DNA incorporated by HIV-1 RT in cytoplasm may confer resistance to the drugs by non-viral mechanism (negative effect) [96] and 3)the excision of NAs from mitochondrial DNA may decrease the potential for chain termination and host toxicity (positive effect) [97].
The genome is constantly under attack from extrinsic and intrinsic damaging agents. Uracil (dU) mis-incorporation in DNA is an intrinsic factor resulting in genomic instability and DNA mutations. The excessive levels of genomic uracil in DNA can modify gene expression by interfering with promoter binding and transcription inhibition, can change transcriptional stalling, or induce DNA strand breaks leading to apoptosis. The factors that influence uracil levels in DNA are cytosine deamination, de novo thymidylate (dTMP) biosynthesis, salvage dTMP biosynthesis, and DNA repair. Furthermore, mis-incorporation occurs when DNA polymerases incorporate dUTP into DNA, in place of dTTP, and the rate of misincorporation is believed to be determined by the intracellular dUTP:dTTP ratio [100, 101]. The enzyme deoxyuridine triphosphate nucleotidohydrolase (dUTPase), which facilitates the conversion of dUTP to dUMP further utilized by thymidylate synthase (TS) for synthesis of dTMP, avoids mis-incorporation of dU into DNA in nucleus by decreasing the dUTP/dTTP ratio [101]. The misincorporation of dU, as a result of accumulation of dUTP, plays a critical role in cytotoxicity mediated by TS inhibitors, such as the commonly used anticancer drug 5-fluorouracil (5-FU) [102]. DNA directed cytotoxicity of chemotherapeutic agents (e.g.5-FU) not only depends on accumulation of dUTP, but may also be determined by the efficiency of the DNA repair mechanisms (e.g. excision repair) which preclude the incidence of the mistake.
Pol γ in mitochondria is incapable to readily correct U:A mismatches [11]. HIV-1 RT in the cytoplasm of HIV-infected cells efficiently inserts the non-canonical dUTP into the proviral DNA and extends the dU-terminated DNA [103]. The misincorporation of dUTP leads to mutagenesis, and to down-regulation of viral gene expression [104].
Within the context of error-correction events, p53 as a DNA binding protein, contributes an external proofreading function; upon excision of the dU, the p53 dissociates, thus letting the transfer of the substrate with the correct 3′-terminus to DNA polymerase and renewal of DNA synthesis.
The biochemical data show that the procession of U:A and mismatched U:G lesions enhances in the presence of recombinant or endogenous cytoplasmic or mitochondrial p53 [105]. p53 in cytoplasm can participate through the intermolecular pathway in a dU-damage-associated repair mechanism by its ability to remove preformed 3′-terminal dUs, thus preventing further extension of 3’ dU-terminated primer during DNA synthesis by HIV-1 RT. Similarly, p53 in mitochondria can function as an exonuclease/proofreader for pol γ by either decreasing the incorporation of non-canonical dUTP into DNA or by promoting the excision of incorporated dU from nascent DNA, thus expanding the spectrum of DNA damage sites exploited for proofreading as a trans-acting protein [106].
During genomic DNA replication another form of replication errors arises during the incorporation of nucleotides carrying the correct base, but the wrong sugar at substantial rates [107]. DNA polymerases often incorporate ribonucleoside triphosphates (rNTPs) into DNA because of the much higher concentration of rNTPs than that of dNTPs in the cellular nucleotide pool. Indeed, more than 106 rNMPs are incorporated during one round of replication of a mammalian genome [107]. Newly incorporated rNMPs destabilize DNA and pose a major threat to genome integrity due to their reactive 2’OH group. The inserted rNs are the most abundant non-canonical nucleotides in the genome. Failure of rN removal is associated with genome instability in the form of mutagenesis, replication stress, DNA breaks, and chromosomal rearrangements. The aberrant accumulation of rNs in the genome leads to human diseases including Aicardi–Goutières syndrome (AGS), the severe autoimmune disease, and tumorigenesis [108]. Mammalian cells have developed strategies to prevent persistent rN accumulation. In eukaryotes, rNs embedded into DNA are primarily repaired by RNase H2-initiated repair pathway. Ribonucleotide excision repair (RER) may be directly coupled to replication and results in rapid post-replicative repair of rNMPs [108]. Remarkably, exonuclease-proficient yeast and human DNA polymerases can proofread incorporated rNs, albeit inefficiently [107].
Recent studies have demonstrated the importance of p53 in 3′-terminal RER pathway through a functional collaboration with HIV-1 RT, acting in a coordinated manner to attain higher fidelity. p53, functioning as a trans-acting proofreader in cytoplasm, can decrease the stable incorporation of rNs, into DNA by HIV-1 RT [109]. p53 can influence events needed for RER by possessing the compatible biochemical properties: p53 is pertinent in the correction of replication errors produced by HIV-1 RT during distinct steps of rN incorporation through intermolecular pathway: by removal pre-existing 3′-terminal rN; by reducing rN incorporation; by preventing extension of a 3′ rN-terminated primer, by attenuating stable incorporation of rNs. Thus, p53, functioning as a trans-acting proofreader in cytoplasm, can decrease the stable incorporation of rNs.
The fact that p53 in cytoplasm can edit an incorrect sugar irrespective of the nature of base, expands the role of p53 as a proofreader in the repair of replication errors by removing both a base mismatch and an incorrect sugar.
