\r\n\tThe WHO classification in 2007; was based on the histogenesis and cell origin of the tumor. In the latest classification made in 2016; to better characterize the tumor and obtain better data on its prognosis; The combination of molecular and genetic biomarkers and histopathological features of the tumor was used. Despite all current treatment approaches, the median survival time is around 12 months in most GBM patients. Compared with the situation of some types of successfully treated cancers; the survival time of GBM patients is not at an acceptable level today. In the treatment of CNS tumors; surgery, chemotherapy, and radiation treatments (x-rays, gamma rays, electron and proton beams) are used. The therapeutic potential of chemotherapy; New strategies are needed to increase drug concentration at the diseased site, as this largely depends on the ability of the chemotherapeutic agent to achieve effective concentrations at tumor localization. Based on our better understanding of the genetic and molecular characteristics of CNS tumors; Targeted therapies, including vaccines, and treatment protocols such as immunotherapy are promising developments.
\r\n
\r\n\tThis book supposes to be written by many authors who have an internationally honored place in their field to share their ideas about the treatment of CNS tumors. Surgery, Radiotherapy, Chemotherapy and Antiangiogenic Therapy Protocols, Immunotherapy, Molecular Therapy, Specific target-agents therapy with Nanoparticles and Gene Therapy for CNS tumors among the book chapters. \r\n\tIn these sections; there are many practical pieces of information that can help the students who graduated from the Medicine Faculty and specialist doctors who are interested in Neurosurgery.
",isbn:"978-1-80356-753-2",printIsbn:"978-1-80356-752-5",pdfIsbn:"978-1-80356-754-9",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"4eb1e918eaec0a815088bc84c834bf3c",bookSignature:"Associate Prof. Feyzi Birol Sarica",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11888.jpg",keywords:"Symptoms, Clinical Presentation, Histopathology, Molecular Biology, Surgery, Surgical Treatment, Radiosurgery, Radiation Therapy, Antiangiogenic Therapy, Immunotherapy, Repeat Surgery, Prognostic Factors",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 25th 2022",dateEndSecondStepPublish:"May 31st 2022",dateEndThirdStepPublish:"July 30th 2022",dateEndFourthStepPublish:"October 18th 2022",dateEndFifthStepPublish:"December 17th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"3 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Dr.Sarica is currently serving as the Chairman of the Department of Neurosurgery at the Giresun University. He has 23 articles published in Internationally recognized journals, 8 articles published in Nationally published journals, 12 poster papers presented in International Scientific Congresses, 65 poster papers presented in National Scientific Congresses, and 2 chapters published in Proceeding Books.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"45313",title:"Associate Prof.",name:"Feyzi Birol",middleName:null,surname:"Sarica",slug:"feyzi-birol-sarica",fullName:"Feyzi Birol Sarica",profilePictureURL:"https://mts.intechopen.com/storage/users/45313/images/system/45313.png",biography:"Associate Professor Feyzi Birol SARICA born in 1971 in Germany graduated the Medicine Faculty of Ankara University in 1997 and received the title of Medical Doctor. In 2005, he gaves his expertise thesis named “Prognostic factors in Supratentorial Glial Tumors” at the Neurosurgery Clinic of Ankara Numune Education and Research Hospital and received the title of Neurosurgery Specialist Doctor by Turkish Board Certification. He worked firstly as a Neurosurgery Specialist Doctor and then as an Lecturer in Adana Education and Research Hospital of Medicine Faculty of Baskent University between 2006-2015 years. He worked at the Kudret International Hospital in Ankara in 2016. He started to work as Assistant Professor at Department of Neurosurgery of Medicine Faculty of Giresun University in 2017. He took the title of Associate Professor in March 2018. He is currently serving as the Chairman of the Department of Neurosurgery in Giresun University. He has memberships at Turkish Neurosurgical Society and Nervous System Surgery Association.\r\n\r\nHe has 23 articles published in Internationally recognized journals, 8 articles published in Nationally published journals, 12 poster papers presented in International Scientific Congresses, 65 poster papers presented in National Scientific Congresses and published in Proceeding Books, and 2 International Book Chapter wroten within SCI Index. He participated in Microneurosurgery, Cerebrovascular Surgery, Skull Base Surgery, Gamma Knife Radiosurgery, Hydrocephalus, and Spinal Dysraphism Training. He also participated in many Scientific Congresses, Symposiums and Workshops. He is interested in General Neurosurgery as well as Neurooncology and Cerebrovascular Surgery in recent years.",institutionString:"Giresun University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Giresun University",institutionURL:null,country:{name:"Turkey"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"440212",firstName:"Elena",lastName:"Vracaric",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/440212/images/20007_n.jpg",email:"elena@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"6550",title:"Cohort Studies in Health Sciences",subtitle:null,isOpenForSubmission:!1,hash:"01df5aba4fff1a84b37a2fdafa809660",slug:"cohort-studies-in-health-sciences",bookSignature:"R. Mauricio Barría",coverURL:"https://cdn.intechopen.com/books/images_new/6550.jpg",editedByType:"Edited by",editors:[{id:"88861",title:"Dr.",name:"R. Mauricio",surname:"Barría",slug:"r.-mauricio-barria",fullName:"R. Mauricio Barría"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9500",title:"Recent Advances in Bone Tumours and Osteoarthritis",subtitle:null,isOpenForSubmission:!1,hash:"ea4ec0d6ee01b88e264178886e3210ed",slug:"recent-advances-in-bone-tumours-and-osteoarthritis",bookSignature:"Hiran Amarasekera",coverURL:"https://cdn.intechopen.com/books/images_new/9500.jpg",editedByType:"Edited by",editors:[{id:"67634",title:"Dr.",name:"Hiran",surname:"Amarasekera",slug:"hiran-amarasekera",fullName:"Hiran Amarasekera"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. 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"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2270",title:"Fourier Transform",subtitle:"Materials Analysis",isOpenForSubmission:!1,hash:"5e094b066da527193e878e160b4772af",slug:"fourier-transform-materials-analysis",bookSignature:"Salih Mohammed Salih",coverURL:"https://cdn.intechopen.com/books/images_new/2270.jpg",editedByType:"Edited by",editors:[{id:"111691",title:"Dr.Ing.",name:"Salih",surname:"Salih",slug:"salih-salih",fullName:"Salih Salih"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"117",title:"Artificial Neural Networks",subtitle:"Methodological Advances and Biomedical Applications",isOpenForSubmission:!1,hash:null,slug:"artificial-neural-networks-methodological-advances-and-biomedical-applications",bookSignature:"Kenji Suzuki",coverURL:"https://cdn.intechopen.com/books/images_new/117.jpg",editedByType:"Edited by",editors:[{id:"3095",title:"Prof.",name:"Kenji",surname:"Suzuki",slug:"kenji-suzuki",fullName:"Kenji Suzuki"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3828",title:"Application of Nanotechnology in Drug Delivery",subtitle:null,isOpenForSubmission:!1,hash:"51a27e7adbfafcfedb6e9683f209cba4",slug:"application-of-nanotechnology-in-drug-delivery",bookSignature:"Ali Demir Sezer",coverURL:"https://cdn.intechopen.com/books/images_new/3828.jpg",editedByType:"Edited by",editors:[{id:"62389",title:"PhD.",name:"Ali Demir",surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"67039",title:"The Microvine: A Versatile Plant Model to Boost Grapevine Studies in Physiology and Genetics",doi:"10.5772/intechopen.86166",slug:"the-microvine-a-versatile-plant-model-to-boost-grapevine-studies-in-physiology-and-genetics",body:'\n
\n
1. Introduction
\n
As a perennial fruit crop, the grapevine (Vitis vinifera) needs a long juvenile period before the reproductive cycle starts. Even vine cuttings from adult plants allow the production of fruits only from the second year. Moreover, during the adult phase, common cultivars produce reproductive organs only once per growing cycle (generally once per year) and per proleptic axis. These biological features, together with the large size of an adult vine, represent major drawbacks for precise physiological, ecophysiological, and omics experiments on the plant and fruit development under well-controlled conditions. Furthermore, those characteristics of normal vines slow down advances in genetics and breeding.
\n
The microvine ML1 is a somatic variant obtained though somatic embryogenesis from Pinot Meunier cultivar. This phenotype results from a somatic mutation in the Vvgai1 gene involved in gibberellin signaling. The mutation is originally present at the heterozygous state in the epidermal cells of Pinot Meunier, being responsible for its well-known hairy phenotype. However, the introduction of the mutation in all cell layers resulted in a miniaturization of all vegetative organs and in a conversion of tendrils into inflorescences, which leads to a continuous flowering and fruiting along vegetative axes.
\n
The small size of the microvine renders this grapevine model very convenient for experiments in usual growth chambers, where a tight control of environmental factors (radiation, vapor pressure deficit (VPD), temperature, water and nutrient supplies) is possible, in contrast with experiments under vineyard conditions. Indeed, it is possible to grow the vines up to densities of 15–30 plants/m2 and to limit their height to 1.2 m. Under such conditions, the most advanced fruits are mature 5–6 months after plantation of cuttings or seedlings, and the vegetative axis displays all developmental stages from young inflorescences (distal phytomers) to flowering, berry growth, and ripening (proximal phytomers). Under stable controlled conditions, the spatial gradients of vegetative and reproductive development of the microvine mimic well the temporal development of each phytomer, which allows to infer kinetic data from one-off spatial information along the proleptic axis.
\n
In controlled conditions, microvine allows to experiment on berry development all year long, which greatly accelerates studies on physiology and molecular biology. Furthermore, by reducing the time lag between two generations and by increasing the precision of phenotyping, genetic approaches are much more efficient than the ones generally performed with macrovines. In the first section of the paper, we describe the genetic and molecular mechanisms underlying the phenotypes of the microvine and derived lines. Then, we review typical experimental designs that can be designed with the microvine. In the last section, we review recent project using this model to study grapevine development and fruit physiology and to identify quantitative trait loci (QTLs) of agronomic traits.
\n
\n
\n
2. Biological origin of the microvine
\n
\n
2.1 Tissue chimerism and phenotypic consequences
\n
The meristem of higher plants is organized in several cell layers. The outermost, which corresponds to epidermal cells, results from anticlinal divisions (i.e., following a plane of division perpendicular to the surface). This tissue which covers all the organs of the shoot system develops as a single cell layer [1]. Underneath, a multicellular zone, called L2 cell layer, is at the origin of all subepidermal tissues, following multidirectional divisions (i.e., primary structures but also lateral meristems, vascular cambium, phellogen, and their derivative tissues). No further, deeper cell layer (L3 cell layer), which forms in some species the core of shoot organs (pith), has been clearly identified in the grapevine yet [2].
\n
In general, these cell lines that derive from initial cells located at the tip of the apical dome do not mix, unless there is an accident during cells multiplication. The organization in L1 and L2 cell layers is found in the various organs that derive from the shoot apical meristem (SAM) and in particular in the axillary meristems at the origin of caulinar organs. Because a somatic mutation is initially a single cellular event, it leads to the setting of chimeric tissues or organs, i.e., composed of cells of different genotypes and potentially displaying some phenotypic diversity [2]. When a somatic mutation appears laterally to a meristem, changes can only be distributed in the sector of the mutated organ. If the mutation occurs in an initial cell of a meristem, it can spread to all the tissues derived from the mutated cell. The resulting structure is a chimeric and periclinal genotype, i.e., including cell layers that are not all genetically identical. Periclinal chimeras can be stabilized by vegetative propagation, i.e., by cuttings or by grafting.
\n
A somatic mutation can invade all the cell layers and spread uniformly to all derivative tissues, provided that the three following conditions are fulfilled: (i) the mutation is not lethal for the plant, (ii) the mutation appears in an initial cell within a meristem, and (iii) the mutation is established, by cell substitution in both L1 and L2 cell layers [2]. The probability of simultaneous occurrence of these three conditions being very low, most of the mutations therefore develop sectorially or periclinally and give rise to chimeric tissues and organs.
\n
In the 1990s, thanks to the use of codominant genetic markers (microsatellites, RFLP), the existence of genetic chimerism has been demonstrated in several vine varieties. As such, Franks et al. [3] showed that Pinot Meunier can display up to three alleles for some loci, whereas a vine, having a diploid genome, can theoretically only show one allelic form per homozygous locus and two allelic forms for a heterozygous locus. Boss and Thomas [4] were able to de-chimerise Pinot Meunier by somatic embryogenesis. They characterized the resulting L1 and L2 genotypes and studied the associated phenotypes. This work showed that Pinot Meunier carries a mutation in VvGAI1 gene in the L1 layer which confers the hairy phenotype to the variety (Figure 1).
\n
Figure 1.
Genetic structures of pinot noir and pinot Meunier and their respective apex phenotypes. Pinot Meunier is a somatic variant of pinot noir, which carries the mutation (Vvgai1) at heterozygous status. Localized in the epidermal cells (L1 cell layer), the mutation exacerbates the hairiness of vegetative organs of this variety (http://plantgrape.plantnet-project.org/en), without any other significant phenotypic change.
\n
Plants regenerated from L1 or L2 cells exhibited very different phenotypes. The plants obtained from the deepest cell layer (L2) no longer had a mutation at VvGAI1 locus and presented phenotypic traits very close to Pinot Noir. Conversely, the plants derived from L1 cells that retained a mutated version of Vvgai1 associated with a wild-type allele VvGAI1 were dwarf and hairy and displayed a full conversion of all tendrils into inflorescences (Figure 2). This phenotype has been called microvine, due to the small size of the mutant.
\n
Figure 2.
By somatic embryogenesis from anthers of pinot Meunier, it is possible to obtain two types of plants. One, which no longer carries the mutation of VvGAI in the L1 and L2 cell layers, has a phenotype similar to pinot noir (large size, juvenility period, main production of clusters from proleptic axes, i.e., winter buds). The other, which carries the mutation of VvGAI in all the tissues, displays a miniaturized phenotype and extreme hairiness and produces inflorescences both in the winter buds and from the conversion of tendrils in inflorescences. In the figure, the numbers associated with VvGAI allele correspond to the nucleotide base length (bp) of the VVS2 microsatellite marker [4].
\n
Thus, the microvine has the Vvgai1 mutation present in both cell layers that confers a very different phenotype from the Pinot Meunier from which it derives and which only bears the mutation in the L1 cell layer. Another interesting feature is related to the genetic status of the mutation in the microvine. Although it is present in both cell layers, the VvGAI locus is heterozygous, i.e., each cell is carrying a mutated allele Vvgai1 is associated with a wild-type allele VvGAI1. Because Vvgai1 is not a lethal mutation nor for the sporophyte or the gametophyte, this status can be rearranged by selfing in three genotypes:
Homozygous VvGAI1/VvGAI1, which corresponds to a vine without any mutation at the locus. The phenotype associated with this genetic status is non-dwarf, similar to classical macrovine varieties.
Heterozygote VvGAI1/Vvgai, which corresponds to the same genotype and (dwarf) phenotype than the original microvine ML1.
Homozygotous Vvgai1/Vvgai1, which corresponds to plants carrying both alleles in a mutated version. The phenotype associated with this status, called picovine, corresponds to an extreme dwarfism, with plants displaying very miniaturized shoot organs [4] (Figure 3).
\n
Figure 3.
The three genotypes/phenotypes that can be obtained by selfing from the microvine (VvGAI1/Vvgai1): left, extremely miniaturized vines that carries the homozygous locus Vvgai1/Vvgai1, called picovines; middle, individuals with the same phenotype as the microvine, heterozygous for the mutation (VvGAI1/Vvgai1); and right, normal-sized plants that no longer carry mutated alleles, homozygous for the non-mutated form of the gene (VvGAI1/VvGAI1).
\n
Another interesting feature, linked to the heterozygous status VvGAI/Vvgai1, is the possibility to return to non-dwarf phenotype. Indeed, by crossing a microvine (VvGAI1/Vvgai1) with a classic grapevine variety, i.e., a macrovine (VvGAI1/VvGAI1), it is possible to recover 50% of individuals with a microvine phenotype and 50% of individuals with the characteristics of a non-dwarf grapevine.
\n
\n
\n
2.2 Molecular mechanisms associated with the mutation Vvgai1
\n
The comparison of the allelic VvGAI forms present in Pinot Meunier and the microvine [4, 5] showed that the mutation corresponds to a modification of a single nucleotide in the DELLA motif of the protein, which is important for gibberellin signaling.
\n
After transient transformation of epidermal onion cells, green fluorescent protein (GFP) fusions to VvGAI1 and Vvgai1 sequences responded differently to gibberellin applications. The GFP signal of the GAI1::GFP fusion disappears rapidly from the nucleus under the effect of gibberellins, which indicates its degradation following the hormonal stimulus. On the contrary, the gai1::GFP translational protein fusion remains insensitive to hormonal signaling, which indicates that the mutation in the DELLA motif abolishes the property of the protein to be degraded when triggered by gibberellins [5].
\n
The GAI gene is known to be an important regulator of vegetative growth and reproductive development [6]. In grapevine, gibberellins, produced under shade, stimulate growth and inhibit the formation of inflorescences [7]. This effect is mediated by the nuclear protein GAI1, which, in its mutated form gai1, no longer transmits the hormonal signaling [5]. Thus, vegetative growth and the inhibition of the conversion of tendrils into inflorescences are no longer maintained which explains the dwarf phenotype and the continuous fructification along the stems. The characterization of the expression profiles of different isogenes of VvGAI revealed that Vvgai1 is mainly expressed in vegetative organs such as buds and young leaves, while other forms are expressed in reproductive organs (unpublished data). For instance, Vvgai2, which does not have any mutation in the DELLA protein motif, is expressed in reproductive organs from flowering to ripening [5]. This explains why Vvgai1 mutation does not interfere directly with berry developmental program which is similar to non-dwarf varieties.