Mammalian cells have evolved multiple strategies to safeguard the genetic information to prevent the fixation of genetic damage induced by endogenous and exogenous mutagens [16]. p53 protein plays a crucial role in the regulation of cell fate determination in response to a variety of cellular stresses. p53 may exert the functional heterogeneity in its non-induced and in its activated state [16]. Remarkably, DNA repair transcription-independent functions of wtp53, contributing to tumor suppression, were found to protect cells from DNA damage independently of the transcription-mediated functions of p53 [25]. Thus, a more comprehensive understanding of how p53 transcription- independent functions are induced in response to a variety of cellular insults is vital. This report focuses on direct roles of p53 in DNA repair during DNA replication in various compartments of the cell. Apparently, p53 has more than one contributions to DNA replication fidelity, which could depend on sub-cellular localization of p53, on the type and incidence of replication obstacles, on the levels of p53 protein [28].
p53 is able to elicit a spectrum of different effective DNA repair pathways in nucleus, cytoplasm and mitochondria (Figure 4). Within the nucleus, p53 regulates different repair mechanisms, in response to endogenous and exogenous replicative stress
p53 functions in DNA repair. p53 under both normal and stress conditions, can help cellular and viral DNA polymerases to promote the repair of DNA in various cellular compartments. The result of p53 activation depends on many variables, including the extent of the stress or damage. In this model, basal p53 activity or that induced by stress signals elicits the protector responses that support the repair of genotoxic damage by various pathways.
In the cytoplasm, p53 may contribute effective proofreading for exonuclease-deficient DNA polymerases (
Within the mitochondria, various studies illustrated the participation of p53 in mtDNA repair in a variety of systems: a)p53 enhances BER through direct interaction with the repair complex in mouse liver and cancer cells [87]. b) Intra-mitochondrial p53 provides an error-repair proofreading function for pol γ by excision of misincorporated nucleotides [89]. c)p53 is proficient of hydrolyzing the 8-oxo-7,8-dihydro-2′-deoxy-guanosine (8-oxodG) present at the 3′-end of DNA, a well-known marker of oxidative stress [88]. d)p53 regulates mtDNA copy number, which may impact mitochondrial and cellular functions [112].
Therapeutic strategies based on p53 are particularly interesting because they exploit the cancer cell’s intrinsic genome instability and predisposition to cell death-apoptosis [90, 91]. The role of p53 is predominantly relevant with respect to the development of anticancer and antiviral therapies. Removal of drugs by 3′ → 5′ exonuclease activity may also facilitate resistance to anti-cancer or anti-viral treatments. Clinical drug resistance limits the efficacy of these compounds. Uncovering the mechanisms, which are responsible for DNA repair of NA-induced DNA damage will have therapeutic value. The p53 protein is able to remove incorporated NA. The stress induced activation of p53 that occurs during anti-cancer or anti-viral therapy has negative and positive effects. p53 may remove incorporated therapeutic NAs from DNA or trigger apoptosis. More studies regarding functions of p53 in genome integrity and cancer evolution may facilitate drug screening and better design of therapeutic approaches.
The functional interaction between p53 and DNA polymerase may have important consequences for the maintenance of genomic integrity and in the development of p53- targeted clinical therapies. Further assessments are required to establish the role of p53 in DNA replication and the significance of these functions in various cellular compartments and treatment responses. Studies on the biology of various mutant p53 isoforms and their interaction with the factors involved in DNA repair and apoptosis, will be relevant to establish whether the direct involvement of p53 in DNA repair is a tumor suppressor function of this important anti-oncogene. Characterization of exonuclease-deficient H115N mutant p53 revealed that although exonuclease-mutant H115N p53 can induce cell cycle arrest more efficiently than wild-type p53, its ability to produce apoptosis in DNA damaged cells is markedly impaired [113]. By utilizing various function-mutant p53 isoforms, more studies must be conducted on the biology of mutant p53 forms and their interaction with the factors involved in DNA repair and apoptosis, in order to recognize the molecular mechanisms that mediate p53-dependent control of DNA replication by cellular and viral DNA polymerases.
p53 has a dual role in response to therapy, as exonuclease that by excision of incorporated anti-cancer drugs may confer resistance to drugs or as mediator of cell death induced by chemotherapy [93]. p53, by removal of the incorporated NA, could confer a cellular resistance mechanism to the antiviral compounds. Finally, the excision of NAs from mitochondrial DNA may decrease the potential for chain termination and host toxicity. These features could serve as a template for the development of p53-targeting therapies.
The control of the viral mutation rate could be a practical anti-retroviral strategy. The mutagenic capacity of a low fidelity DNA polymerase will be decreased through increase in exonuclease concentration or exonuclease targeting (increase in local p53 concentration). It is important to further elucidate the molecular mechanisms involved in governing fidelity not only at a molecular level (
A major issue in the future would be to characterize the cellular and biological functions of p53 in mitochondria in response to various stresses. There are many missing links about the biological functions of mitochondrial p53 that are required to be investigated. Whether p53 defines the percent of mutated mtDNA (heteroplasmy in a cell)? Uncovering the mechanisms by which pol γ-mediated mtDNA mutations and depletion are manifested in cells in the absence and presence of p53 is significant step in understanding underlying causes for mtDNA–related diseases. Depletion and mutation of mtDNA may lead to cellular respiratory dysfunction and release of reactive oxidative species, resulting in cellular damage [99]. Future NAs should provide higher specificity for HIV-RT and lower incorporation by pol γ to diminish mitochondrial toxicity. Whether the effective targeting of p53 in mitochondria by error-correction functions, may result in decrease of mitochondrial toxicity in response to conventional anti-viral therapies? Understanding how p53 can be imported into mitochondria, will be important and could contribute toward the design of new therapies for various diseases.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. 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by",editors:[{id:"7153",title:"Prof.",name:"Gustavo",middleName:null,surname:"Morari Do Nascimento",slug:"gustavo-morari-do-nascimento",fullName:"Gustavo Morari Do Nascimento"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2328",title:"Clay Minerals in Nature",subtitle:"Their Characterization, Modification and Application",isOpenForSubmission:!1,hash:"112c3a1f61e5fe575b0a49a9013ebe88",slug:"clay-minerals-in-nature-their-characterization-modification-and-application",bookSignature:"Marta Valaškova and Gražyna Simha Martynkova",coverURL:"https://cdn.intechopen.com/books/images_new/2328.jpg",editedByType:"Edited by",editors:[{id:"128173",title:"Dr.",name:"Marta",middleName:null,surname:"Valaskova",slug:"marta-valaskova",fullName:"Marta 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With an increasing understanding of clay structure, montmorillonite is realized viable for an enhanced performance in a variety of materials and products in the areas of catalysis, food additive, antibacterial function, polymer, sorbent, etc. Significant development in the use and application of montmorillonite is seen in recent time. This chapter provides an overview of montmorillonite, structure, and properties and particularly discusses its recent utilization in important materials. Montmorillonite is introduced in terms of its natural sources, chemical structure, physical and chemical properties, and functional utilization. The important physical and chemical properties are summarized as particle and layered structure, molecular structure and cation exchange effect, barrier property, and water sorption. This is followed by the important functional utilizations of montmorillonite based on the effects of its chemical structure. The important functional utilization of montmorillonite includes food additive for health and stamina, for antibacterial activity against tooth and gum decay, as sorbent for nonionic, anionic, and cationic dyes, and the use as catalyst in organic synthesis. The environment concerns, to date, do not indicate the adversity for particles used as additive. Studies will be useful which are clearly based on any montmorillonite structure to describe environmental effects.",book:{id:"6561",slug:"current-topics-in-the-utilization-of-clay-in-industrial-and-medical-applications",title:"Current Topics in the Utilization of Clay in Industrial and Medical Applications",fullTitle:"Current Topics in the Utilization of Clay in Industrial and Medical Applications"},signatures:"Faheem Uddin",authors:[{id:"228107",title:"Prof.",name:"Faheem",middleName:null,surname:"Uddin",slug:"faheem-uddin",fullName:"Faheem Uddin"}]},{id:"38850",doi:"10.5772/47790",title:"Clay Minerals from the Perspective of Oil and Gas Exploration",slug:"clay-minerals-from-the-perspective-of-oil-and-gas-exploration",totalDownloads:16109,totalCrossrefCites:18,totalDimensionsCites:45,abstract:null,book:{id:"2328",slug:"clay-minerals-in-nature-their-characterization-modification-and-application",title:"Clay Minerals in Nature",fullTitle:"Clay Minerals in Nature - Their Characterization, Modification and Application"},signatures:"Shu Jiang",authors:[{id:"138867",title:"Dr.",name:"Shu",middleName:null,surname:"Jiang",slug:"shu-jiang",fullName:"Shu Jiang"}]},{id:"38859",doi:"10.5772/51237",title:"Vermiculite: Structural Properties and Examples of the Use",slug:"vermiculite-structural-properties-and-examples-of-the-use",totalDownloads:4803,totalCrossrefCites:8,totalDimensionsCites:44,abstract:null,book:{id:"2328",slug:"clay-minerals-in-nature-their-characterization-modification-and-application",title:"Clay Minerals in Nature",fullTitle:"Clay Minerals in Nature - Their Characterization, Modification and Application"},signatures:"Marta Valášková and Gražyna Simha Martynková",authors:[{id:"128173",title:"Dr.",name:"Marta",middleName:null,surname:"Valaskova",slug:"marta-valaskova",fullName:"Marta Valaskova"}]},{id:"38858",doi:"10.5772/50172",title:"Role of Clay Minerals in Chemical Evolution and the Origins of Life",slug:"role-of-clay-minerals-in-chemical-evolution-and-the-origin-of-life",totalDownloads:4774,totalCrossrefCites:19,totalDimensionsCites:34,abstract:null,book:{id:"2328",slug:"clay-minerals-in-nature-their-characterization-modification-and-application",title:"Clay Minerals in Nature",fullTitle:"Clay Minerals in Nature - Their Characterization, Modification and Application"},signatures:"Hideo