\n
\n
\n
\n
3. Application of the use of the microvine
\n
\n
3.1 Vegetative development
\n
Several experiments have been conducted outdoor and in controlled environments to characterize the vegetative development of the proleptic axis of the microvine [8]. Different day/night temperature treatments were applied (22/12, 25/15, 30/15, 30/20, 30/25°C), while VPD was maintained constant (about 1 kPa). These experiments showed that the vegetative organogenesis rhythm of the microvine is similar to that of non-dwarf vines. Indeed, its phyllochron (leaf emission rate) is around 24°C, similarly to other varieties of V. vinifera such as Grenache [10], and it fluctuates only slightly with temperature and radiation variations between experiments (photosynthetically active radiation (PAR) has been experimented from 19 to 25 mol.m−2d−1).
\n
The duration of leaf and internode growth of the microvine is also similar to that of non-dwarf vines, lasting ca. 220°C (i.e., 20 days at 25/15°C) for leaves and ca. 150°C (i.e., 14 days under the same conditions) for internodes [9, 10]. The most significant phenotypic difference, induced by Vvgai1, is the size limitation of vegetative organs. The leaf area is reduced by half in the microvine compared to non-dwarf vines, and internodes are five times shorter. The dwarf phenotype is thus very valuable to conduct experiments under very well-controlled conditions in small growth chambers. Such property permits to study the impacts of single or combined abiotic factors (radiation, temperature, VPD, CO2) on plant growth and development while minimizing uncontrolled biases arising from environmental fluctuation in field studies on perennial vines.
\n
However, the shortening of the internodes increases leaf shading and promotes the development of fungal diseases as compared to non-dwarf vine. The control of powdery mildew (Erysiphe necator) on leaves and green berries or gray mold (Botrytis) on ripening fruits requires a strict phytosanitary management. To improve the microclimate of the clusters, it is recommended to systematically remove the lateral branches to reduce the plant to a single proleptic axis and to systematically eliminate one leaf out of three, e.g., removing the leaves of all P0 phytomers which do not bear any inflorescence. Also, for the most fertile lines, it is necessary to control the number of ripening berries to avoid source/sink unbalance that could be prejudicial to the growth and the formation of new inflorescences as well as the accumulation of metabolites in the fruits. Because the microvine displays several levels of cluster at ripening stages, a good balance is achieved by limiting the number of ripening berries to 8–15 per cluster.
\n
\n
\n
3.2 Reproductive development
\n
The reproductive development of the microvine is divided into two distinct and simultaneously occurring patterns: (i) the fructification of proleptic shoots from preformed inflorescence primordia within winter buds and (ii) the continuous fruiting of proleptic and sylleptic axes resulting from the conversion of tendrils into inflorescences.
\n
\n
3.2.1 Fruiting from winter buds (two successive seasons)
\n
In the grapevine, as for many other perennial fruit crops, fruit formation occurs during 2 consecutive years. The first step starts with the initiation and differentiation of inflorescence primordia in the winter buds prior to endo-dormancy until approximately the end of summer or beginning of autumn. During the subsequent cycle after the break of dormancy, approximately 2 weeks before budburst, the inflorescences resume their development and complete flower organogenesis and subsequently flowering in spring [6]. The level of differentiation of microvine winter buds (i.e., the number of preformed phytomers and inflorescence primordia) was analyzed during 80 days of growth under controlled environmental conditions (25/15°C day/night temperature, VPD 1 kPa, photoperiod 12 h). Two imaging methods were compared, the classic microscopy dissection and the noninvasive X-ray micro-tomography [11], with a resolution of 9 𝝁m. These observations showed that winter buds of the microvine harbor a complex formed of primary, secondary, and tertiary buds of decreasing fertility, as non-dwarf vines [12]. The maximum fertility of the primary buds is two inflorescences in the microvine, whereas it can reach three or even four in some non-dwarf varieties. These inflorescences are inserted into phytomers n°4 to n°6 with an acropetal development as for macrovines [12, 13]. The lignification of the stem which develops from the vegetative axis base is concomitant with the slowdown of bud development and probably its entry into endo-dormancy, similarly as for non-dwarf vines [14].
\n
\n
\n
3.2.2 Continuous flowering and fruiting (one single growing season)
\n
The microvine has the particularity to develop inflorescences from tendrils along proleptic and sylleptic axes (Figure 4), which result in a continuous flowering and fruiting processes. A gradient of reproductive development stages is thus present simultaneously along the proleptic axis from the differentiation of inflorescences until maturity. This characteristic offers the opportunity to evaluate abiotic or biotic stress impacts on all reproductive stages of development along the proleptic axis simultaneously.
\n
Figure 4.
Vegetative and reproductive development of the ML1 somaclone n°7, a microvine line regenerated from pinot Meunier cl. ENTAV 8 according to the method described by Torregrosa [15]. Top left, longitudinal section of an apex showing the preformation of 7–9 phytomers before emergence of caulinar organs. Upper middle, emergence of young inflorescences just below the apex. We note the very hairy appearance of the apex of the microvine ML1. On the middle, an 8-month-old ML1 microvine displaying all the sequences of the reproductive development from flowering to fruit ripening. Bottom left, a focus on the phytomers carrying bunches shifting from green to ripening stages and the concomitant lignification of the shoot (leaves have been removed for the clearness of the photograph). Top right, section of a winter bud analyzed by tomography. Bottom right, a longitudinal section of a winter bud exhibiting a lateral inflorescence primordium (IP) on the primary bud axis and a secondary preformed vegetative axis on the left side.
\n
Top right, section of a winter bud analyzed by tomography. Bottom right, a longitudinal section of a winter bud exhibiting a lateral inflorescence primordium (IP) on the primary bud axis and a secondary preformed vegetative axis on the left side.
\n
The synchronism between vegetative development and fruiting of the microvine also simplifies the study of their interactions compared to macrovines. The impact of contrasted source/sink balance on fruiting can be easily studied by manipulating shoot or fruit load (number of growing axes and/or number of leaves/inflorescence per axis). The continuous fruiting was found to be stable under standard environmental conditions (25/15°C day/night temperature, VPD 1 kPa, photoperiod 12 h) and when the leaf area to fruit fresh weight was less than 1 m2.kg−1. On the contrary, the capacity of flowering is strongly altered in the presence of abiotic or biotic stresses. High temperature (> 33°C), low radiation levels (PAR < 15 mol.m−2.j−1), or high VPD (>3 kPa) can induce inflorescences abortion and disrupt the continuity of the reproductive gradient along stem axes. The sensitivity of inflorescence development was found higher when the C reserves (starch) were reduced, in particular, in young plants. Thus, although it is possible to obtain fruiting organs from 5-month-old microvine cuttings, it is advisable to use 1-year-old or older plants that are much less susceptible to inflorescence abortion [16]. In experiments conducted in our lab, we obtained successive cycles of fruiting for at least 5 years without repotting.
\n
The size of inflorescences of microvines is smaller (10–50 berries per cluster in average) than that of macrovines [17, 18, 19]. However, flowers and young fruits of the microvine do not display a very high abscission rate as observed in non-dwarf varieties. The development of flowers and berries is identical to non-dwarf vines. Flowering (50% of open flowers) occurs 320°C GDD (growing degree days) after the phytomer emission (i.e., 30 days at 25/15°C), which is comparable to the duration between budburst and flowering in the non-dwarf vines [18]. Ripening (onset of sugar loading) starts at ca. 500°C GDD (i.e., 47 days at 25/15°C) after flowering, and the physiological ripening (when metabolite loading stops) is reached at ca. 900°C GDD (i.e., 80 days at 25/15°C) after flowering or 30 days after the start of sugar loading. This behavior is similar in macrovines [18, 20]. Thus, berries of the ML1 microvine reach a final individual size of 1.2 g, comparable to that of cv. Pinot meunier, from which this line derives. At physiological ripening, berries contain about 0.8 mmol berry-1 of soluble sugars in non-limiting water supply conditions which is similar to other varieties of V. vinifera (Figure 5).
\n
Figure 5.
Spatiotemporal distribution of the reproductive developmental stages from flowering to ripening. On the abscissa, the calendar time in DAF (days after flowering) was recalculated for each phytomer converting the corresponding plastochron index in thermal time and inferred in calendar time with the phyllochron. Kinetics of fresh fruit weight and the contents of major primary metabolites and potassium are presented in quantity per fruit unit.
\n
\n
\n
\n
3.3 Genetics and genomics
\n
\n
3.3.1 Genetic mapping and pre-breeding
\n
The microvine provides different advantages over non-dwarf vines to speed up or facilitate genetics. Since the mutation is transmissible by hybridization and has a codominant effect, it is possible to cross microvines (VvGAI1/Vvgai1) or picovines (Vvgai1/Vvgai1) with non-dwarf genotypes, i.e., without the mutation (VvGAI1/VvGAI1), to create microvine segregating populations. In the first case, 50% of individuals will display the microvine phenotype, while using picovines as parent, 100% of the progeny exhibit a dwarf behavior.
\n
The VvGAI1 gene is located on chromosome n°1, while the QTL determining grapevine flower sex is located on chromosome n°2. That means both loci segregate independently, and it is therefore possible to use female microvines or picovines, which facilitates crosses by avoiding the time-consuming emasculation and reducing the risk of selfing [19]. On the other hand, when a female microvine (f/f) is crossed with a hermaphrodite genotype (H/f, the most common genotype in V. vinifera varieties), the population will be composed of 50% of female plants and 50% of hermaphroditic plants. For instance, by crossing between the PV00C001V0008 [19] and the fleshless berry mutant of the ugni blanc [21], a range of genotypes and phenotypes can be obtained [5].
\n
This progeny is composed of 100% microvines (since the female parent has a Vvgai1/Vvgai1 genotype) and a very small proportion of individuals with both hermaphrodite flowers and pigmented berries. Indeed, these two characters are present at the homozygous recessive state in one parent (f/f and n/n) and in the heterozygous dominant state in the other (H/f and N/n). It should be noted that since ugni blanc is heterozygous at the sex locus (H/f), while the picovine is f/f, selecting hermaphrodite individuals leads to a segregation distortion in the progeny of the genetic traits determined on the chromosome n°2.
\n
As the microvine produces inflorescences as long as vegetative growth is maintained, it becomes possible to cross all year around without being hampered by seasonality. Under standard thermal and photoperiodic conditions (25/15°C day/night temperature, VPD 1 kPa, photoperiod 12 h), the microvine produces two to three new inflorescences per week, which enables to make hybridizations during long periods in repeating the crosses on the same plants. This also reduces the number of plants required for crosses and therefore experimental space while spreading the hybridization effort over selected and potentially long periods.
\n
One to two months after a cross, it is possible to start harvesting seeds [22] to rescue zygotic embryos, which makes possible to establish a population maintained and amplifiable by micropropagation or microcuttings [23]. After a few micropropagation cycles, in vitro plants can be acclimatized to greenhouse conditions, and the first grapes are obtained within 12 months after the crosses. Thus, in less than a year, it is possible to start the study of the characteristics of the fruits and to proceed to new crossings to recover F2 populations. These speed up genetic mapping studies because it becomes possible to link a genotype and a phenotype in either F1 or F2 progenies in a few months instead of several years when using macrovines [23, 24].
\n
Moreover, if a trait can be inherited through such crosses, it is possible to recover non-dwarf phenotypes (GAI1/GAI1) that can be directly proposed as breeding material. Indeed, 50% of the individuals from a cross between a microvine (VvGAI1/Vvgai1) and a macrovine (VvGAI1/VvGAI1) exhibit the same biological properties as conventional non-dwarf varieties. Thus, the microvine can be used both for the identification of QTLs of interest and also to combine or pyramid characters of interest in a pre-breeding perspective.
\n
\n
\n
3.3.2 Functional genomics
\n
The biological properties of the microvine are also of great interest for functional genomics [26]. Indeed, grapevine, as other perennial plants, is a difficult plant model to study the genes regulating the development of reproductive organs. The difficulty comes from its long juvenile period, its discontinuous fructification from winter buds, and the handling of large plants. The genetic transformation of classical varieties [28] requires several years to obtain adult plants and study the phenotypes linked to the ectopic expression of candidate genes.
\n
With microvine, starting from embryogenic tissues compatible to Agrobacterium tumefaciens-mediated transformation (Figure 6), it is possible to recover transgenic fruiting plants in less than 1 year [19]. As for classical genetics, it is then easy to derive F2 lines to establish transgenic loci at homozygous state for further studies. In addition, the microvines have a very good aptitude for transformation by Agrobacterium rhizogenes, allowing to obtain transgenic organs stabilizable in axenic culture in a few weeks [25, 29, 30].
\n
Figure 6.
From competent embryogenic tissues (top left), it is possible to regenerate transgenic plants in a few months and obtain reproductive organs in less than a year. This allows the study of the regulation of flower and fruit development within shorter delays than with the non-dwarf vines. On the right, a microvine line V9 overexpressing the gene VvHB was identified as a major regulator of the development of the flesh in grapevine fruit [27]. Using genetically modified microvines, it is possible to segregate the transgenes in different genotypic configurations or combine them with various other transgenic traits or not.
\n
\n
\n
\n
\n
4. Temporal inference of spatial observations obtained on the proleptic axis
\n
We have tested the possibility of converting spatial observations (along the proleptic axis) into temporal dynamics at a given stage of vegetative or reproductive development.
\n
\n
4.1 Temporal conversion of spatial profiles
\n
Under controlled and stable environment (25/15°C day/night temperature, VPD 1 kPa, photoperiod 12 h), the development of the proleptic axis of the microvine is stable. The phyllochron is constant reaching ca. 24°C. The growing dynamics of leaves (surface) and berries (volume) from continuous fructification was found to be constant at a given level of phytomer, regardless of the date of bud break [20]. The growth durations of leaves and berries (herbaceous phase) are ca. 220°C after the emission of the phytomer and 500°C after flowering, respectively, as mentioned in Section 2.2. The development of these organs is also spatially stable: the dynamics of leaf area and berry volumes (herbaceous phase) for all levels of phytomer are superimposed when they are represented as a function of cumulative thermal time after the emission of the corresponding phytomer.
\n
Based on these outcomes, the conversion of spatial dynamics of leaf and berry development along the stems into time profiles was tested (Figure 7). For this purpose, the positions of the phytomers along the axis were converted into cumulated thermal time after their emission by multiplying their plastochron index (or rank position from the apex) by the phyllochron. The temporal profiles of leaf area and berry volume (green growth phase) resulting from this spatiotemporal conversion are similar to the real temporal profiles obtained at a given level of phytomer [8, 20, 31]. This property makes it possible to reconstruct temporal dynamics of development from a single spatial observation of the axis at a given stage. The flow of biomass or metabolites within the organs and their responses to environmental constraints were then addressed using those calculated temporal profiles (Section 5.1).
\n
Figure 7.
Conversion of leaf and young berry growth data collected from the position along the microvine main shoot (plastochron index) into cumulated thermal time after phytomer emergence.
\n
\n
\n
4.2 Dynamics of inflorescence differentiation within winter buds
\n
The spatiotemporal conversion approach presented above can also be used to characterize the evolution of winter bud development along the proleptic axis of the microvine [12]. Bud development was analyzed on microvines grown under standard environmental conditions (25/15°C day/night temperature, VPD 1 kPa, photoperiod 12 h), as explained in Section 3.2.1. The number of preformed phytomers initiated by primary axes within buds increases linearly as a function of the plastochron index (PI) of the proleptic axis in the non-lignified zone (PI < 25). The temporal dynamics of bud development were calculated from the spatial profiles using the proleptic axis PI x phyllochron. The primary axis of the bud displayed a maximum of six phytomers from IP 25 (lignified zone), i.e., 625°C or 57 days after its initiation (phyllochron of 24°C). A maximum of two inflorescence primordia was observed in this zone. The primordia of the first and second inflorescences, located between the preformed phytomers n°4 and n°6 of the primary axis, were initiated from IP 13 and 26 of the proleptic axis, respectively, corresponding to 325°C (or 30 days) and 650°C (or 60 days) after bud initiation. The timing of inflorescence primordium development in winter buds in non-dwarf vines [32] is similar to our observations on microvines. This pattern of winter bud development parameterized for the microvine can be used to evaluate, and potentially predict, the environmental stress impacts during the season 1 on the fructification potential of the season 2.
\n
\n
\n
4.3 Dynamics of fruit development deriving from neo-formed inflorescence
\n
The primary characterization of fruit development along a microvine axis showed that the microvine berry displays the two classical growth phases as observed for berries of macrovines [32, 33]. Microvine berry growth and metabolite accumulation were analyzed in details [34]. Ten microvines were grown under controlled conditions in a climatic room (30/22°C day/night temperature, photoperiod 14 h, VPD 1 kPa, PAR 400 mmol.m−2 s−1). Sampling was performed when proximal fruits attained physiological maturity and when maximum berry volume was reached. Sampling of the present reproductive organs from fruit set to maturity was performed at the same time for each plant. Analysis of the main berry compounds (malic acid, tartaric acid, glucose, fructose, proline) has been carried out. To normalize the stages of development between plants, the spatiotemporal conversion described above was applied using the individual phyllochron of each plant.