Hashizume",authors:[{id:"142318",title:"Dr.",name:"Hideo",middleName:null,surname:"Hashizume",slug:"hideo-hashizume",fullName:"Hideo Hashizume"}]},{id:"49766",doi:"10.5772/62082",title:"Charging Behavior of Clays and Clay Minerals in Aqueous Electrolyte Solutions — Experimental Methods for Measuring the Charge and Interpreting the Results",slug:"charging-behavior-of-clays-and-clay-minerals-in-aqueous-electrolyte-solutions-experimental-methods-f",totalDownloads:3140,totalCrossrefCites:9,totalDimensionsCites:20,abstract:"We discuss the charging behavior of clays and clay minerals in aqueous electrolyte solutions. Clay platelets exhibit different charging mechanisms on the various surfaces they expose to the solution. Thus, the basal planes have a permanent charge that is typically considered to be independent of pH, whereas the edge surfaces exhibit the amphoteric behavior and pH-dependent charge that is typical of oxide minerals. Background electrolyte concentration and composition may affect these two different mechanisms of charging in different ways. To guide and to make use of these unique properties in technical application, it is necessary to understand the effects of the various master variables (i.e. pH and background salt composition and concentration). However, how to disentangle the various contributions to the charge that is macroscopically measurable via conventional approaches (i.e. electrokinetics, potentiometric titrations, etc.) remains a challenge. The problem is depicted by discussing in detail the literature data on kaolinite obtained with crystal face specificity. Some results from similar experiments on related substrates are also discussed. As an illustration of the complexity, we have carried out extensive potentiometric mass and electrolyte titrations on artificial clay samples (Na-, Ca-, and Mg-montmorillonite). A wide variety of salts was used, and it was found that the different electrolytes had different effects on the end point of mass titrations. In the case of a purified sample (i.e. no acid-base impurities), the end point of a mass titration (the plateau of pH achieved for the highest concentrations of solid), in principle, corresponds to the point of zero net proton and hydroxide consumption, at which in ideal systems, such as oxide minerals, the net proton surface charge density is zero. To such concentrated (dense) suspensions of clay particles, aliquots of salts can be added and the resulting pH indicates the specificity of a given salt for a given clay particle system. In the experimental data, some ambiguity remains, which calls for further detailed and comprehensive studies involving the application of all the available techniques to one system. Although, right now, the overall picture appears to be clear from a generic point of view (i.e. concerning the trends), clearly, in a quantitative sense, huge differences occur for nominally identical systems and only such a comprehensive study will allow to proof the current phenomenological picture and allow the next step to be taken to understand the fine details of the complex clay-electrolyte solution interfaces.",book:{id:"5073",slug:"clays-clay-minerals-and-ceramic-materials-based-on-clay-minerals",title:"Clays, Clay Minerals and Ceramic Materials Based on Clay Minerals",fullTitle:"Clays, Clay Minerals and Ceramic Materials Based on Clay Minerals"},signatures:"Tajana Preocanin, Ahmed Abdelmonem, Gilles Montavon and\nJohannes Luetzenkirchen",authors:[{id:"111676",title:"Prof.",name:"Tajana",middleName:null,surname:"Preocanin",slug:"tajana-preocanin",fullName:"Tajana Preocanin"},{id:"176270",title:"Dr.",name:"Johannes",middleName:null,surname:"Luetzenkirchen",slug:"johannes-luetzenkirchen",fullName:"Johannes Luetzenkirchen"},{id:"180461",title:"Dr.",name:"Ahmed",middleName:null,surname:"Abdelmonem",slug:"ahmed-abdelmonem",fullName:"Ahmed Abdelmonem"},{id:"180462",title:"Dr.",name:"Gilles",middleName:null,surname:"Montavon",slug:"gilles-montavon",fullName:"Gilles Montavon"}]}],mostDownloadedChaptersLast30Days:[{id:"60931",title:"The Importance of Clay in Geotechnical Engineering",slug:"the-importance-of-clay-in-geotechnical-engineering",totalDownloads:5282,totalCrossrefCites:8,totalDimensionsCites:11,abstract:"Clay is a very important material in geotechnical engineering, because it is often observed in geotechnical engineering practice. Generally, this soil type has numerous problems due to its low strength, high compressibility and high level of volumetric changes. Clay needs to be improved before it can be used in road construction, dams, slurry walls, airports and waste landfills. Improved gradation, a reduction in plasticity and swelling potential, as well as an increase in strength and workability, generally improve the stability of clay. Clay is a fine-grained soil, but not all fine-grained soils are clay. Clay minerals are very electrochemically active; thus, they affect soil microstructures. Due to these characteristics, many important soil problems related to clay have been observed in the past, the importance of which is understood. In this chapter, the properties of clay, as well as the use of clay in geotechnical engineering and geotechnical studies on clay, are examined.",book:{id:"6561",slug:"current-topics-in-the-utilization-of-clay-in-industrial-and-medical-applications",title:"Current Topics in the Utilization of Clay in Industrial and Medical Applications",fullTitle:"Current Topics in the Utilization of Clay in Industrial and Medical Applications"},signatures:"Nazile Ural",authors:[{id:"227767",title:"Associate Prof.",name:"Nazile",middleName:null,surname:"Ural",slug:"nazile-ural",fullName:"Nazile Ural"}]},{id:"61845",title:"Montmorillonite: An Introduction to Properties and Utilization",slug:"montmorillonite-an-introduction-to-properties-and-utilization",totalDownloads:5506,totalCrossrefCites:44,totalDimensionsCites:78,abstract:"Clay mineral is an important material available in nature. With an increasing understanding of clay structure, montmorillonite is realized viable for an enhanced performance in a variety of materials and products in