\n
The data presented in Rienth et al. [35, 36] shows that microvine fruit accumulates malic acid during the green growth stage for about 40 days after fruit set, until it ceases when the lag phase (herbaceous plateau), which separates the two growth phases, is reached. At the end of the herbaceous phase, at the 24 hours lasting véraison phase, the degradation of malic acid is triggered simultaneously with the accumulation of sugars and proline, which is often used as an indicator of ripening. These processes proceed throughout the second growth or ripening phase. With regard to tartaric acid, we found that it is also accumulated only during the first growth phase as for macrovines and that its amount remains quasi-constant during the ripening phase. The slight decreases in tartaric observed during ripening might be attributed either to enhanced tartaric precipitations as shown by Rosti et al. [37] or variations of microenvironment depending on bunche rank. At the end of green growth stage, the two major organic acids represent approximately 500 mEq, which is comparable to the acidity of the fruit of macrovines. The accumulation of sugars, triggered from the veraison, continues until the moment when the phloem unloading is slowed down (maximum volume of the fruit). From this point, the amount of sugars per berry remains constant, but the concentration increases due the loss of berry volume during over-ripening.
\n
\n
\n
\n
5. Examples of studies performed with the microvine
\n
\n
5.1 Impacts of temperature on carbon fluxes and fruiting
\n
The impact of elevated temperature on growth and carbon distribution between vegetative and reproductive organs was investigated. Two contrasting thermal regimes with a difference of 8° C (30/20°C vs. 22/12°C day/night temperature) were imposed during a period of 450°C GDD. The VPD was 1 kPa and the PAR 19 mol.m−2.d−1 for the two thermal regimes. The biomass, size, and carbon contents of the leaves, internodes, and berries were characterized from spatial observations at harvest and converted into temporal profiles according to the method described in Section 4. Only the organs that developed during heat treatments, i.e., vegetative phytomers younger than 450°C GDD at harvest and the reproductive phytomers, which were at pre-flowering stage at the beginning of experiments, were retained for analysis. Luchaire et al. [20, 36] have shown that high temperature accelerates the growth and the accumulation of biomass in vegetative organs (leaves and internodes) in thermal time, at the expense of the accumulation of sugars in internodes and the surface area to mass of the leaves (thinner leaves).
\n
Under high temperature, the growth and accumulation of biomass of the fruit slowed down on a thermal time basis. Sugar loading of proximal phytomers (from the post-flowering stage to onset of heat treatment) was also delayed by ca. 400°C GDD at high temperatures. High temperatures increased inflorescence abortion rate (+ 20%) at pre-flowering stages, concomitantly with the beginning of sugar loading in the proximal clusters ripening [20, 36, 38]. These results suggest that high temperature decouples vegetative and reproductive development, increasing the total biomass of vegetative organs while reducing the accumulation of carbon reserves and hampering continuous fruiting.
\n
\n
\n
5.2 Circadian variations of the grape transcriptome
\n
Transcriptomic studies are difficult to run with macrovines grown outdoor because of the seasonality of fruiting and the day-to-day environment fluctuations. Thus, while transcriptomics is a very common approach today to understand the genetic mechanisms regulating grape development, no work has attempted to describe the circadian evolution of the grape transcriptome. The results published by Rienth et al. [39] were the first for a perennial fleshly fruit that addressed this topic. For this experiment microvines were grown in climatic growth chambers [40] under controlled environments (30/20°C day/night temperature, photoperiod 14 h, VPD 1kPA) for 3 months to encompass a complete reproductive cycle from flowering to ripening. When most proximal grapes reached physiological maturity, berry samples from two green and two ripening developmental stages were collected at different periods of the photo and nyctiperiod, and a whole genome transcriptomic analysis was carried out by Nimblegen® Vitis 12x microarrays.
\n
All genes modulated during the day also showed some variation of expression at night, with 1843 genes that are only regulated at night. The detection of this very large number of specifically regulated genes during the night emphasized the importance of the regulatory mechanisms associated with the nocturnal fruit development. The comparison of differentially modulated transcripts between day and night at different stages showed that circadian regulation was very specific to the stage of development with only nine commonly deregulated genes between day and night at all stages. With respect to activated or deactivated functional categories, genes related to photosynthesis appear strongly repressed at night, in particular in young green berry, and several functional categories related to secondary metabolism (phenylalanine) and abiotic stress have shown strong overexpression at night at all developmental stages.
\n
\n
\n
5.3 Effect of temperature on grape development
\n
Until recently, the studies on the effect of temperature on grape development have only been performed using non-dwarf varieties, with the experimental limits associated with this model. Rienth et al. [41, 42] were the first to perform temperature experiments using microvines grown under tightly controlled environmental factors (photoperiod, light intensity, temperature, VPD, water, and mineral supply). This study was carried out with the ML1 microvine applying temperature gradients ranging from 12 to 35°C during 2 h to 4 weeks.
\n
A first series of experiments focused on short-term stress effects (2 h, 35°C) of microvine fruits at different stages between green growth and ripening sampled during day and night. Nimblegen® Vitis 12x microarray assays revealed that a large number of genes (5653) respond to the increase in temperature, at all stages of development (Figure 8). Temperature effect was time and mainly development stage specific, with berries close to veraison being the most reactive to temperature elevation, especially for some categories such as anthocyanin synthesis which was specifically heat repressed at this stage. Furthermore, various genes of secondary metabolism (phenylalanine, anthocyanins) are repressed at the veraison, by high temperature with a larger number of genes regulated during the nocturnal phase.
\n
Figure 8.
Schema of the expression changes induced by temperature elevation for some genes of the central metabolism during the grapevine fruit development.
\n
Long-term thermal stresses (> 30 days) were also experimented using various temperature charts to several stages of grape development, taking into account circadian variations of the transcriptome [41]. In these studies, we used high-throughput transcriptomic analysis through RNA-seq (Illumina technology). A total of 10,788 genes could be detected as a function of stage, temperature regime, and photoperiod. The importance of “heat shock”-type genes with highly variable expression patterns as a function of the duration of the stress, the circadian cycle, and the stage of development of the fruit has been highlighted. The rise in temperature led to an acceleration of fruit growth during the green growth phase. In fruit at the onset of ripening, the temperature increased the respiration of malic acid and delayed the accumulation of sugars and downregulating key genes of the flavonoid pathway. For the first time, a decoupling of sugar accumulation and malic acid respiration during ripening could be observed and related to the change in carbohydrate status of the plant as a function of temperature [9].
\n
A number of genes known to display an induction at veraison and thereafter were confirmed in microvines displaying a remarkably stable expression pattern with respect to temperature (SPS1, sucrose phosphate synthase 1; XET, xyloglucanendotransglucosidase; thaumatin; MRIP, ripening-induced protein1-like precursor (proline-rich cell wall). However, other well-known ripening-induced proteins were induced in the cold in green stage (GRIP3/4, grape ripening-induced protein ¾, ethylene-responsive 1B, putative extensin proline-rich, cell wall chitinase). During the long-term low T° treatment, fruit transcriptomic analyses showed an overexpression of key enzymes linked to both glycolysis (PK, pyruvate kinase) and malic acid synthesis (PEPce, phosphoenolpyruvate carboxylase; MDH, malate dehydrogenase). Temperature variation also impacted posttranscriptional regulation mechanism such as the PPCK (phosphoenol pyruvate carboxylase kinase) which is overexpressed under heat. This gene expression pattern confirmed physiological observations of sugar-acid decoupling and suggests that under cool condition, where the plant energetic status is more comfortable due to lower vegetative growth and cellular respiration rate, malic acid respiration, as a supplemental energy source in the fruit, is not compulsory. In cool climate, the allocation of carbon to the fruit can support glycolysis, malate synthesis, and sugar accumulation into the vacuole. Conversely, under hot climate, cytoplasmic sugars could be limiting when the cell starts to accumulate sugar in the vacuole at the onset of ripening. Thus, the malate would be drained from the vacuole to supply energy through respiration and/or through H+/sugar exchange at the tonoplast.
\n
\n
\n
5.4 Identification of QTLs of development stable under fluctuating environments
\n
Air temperature elevation combined with the shift of all phenological stages to warmer period is causing critical changes on vine yield and grape composition. Plant breeding has the potential to offer new cultivars with stable yield and quality under warmer conditions, but this requires the identification of stable genetic traits. The investigation about the stability of developmental QTLs with regard to abiotic factors is complicated with the non-dwarf varieties, because of its biological properties (long juvenile period, big size of the plants). Most of previous studies were carried out outdoors, in uncontrolled environmental conditions and with a relatively low experimental flow.
\n
Houel et al. [25] reported the first experiment performed with microvines, to identify QTLs of vegetative and reproductive development, testing their stability under fluctuating environments. A F1 mapping population consisting of 129 microvines derived from the PV00C001V0008 x ugni blanc fleshless berry mutant was genotyped using an Illumina® 18 K SNPs chip (single-nucleotide polymorphism). Forty-three vegetative and reproductive traits were phenotyped over four vegetative cycles in the field, and a subset of 22 characters were measured over two climatic chamber culture cycles under two contrasting temperature regimes. Ten stable QTLs were identified for the development and composition of the berry and the leaf area on the parental genetic maps. A new major QTL accounting for up to 44% of variance of the berry weight was identified on the chromosome 7 in the ugni blanc parent. This QTL co-locates with QTLs of number of seeds per berry (accounting for up to 76% of the total variance), QTLs of fruit acidity before maturation (up to 35% of explained variance), and yield components such as the number of clusters and berries per cluster (up to 25% explained variance). In addition, a minor leaf surface QTL was found on the chromosome 4 in the same parent. This study which combined the use of microvine population to boost and facilitate the phenotyping with high-throughput genotyping technologies was innovative in grapevine genetics and also for perennial fruit crops. It allowed the identification of 10 stable QTLs, including the first QTLs of V. vinifera berry acidity detected in an intraspecific cross.
\n
This progeny was also included in a study addressing the diversity for fruit volume, main sugar, and organic acid amounts in V. vinifera [43]. A panel of 33 genotypes, including 12 grapevine varieties and 21 microvine offspring, were characterized. Fruit phenotyping focused on two critical stages of fruit development: the end of green growth phase when organic acidity reaches a maximum and the physiological ripe stage when sugar unloading and water uptake stop. To determine the date of sampling for each critical stage, fruit texture and growth were carefully monitored. Analyses at both stages revealed large phenotypic variation for malic and tartaric acids as well as for sugars and berry size. At ripe stage, fruit fresh weight ranged from 1.04 to 5.25 g and sugar concentration from 751 to 1353 mmol.L−1. The content in organic acids varied both in quantity (from 80 to 361 meq.L−1) and in composition, with malic to tartaric acid ratio ranging from 0.13 to 3.62. At the inter-genotypic level, data showed no link between berry growth and osmoticum accumulation per fruit unit, suggesting that berry water uptake is not only dependent on fruit osmotic potential. The report showed that diversity for berry size, sugar accumulation, and malic to tartaric acid ratio could be exploited through crossbreeding.
\n
These studies which (i) identified genotypes with contrasted fruit composition for compounds controlled by environmental factors and (ii) mapped QTLs of development, including for berry composition, provide interesting prospects to mitigate some adverse effects of climate warming on viticulture.
\n
\n
\n
5.5 Identification of the genetic traits of aromatic character of cabernet sauvignon
\n
Methoxypyrazines are a family of volatile compounds found in many fruits and vegetables and especially in grapes, providing herbaceous flavors (green capsicum aroma) to the wines of some varieties such as Cabernet Sauvignon or sauvignon blanc. While several methoxypyrazine biosynthetic pathways have been proposed, none of the metabolic steps have been genetically confirmed. Dunlevy et al. [24] used a F2 population derived from a F1 microvine obtained by crossing the Cabernet Sauvignon and a picovine. The Cabernet Sauvignon variety is capable of producing the molecule 3-isobutyl-2-methoxypyrazine (IBMP), the major compound associated with capsicum flavors, while the microvine that derives from Pinot Meunier produces very little amount of this compound. In F1 offspring, all individuals produced IBMP, suggesting a homozygote dominant genotypic status for this trait in Cabernet Sauvignon. The phenotyping of the F2 individuals identified 43 lines able to accumulate IBMP, while 21 individuals lacked this compound confirming the dominant homozygous genotype for Cabernet Sauvignon and the homozygous recessive genotype for picovine progenitor.
\n
After genotyping and phenotyping, the entire F2 progeny, a 2.3 Mb locus determining IBMP accumulation in grape berries, was found on chromosome n°3. Of the 261 genes identified in the corresponding QTL, two candidate methyltransferase genes have been identified, VvOMT3 and VvOMT4. Screening a collection of 91 grapevine genotypes differentially accumulating IBMP into the grapes indicated VvOMT3 as the most likely candidate to explain the genetic determinism of the green capsicum trait in grapevine fruits. Moreover, the data suggested that the low level of methoxypyrazines found in most cultivated grape varieties resulted from human selection for mutations in methyltransferase. The markers identifying this locus are valuable tools for the selection of grape varieties that are aromatically typified by IBMP and recalling Cabernet wines.
\n
\n
\n
5.6 Effect of application of exogenous stimulants of fruit metabolism
\n
The microvine plant model which displays unique reproductive organ behavior offers new experimental options for grapevine fruit physiological studies, not only because of the size of the plants which facilitate experimental handling in greenhouse or growth cabinet but also because it is possible to study several developmental stages at once. Taking advantage of the biological properties of the microvine, two studies were recently performed to study the impact of exogenous compound application to the ML1 microvine grapes on the aroma accumulation during ripening. The first study was about the impact of vine-shoot aqueous extracts, which have been proposed as bio-stimulants to be sprayed to the canopy to modify wine aromatic profile. Sanchez-Gomez et al. [44] experimented the effect of vine-shoot extract foliar application on the composition of the grapes at 21 stages of development. The application was carried out from BBCH53 (detached inflorescences) to BBCH85 (berry softening) to reveal stage-specific responses of the accumulation of glycosylated aroma precursors at BBCH89 (ripe stage). Fifty grape sampling time points spreading to 86 days were established and normalized using the cumulative growing degree days parameter. The results confirmed that vine-shoot extract treatment had a positive impact on the accumulation of glycosylated compounds [45], especially aglycones such as alcohols, terpenes, and C13-norisoprenoids, with a higher impact when the treatment was applied at grape ripening stage.
\n
The same approach was carried out to characterize the behavior of glycosylated aroma precursors in microvine fruits after foliar application of guaiacol. Previous outdoor experiments have showed that spraying guaiacol on vines could modify the contents of aroma compounds in grape and grape-derived wines. It was shown that such treatments could increase guaiacol glycoconjugates in leaves, shoots, and fruits of Monastrell variety, where there was a release of aglycone compounds during wine processing. However, the effect of such application and its timing on glycosylated aroma precursor pool remained unstudied. Sanchez-Gomez [46] studied the effect of guaiacol sprays when applied at several fruit developmental stages on glycosylated compound accumulation. The applications were carried out from phenological stage BBCH71 (fruit set) to BBCH85 (berry softening), to reveal stage-specific responses of the accumulation of glycosylated aroma precursors at BBCH89 (ripe stage). Data confirmed that guaiacol is an elicitor of the accumulation of glycosylated aromatic compounds in the microvine fruit, with a higher efficiency of application during ripening stages of the fruits. Geraniol, a terpene compound, exhibited the higher increase increment with up to 50-fold high concentration after guaiacol spraying than in the control.
\n
\n
\n
\n
6. Conclusions
\n
The studies summarized here have shown that at a given phytomer level, the development of the vegetative and reproductive organs of the microvine exhibits comparable kinetics to those of non-dwarf vines grown outdoor. Given its original biological properties (small size, continuous fructification, possibility of inferring temporal observations from spatial data), this model can be used in fundamental studies on vine response to abiotic constraints or on fruit physiology under well-controlled environments. Thus, the microvine has already been used as a model in several scientific experiments on the effect of temperature on the vegetative and reproductive development, on changes in gene expression in grapes, and their plasticity under high temperature. This model has also shown its potential to accelerate conventional and reverse genetic approaches, including the identification of genetic determinants of developmental traits stable under fluctuating thermal conditions or major loci controlling the composition of the grapes. Studies are underway to use this model to study the impact of physical factors (drought, CO2 concentration, temperature, etc.) on the development of the vine and the quality of the grapes but also to develop tools (markers of QTLs, pre-breeding lines pyramiding several agronomic traits of interest) for the selection of new varieties displaying original properties, i.e., traits of adaptation to climate changes.
\n
\n
Acknowledgments
\n
These studies were supported by fundings from the following agencies or institutions: National Research Agency—Genopole (DURAVITIS project ANR-2010-GENM-004-01), Montpellier SupAgro, the departments EA (Environment-Agronomy) and BAP (Plant Biology and Improvement) of INRA, the Poupelain Foundation, the European Eurasia 2 thesis mobility programs, EulaLink, and the Brazilian CNPq scientific cooperation program. Special thanks to Mark Thomas, Pat Corena, Don MacKenzy, and Ian Dry from CSIRO Agriculture (Adelaide) for mentoring and helping during some important steps of these experiments.