the areas of catalysis, food additive, antibacterial function, polymer, sorbent, etc. Significant development in the use and application of montmorillonite is seen in recent time. This chapter provides an overview of montmorillonite, structure, and properties and particularly discusses its recent utilization in important materials. Montmorillonite is introduced in terms of its natural sources, chemical structure, physical and chemical properties, and functional utilization. The important physical and chemical properties are summarized as particle and layered structure, molecular structure and cation exchange effect, barrier property, and water sorption. This is followed by the important functional utilizations of montmorillonite based on the effects of its chemical structure. The important functional utilization of montmorillonite includes food additive for health and stamina, for antibacterial activity against tooth and gum decay, as sorbent for nonionic, anionic, and cationic dyes, and the use as catalyst in organic synthesis. The environment concerns, to date, do not indicate the adversity for particles used as additive. Studies will be useful which are clearly based on any montmorillonite structure to describe environmental effects.",book:{id:"6561",slug:"current-topics-in-the-utilization-of-clay-in-industrial-and-medical-applications",title:"Current Topics in the Utilization of Clay in Industrial and Medical Applications",fullTitle:"Current Topics in the Utilization of Clay in Industrial and Medical Applications"},signatures:"Faheem Uddin",authors:[{id:"228107",title:"Prof.",name:"Faheem",middleName:null,surname:"Uddin",slug:"faheem-uddin",fullName:"Faheem Uddin"}]},{id:"49271",title:"Ceramic Materials Based on Clay Minerals in Cultural Heritage Study",slug:"ceramic-materials-based-on-clay-minerals-in-cultural-heritage-study",totalDownloads:3187,totalCrossrefCites:5,totalDimensionsCites:9,abstract:"The artifacts belonging to the ceramic heritage are mostly based on all clay types used by humans over the ages, because the sources of clays were easily available and people were interested to produce ceramics and pottery. This is the reason why the conservation of cultural heritage is of great concern. Ceramics (Greek κεράμιον Keramion) is a material obtained by shaping and firing clay. In the Romanian history, many ceramic pieces, of great diversity, have been discovered, and most of them are used in traditional households. Ceramic materials based on clay minerals in cultural heritage (ceramic heritage) involve techniques of characterization of raw materials and ceramic objects based on clays, discovered in different archaeological sites, leading to some results about the production technology, provenance, authentication, and historical appartenance on Romanian territory. The chemical composition of ancient ceramics and pigments decorating them, excavated from different Romanian archaeological sites, suggested a chemical composition of ceramic based on clay minerals (kaolinite, illite, and smectite), while the pigments belonging to them contained red pigments (hematite or ocher), manganese oxides (brown pigments), and magnetite or carbon of vegetable origin (black-pigmented layers).",book:{id:"5073",slug:"clays-clay-minerals-and-ceramic-materials-based-on-clay-minerals",title:"Clays, Clay Minerals and Ceramic Materials Based on Clay Minerals",fullTitle:"Clays, Clay Minerals and Ceramic Materials Based on Clay Minerals"},signatures:"Rodica-Mariana Ion, Radu-Claudiu Fierăscu, Sofia Teodorescu, Irina\nFierăscu, Ioana-Raluca Bunghez, Daniela Ţurcanu-Caruţiu and\nMihaela-Lucia Ion",authors:[{id:"137269",title:"Dr.",name:"Radu Claudiu",middleName:null,surname:"Fierascu",slug:"radu-claudiu-fierascu",fullName:"Radu Claudiu Fierascu"},{id:"171504",title:"Prof.",name:"Rodica-Mariana",middleName:null,surname:"Ion",slug:"rodica-mariana-ion",fullName:"Rodica-Mariana Ion"},{id:"176479",title:"Dr.",name:"Sofia",middleName:null,surname:"Teodorescu",slug:"sofia-teodorescu",fullName:"Sofia Teodorescu"},{id:"176480",title:"Dr.",name:"Irina",middleName:null,surname:"Fierascu",slug:"irina-fierascu",fullName:"Irina Fierascu"},{id:"176481",title:"Dr.",name:"Ioana Raluca",middleName:null,surname:"Bunghez",slug:"ioana-raluca-bunghez",fullName:"Ioana Raluca Bunghez"},{id:"176482",title:"Prof.",name:"Daniela",middleName:null,surname:"Turcanu-Carutiu",slug:"daniela-turcanu-carutiu",fullName:"Daniela Turcanu-Carutiu"},{id:"176483",title:"Dr.",name:"Mihaela-Lucia",middleName:null,surname:"Ion",slug:"mihaela-lucia-ion",fullName:"Mihaela-Lucia Ion"}]},{id:"62742",title:"Development of Clay Nanoparticles Toward Bio and Medical Applications",slug:"development-of-clay-nanoparticles-toward-bio-and-medical-applications",totalDownloads:1963,totalCrossrefCites:8,totalDimensionsCites:14,abstract:"Clay nanoparticles are among the most applicable and cost-affordable materials, all of which have a variety of applications in case of medical science. In this chapter, key characteristics of the clay nanoparticles along with their major groups, structure, morphology, and physicochemical properties were evaluated. Thereafter, the applications of clay nanoparticles in the field of nanocomposite, polymeric matrices, and medicine were investigated, while specimen production procedures were also reviewed. The main focus of this chapter is to investigate the applications of clay nanoparticles in bio- and medical science. In fact, organically modified clay nanoparticles (organoclays) are an attractive class of hybrid organic–inorganic nanomaterials with potential applications in case of polymer nanocomposites, rheological properties modification, and drug delivery carrier.",book:{id:"6561",slug:"current-topics-in-the-utilization-of-clay-in-industrial-and-medical-applications",title:"Current Topics in the Utilization of Clay in Industrial and Medical Applications",fullTitle:"Current Topics in the Utilization of Clay in Industrial and Medical Applications"},signatures:"Seyyed Mojtaba Mousavi, Seyyed Alireza Hashemi, Sarvenaz Salahi,\nMojgan Hosseini, Ali Mohammad Amani and Aziz