\n
\n',keywords:"research tools, microvine, grapevine model, physiology, genetics",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/67039.pdf",chapterXML:"https://mts.intechopen.com/source/xml/67039.xml",downloadPdfUrl:"/chapter/pdf-download/67039",previewPdfUrl:"/chapter/pdf-preview/67039",totalDownloads:1176,totalViews:0,totalCrossrefCites:3,totalDimensionsCites:4,totalAltmetricsMentions:0,introChapter:null,impactScore:1,impactScorePercentile:63,impactScoreQuartile:3,hasAltmetrics:0,dateSubmitted:"November 10th 2018",dateReviewed:"April 2nd 2019",datePrePublished:"May 10th 2019",datePublished:"September 4th 2019",dateFinished:"May 10th 2019",readingETA:"0",abstract:"The microvine is a grapevine somatic variant. The Vvgai1 mutation results in a miniaturization of the vegetative organs of the plant keeping fruit size intact and a systematic conversion of tendrils into inflorescences. The physiological characterization of the vegetative and reproductive development of the microvine makes it possible to infer kinetic data from spatial phenotypes. This biological model allows experiments on vine and grape development in tightly controlled conditions, which greatly accelerate physiology, molecular biology, as well as genetic studies. After introducing the main biological properties of the microvine, main results from various research programs performed with the microvine model will be presented.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/67039",risUrl:"/chapter/ris/67039",book:{id:"8054",slug:"advances-in-grape-and-wine-biotechnology"},signatures:"Anne Pellegrino, Charles Romieu, Markus Rienth and Laurent Torregrosa",authors:[{id:"284414",title:"Prof.",name:"Laurent",middleName:null,surname:"Torregrosa",fullName:"Laurent Torregrosa",slug:"laurent-torregrosa",email:"laurent.torregrosa@supagro.fr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Montpellier SupAgro",institutionURL:null,country:{name:"France"}}},{id:"285872",title:"Dr.",name:"Charles",middleName:null,surname:"Romieu",fullName:"Charles Romieu",slug:"charles-romieu",email:"charles.romieu@inra.fr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"285873",title:"Dr.",name:"Anne",middleName:null,surname:"Pellegrino",fullName:"Anne Pellegrino",slug:"anne-pellegrino",email:"anne.pellegrino@supagro.fr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Montpellier SupAgro",institutionURL:null,country:{name:"France"}}},{id:"298280",title:"Dr.",name:"Markus",middleName:null,surname:"Rienth",fullName:"Markus Rienth",slug:"markus-rienth",email:"markus.rienth@changins.ch",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Biological origin of the microvine",level:"1"},{id:"sec_2_2",title:"2.1 Tissue chimerism and phenotypic consequences",level:"2"},{id:"sec_3_2",title:"2.2 Molecular mechanisms associated with the mutation Vvgai1",level:"2"},{id:"sec_5",title:"3. Application of the use of the microvine",level:"1"},{id:"sec_5_2",title:"3.1 Vegetative development",level:"2"},{id:"sec_6_2",title:"3.2 Reproductive development",level:"2"},{id:"sec_6_3",title:"3.2.1 Fruiting from winter buds (two successive seasons)",level:"3"},{id:"sec_7_3",title:"3.2.2 Continuous flowering and fruiting (one single growing season)",level:"3"},{id:"sec_9_2",title:"3.3 Genetics and genomics",level:"2"},{id:"sec_9_3",title:"3.3.1 Genetic mapping and pre-breeding",level:"3"},{id:"sec_10_3",title:"3.3.2 Functional genomics",level:"3"},{id:"sec_13",title:"4. Temporal inference of spatial observations obtained on the proleptic axis",level:"1"},{id:"sec_13_2",title:"4.1 Temporal conversion of spatial profiles",level:"2"},{id:"sec_14_2",title:"4.2 Dynamics of inflorescence differentiation within winter buds",level:"2"},{id:"sec_15_2",title:"4.3 Dynamics of fruit development deriving from neo-formed inflorescence",level:"2"},{id:"sec_17",title:"5. Examples of studies performed with the microvine",level:"1"},{id:"sec_17_2",title:"5.1 Impacts of temperature on carbon fluxes and fruiting",level:"2"},{id:"sec_18_2",title:"5.2 Circadian variations of the grape transcriptome",level:"2"},{id:"sec_19_2",title:"5.3 Effect of temperature on grape development",level:"2"},{id:"sec_20_2",title:"5.4 Identification of QTLs of development stable under fluctuating environments",level:"2"},{id:"sec_21_2",title:"5.5 Identification of the genetic traits of aromatic character of cabernet sauvignon",level:"2"},{id:"sec_22_2",title:"5.6 Effect of application of exogenous stimulants of fruit metabolism",level:"2"},{id:"sec_24",title:"6. Conclusions",level:"1"},{id:"sec_25",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Torregrosa L. Génétique du développement et de la résistance chez la vigne. In: Carbonneau A, editor. Traité de la vigne: Physiologie, terroir, culture. 2nd ed. Paris, France. EAN13: 9782100726691: Dunod; 2015. pp. 237-262\n'},{id:"B2",body:'Torregrosa L, Fernandez L, Bouquet A, Boursiquot JM, Pelsy F, Martinez-Zapater JM. Origins and consequences of somatic variation in grapevine. In: Kole C, editor. Genetics, Genomics and Breeding of Grapes. Enfield, New Hampshire, USA: Science Publishers; 2010. pp. 68-92. DOI: 10.1201/b10948-4\n'},{id:"B3",body:'Franks T, Botta R, Thomas MR. Chimerism in grapevines: Implications for cultivar identity, ancestry and genetic improvement. Theoretical and Applied Genetics. 2002;104:192-199\n'},{id:"B4",body:'Boss PK, Thomas MR. Association of dwarfism and floral induction with a grape ‘green revolution’ mutation. Nature. 2000;416:847-850\n'},{id:"B5",body:'Torregrosa L, Rienth M, Luchaire N, Alcantara Novelli Dias F, Bigard A, Chatbanyong R, et al. The microvine, a biological model, very versatile and efficient to boost grapevine research in physiology and genetics. In: 39th OIV meeting. Bento Gonzalvez, Brazil; 24-28 October 2016\n'},{id:"B6",body:'Carmona MJ, Chaïb J, Martınez-Zapater JM, Thomas MR. A molecular genetic perspective of reproductive development in grapevine. Journal of Experimental Botany. 2008;59:2579-2596. DOI: 10.1093/jxb/ern160\n'},{id:"B7",body:'Coombe BJ. Effects of growth retardants on Vitis vinifera L. Vitis. 1967;6:278-287\n'},{id:"B8",body:'Luchaire N, Rienth M, Nehe A, Torregrosa L, Romieu C, Muller B, et al. The Microvine: An ecophysiological model for grapevine. In: 18th Int. Symp. GiESCO, 7-11 July, Porto, Portugal. 2013\n'},{id:"B9",body:'Romieu C, Lecourieux D, Rienth M, Luchaire N, Chatbanyong R, Shahood R, et al. Temperature impacts on grapevine physiology and development at both plant and organ levels. In: Xth ISGPB, 13-15 june, Verona, Italy\n'},{id:"B10",body:'Lebon E, Pellegrino A, Tardieu F, Lecoeur J. Shoot development in grapevine (Vitis vinifera) is affected by the modular branching pattern of the stem and intra-and-inter shoot trophic competition. Annals of Botany. 2004;93:263-274\n'},{id:"B11",body:'Larabell CA, Nugent KA. Imaging cellular architecture with X-rays. Current Opinion in Structural Biology. 2010;20:623-631. DOI: 10.1016/j.sbi.2010.08.008\n'},{id:"B12",body:'Alcântara Novelli Dias F, Torregrosa L, Luchaire N, Houel C, Pellegrino A. The microvine, a model to study the effect of temperature on the grapevine latent bud. OenoOne (in revision)\n'},{id:"B13",body:'Carolus M. Description des stades du développement des primordia inflorescentiels durant l\'organogenèse des bourgeons latents de la vigne (Vitis vinifera L. cv Merlot). Connaissance de la Vigne et du Vin. 1971;2:163-173\n'},{id:"B14",body:'Bernard AC. Contribution à l\'étude de la biologie et des méristèmes des vitacées [Thèse d\'Etat de l\'Univ]. France: Montpellier; 1980. 216 p\n'},{id:"B15",body:'Torregrosa L. A simple and efficient method to obtain stable embryogenic cultures from anthers of Vitis vinifera L. Vitis; 1998;37:91-92\n'},{id:"B16",body:'Luchaire N, Torregrosa L, Gibon Y, Rienth M, Romieu C, Turc O, et al. Yield reduction under high temperature is paired with a low carbon status in microvine. In: Xth ISGPB meeting, Verona, Italy. 13-15 June 2016\n'},{id:"B17",body:'Pratt C. Reproductive anatomy in cultivated grapes—A review. American Journal of Enology and Viticulture. 1971;22:92-109\n'},{id:"B18",body:'Mullins MG, Bouquet A, Williams LE. Biology of the Grapevine. UK: Cambridge University Press; 1992. 252 p\n'},{id:"B19",body:'Chaib J, Torregrosa L, Mackenzie D, Corena P, Bouquet A, Thomas MR. The microvine—A model system for rapid forward and reverse genetics of grapevines. The Plant Journal. 2010;61:1083-1092\n'},{id:"B20",body:'Luchaire N, Rienth M, Romieu C, Nehe A, Chatbanyong R, Houel C, et al. Pellegrino A Microvine Fruitfulness Loss under Elevated Temperature Is Conditioned by the Initial Plant Vigor and Carbohydrate Pool. In: Exploring the Microvine developmental and physiological adaptation mechanisms to elevated temperature: characterization of the impact on carbon balance and its involvement in early reproductive development failure. PhD of Montpellier SupAgro. 2015. www.theses.fr/2015NSAM0011\n'},{id:"B21",body:'Fernandez L, Romieu C, Moing A, Bouquet A, Maucourt M, Thomas MR, et al. The grapevine fleshless berry mutation: A unique genotype to investigate differences between fleshy and non-fleshy fruit. Plant Physiology. 2006;140:537-547\n'},{id:"B22",body:'Chatbanyong R, Torregrosa L. A highly efficient embryo rescue protocol to recover a progeny from of the microvine. Vitis. 2015;54:41-46\n'},{id:"B23",body:'Bouquet A, Torregrosa L. Micropropagation of grapevine (Vitis spp.). In: Jain SM, Ishii K, editors. Micropropagation of Woody Trees and Fruits. Dordrecht, The Netherlands: Kluwer Academic Pub; 2003. pp. 3119-3352\n'},{id:"B24",body:'Dunlevy JD, Dennis EG, Soole KL, Perkins MV, Davies C, Bos PK. A methyltransferase essential for the methoxypyrazine derived flavour of wine. The Plant Journal. 2013;75:606-617. DOI: 10.1111/tpj.12224\n'},{id:"B25",body:'Houel C, Chatbanyong R, Doligez A, Rienth M, Foria S, Luchaire N, et al. Identification of stable QTLs for vegetative and reproductive traits in the microvine (Vitis vinifera L.) using the 18K Infinium chip. BMC Plant Biology. 2015;15:205. DOI: DOI 10.1186/s12870-015-0588-0\n'},{id:"B26",body:'Vidal JR, Gomez C, Cutanda MC, Shrestha B, Bouquet A, Thomas MR, et al. Use of gene tranfer technology for functional studies in grapevine. Australian Journal of Grape and Wine Research. 2010;16:138-151\n'},{id:"B27",body:'Fernandez L, Torregrosa L, Terrier N, Sreekantan L, Grimplet J, Davies C, et al. Identification of genes associated with flesh morphogenesis in grapevine (V. vinifera L.) berry. Plant Molecular Biology. 2007;63:307-323\n'},{id:"B28",body:'Torregrosa L, Vialet S, Adivéze A, Iocco-Corena P, Thomas MR. Grapevine (Vitis vinifera L.). In: Wang K, editor. Agrobacterium Protocols. 3nd ed. New York, USA: Springer Science + Business Media; 2015. pp. 177-194\n'},{id:"B29",body:'Cutanda-Perez MC, Ageorges A, Gomez C, Vialet S, Romieu C, Torregrosa L. Ectopic expression of the VlmybA1 in grapevine activates a narrow set of genes involved in anthocyanin synthesis and transport. Plant Molecular Biology. 2009;69:633-648\n'},{id:"B30",body:'Huang YF, Vialet S, Guiraud JL, Torregrosa L, Bertrand Y, Cheynier V, et al. A negative MYB regulator of proanthocyanidin accumulation, identified through expression quantitative locus mapping in grape berry. The New Phytologist. 2013;203:795-809. DOI: 10.1111/nph.12557\n'},{id:"B31",body:'Luchaire N, Rienth M, Romieu C, Torregrosa L, Gibon Y, Turc O, et al. Role of plant carbon status in yield components responses to elevated temperatures in microvine. In: 19th Int. Symp. GiESCO, 1-5 June, Gruissan, France. 2015\n'},{id:"B32",body:'Vasconcelos MC, Greven M, Winefield CS, Trought MCT, Raw V. The flowering process of Vitis vinifera: A review. American Journal of Enology and Viticulture. 2009;60:4\n'},{id:"B33",body:'Conde C, Silva P, Fontes N, Dias ACP, Tavares RM, Sousa MJ, et al. Biochemical changes throughout grape berry development and fruit and wine quality. Food. 2007;1:1-22\n'},{id:"B34",body:'Rienth M, Jaquerod A, Romieu C, Torregrosa L. La microvigne : un outil novateur pour la recherche et pour l’enseignement de la biologie de la vigne. Revue Suisse de Viticulture, Arboriculture, Horticulture. 2016;48:132-135\n'},{id:"B35",body:'Rienth M, Romieu C, Gregan R, Walsh C, Torregrosa L, Kelly M. Validation and application of an improved method for the rapid determination of proline in grape berries. Journal of Agricultural and Food Chemistry. 2014;62:3384-3389. DOI: 10.1021/jf404627\n'},{id:"B36",body:'Luchaire N, Mallent M, Bediee A, Muller B, Torregrosa L, Pellegrino A. The carbon balance of microvine plants is decreased under elevated temperature. In: EPSO Congress, 22-26 June, Dublin, Ireland. 2014\n'},{id:"B37",body:'Rösti J, Schumann M, Cleroux M, Lorenzini F, Zufferey V, Rienth M. Effect of drying on tartaric acid and malic acid in shiraz and merlot berries. Australian Journal of Grape and Wine Research. 2018;24:421-429. DOI: 10.1111/ajgw.12344\n'},{id:"B38",body:'Muller B, Luchaire N, Oury V, Tardieu F, Gibon Y, Torregrosa L, et al. Is failure of reproductive development under water or heat stress due to C shortage? In: SEB Symp., Brighton, 3-7 July, England. 2016\n'},{id:"B39",body:'Rienth M, Torregrosa L, Kelly M, Luchaire N, Grimplet J, Romieu C. The transcriptomic control of berry development is more important at night than at day. PLoS One. 2014;9:e88844\n'},{id:"B40",body:'Rienth R, Dauzat M, Pellegrino A, Lopez G, Torregrosa L, Romieu C. First observations of the microvine development under 100% LED (light emitting diodes) illumination. Vitis. 2012;51:167-173\n'},{id:"B41",body:'Rienth M, Torregrosa L, Luchaire N, Chatbanyong R, Lecourieux D, Kelly M, et al. Day and night heat stress trigger different transcriptomic responses in green and ripening grapevine (Vitis vinifera) fruit. BMC Plant Biology. 2014. DOI: 10.1186/1471-2229-14-108\n'},{id:"B42",body:'Rienth M, Torregrosa L, Gauthier S, Ardisson M, Brillouet JL, Romieu C. Temperature desynchronizes sugar and organic acid metabolism in ripening grapevine fruits and remodels its transcriptome. BMC Plant Biology. 2016;16:164. DOI: DOI 10.1186/s12870-016-0850-0\n'},{id:"B43",body:'Bigard A, Berhe DT, Maoddi E, Sire Y, Boursiquot JM, Ojeda H, et al. Vitis vinifera L. fruit diversity to breed varieties anticipating climate changes. Frontiers in Plant Science. 2018;9:455. DOI: 10.3389/fpls.2018.00455\n'},{id:"B44",body:'Sanchez-Gomez R, Torregrosa L, Zalacain A, Ojeda O, Bouckenooghe V, Schneider R, et al. The microvine, a plant model to study the effect of vine-shoot extract on the accumulation of glycosylated aroma precursors in grapes. Journal of the Science of Food and Agriculture. 2018;98:3031-3040. DOI: 10.1002/jsfa.8802\n'},{id:"B45",body:'Alem H, Rigou P, Schneider R, Ojeda H, Torregrosa L. Impact of agronomic practices on grape aroma composition: A review. Journal of the Science of Food and Agriculture. 2018;98:975-985. DOI: 10.1002/jsfa.9327\n'},{id:"B46",body:'Sánchez-Gómez R, Torregrosa L, Zalacain A, Ojeda H, Bouckenooghed V, Schneider R, et al. Behavior of glycosylated aroma precursors in microvine fruits after guaiacol foliar application. Scientia Horticulturae. 2019;246:3031-3040. DOI: 10.1016/j.scienta.2018.11.068\n'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Anne Pellegrino",address:null,affiliation:'