Babapoor",authors:[{id:"208535",title:"M.Sc.",name:"Seyyed Alireza",middleName:null,surname:"Hashemi",slug:"seyyed-alireza-hashemi",fullName:"Seyyed Alireza Hashemi"},{id:"217960",title:"Mr.",name:"Seyyed Mojtaba",middleName:null,surname:"Mousavi",slug:"seyyed-mojtaba-mousavi",fullName:"Seyyed Mojtaba Mousavi"},{id:"217961",title:"Dr.",name:"Ali Mohammad",middleName:null,surname:"Amani",slug:"ali-mohammad-amani",fullName:"Ali Mohammad Amani"}]},{id:"38850",title:"Clay Minerals from the Perspective of Oil and Gas Exploration",slug:"clay-minerals-from-the-perspective-of-oil-and-gas-exploration",totalDownloads:16117,totalCrossrefCites:18,totalDimensionsCites:45,abstract:null,book:{id:"2328",slug:"clay-minerals-in-nature-their-characterization-modification-and-application",title:"Clay Minerals in Nature",fullTitle:"Clay Minerals in Nature - Their Characterization, Modification and Application"},signatures:"Shu Jiang",authors:[{id:"138867",title:"Dr.",name:"Shu",middleName:null,surname:"Jiang",slug:"shu-jiang",fullName:"Shu Jiang"}]}],onlineFirstChaptersFilter:{topicId:"669",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:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:122,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,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:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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",coverUrl:"https://cdn.intechopen.com/series/covers/23.jpg",latestPublicationDate:"August 1st, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:0,editor:{id:"280770",title:"Dr.",name:"Katherine K.M.",middleName:null,surname:"Stavropoulos",slug:"katherine-k.m.-stavropoulos",fullName:"Katherine K.M. Stavropoulos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRdFuQAK/Profile_Picture_2022-05-24T09:03:48.jpg",biography:"Katherine Stavropoulos received her BA in Psychology from Trinity College, in Connecticut, USA and her Ph.D. in Experimental Psychology from the University of California, San Diego. She completed her postdoctoral work at the Yale Child Study Center with Dr. James McPartland. Dr. Stavropoulos’ doctoral dissertation explored neural correlates of reward anticipation to social versus nonsocial stimuli in children with and without autism spectrum disorders (ASD). She has been a faculty member at the University of California, Riverside in the School of Education since 2016. Her research focuses on translational studies to explore the reward system in ASD, as well as how anxiety contributes to social challenges in ASD. She also investigates how behavioral interventions affect neural activity, behavior, and school performance in children with ASD. She is also involved in the diagnosis of children with ASD and is a licensed clinical psychologist in California. 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She has run and participated in several funded and non-funded projects on the teaching of Science, Social Sciences, and ICT in education. She also has the experience of participating in five Erasmus+ projects.",institutionString:"University of Crete",institution:{name:"University of Crete",institutionURL:null,country:{name:"Greece"}}},editorThree:null},{id:"90",title:"Human Development",coverUrl:"https://cdn.intechopen.com/series_topics/covers/90.jpg",isOpenForSubmission:!0,annualVolume:11974,editor:{id:"191040",title:"Dr.",name:"Tal",middleName:null,surname:"Dotan Ben-Soussan",slug:"tal-dotan-ben-soussan",fullName:"Tal Dotan Ben-Soussan",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBf1QAG/Profile_Picture_2022-03-18T07:56:11.jpg",biography:"Tal Dotan Ben-Soussan, Ph.D., is the director of the Research Institute for Neuroscience, Education and Didactics (RINED) – Paoletti Foundation. Ben-Soussan leads international studies on training and neuroplasticity from neurophysiological and psychobiological perspectives. As a neuroscientist and bio-psychologist, she has published numerous articles on neuroplasticity, movement and meditation. She acts as an editor and reviewer in several renowned journals and coordinates international conferences integrating theoretical, methodological and practical approaches on various topics, such as silence, logics and neuro-education. 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She is a member of the Coordination and Scientific Committees of the doctoral program “Tropical Knowledge and Management” (NOVA), Master in Biotechnology (UEM), and Master in Conservation Biology (GNP); and a national expert for Food and Nutrition Security and Sustainable Agriculture - High-Level Policy Dialogue EU-Africa. 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Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:229,paginationItems:[{id:"318170",title:"Dr.",name:"Aneesa",middleName:null,surname:"Moolla",slug:"aneesa-moolla",fullName:"Aneesa Moolla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/318170/images/system/318170.png",biography:"Dr. Aneesa Moolla has extensive experience in the diverse fields of health care having previously worked in dental private practice, at the Red Cross Flying Doctors association, and in healthcare corporate settings. She is now a lecturer at the University of Witwatersrand, South Africa, and a principal researcher at the Health Economics and Epidemiology Research Office (HE2RO), South Africa. Dr. Moolla holds a Ph.D. in Psychology with her research being focused on mental health and resilience. In her professional work capacity, her research has further expanded into the fields of early childhood development, mental health, the HIV and TB care cascades, as well as COVID. She is also a UNESCO-trained International Bioethics Facilitator.",institutionString:"University of the Witwatersrand",institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419588",title:"Ph.D.",name:"Sergio",middleName:"Alexandre",surname:"Gehrke",slug:"sergio-gehrke",fullName:"Sergio Gehrke",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038WgMKQA0/Profile_Picture_2022-06-02T11:44:20.jpg",biography:"Dr. Sergio Alexandre Gehrke is a doctorate holder in two fields. The first is a Ph.D. in Cellular and Molecular Biology from the Pontificia Catholic University, Porto Alegre, Brazil, in 2010 and the other is an International Ph.D. in Bioengineering from the Universidad Miguel Hernandez, Elche/Alicante, Spain, obtained in 2020. In 2018, he completed a postdoctoral fellowship in Materials Engineering in the NUCLEMAT of the Pontificia Catholic University, Porto Alegre, Brazil. He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. In addition, he is also a Collaborating Professor in several Postgraduate programs at different universities all over the world.",institutionString:null,institution:{name:"Universidad Católica San Antonio de Murcia",country:{name:"Spain"}}},{id:"342152",title:"Dr.",name:"Santo",middleName:null,surname:"Grace Umesh",slug:"santo-grace-umesh",fullName:"Santo Grace Umesh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/342152/images/16311_n.jpg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"333647",title:"Dr.",name:"Shreya",middleName:null,surname:"Kishore",slug:"shreya-kishore",fullName:"Shreya Kishore",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333647/images/14701_n.jpg",biography:"Dr. Shreya Kishore completed her Bachelor in Dental Surgery in Chettinad Dental College and Research Institute, Chennai, and her Master of Dental Surgery (Orthodontics) in Saveetha Dental College, Chennai. She is also Invisalign certified. She’s working as a Senior Lecturer in the Department of Orthodontics, SRM Dental College since November 2019. She is actively involved in teaching orthodontics to the undergraduates and the postgraduates. Her clinical research topics include new orthodontic brackets, fixed appliances and TADs. She’s published 4 articles in well renowned indexed journals and has a published patency of her own. Her private practice is currently limited to orthodontics and works as a consultant in various clinics.",institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"323731",title:"Prof.",name:"Deepak M.",middleName:"Macchindra",surname:"Vikhe",slug:"deepak-m.-vikhe",fullName:"Deepak M. Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. His research interests include root canal morphology, functionally graded concept, dental biomaterials, epidemiology and dental education, biomimetic restoration, finite element analysis and endodontic regeneration. Dr. Madfa has numerous international publications, full articles, two patents, a book and a book chapter. Furthermore, he won 14 international scientific awards. Furthermore, he is involved in many academic activities ranging from editorial board member, reviewer for many international journals and postgraduate students' supervisor. Besides, I deliver many courses and training workshops at various scientific events. Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\r\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\r\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Orthodontist, Assoc Prof in the Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. After graduating from TED Ankara College in 1986, she attended the Hacettepe University, Faculty of Dentistry in Ankara. \nIn 1993 she attended the Gazi University, Faculty of Dentistry, Department of Orthodontics for her PhD education. After finishing the PhD education, she worked as orthodontist in Ankara Dental Hospital under the Turkish Government, Ministry of Health and in a special Orthodontic Clinic till 2011. Between 2011 and 2016, Dr. Deniz Uzuner worked as a specialist in the Department of Orthodontics, Faculty of Dentistry, Gazi University in Ankara/Turkey. In 2016, she was appointed associate professor. Dr. Deniz Uzuner has authored 23 Journal Papers, 3 Book Chapters and has had 39 oral/poster presentations. She is a member of the Turkish Orthodontic Society. Her knowledge of English is at an advanced level.",institutionString:null,institution:null},{id:"332914",title:"Dr.",name:"Muhammad Saad",middleName:null,surname:"Shaikh",slug:"muhammad-saad-shaikh",fullName:"Muhammad Saad Shaikh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jinnah Sindh Medical University",country:{name:"Pakistan"}}},{id:"315775",title:"Dr.",name:"Feng",middleName:null,surname:"Luo",slug:"feng-luo",fullName:"Feng Luo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sichuan University",country:{name:"China"}}},{id:"344229",title:"Dr.",name:"Sankeshan",middleName:null,surname:"Padayachee",slug:"sankeshan-padayachee",fullName:"Sankeshan Padayachee",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"315727",title:"Ms.",name:"Kelebogile A.",middleName:null,surname:"Mothupi",slug:"kelebogile-a.-mothupi",fullName:"Kelebogile A. Mothupi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"423519",title:"Dr.",name:"Sizakele",middleName:null,surname:"Ngwenya",slug:"sizakele-ngwenya",fullName:"Sizakele Ngwenya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"337613",title:"Mrs.",name:"Tshakane",middleName:null,surname:"R.M.D. Ralephenya",slug:"tshakane-r.m.d.-ralephenya",fullName:"Tshakane R.M.D. Ralephenya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419270",title:"Dr.",name:"Ann",middleName:null,surname:"Chianchitlert",slug:"ann-chianchitlert",fullName:"Ann Chianchitlert",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419271",title:"Dr.",name:"Diane",middleName:null,surname:"Selvido",slug:"diane-selvido",fullName:"Diane Selvido",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419272",title:"Dr.",name:"Irin",middleName:null,surname:"Sirisoontorn",slug:"irin-sirisoontorn",fullName:"Irin Sirisoontorn",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}}]}},subseries:{item:{id:"4",type:"subseries",title:"Fungal Infectious Diseases",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment",scope:"Fungi are ubiquitous and there are almost no non-pathogenic fungi. Fungal infectious illness prevalence and prognosis are determined by the exposure between fungi and host, host immunological state, fungal virulence, and early and accurate diagnosis and treatment. \r\nPatients with both congenital and acquired immunodeficiency are more likely to be infected with opportunistic mycosis. Fungal infectious disease outbreaks are common during the post- disaster rebuilding era, which is characterised by high population density, migration, and poor health and medical conditions.