LEPSE, Montpellier University, CIRAD, INRA, Montpellier SupAgro, France
AGAP, Montpellier University, CIRAD, INRA, Montpellier SupAgro, France
'}],corrections:null},book:{id:"8054",type:"book",title:"Advances in Grape and Wine Biotechnology",subtitle:null,fullTitle:"Advances in Grape and Wine Biotechnology",slug:"advances-in-grape-and-wine-biotechnology",publishedDate:"September 4th 2019",bookSignature:"Antonio Morata and Iris Loira",coverURL:"https://cdn.intechopen.com/books/images_new/8054.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-78984-613-3",printIsbn:"978-1-78984-612-6",pdfIsbn:"978-1-78985-699-6",reviewType:"peer-reviewed",numberOfWosCitations:39,isAvailableForWebshopOrdering:!0,editors:[{id:"180952",title:"Prof.",name:"Antonio",middleName:null,surname:"Morata",slug:"antonio-morata",fullName:"Antonio Morata"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"186423",title:"Dr.",name:"Iris",middleName:null,surname:"Loira",slug:"iris-loira",fullName:"Iris Loira"},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1411"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"67039",type:"chapter",title:"The Microvine: A Versatile Plant Model to Boost Grapevine Studies in Physiology and Genetics",slug:"the-microvine-a-versatile-plant-model-to-boost-grapevine-studies-in-physiology-and-genetics",totalDownloads:1176,totalCrossrefCites:3,signatures:"Anne Pellegrino, Charles Romieu, Markus Rienth and Laurent Torregrosa",reviewType:"peer-reviewed",authors:[{id:"284414",title:"Prof.",name:"Laurent",middleName:null,surname:"Torregrosa",fullName:"Laurent Torregrosa",slug:"laurent-torregrosa"},{id:"285872",title:"Dr.",name:"Charles",middleName:null,surname:"Romieu",fullName:"Charles Romieu",slug:"charles-romieu"},{id:"285873",title:"Dr.",name:"Anne",middleName:null,surname:"Pellegrino",fullName:"Anne Pellegrino",slug:"anne-pellegrino"},{id:"298280",title:"Dr.",name:"Markus",middleName:null,surname:"Rienth",fullName:"Markus Rienth",slug:"markus-rienth"}]},{id:"67444",type:"chapter",title:"Somatic Variation and Cultivar Innovation in Grapevine",slug:"somatic-variation-and-cultivar-innovation-in-grapevine",totalDownloads:1067,totalCrossrefCites:4,signatures:"Pablo Carbonell-Bejerano, Carolina Royo, Nuria Mauri, Javier Ibáñez and José Miguel Martínez Zapater",reviewType:"peer-reviewed",authors:[{id:"287215",title:"Prof.",name:"Jose Miguel",middleName:null,surname:"Martinez Zapater",fullName:"Jose Miguel Martinez Zapater",slug:"jose-miguel-martinez-zapater"},{id:"287226",title:"Dr.",name:"Javier",middleName:null,surname:"Ibáñez",fullName:"Javier Ibáñez",slug:"javier-ibanez"},{id:"300441",title:"Dr.",name:"Pablo",middleName:null,surname:"Carbonell-Bejerano",fullName:"Pablo Carbonell-Bejerano",slug:"pablo-carbonell-bejerano"},{id:"300442",title:"Dr.",name:"Carolina",middleName:null,surname:"Royo",fullName:"Carolina Royo",slug:"carolina-royo"},{id:"300444",title:"Dr.",name:"Nuria",middleName:null,surname:"Mauri",fullName:"Nuria Mauri",slug:"nuria-mauri"}]},{id:"66454",type:"chapter",title:"Reconstruction of Parental SSR Haplotypes from a Single Grape Seed",slug:"reconstruction-of-parental-ssr-haplotypes-from-a-single-grape-seed",totalDownloads:804,totalCrossrefCites:0,signatures:"Gizella Győrffyné Jahnke, Zóra Annamária Nagy, Csaba Németh, Gyöngyi Knolmajerné Szigeti and János Májer",reviewType:"peer-reviewed",authors:[{id:"112875",title:"Ph.D.",name:"Gizella",middleName:null,surname:"Győrffyné Dr. Jahnke",fullName:"Gizella Győrffyné Dr. Jahnke",slug:"gizella-gyorffyne-dr.-jahnke"},{id:"292790",title:"Dr.",name:"Zóra Annamária",middleName:null,surname:"Nagy",fullName:"Zóra Annamária Nagy",slug:"zora-annamaria-nagy"},{id:"292791",title:"MSc.",name:"Csaba",middleName:null,surname:"Németh",fullName:"Csaba Németh",slug:"csaba-nemeth"},{id:"292792",title:"MSc.",name:"Gyöngyi",middleName:null,surname:"Knolmajerné Szgeti",fullName:"Gyöngyi Knolmajerné Szgeti",slug:"gyongyi-knolmajerne-szgeti"},{id:"292793",title:"Dr.",name:"János",middleName:null,surname:"Májer",fullName:"János Májer",slug:"janos-majer"}]},{id:"66481",type:"chapter",title:"Ampelographic and Genetic Characterization of Montenegrin Grapevine Varieties",slug:"ampelographic-and-genetic-characterization-of-montenegrin-grapevine-varieties",totalDownloads:1015,totalCrossrefCites:1,signatures:"Vesna Maraš",reviewType:"peer-reviewed",authors:[{id:"154745",title:"Dr.",name:"Vesna",middleName:null,surname:"Maras",fullName:"Vesna Maras",slug:"vesna-maras"}]},{id:"67833",type:"chapter",title:"Effects of Vine Water Status on Yield Components, Vegetative Response and Must and Wine Composition",slug:"effects-of-vine-water-status-on-yield-components-vegetative-response-and-must-and-wine-composition",totalDownloads:1161,totalCrossrefCites:5,signatures:"Pilar Baeza, Pedro Junquera, Emilio Peiro, José Ramón Lissarrague, David Uriarte and Mar Vilanova",reviewType:"peer-reviewed",authors:[{id:"222515",title:"Dr.",name:"David",middleName:null,surname:"Uriarte",fullName:"David Uriarte",slug:"david-uriarte"},{id:"285912",title:"Dr.Ing.",name:"Pilar",middleName:null,surname:"Baeza",fullName:"Pilar Baeza",slug:"pilar-baeza"},{id:"285917",title:"Dr.",name:"Mar",middleName:null,surname:"Vilanova",fullName:"Mar Vilanova",slug:"mar-vilanova"},{id:"285919",title:"Dr.",name:"Pedro",middleName:null,surname:"Junquera",fullName:"Pedro Junquera",slug:"pedro-junquera"},{id:"285922",title:"Dr.",name:"Jose Ramón",middleName:null,surname:"Lissarrague",fullName:"Jose Ramón Lissarrague",slug:"jose-ramon-lissarrague"}]},{id:"66619",type:"chapter",title:"Contribution of the Microbiome as a Tool for Estimating Wine’s Fermentation Output and Authentication",slug:"contribution-of-the-microbiome-as-a-tool-for-estimating-wine-s-fermentation-output-and-authenticatio",totalDownloads:1126,totalCrossrefCites:5,signatures:"Dimitrios A. Anagnostopoulos, Eleni Kamilari and Dimitrios Tsaltas",reviewType:"peer-reviewed",authors:[{id:"180885",title:"Associate Prof.",name:"Dimitris",middleName:null,surname:"Tsaltas",fullName:"Dimitris Tsaltas",slug:"dimitris-tsaltas"},{id:"203761",title:"MSc.",name:"Dimitris",middleName:null,surname:"Anagnostopoulos",fullName:"Dimitris Anagnostopoulos",slug:"dimitris-anagnostopoulos"},{id:"271801",title:"Ms.",name:"Elena",middleName:null,surname:"Kamilari",fullName:"Elena Kamilari",slug:"elena-kamilari"}]},{id:"65971",type:"chapter",title:"Biodiversity of Saccharomyces cerevisiae Yeasts in Spontaneous Alcoholic Fermentations: Typical Cellar or Zone Strains?",slug:"biodiversity-of-em-saccharomyces-cerevisiae-em-yeasts-in-spontaneous-alcoholic-fermentations-typical",totalDownloads:879,totalCrossrefCites:2,signatures:"Pilar Santamaría, Rosa López, Maria del Patrocinio Garijo, Rocío Escribano, Lucía González-Arenzana, Isabel López-Alfaro and Ana Rosa Gutiérrez",reviewType:"peer-reviewed",authors:[{id:"287071",title:"Prof.",name:"Ana Rosa",middleName:null,surname:"Gutiérrez Viguera",fullName:"Ana Rosa Gutiérrez Viguera",slug:"ana-rosa-gutierrez-viguera"},{id:"287073",title:"Dr.",name:"Pilar",middleName:null,surname:"Santamaría",fullName:"Pilar Santamaría",slug:"pilar-santamaria"},{id:"287074",title:"Dr.",name:"Rosa",middleName:null,surname:"López",fullName:"Rosa López",slug:"rosa-lopez"},{id:"287075",title:"Dr.",name:"Maria Del Patrocinio",middleName:null,surname:"Garijo",fullName:"Maria Del Patrocinio Garijo",slug:"maria-del-patrocinio-garijo"},{id:"287076",title:"Dr.",name:"Lucia",middleName:null,surname:"González-Arenzana",fullName:"Lucia González-Arenzana",slug:"lucia-gonzalez-arenzana"},{id:"287077",title:"Dr.",name:"Isabel",middleName:null,surname:"López-Alfaro",fullName:"Isabel López-Alfaro",slug:"isabel-lopez-alfaro"},{id:"292579",title:"Mrs.",name:"Rocío",middleName:null,surname:"Escribano-Viana",fullName:"Rocío Escribano-Viana",slug:"rocio-escribano-viana"}]},{id:"67363",type:"chapter",title:"Yeast Strain Optimization for Enological Applications",slug:"yeast-strain-optimization-for-enological-applications",totalDownloads:1055,totalCrossrefCites:1,signatures:"David José Moreira Ferreira and Jessica Noble",reviewType:"peer-reviewed",authors:[{id:"301168",title:"Dr.",name:"Pepe",middleName:null,surname:"Heras",fullName:"Pepe Heras",slug:"pepe-heras"}]},{id:"67572",type:"chapter",title:"Strategies to Improve the Freshness in Wines from Warm Areas",slug:"strategies-to-improve-the-freshness-in-wines-from-warm-areas",totalDownloads:941,totalCrossrefCites:4,signatures:"Antonio Morata, Iris Loira, Juan Manuel del Fresno, Carlos Escott, María Antonia Bañuelos, Wendu Tesfaye, Carmen González, Felipe Palomero and Jose Antonio Suárez Lepe",reviewType:"peer-reviewed",authors:[{id:"180952",title:"Prof.",name:"Antonio",middleName:null,surname:"Morata",fullName:"Antonio Morata",slug:"antonio-morata"},{id:"186423",title:"Dr.",name:"Iris",middleName:null,surname:"Loira",fullName:"Iris Loira",slug:"iris-loira"},{id:"186424",title:"Prof.",name:"Jose Antonio",middleName:null,surname:"Suárez Lepe",fullName:"Jose Antonio Suárez Lepe",slug:"jose-antonio-suarez-lepe"},{id:"201384",title:"Prof.",name:"Carmen",middleName:null,surname:"González",fullName:"Carmen González",slug:"carmen-gonzalez"},{id:"203775",title:"Prof.",name:"María Antonia",middleName:null,surname:"Bañuelos",fullName:"María Antonia Bañuelos",slug:"maria-antonia-banuelos"},{id:"203776",title:"Dr.",name:"Carlos",middleName:null,surname:"Escott",fullName:"Carlos Escott",slug:"carlos-escott"},{id:"287144",title:"Dr.",name:"Wendu",middleName:null,surname:"Tesfaye",fullName:"Wendu Tesfaye",slug:"wendu-tesfaye"},{id:"300828",title:"Dr.",name:"Juan Manuel",middleName:null,surname:"Del Fresno",fullName:"Juan Manuel Del Fresno",slug:"juan-manuel-del-fresno"},{id:"300833",title:"Dr.",name:"Felipe",middleName:null,surname:"Palomero",fullName:"Felipe Palomero",slug:"felipe-palomero"}]},{id:"67144",type:"chapter",title:"Yeast from Distillery Plants: A New Approach",slug:"yeast-from-distillery-plants-a-new-approach",totalDownloads:1416,totalCrossrefCites:0,signatures:"Beatriz García-Béjar, Pilar Fernández-Pacheco, Ana Briones and María Arévalo-Villena",reviewType:"peer-reviewed",authors:[{id:"62660",title:"Dr.",name:"Ana",middleName:null,surname:"Briones",fullName:"Ana Briones",slug:"ana-briones"},{id:"289388",title:"Prof.",name:"María",middleName:null,surname:"Arévalo-Villena",fullName:"María Arévalo-Villena",slug:"maria-arevalo-villena"},{id:"289389",title:"Mrs.",name:"Beatriz",middleName:null,surname:"García-Béjar",fullName:"Beatriz García-Béjar",slug:"beatriz-garcia-bejar"},{id:"289928",title:"Mrs.",name:"Pilar",middleName:null,surname:"Fernández-Pacheco",fullName:"Pilar Fernández-Pacheco",slug:"pilar-fernandez-pacheco"}]},{id:"66611",type:"chapter",title:"Improvement of the Bioactive Profile in Wines and Its Incidence on Human Health: Technological Strategies",slug:"improvement-of-the-bioactive-profile-in-wines-and-its-incidence-on-human-health-technological-strate",totalDownloads:980,totalCrossrefCites:2,signatures:"Ricardo Vejarano, Angie Gil-Calderón, Valeria Díaz-Silva and Jackeline León-Vargas",reviewType:"peer-reviewed",authors:[{id:"286187",title:"Dr.",name:"Ricardo",middleName:null,surname:"Vejarano",fullName:"Ricardo Vejarano",slug:"ricardo-vejarano"},{id:"287141",title:"Prof.",name:"Jackeline",middleName:null,surname:"León-Vargas",fullName:"Jackeline León-Vargas",slug:"jackeline-leon-vargas"},{id:"287142",title:"Ms.",name:"Angie",middleName:null,surname:"Gil-Calderón",fullName:"Angie Gil-Calderón",slug:"angie-gil-calderon"},{id:"287143",title:"Ms.",name:"Valeria",middleName:null,surname:"Díaz-Silva",fullName:"Valeria Díaz-Silva",slug:"valeria-diaz-silva"}]},{id:"66657",type:"chapter",title:"Main Operating Conditions That Can Influence the Evolution of Wines during Long-Term Storage",slug:"main-operating-conditions-that-can-influence-the-evolution-of-wines-during-long-term-storage",totalDownloads:1001,totalCrossrefCites:0,signatures:"Francesca Venturi, Chiara Sanmartin, Isabella Taglieri, Giuseppe Ferroni, Mike Frank Quartacci, Cristina Sgherri, Xiaoguo Ying, Gianpaolo Andrich and Angela Zinnai",reviewType:"peer-reviewed",authors:[{id:"286979",title:"Ph.D.",name:"Francesca",middleName:null,surname:"Venturi",fullName:"Francesca Venturi",slug:"francesca-venturi"},{id:"287234",title:"Prof.",name:"Angela",middleName:null,surname:"Zinnai",fullName:"Angela Zinnai",slug:"angela-zinnai"},{id:"287235",title:"Ph.D.",name:"Chiara",middleName:null,surname:"Sanmartin",fullName:"Chiara Sanmartin",slug:"chiara-sanmartin"},{id:"287236",title:"Dr.",name:"Isabella",middleName:null,surname:"Taglieri",fullName:"Isabella Taglieri",slug:"isabella-taglieri"},{id:"293193",title:"Dr.",name:"Giuseppe",middleName:null,surname:"Ferroni",fullName:"Giuseppe Ferroni",slug:"giuseppe-ferroni"},{id:"293194",title:"Prof.",name:"Mike Frank",middleName:null,surname:"Quartacci",fullName:"Mike Frank Quartacci",slug:"mike-frank-quartacci"},{id:"293195",title:"Dr.",name:"Cristina",middleName:null,surname:"Sgherri",fullName:"Cristina Sgherri",slug:"cristina-sgherri"},{id:"293196",title:"Dr.",name:"Xiaoguo",middleName:null,surname:"Ying",fullName:"Xiaoguo Ying",slug:"xiaoguo-ying"},{id:"293197",title:"Prof.",name:"Gianpaolo",middleName:null,surname:"Andrich",fullName:"Gianpaolo Andrich",slug:"gianpaolo-andrich"}]},{id:"66663",type:"chapter",title:"Air Depleted and Solvent Impregnated Cork Powder as a New Natural and Sustainable Wine Fining Agent",slug:"air-depleted-and-solvent-impregnated-cork-powder-as-a-new-natural-and-sustainable-wine-fining-agent",totalDownloads:846,totalCrossrefCites:2,signatures:"Luís Filipe da Mota Ribeiro, Maria Fernanda Gil Cosme Martins and Fernando Hermínio Ferreira Milheiro Nunes",reviewType:"peer-reviewed",authors:[{id:"186819",title:"Prof.",name:"Fernanda",middleName:null,surname:"Cosme",fullName:"Fernanda Cosme",slug:"fernanda-cosme"},{id:"283748",title:"Ph.D.",name:"Luís",middleName:null,surname:"Filipe-Ribeiro",fullName:"Luís Filipe-Ribeiro",slug:"luis-filipe-ribeiro"},{id:"283750",title:"Prof.",name:"Fernando",middleName:null,surname:"M. Nunes",fullName:"Fernando M. Nunes",slug:"fernando-m.-nunes"}]},{id:"67132",type:"chapter",title:"Alcohol Reduction by Physical Methods",slug:"alcohol-reduction-by-physical-methods",totalDownloads:1004,totalCrossrefCites:0,signatures:"Matthias Schmitt and Monika Christmann",reviewType:"peer-reviewed",authors:[{id:"287696",title:"Dr.",name:"Matthias",middleName:null,surname:"Schmitt",fullName:"Matthias Schmitt",slug:"matthias-schmitt"},{id:"289487",title:"Prof.",name:"Monika",middleName:null,surname:"Christmann",fullName:"Monika Christmann",slug:"monika-christmann"}]},{id:"67760",type:"chapter",title:"Production and Marketing of Low-Alcohol Wine",slug:"production-and-marketing-of-low-alcohol-wine",totalDownloads:1334,totalCrossrefCites:3,signatures:"Tamara Bucher, Kristine Deroover and Creina Stockley",reviewType:"peer-reviewed",authors:[{id:"289140",title:"Dr.",name:"Creina",middleName:null,surname:"Stockley",fullName:"Creina Stockley",slug:"creina-stockley"},{id:"289141",title:"Dr.",name:"Tamara",middleName:null,surname:"Bucher",fullName:"Tamara Bucher",slug:"tamara-bucher"},{id:"289142",title:"Ms.",name:"Kristine",middleName:null,surname:"Deroover",fullName:"Kristine Deroover",slug:"kristine-deroover"}]}]},relatedBooks:[{type:"book",id:"10901",title:"Grapes and Wine",subtitle:null,isOpenForSubmission:!1,hash:"5d7f2aa74874444bc6986e613ccebd7c",slug:"grapes-and-wine",bookSignature:"Antonio Morata, Iris Loira and Carmen González",coverURL:"https://cdn.intechopen.com/books/images_new/10901.jpg",editedByType:"Edited by",editors:[{id:"180952",title:"Prof.",name:"Antonio",surname:"Morata",slug:"antonio-morata",fullName:"Antonio Morata"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"77973",title:"Integrated Pest Management of Lobesia botrana with Microorganism in Vineyards: An Alternative for Clean Grapes Production",slug:"integrated-pest-management-of-em-lobesia-botrana-em-with-microorganism-in-vineyards-an-alternative-f",signatures:"Fabiola Altimira, Nancy Vitta and Eduardo Tapia",authors:[{id:"354960",title:"Dr.",name:"Eduardo",middleName:null,surname:"Tapia",fullName:"Eduardo Tapia",slug:"eduardo-tapia"},{id:"422086",title:"Dr.",name:"Fabiola",middleName:null,surname:"Altimira",fullName:"Fabiola Altimira",slug:"fabiola-altimira"},{id:"422087",title:"MSc.",name:"Nancy",middleName:null,surname:"Vitta",fullName:"Nancy Vitta",slug:"nancy-vitta"}]},{id:"77616",title:"Management of Pesticides from Vineyard to Wines: Focus on Wine Safety and Pesticides Removal by Emerging Technologies",slug:"management-of-pesticides-from-vineyard-to-wines-focus-on-wine-safety-and-pesticides-removal-by-emerg",signatures:"Georgiana-Diana Dumitriu (Gabur), Carmen Teodosiu and Valeriu V. Cotea",authors:[{id:"353192",title:"Dr.",name:"Georgiana-Diana",middleName:null,surname:"Dumitriu (Gabur)",fullName:"Georgiana-Diana Dumitriu (Gabur)",slug:"georgiana-diana-dumitriu-(gabur)"},{id:"421058",title:"Prof.",name:"Carmen",middleName:null,surname:"Teodosiu",fullName:"Carmen Teodosiu",slug:"carmen-teodosiu"},{id:"421064",title:"Dr.",name:"Valeriu V.",middleName:null,surname:"Cotea",fullName:"Valeriu V. Cotea",slug:"valeriu-v.-cotea"}]},{id:"78970",title:"Alternatives to CU Applications in Viticulture: How R&D Projects Can Provide Applied Solutions, Helping to Establish Legislation Limits",slug:"alternatives-to-cu-applications-in-viticulture-how-r-d-projects-can-provide-applied-solutions-helpin",signatures:"Mario De La Fuente, David Fernández-Calviño, Bartosz Tylkowski, Josep M. Montornes, Magdalena Olkiewicz, Ruth Pereira, Anabela Cachada, Tito Caffi, Giorgia Fedele and Felicidad De Herralde",authors:[{id:"125032",title:"Dr.",name:"Tito",middleName:null,surname:"Caffi",fullName:"Tito Caffi",slug:"tito-caffi"},{id:"355892",title:"Dr.Ing.",name:"Mario",middleName:null,surname:"de la Fuente",fullName:"Mario de la Fuente",slug:"mario-de-la-fuente"},{id:"417758",title:"Dr.",name:"Felicidad",middleName:null,surname:"De Herralde",fullName:"Felicidad De Herralde",slug:"felicidad-de-herralde"},{id:"427872",title:"Prof.",name:"David",middleName:null,surname:"Fernández-Calviño",fullName:"David Fernández-Calviño",slug:"david-fernandez-calvino"},{id:"427873",title:"Mr.",name:"Bartosz",middleName:null,surname:"Tylkowski",fullName:"Bartosz Tylkowski",slug:"bartosz-tylkowski"},{id:"427874",title:"Dr.",name:"Josep M.",middleName:"M.",surname:"Montornes",fullName:"Josep M. Montornes",slug:"josep-m.-montornes"},{id:"427875",title:"Mrs.",name:"Magdalena",middleName:null,surname:"Olkiewicz",fullName:"Magdalena Olkiewicz",slug:"magdalena-olkiewicz"},{id:"427877",title:"Prof.",name:"Ruth",middleName:null,surname:"Pereira",fullName:"Ruth Pereira",slug:"ruth-pereira"},{id:"427878",title:"Prof.",name:"Anabela",middleName:null,surname:"Cachada",fullName:"Anabela Cachada",slug:"anabela-cachada"},{id:"427902",title:"Mrs.",name:"Giorgia",middleName:null,surname:"Fedele",fullName:"Giorgia Fedele",slug:"giorgia-fedele"}]},{id:"78275",title:"Artificial Intelligence and Big Data Analytics in Vineyards: A Review",slug:"artificial-intelligence-and-big-data-analytics-in-vineyards-a-review",signatures:"Nathaniel K. Newlands",authors:[{id:"356321",title:"Dr.",name:"Nathaniel K.",middleName:"K.",surname:"Newlands",fullName:"Nathaniel K. Newlands",slug:"nathaniel-k.-newlands"}]},{id:"77752",title:"Biological Characteristics of Native Grape Cultivars of Crimean Region and Availability of Their Use in Breeding",slug:"biological-characteristics-of-native-grape-cultivars-of-crimean-region-and-availability-of-their-use",signatures:"Svetlana Levchenko, Irina Vasylyk, Vladimir Volynkin, Vladimir Likhovskoy and Alla Polulyakh",authors:[{id:"252760",title:"Dr.",name:"Vladimir",middleName:null,surname:"Volynkin",fullName:"Vladimir Volynkin",slug:"vladimir-volynkin"},{id:"253335",title:"Dr.",name:"Svetlana",middleName:null,surname:"Levchenko",fullName:"Svetlana Levchenko",slug:"svetlana-levchenko"},{id:"253336",title:"Dr.",name:"Irina",middleName:null,surname:"Vasylyk",fullName:"Irina Vasylyk",slug:"irina-vasylyk"},{id:"313760",title:"Dr.",name:"Vladimir",middleName:null,surname:"Likhovskoy",fullName:"Vladimir Likhovskoy",slug:"vladimir-likhovskoy"},{id:"355118",title:"Dr.",name:"Alla",middleName:null,surname:"Polulyakh",fullName:"Alla Polulyakh",slug:"alla-polulyakh"}]},{id:"77669",title:"Romanian Organic and Conventional Red Grapes Vineyards as Potential Sources of High Value-Added Products, in a Circular Economy Approach",slug:"romanian-organic-and-conventional-red-grapes-vineyards-as-potential-sources-of-high-value-added-prod",signatures:"Cristina Mihaela Nicolescu, Marius Bumbac, Cristiana Radulescu, Lavinia Claudia Buruleanu, Radu Lucian Olteanu, Laura Monica Gorghiu, Gabriela Teodorescu and Carmen Georgeta Holban",authors:[{id:"139924",title:"Prof.",name:"Lavinia Claudia",middleName:null,surname:"Buruleanu",fullName:"Lavinia Claudia Buruleanu",slug:"lavinia-claudia-buruleanu"},{id:"271462",title:"Prof.",name:"Cristiana",middleName:null,surname:"Radulescu",fullName:"Cristiana Radulescu",slug:"cristiana-radulescu"},{id:"271532",title:"Dr.",name:"Cristina Mihaela",middleName:null,surname:"Nicolescu",fullName:"Cristina Mihaela Nicolescu",slug:"cristina-mihaela-nicolescu"},{id:"271533",title:"Dr.",name:"Radu Lucian",middleName:null,surname:"Olteanu",fullName:"Radu Lucian Olteanu",slug:"radu-lucian-olteanu"},{id:"271534",title:"Dr.",name:"Marius",middleName:null,surname:"Bumbac",fullName:"Marius Bumbac",slug:"marius-bumbac"},{id:"356828",title:"Dr.",name:"Laura Monica",middleName:null,surname:"Gorghiu",fullName:"Laura Monica Gorghiu",slug:"laura-monica-gorghiu"},{id:"356830",title:"Dr.",name:"Gabriela",middleName:null,surname:"Teodorescu",fullName:"Gabriela Teodorescu",slug:"gabriela-teodorescu"},{id:"356831",title:"Mrs.",name:"Carmen Georgeta",middleName:null,surname:"Holban",fullName:"Carmen Georgeta Holban",slug:"carmen-georgeta-holban"}]},{id:"78620",title:"Table Grapes: There Is More to Vitiviniculture than Wine…",slug:"table-grapes-there-is-more-to-vitiviniculture-than-wine-",signatures:"Ana Cristina Agulheiro-Santos, Marta Laranjo and Sara Ricardo-Rodrigues",authors:[{id:"95242",title:"Dr.",name:"Marta",middleName:null,surname:"Laranjo",fullName:"Marta Laranjo",slug:"marta-laranjo"},{id:"292171",title:"Prof.",name:"Ana Cristina",middleName:null,surname:"Agulheiro-Santos",fullName:"Ana Cristina Agulheiro-Santos",slug:"ana-cristina-agulheiro-santos"},{id:"355883",title:"MSc.",name:"Sara",middleName:null,surname:"Ricardo-Rodrigues",fullName:"Sara Ricardo-Rodrigues",slug:"sara-ricardo-rodrigues"}]},{id:"77834",title:"An Overview on Saccharomyces cerevisiae Indigenous Strains Selection Methods",slug:"an-overview-on-em-saccharomyces-cerevisiae-em-indigenous-strains-selection-methods",signatures:"Laura Pulcini, Elisa Gamalero, Antonella Costantini, Enrico Tommaso Vaudano, Christos Tsolakis and Emilia Garcia-Moruno",authors:[{id:"414840",title:"Ph.D. Student",name:"Laura",middleName:null,surname:"Pulcini",fullName:"Laura Pulcini",slug:"laura-pulcini"},{id:"422492",title:"Prof.",name:"Elisa",middleName:null,surname:"Gamalero",fullName:"Elisa Gamalero",slug:"elisa-gamalero"},{id:"422494",title:"Dr.",name:"Antonella",middleName:null,surname:"Costantini",fullName:"Antonella Costantini",slug:"antonella-costantini"},{id:"422496",title:"Dr.",name:"Enrico Tommaso",middleName:null,surname:"Vaudano",fullName:"Enrico Tommaso Vaudano",slug:"enrico-tommaso-vaudano"},{id:"422498",title:"Dr.",name:"Christos",middleName:null,surname:"Tsolakis",fullName:"Christos Tsolakis",slug:"christos-tsolakis"},{id:"422499",title:"Dr.",name:"Emilia",middleName:null,surname:"Garcia-Moruno",fullName:"Emilia Garcia-Moruno",slug:"emilia-garcia-moruno"}]},{id:"77189",title:"Genetically Modified Yeasts in Wine Biotechnology",slug:"genetically-modified-yeasts-in-wine-biotechnology",signatures:"Cecilia Picazo, Víctor Garrigós, Emilia Matallana and Agustín Aranda",authors:[{id:"35057",title:"Prof.",name:"Emilia",middleName:null,surname:"Matallana",fullName:"Emilia Matallana",slug:"emilia-matallana"},{id:"353382",title:"Dr.",name:"Agustín",middleName:null,surname:"Aranda",fullName:"Agustín Aranda",slug:"agustin-aranda"},{id:"353622",title:"Dr.",name:"Cecilia",middleName:null,surname:"Picazo",fullName:"Cecilia Picazo",slug:"cecilia-picazo"},{id:"353623",title:"Dr.",name:"Víctor",middleName:null,surname:"Garrigós",fullName:"Víctor Garrigós",slug:"victor-garrigos"}]},{id:"79305",title:"Determining Glucose Isomerase Activity in Different Wine Environments to Prevent Sluggish or Stuck Fermentations by Using Glucose Isomerase",slug:"determining-glucose-isomerase-activity-in-different-wine-environments-to-prevent-sluggish-or-stuck-f",signatures:"Nahide Seray Kahraman and Haluk Hamamci",authors:[{id:"356870",title:"Prof.",name:"Haluk",middleName:null,surname:"Hamamci",fullName:"Haluk Hamamci",slug:"haluk-hamamci"},{id:"435862",title:"M.Sc.",name:"Nahide",middleName:"Seray",surname:"Seray Kahraman",fullName:"Nahide Seray Kahraman",slug:"nahide-seray-kahraman"}]},{id:"78993",title:"pH Control and Aroma Improvement Using the Non-Saccharomyces Lachancea thermotolerans and Hanseniaspora spp. Yeasts to Improve Wine Freshness in Warm Areas",slug:"ph-control-and-aroma-improvement-using-the-non-em-saccharomyces-lachancea-thermotolerans-em-and-em-h",signatures:"Antonio Morata, Carlos Escott, Iris Loira, Juan Manuel Del Fresno, Cristian Vaquero, María Antonia Bañuelos, Felipe Palomero, Carmen López and Carmen González",authors:[{id:"180952",title:"Prof.",name:"Antonio",middleName:null,surname:"Morata",fullName:"Antonio Morata",slug:"antonio-morata"},{id:"186423",title:"Dr.",name:"Iris",middleName:null,surname:"Loira",fullName:"Iris Loira",slug:"iris-loira"},{id:"201384",title:"Prof.",name:"Carmen",middleName:null,surname:"González",fullName:"Carmen González",slug:"carmen-gonzalez"},{id:"203775",title:"Prof.",name:"María Antonia",middleName:null,surname:"Bañuelos",fullName:"María Antonia Bañuelos",slug:"maria-antonia-banuelos"},{id:"203776",title:"Dr.",name:"Carlos",middleName:null,surname:"Escott",fullName:"Carlos Escott",slug:"carlos-escott"},{id:"300828",title:"Dr.",name:"Juan Manuel",middleName:null,surname:"Del Fresno",fullName:"Juan Manuel Del Fresno",slug:"juan-manuel-del-fresno"},{id:"300833",title:"Dr.",name:"Felipe",middleName:null,surname:"Palomero",fullName:"Felipe Palomero",slug:"felipe-palomero"},{id:"357315",title:"MSc.",name:"Cristian",middleName:null,surname:"Vaquero",fullName:"Cristian Vaquero",slug:"cristian-vaquero"},{id:"428683",title:"Prof.",name:"Carmen",middleName:null,surname:"López",fullName:"Carmen López",slug:"carmen-lopez"}]},{id:"79110",title:"Microbial Decontamination by Pulsed Electric Fields (PEF) in Winemaking",slug:"microbial-decontamination-by-pulsed-electric-fields-pef-in-winemaking",signatures:"Carlota Delso, Alejandro Berzosa, Jorge Sanz, Ignacio Álvarez and Javier Raso",authors:[{id:"311454",title:"Dr.",name:"Ignacio",middleName:null,surname:"Alvarez",fullName:"Ignacio Alvarez",slug:"ignacio-alvarez"},{id:"311462",title:"Prof.",name:"Javier",middleName:null,surname:"Raso",fullName:"Javier Raso",slug:"javier-raso"},{id:"437477",title:"Dr.",name:"Carlota",middleName:null,surname:"Delso",fullName:"Carlota Delso",slug:"carlota-delso"},{id:"437478",title:"MSc.",name:"Alejandro",middleName:null,surname:"Berzosa",fullName:"Alejandro Berzosa",slug:"alejandro-berzosa"},{id:"437479",title:"MSc.",name:"Jorge",middleName:null,surname:"Sanz",fullName:"Jorge Sanz",slug:"jorge-sanz"}]},{id:"77989",title:"Influence of Skin-Contact Treatment on Aroma Profile of Malvasia Aromatica Wines in D.O. “Vinos de Madrid”",slug:"influence-of-skin-contact-treatment-on-aroma-profile-of-malvasia-em-aromatica-em-wines-in-d-o-vinos-",signatures:"Julia Crespo, Valeria Romero, Margarita García, Teresa Arroyo and Juan M. Cabellos",authors:[{id:"182064",title:"Dr.",name:"Teresa",middleName:null,surname:"Arroyo",fullName:"Teresa Arroyo",slug:"teresa-arroyo"},{id:"182068",title:"Ms.",name:"Margarita",middleName:null,surname:"García",fullName:"Margarita García",slug:"margarita-garcia"},{id:"356422",title:"Dr.",name:"Juan Mariano",middleName:null,surname:"Cabellos",fullName:"Juan Mariano Cabellos",slug:"juan-mariano-cabellos"},{id:"356615",title:"Dr.",name:"Julia",middleName:null,surname:"Crespo",fullName:"Julia Crespo",slug:"julia-crespo"},{id:"420922",title:"Ms.",name:"Valeria",middleName:null,surname:"Romero",fullName:"Valeria Romero",slug:"valeria-romero"}]},{id:"78229",title:"Winemaking in Cold Regions with Buried Viticulture in China",slug:"winemaking-in-cold-regions-with-buried-viticulture-in-china",signatures:"Ma Tengzhen and Han Shunyu",authors:[{id:"355837",title:"Dr.",name:"Ma",middleName:null,surname:"Tengzhen",fullName:"Ma Tengzhen",slug:"ma-tengzhen"},{id:"428394",title:"Dr.",name:"Han",middleName:null,surname:"Shunyu",fullName:"Han Shunyu",slug:"han-shunyu"}]},{id:"79978",title:"White Wine Protein Instability: Origin, Preventive and Removal Strategies",slug:"white-wine-protein-instability-origin-preventive-and-removal-strategies",signatures:"Luís Filipe-Ribeiro, Fernanda Cosme and Fernando M. Nunes",authors:[{id:"186819",title:"Prof.",name:"Fernanda",middleName:null,surname:"Cosme",fullName:"Fernanda Cosme",slug:"fernanda-cosme"},{id:"283748",title:"Ph.D.",name:"Luís",middleName:null,surname:"Filipe-Ribeiro",fullName:"Luís Filipe-Ribeiro",slug:"luis-filipe-ribeiro"},{id:"283750",title:"Prof.",name:"Fernando",middleName:null,surname:"M. Nunes",fullName:"Fernando M. Nunes",slug:"fernando-m.