\r\nSystemic or local fungal infection is mainly associated with the fungi directly inhaled or inoculated in the environment during the disaster. The most common fungal infection pathways are human to human (anthropophilic), animal to human (zoophilic), and environment to human (soilophile). Diseases are common as a result of widespread exposure to pathogenic fungus dispersed into the environment. \r\nFungi that are both common and emerging are intertwined. 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",hasOnlineFirst:!0,hasPublishedBooks:!1,annualVolume:11400,editor:{id:"174134",title:"Dr.",name:"Yuping",middleName:null,surname:"Ran",slug:"yuping-ran",fullName:"Yuping Ran",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9d6QAC/Profile_Picture_1630330675373",biography:"Dr. Yuping Ran, Professor, Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China. Completed the Course Medical Mycology, the Centraalbureau voor Schimmelcultures (CBS), Fungal Biodiversity Centre, Netherlands (2006). International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. Vice-chief of the editorial board of Chinses Journal of Mycology, China. Board Member and Chair of Mycology Group of Chinese Society of Dermatology.",institutionString:null,institution:{name:"Sichuan University",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null,series:{id:"6",title:"Infectious Diseases",doi:"10.5772/intechopen.71852",issn:"2631-6188"},editorialBoard:[{id:"302145",title:"Dr.",name:"Felix",middleName:null,surname:"Bongomin",slug:"felix-bongomin",fullName:"Felix Bongomin",profilePictureURL:"https://mts.intechopen.com/storage/users/302145/images/system/302145.jpg",institutionString:null,institution:{name:"Gulu University",institutionURL:null,country:{name:"Uganda"}}},{id:"45803",title:"Ph.D.",name:"Payam",middleName:null,surname:"Behzadi",slug:"payam-behzadi",fullName:"Payam Behzadi",profilePictureURL:"https://mts.intechopen.com/storage/users/45803/images/system/45803.jpg",institutionString:"Islamic Azad University, Tehran",institution:{name:"Islamic Azad University, Tehran",institutionURL:null,country:{name:"Iran"}}}]},onlineFirstChapters:{paginationCount:10,paginationItems:[{id:"82804",title:"Psychiatric Problems in HIV Care",doi:"10.5772/intechopen.106077",signatures:"Seggane Musisi and Noeline Nakasujja",slug:"psychiatric-problems-in-hiv-care",totalDownloads:1,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Future Opportunities and Tools for Emerging Challenges for HIV/AIDS Control",coverURL:"https://cdn.intechopen.com/books/images_new/11575.jpg",subseries:{id:"6",title:"Viral Infectious Diseases"}}},{id:"82817",title:"Perspective Chapter: Microfluidic Technologies for On-Site Detection and Quantification of Infectious Diseases - The Experience with SARS-CoV-2/COVID-19",doi:"10.5772/intechopen.105950",signatures:"Andres Escobar and Chang-qing Xu",slug:"perspective-chapter-microfluidic-technologies-for-on-site-detection-and-quantification-of-infectious",totalDownloads:2,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"SARS-CoV-2 Variants - Two Years After",coverURL:"https://cdn.intechopen.com/books/images_new/11573.jpg",subseries:{id:"6",title:"Viral Infectious Diseases"}}},{id:"82667",title:"Perspective Chapter: Analysis of SARS-CoV-2 Indirect Spreading Routes and Possible Countermeasures",doi:"10.5772/intechopen.105914",signatures:"Cesare Saccani, Marco Pellegrini and Alessandro Guzzini",slug:"perspective-chapter-analysis-of-sars-cov-2-indirect-spreading-routes-and-possible-countermeasures",totalDownloads:8,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"SARS-CoV-2 Variants - Two Years After",coverURL:"https://cdn.intechopen.com/books/images_new/11573.jpg",subseries:{id:"6",title:"Viral Infectious Diseases"}}},{id:"82559",title:"Perspective Chapter: Bioinformatics Study of the Evolution of SARS-CoV-2 Spike Protein",doi:"10.5772/intechopen.105915",signatures:"Črtomir Podlipnik, Radostina Alexandrova, Sebastian Pleško, Urban Bren and Marko Jukič",slug:"perspective-chapter-bioinformatics-study-of-the-evolution-of-sars-cov-2-spike-protein",totalDownloads:14,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"SARS-CoV-2 Variants - Two Years After",coverURL:"https://cdn.intechopen.com/books/images_new/11573.jpg",subseries:{id:"6",title:"Viral Infectious Diseases"}}},{id:"82521",title:"Challenges in Platelet Functions in HIV/AIDS Management",doi:"10.5772/intechopen.105731",signatures:"Gordon Ogweno",slug:"challenges-in-platelet-functions-in-hiv-aids-management",totalDownloads:16,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Future Opportunities and Tools for Emerging Challenges for HIV/AIDS Control",coverURL:"https://cdn.intechopen.com/books/images_new/11575.jpg",subseries:{id:"6",title:"Viral Infectious Diseases"}}},{id:"82552",title:"Perspective Chapter: SARS-CoV-2 Variants - Two Years Post-Onset of the Pandemic",doi:"10.5772/intechopen.105913",signatures:"Adekunle Sanyaolu, Aleksandra Marinkovic, Stephanie Prakash, Chuku Okorie, Abdul Jan, Priyank Desai, Abu Fahad Abbasi, Jasmine Mangat, Zaheeda Hosein, Kareem Hamdy, Nafees Haider, Nasar Khan, Rochelle Annan, Olanrewaju Badaru, Ricardo Izurieta and Stella Smith",slug:"perspective-chapter-sars-cov-2-variants-two-years-post-onset-of-the-pandemic",totalDownloads:13,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"SARS-CoV-2 Variants - Two Years After",coverURL:"https://cdn.intechopen.com/books/images_new/11573.jpg",subseries:{id:"6",title:"Viral Infectious Diseases"}}},{id:"82367",title:"Spatial Variation and Factors Associated with Unsuppressed HIV Viral Load among Women in an HIV Hyperendemic Area of KwaZulu-Natal, South Africa",doi:"10.5772/intechopen.105547",signatures:"Adenike O. 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We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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