-nunes"}]},{id:"78151",title:"The Light Struck Taste of Wines",slug:"the-light-struck-taste-of-wines",signatures:"Ana María Mislata, Miquel Puxeu, Monserrat Mestres and Raúl Ferrer-Gallego",authors:[{id:"290229",title:"Ms.",name:"Ana",middleName:null,surname:"María Mislata",fullName:"Ana María Mislata",slug:"ana-maria-mislata"},{id:"290230",title:"Dr.",name:"Miquel",middleName:null,surname:"Puxeu",fullName:"Miquel Puxeu",slug:"miquel-puxeu"},{id:"353129",title:"Dr.",name:"Raúl",middleName:null,surname:"Ferrer-Gallego",fullName:"Raúl Ferrer-Gallego",slug:"raul-ferrer-gallego"},{id:"423524",title:"Prof.",name:"Montserrat",middleName:null,surname:"Mestres",fullName:"Montserrat Mestres",slug:"montserrat-mestres"}]},{id:"81659",title:"State-of-the-Art Knowledge about 2,4,6-Trichloroanisole (TCA) and Strategies to Avoid Cork Taint in Wine",slug:"state-of-the-art-knowledge-about-2-4-6-trichloroanisole-tca-and-strategies-to-avoid-em-cork-taint-em",signatures:"Andrii Tarasov, Miguel Cabral, Christophe Loisel, Paulo Lopes, Christoph Schuessler and Rainer Jung",authors:[{id:"452109",title:"Dr.",name:"Andrii",middleName:null,surname:"Tarasov",fullName:"Andrii Tarasov",slug:"andrii-tarasov"},{id:"452236",title:"Dr.",name:"Miguel",middleName:null,surname:"Cabral",fullName:"Miguel Cabral",slug:"miguel-cabral"},{id:"452237",title:"Dr.",name:"Christophe",middleName:null,surname:"Loisel",fullName:"Christophe Loisel",slug:"christophe-loisel"},{id:"452238",title:"Dr.",name:"Paulo",middleName:null,surname:"Lopes",fullName:"Paulo Lopes",slug:"paulo-lopes"},{id:"452239",title:"Dr.",name:"Christoph",middleName:null,surname:"Schüßler",fullName:"Christoph Schüßler",slug:"christoph-schussler"},{id:"470332",title:"Dr.",name:"Rainer",middleName:null,surname:"Jung",fullName:"Rainer Jung",slug:"rainer-jung"}]},{id:"79500",title:"New Insights about the Influence of Yeasts Autolysis on Sparkling Wines Composition and Quality",slug:"new-insights-about-the-influence-of-yeasts-autolysis-on-sparkling-wines-composition-and-quality",signatures:"Pere Pons-Mercadé, Pol Giménez, Glòria Vilomara, Marta Conde, Antoni Cantos, Nicolas Rozès, Sergi Ferrer, Joan Miquel Canals and Fernando Zamora",authors:[{id:"429540",title:"Prof.",name:"Fernando",middleName:null,surname:"Zamora",fullName:"Fernando Zamora",slug:"fernando-zamora"},{id:"439843",title:"Dr.",name:"Pere",middleName:null,surname:"Pons-Mercadé",fullName:"Pere Pons-Mercadé",slug:"pere-pons-mercade"},{id:"439844",title:"Mr.",name:"Pol",middleName:null,surname:"Giménez",fullName:"Pol Giménez",slug:"pol-gimenez"},{id:"439845",title:"Ms.",name:"Glòria",middleName:null,surname:"Vilomara",fullName:"Glòria Vilomara",slug:"gloria-vilomara"},{id:"439846",title:"Ms.",name:"Marta",middleName:null,surname:"Conde",fullName:"Marta Conde",slug:"marta-conde"},{id:"439847",title:"Mr.",name:"Antoni",middleName:null,surname:"Cantos",fullName:"Antoni Cantos",slug:"antoni-cantos"},{id:"439848",title:"Dr.",name:"Nicolas",middleName:null,surname:"Rozès",fullName:"Nicolas Rozès",slug:"nicolas-rozes"},{id:"439849",title:"Dr.",name:"Sergi",middleName:null,surname:"Ferrer",fullName:"Sergi Ferrer",slug:"sergi-ferrer"},{id:"439851",title:"Dr.",name:"Joan",middleName:null,surname:"Miquel Canals",fullName:"Joan Miquel Canals",slug:"joan-miquel-canals"}]}]}],publishedBooks:[{type:"book",id:"6077",title:"Grapes and Wines",subtitle:"Advances in Production, Processing, Analysis and Valorization",isOpenForSubmission:!1,hash:"61fe601d66e441800c8ed9503f86280f",slug:"grapes-and-wines-advances-in-production-processing-analysis-and-valorization",bookSignature:"António Manuel Jordão and Fernanda Cosme",coverURL:"https://cdn.intechopen.com/books/images_new/6077.jpg",editedByType:"Edited by",editors:[{id:"186821",title:"Prof.",name:"António",surname:"M. Jordão",slug:"antonio-m.-jordao",fullName:"António M. Jordão"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8054",title:"Advances in Grape and Wine Biotechnology",subtitle:null,isOpenForSubmission:!1,hash:"f6b9b3b3d887ed9e7c0ad09cb07edf2b",slug:"advances-in-grape-and-wine-biotechnology",bookSignature:"Antonio Morata and Iris Loira",coverURL:"https://cdn.intechopen.com/books/images_new/8054.jpg",editedByType:"Edited by",editors:[{id:"180952",title:"Prof.",name:"Antonio",surname:"Morata",slug:"antonio-morata",fullName:"Antonio Morata"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10901",title:"Grapes and Wine",subtitle:null,isOpenForSubmission:!1,hash:"5d7f2aa74874444bc6986e613ccebd7c",slug:"grapes-and-wine",bookSignature:"Antonio Morata, Iris Loira and Carmen González",coverURL:"https://cdn.intechopen.com/books/images_new/10901.jpg",editedByType:"Edited by",editors:[{id:"180952",title:"Prof.",name:"Antonio",surname:"Morata",slug:"antonio-morata",fullName:"Antonio Morata"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],publishedBooksByAuthor:[{type:"book",id:"8054",title:"Advances in Grape and Wine Biotechnology",subtitle:null,isOpenForSubmission:!1,hash:"f6b9b3b3d887ed9e7c0ad09cb07edf2b",slug:"advances-in-grape-and-wine-biotechnology",bookSignature:"Antonio Morata and Iris Loira",coverURL:"https://cdn.intechopen.com/books/images_new/8054.jpg",editedByType:"Edited by",editors:[{id:"180952",title:"Prof.",name:"Antonio",surname:"Morata",slug:"antonio-morata",fullName:"Antonio Morata"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},onlineFirst:{chapter:{type:"chapter",id:"74781",title:"The Anti-Cancer Effects of Anti-Parasite Drug Ivermectin in Ovarian Cancer",doi:"10.5772/intechopen.95556",slug:"the-anti-cancer-effects-of-anti-parasite-drug-ivermectin-in-ovarian-cancer",body:'
1. Introduction
Ivermectin is chemically derived from avermectin that was discovered and isolated from soil in Jan by Omura in 1973 [1]. It was approved by Federal Drug Administration (FDA) to use for anti-parasite drug in 1987, which has significantly improved global public health as an antiparasite medicine [2]. In 2015, its discovers Drs. Omura and Campbell earned the Nobel Prize in physiology or medicine [2]. Recent years, many studies have demonstrated that ivermectin has extensive roles in anti-bacteria, anti-virus, and anticancer, except for its anti-parasite effects [3, 4, 5]. Its anticancer effect has been shown by many in vitro and in vivo experiments in multiple cancers, including ovarian cancer, breast cancer, triple-negative breast cancer, cervical cancer, lung cancer, gastric cancer, colon cancer, glioblastoma, melanoma, and leukemia [4, 6], with a wide safe and clinically reachable drug concentration of anticancer according to its pharmacokinetic range in treatment of a parasite-infected patient [7]. It offers a promising opportunity to develop a new anticancer drug via drug repositioning of this existing compound with confirmed clinical safety [8].
Ovarian cancer, a very common cancer with high mortality and poor survival in women [9, 10], are involved in multiple signaling pathway network changes [11, 12]. Many intracellular molecules and signaling pathways would be the targets of ivermectin [13]. Ivermectin have shown a potential addition role for ovarian cancer treatment. For example, ivermectin can improve the chemosensitivity of overran cancer via targeting Akt/mTOR signaling pathway [14], and can inhibit PAK1-dependent growth of ovarian cancer cells via blocking the oncogenic kinase PAK1 [15]. Ivermectin also acts as a PAK1 inhibitor to induce autophagy in breast cancer [16]. Ivermectin can enhance p53 expression and cytochrome C release, and reduce the expression levels of CDK2, CDK4, CDK6, Bcl-2, cyclin E, and cyclin D1 in glioblastoma, those promoted the cancer cell apoptosis [17]. Ivermectin can inhibit cancer cell proliferation via decreasing YAP1 protein expression in the Hippo pathway [18]. Ivermectin represses WNT-TCF pathway in WNT-TCF-dependent disease [19]. Ivermectin can promote TFE3 (Ser321) dephosphorylation to block the binding between TFE3 and 14-3-3, and induce TFE3 accumulation in the nucleus of human melanoma cells [20]. Moreover, ivermectin also affects other signaling pathway network in human cancers, including oxidative stress, mitochondrial dysfunction, angiogenesis, epithelial-mesenchymal transition, drug resistance, and stemness in tumor [6]. Thereby, ivermectin demonstrates the potential therapeutic efficiency in multiple malignant tumors.
This book chapter discussed the anti-cancer effects of ivermectin on ovarian cancer in the following aspects: (i) ivermectin inhibited cell proliferation and growth, blocked cell cycle progression, and promoted cell apoptosis in ovarian cancer [4, 21]; (ii) ivermectin inhibited ovarian cancer growth through molecular networks to target the key molecules in energy metabolism pathways, including glycolysis, Kreb’s cycle, oxidative phosphorylation, and lactate shuttle pathways [21]; (iii) Integrated omics revealed that ivermectin mediated lncRNA-EIF4A3-mRNA axes in ovarian cancer to exert its anticancer capability [4, 13]; and (iv) lasso regression identified the prognostic model of ivermectin-related three-lncRNA signature (ZNRF3-AS1, SOS1-IT1, and LINC00565) that is significantly related to overall survival and clinicopathologic characteristics of ovarian cancers [4].
2. Methods
2.1 Ovarian cancer cell biological behaviors affected by ivermectin
The normal ovarian cells IOSE80 and ovarian cancer cells TOV-21 and SKOV3 were treated with ivermectin to measure ivermectin-mediated ovarian cancer cell biological behavior changes. (i) IOSE80, TOV-21G, and SKOV3 were treated with ivermectin (0–60 μM) for 24 h, followed by the use of CCK8 to measure the IC50 of ivermectin in each cell. (ii) TOV-21G and SKOV3 were treated with ivermectin (0 μM, 10 μM, 20 μM, and 30 μM) for 24 h, followed by the use of EdU assay to measure DNA synthesis in each cell. (iii) TOV-21G and SKOV3 were treated with ivermectin (0 μM, 10 μM, 20 μM, and 30 μM) for 48 h, followed by clonogenic assay to measure the in vitro effects of ivermectin in each cell. (iv)TOV-21G and SKOV3 were treated with ivermectin (0 μM, 10 μM, 20 μM, and 30 μM) for 24 h, followed by flow cytometry to measure cell cycle and cell apoptosis changes in each cell. (v) When A2780 and TOV-21G seeded in 6-well plates were grown to approximately 90% confluency, followed by the use of 10-μl pipette tip to make an artificial wound, and then treated with ivermectin (0 μM, 10 μM, 20 μM, and 30 μM) for 24 h, and measure the wound healing. The relative percentage of wound healing = (the width of wound at 0 h − the width of wound at 24 h)/the width of wound at 0 h. The detailed procedure was described previously [4, 21].
2.2 Ivermectin-mediated pathway network predicted by ingenuity pathway analysis
The classical pathway network analysis software, Ingenuity Pathway Analysis (IPA) (http://www.ingenuity.com) [5] was used to predict ivermectin-related potential target molecules in three energy metabolism pathways. For this analysis, ivermectin and target genes in three energy metabolism pathways are all input into the IPA tool. The detailed procedure was described previously [21]. The predicted ivermectin-mediated targets in energy metabolism pathways were the basis for further experiment verification.
2.3 Ivermectin-mediated target molecule changes in energy metabolism pathways verified at the mRNA and protein levels
TOV-21G and SKOV3 were treated with ivermectin (0 μM, 10 μM, 20 μM, and 30 μM) for 24 h, and 48 h. At the 24 h time point, the RNAs were extracted for quantitative real-time PCR (qRT-PCR) analysis to measure the mRNA expression of target molecules (CS, PDHB, IDH2, IDH3A, IDH3B, PFKP, PKM, MCT1, MCT4, OGDHL, ND2, ND5, CYTB, and UQCRH) in energy metabolism pathways. At the 48 h time point, the proteins were extracted for Western blot analysis to measure the protein expression of target molecules (CS, PDHB, IDH2, IDH3A, IDH3B, PFKP, PKM, MCT1, MCT4, OGDHL, ND2, ND5, CYTB, and UQCRH) in energy metabolism pathways. The detailed procedure was described previously [21].
2.4 Ivermectin-mediated proteome changes in ovarian cancer identified by SILAC-based quantitative proteomics
SILAC (stable isotope labeling with amino acids in cell culture)-based quantitative proteomics was used to identified differentially expressed proteins in ovarian cancer TOV-21G treated with and without 20 μM ivermectin [13]. The identified differentially expressed proteins were used for molecular network and signaling pathway analyses to obtain ivermectin-related signaling pathway networks [13]. The detailed procedure was described previously [13].
2.5 Transcriptomics and clinical data of ovarian cancer patients extracted from TCGA database
Level 3 RNA-seq V2 transcriptomics data of 411 OC patients were extracted from The Cancer Genome Atlas (TCGA) data portal (http://cancergenome.nih.gov/) with the corresponding clinical data, including cancer status (with tumor or tumor-free), clinical stage (stages IIA, IIB, IIC, IIIA, IIIB, IIIC, and IV), neoplasm histologic grade (G1, G2, G3, G4, and GX), anatomic neoplasm subdivision (right, left, and bilateral), age at initial pathologic diagnosis (aged from 30 to 87), lymphatic invasion (yes/no), primary therapy outcome success (complete remission/response, partial remission/response, progressive disease, and stable disease), additional radiation therapy (yes/no), survival time (days), tumor residual disease (no macroscopic disease, 1–10 mm, 11–20 mm, and > 20 mm), survival status (0 = alive, and 1 = dead), and PANCAN (Pan-Cancer Atlas). TANRIC (http://ibl.mdanderson.org/tanric/design/basic/index.html) was used for survival analysis of lncRNAs in ovarian cancer. The large-scale CLIP-Seq data with starBasev 2.0 (http://starbase.sysu.edu.cn/mirCircRNA.php) was used to predict the EIF4A3-binding mRNAs. The Kaplan–Meier method relative to the log-rank test was used for survival analysis of mRNAs in ovarian cancers. Statistical significance was set as p value <0.05. GenCLiP 3 (http://ci.smu.edu.cn/genclip3/analysis.php) was used for pathway enrichment analysis of the association of EIF4A3-binding mRNAs and patient survival rates. The detailed procedure was described previously [4].
2.6 Ivermectin-related lncRNAs verified with qRT-PCR
TRizol® Reagent (Invitrogen, CA, USA) was used to extract total RNAs of cells TOV21G and A2780 treated with different concentration of ivermectin (0 μM, 10 μM, 20 μM, and 30 μM). The extracted total RNAs was reversely transcribed into cDNAs for qRT-PCR analysis of each lncRNA expression, including KIF9-AS1, HCG15, PDCD4-AS1, ZNRF3-AS1, ZNF674-AS1, LINC00565, SOS1-IT1, WWTR1-AS1, PLCH1-AS1, LINC00517, SNHG3, STARD13-IT1, AL109767.1, HOXC-AS3, LEMD1-AS1, and LBX2-AS1. Beta-actin was set as internal control for qRT-PCR analysis. The detailed procedure was described previously [4].
2.7 LncRNA-based prognostic signature optimized with lasso regression for ovarian cancers
Lasso regression means least absolute shrinkage and selection operator regression, which was used to optimize and construct lncRNA-based prognostic signature, and the glmnet R package was used to measure the association between survival risk and lncRNA signature in ovarian cancers. Moreover, univariate and multivariate Cox regression, and Kaplan–Meier method were used to identify overall survival-related clinical characteristics described above in ovarian cancers to confirm the established lncRNA-based prognostic model. The detailed procedure was described previously [4].
2.8 Statistical significance
Benjamini–Hochberg (FDR) for multiple testing was used to correct the p values of IPA, GO, and KEGG analyses. Student’s t test was used for qRT-PCR and western blot data (p < 0.05) with data expression of mean ± SD (n = 3).
3. Results and discussion
3.1 Effects of ivermectin on biological behaviors of ovarian cancers
First, CCK8 experiments were used to measure cell proliferation changes between ovarian cancer cells (SKOV3; TOV-21G) and control cells (IOSE80), treated with and without ivermectin (Figure 1). Each type of cells was significantly inhibited by ivermectin with a dose-dependent relationship. The IC50 (half maximal inhibitory concentration) was 29.46 μM for IOSE80 cells, 20.85 μM for SKOV3, and 22.54 μM for TOV-21G (Figure 1A). The IC50 of ovarian cancers were significantly lower than the normal controls. Further, 20 μM ivermectin - slightly lower than IC50 – can effectively inhibit ovarian cancer proliferation (Figure 1B and C) [21]. For in vivo human trial, the highest FDA-approved ivermectin dose was 200 μg/kg for human use in anti-parasite; however, a study on 68 human subjects found that the dose up to 2,000 μg/kg still worked well without CNS toxicity. The mean area under the curve ratios for the 30 and 60 mg doses were 1.24 and 1.40, indicating a minimal accumulation of ivermectin [5, 22]. These data demonstrate that ivermectin was a well-tolerated safe drug. Second, EdU cell proliferation experiments also confirmed that ivermectin significantly suppressed cell proliferation of ovarian cancers with a time-dependent relationship (Figure 1D-F) [21]. Third, Clonogenic survival experiments confirmed that ivermectin effectively inhibited the formation of cell clones with a time-dependent relationship (Figure 1G-H) [21]. Moreover, 10 μM ivermectin cannot effectively inhibit cell proliferation of ovarian cancers, 30 μM ivermectin caused cell death of ovarian cancers, and 20 μM ivermectin was a suitable dose to significantly suppress growth and proliferation of ovarian cancer cells.
Figure 1.
Ivermectin suppressed ovarian cancer cell proliferation in vitro, measured with CCK8 (A-C), EdU (D-F), and clonogenic experiments (G, H). Reproduced from Li et al. [21], with copyright permission from nature springer publisher, copyright 2020.
3.2 Effects of ivermectin on cell cycle and apoptosis in ovarian cancers
Flow cytometry was used to measure cell cycle and apoptosis of ovarian cancer cells treated with and without ivermectin (Figure 2) [21]. First, the cell proportion was significantly increased in G0/G phase, decreased in S phase, and no change in G2/M phase in the high concentration (20- and 30-μM) compared to the low concentration (0- and 10-μM) of ivermectin groups (Figure 2A-C). Second, compared to control group, the proportion of apoptosis cells was significantly increased in different concentration of ivermectin groups, with a dose-dependent relationship (Figure 2D and E).
Figure 2.
Ivermectin blocked cell cycle progression (A, B, C) and promoted cell apoptosis (D, E) of ovarian cancer cells. Reproduced from Li et al. [21], with copyright permission from nature springer publisher, copyright 2020.
3.3 Effect of ivermectin on cell migration in ovarian cancers
Wound healing experiment was used to test the effect of ivermectin on cell migration of ovarian cancer cells. The results showed that cell migration was significantly inhibited in cells A2780 and TOV-21G after treatment of 20 μM and 30 μM ivermectin (Figure 3) [4].
Figure 3.
Ivermectin inhibited cell migration of ovarian cancer cells TOV-21G relative to control cells A2780, analyzed with wound healing experiments. Reproduced from Li et al. [4], with copyright permission from nature springer publisher, copyright 2020.
3.4 Pharmaceutic molecular network predicted the association of ivermectin with ROS and energy metabolism
Ingenuity Pathway Analysis (IPA) was used for pharmaceutic molecular network analysis of ivermectin. The results showed that ivermectin was significantly associated with reactive oxygen species (ROS) and energy metabolism pathways, including pyruvate kinase muscle (PKM), oxoglutarate dehydrogenase L (OGDHL), mitochondrially encoded NADH dehydrogenase 2 (ND2), mitochondrially encoded NADH dehydrogenase 5 (ND5), CytB, and ubiquinolcytochrome c reductase hinge protein (UQCRH) (Figure 4) [21]. Moreover, ivermectin directly regulated Rbp, CYP3A4, P2RX7, ABCB1, GLRB, ABCG2, P2RX4, P glycoprotein, Abcb1b, strychnine, cytokine, and insulin; and indirectly regulated TNF, APP, MAPK1, ERK1/2, MAPK3, MAPK13, ROS, NFKBIA, testosterone, and STAT3 [21].
Figure 4.
Pharmaceutic molecular network predicted the associations of ivermectin with reactive oxygen species (ROS) and energy metabolism pathways (A) Disease and functional analysis of ivermectin based on IPA database (B-G). The association of ivermectin with PKM (B), OGDHL (C), ND2 (D), UQCRH (E), ND5 (F), and CYTB (G). Reproduced from Li et al. [21], with copyright permission from nature springer publisher, copyright 2020.
3.5 SILAC quantitative proteomics revealed the effects of ivermectin on key proteins in energy metabolism pathways in ovarian cancer cells
SILAC quantitative proteomics was used to detect, identify, and quantify the key protein alterations in energy metabolic pathways in ovarian cancer cells treated with (SILAC: H) and without (SILAC: L) 20 μM ivermectin for 24 h (Table 1) [21]. This study found that ivermectin significantly reduced (i) the expression levels of glycolysis-related enzymes, including ADH5, ENO1, GPI, GAPDH, LDHA, LDHB, PFKP, and PKM; (ii) the Kreb’s cycle-related enzymes, including ACON, PCK2, PDHB, MDH2, CS, IDH2, IDH3A, IDH3B, SUCLG2, and OGDHL; (iii) the OXPHOS-related enzymes, including CYTB, UQCRH, COX17, COX1, COX6C, COX4I1, COX2, COX7A2L, COX7A2, ATP6V0C, and ATP6; and (iv) the lactate shuttle proteins MCT1 and MCT4, in ovarian cancer cells.
Pathway
Protein ID
Gene name
Protein name
Q-value
Intensity H
Intensity L
Ratio H/L
Glycolysis pathway
PFKAP
PFKP
ATP-dependent 6-phosphofructokinase, platelet type
cDNA FLJ53399, highly similar to Monocarboxylate transporter 1
0.00E+00
23799000
115420000
0.53
MOT4
MCT4
Monocarboxylate transporter 4
0.00E+00
818320000
2103700000
0.38
Table 1.
SILAC quantitative proteomics revealed the protein expression changes of key molecules in energy metabolic pathways in ovarian cancer cells TOV-21G treated with (SILAC: H) and without (SILAC: L) 20 μM ivermectin for 24 h. - means the protein expressed in L group but not in H group. + means the protein expressed in H group but not in L group. /means the protein with expressed value 0 in both H and L groups. Ratio H/L means the ratio of the ivermectin-treated group (SILAC: H) to the no ivermectin-treated group (SILAC: L). Reproduced from Li et al. [21], with copyright permission from nature springer publisher, copyright 2020.
3.6 RT-qPCR and Western blot confirmed the effects of ivermectin on the key molecules in energy metabolism pathways at the mRNA and protein levels
RT-qPCR analysis confirmed the mRNA expression alterations of key molecules in energy metabolism pathways in ovarian cancer cells treated with ivermectin (0 μM, 10 μM, 20 μM, and 30 μM) (Figure 5), and further western blot analysis confirmed the protein expression alterations of those corresponding key molecules (Figure 6) [21]. These key molecules included PFKP, and PKM in glycolysis pathway, PDHB, CS, IDH2, IDH3A, IDH3B, and OGDHL in Kreb’s cycle pathway, ND2, ND5, CYTB, and UQCRH in oxidative phosphorylation pathway, MCT1, and MCT4 in lactate shuttle. These results clearly showed that ivermectin regulated energy metabolism pathways in ovarian cancer cells.
Figure 5.
RT-qPCR confirmed the effects of ivermectin on the mRNA expressions of key molecules in the energy metabolism pathways in ovarian cancer cells (a-f). The effects of different concentration of ivermectin (0, 10, 20, and 30 μM) on mRNA expressions of PFKP, PKM, CS, PDHB, IDH2, IDH3A, IDH3B, OGDHL, ND5, ND2, CYTB, UQCRH, MCT1, and MCT4. n = 3. *p < 0.05, **p < 0.01, ***p < 0.001. Reproduced from Li et al. [21], with copyright permission from nature springer publisher, copyright 2020.
Figure 6.
Western blot confirmed the effects of ivermectin on the protein expressions of key molecules in the energy metabolism pathways in ovarian cancer cells. n = 3. *p < 0.05, **p < 0.01, ***p < 0.001. Reproduced from Li et al. [21], with copyright permission from nature springer publisher, copyright 2020.
3.7 Ivermectin regulated lncRNA-EIF4A3-mRNA axis in ovarian cancer cells
Our quantitative mitochondrial proteomics data identified 1198 differentially mitochondrial proteins (mtDEPs) in human ovarian cancer tissues relative to control ovary tissues [11, 23]. Six RNA-binding proteins among those 1198 mtDEPs were identified, including EIF4A3, SFRS1, IGF2BP2, UPF1, C22ORF28, and EWSR1. Of them, only EIF4A3 was predicted to bind to the mRNA of key molecules in energy metabolism pathways. Further, Starbase predicted 3636 EIF4A3-biding mRNAs in various cancer; and of them, 306 EIF4A3-binding mRNAs was associated with ovarian cancer survival rate. Among 306 EIF4A3-binding mRNAs, the protein expressions of 116 EIF4A3-binding mRNAs and EIF4A3 were found to be inhibited by ivermectin, identified by SILAC quantitative proteomics in ovarian cancer cells treated with and without ivermectin (Table 2) [4].
Mediator of RNA polymerase II transcription subunit 20
MED20
0.01
2
0
18220000
NaN
H3BR38
Target of rapamycin complex subunit LST8
MLST8
0
3
0
13473000
NaN
P52815
39S ribosomal protein L12, mitochondrial
MRPL12
0.01
2
0
0
NaN
A0A024R1I3
Pyridoxal phosphate phosphatase
PDXP
0
6
0
40714000
NaN
A0A2R8YDS2
Ras/Rap GTPase-activating protein SynGAP
SYNGAP1
0
2
0
18400000
NaN
J3KQA0
Synaptotagmin-1
SYT1
0
26
0
339450000
NaN
Q5W0C6
Torsin-3A
TOR3A
0
3
0
16493000
NaN
B4DSK7
Mediator of RNA polymerase II transcription subunit 1
MED1
0
2
0
14356000
NaN
Q99549
M-phase phosphoprotein 8
MPHOSPH8
0
12
0
15782000
NaN
Table 2.
The proteins of 116 EIF4A3-biding mRNAs and EIF4A3 were inhibited by ivermectin, identified with SILAC quantitative proteomics in ovarian cancer cells treated with (H) and without (L) ivermectin. Reproduced from Li et al. [4], with copyright permission from nature springer publisher, copyright 2020.
Moreover, TCGA transcriptomics analysis found that 16 lncRNAs had binding sites with EIF4A3 and associated with ovarian cancer survival rate, including SNHG3, HCG15, PDCD4-AS1, KIF9-AS1, ZNRF3-AS1, ZNF674-AS1, LINC00565, SOS1-IT1, WWTR1-AS1, PLCH1-AS1, LINC00517, STARD13-IT1, LEMD1-AS1, AL109767.1, HOXC-AS3, and LBX2-AS1 [23]. Further, RT-qPCR analysis of these 16 lncRNA expressions in ovarian cancer cells treated with ivermectin (0 μM, 10 μM, 20 μM, and 30 μM) compared to control cells, which found 9 lncRNAs (PDCD4-AS1, ZNRF3-AS1, HCG15, KIF9-AS1, LINC00565, ZNF674-AS1, AL109767.1, SOS1-IT1, and LBX2-AS1) were significantly affected by ivermectin (Figure 7) [4].
Figure 7.
RT-qPCR analysis revealed the effects of ivermectin on lncRNAs in ovarian cancers relative to control cells. Reproduced from Li et al. [4], with copyright permission from nature springer publisher, copyright 2020.
These findings clearly demonstrated that ivermectin regulated lncRNA-EIF4A3-mRNA axis in ovarian cancer cells, and these mRNAs included the key molecules in energy metabolism pathways in ovarian cancer cells.
3.8 The prognostic model of ivermectin-related three-lncRNA signature for ovarian cancers identified and optimized by lasso regression
Based on those nine ivermectin-mediated lncRNAs in ovarian cancers, survival analysis and lasso regression were used to identify and optimize the prognostic model of ivermectin-related three-lncRNA signature (ZNRF3-AS1, SOS1-IT1, and LINC00565) (Figure 8) [4]. This prognostic model was significantly related to overall survival and clinicopathologic characteristics in ovarian cancer patients [4], which might benefit for prognostic assessment and personalized drug therapy toward 3P medicine practice in ovarian cancer.
Figure 8.
Lasso regression identified and optimized the prognostic model of ivermectin-related three-lncRNA signature in ovarian cancers. (A and B). Lasso regression complexity is controlled by lambda using the glmnet R package. (C). Overall survival analysis of three-lncRNA signature between high-risk and low-risk groups. Reproduced from Li et al. [4], with copyright permission from nature springer publisher, copyright 2020.
4. Conclusions
Ivermectin, as an old, common, and classic anti-parasite drug, has demonstrated its effective in vitro anti-cancer efficiency for ovarian cancer. Ivermectin significantly inhibited cell proliferation, growth and migration, blocked cell cycle progression, and promoted cell apoptosis of human ovarian cancer cells. Drug pathway network analysis of ivermectin revealed that it was significantly related to the key molecules of four energy metabolism pathways, and RT-qPCR and immunoaffinity blot analyses found that ivermectin significantly regulated these key molecules for those energy metabolism pathways, including PFKP in glycolysis, IDH2 and IDH3B in Kreb’s cycle, ND2, ND5, CYTB, and UQCRH in oxidative phosphorylation, and MCT1 and MCT4 in lactate shuttle. The integrative analysis of TCGA transcriptomics and mitochondrial proteomics in ovarian cancer revealed that 16 survival-related lncRNAs were mediated by ivermectin, which were further confirmed with RT-qPRC in human ovarian cancer cells. SILAC quantitative proteomics analysis revealed that the expressions of RNA-binding protein EIF4A3 and 116 EIF4A3-interacted genes were extensively inhibited by ivermectin. Those 116 EIF4A3-interacted proteins included those key molecules in four energy metabolism pathways, and those lncRNAs regulated EIF4A3-mRNA axes. Thus, ivermectin mediated lncRNA-EIF4A3-mRNA axes in ovarian cancer to exert its anticancer activities. Moreover, lasso regression identified the prognostic model of ivermectin-related three-lncRNA signature (ZNRF3-AS1, SOS1-IT1, and LINC00565), which was significantly associated with overall survival and clinicopathologic characteristics of ovarian cancer patients. These ivermectin-related molecular pattern alterations benefit for prognostic assessment and personalized drug therapy in the context of 3P medicine practice in ovarian cancer.
Moreover, one must realize that these achieved data about the anti-cancer activities of ivermectin in ovarian cancers are derived from the in vitro cell models. It is necessary to expand it into the in vivo animal experiments and pre-clinical and clinical experiments for its real application in ovarian cancers.
Acknowledgments
The authors acknowledge the financial supports from the Shandong First Medical University Talent Introduction Funds (to X.Z.), the Hunan Provincial Hundred Talent Plan (to X.Z.), and the grants from China “863” Plan Project (Grant No. 2014AA020610-1 to XZ).
Conflict of interest
We declare that we have no financial and personal relationships with other people or organizations.
Author’s contributions
X.Z. conceived the concept, designed the manuscript, wrote and critically revised the manuscript, coordinated and was responsible for the correspondence work and financial support. N.L. participated in preparing figures, and partial literature analysis.
Acronyms and abbreviations
FDA
Federal Drug Administration
mtDEPs
differentially mitochondrial proteins
RT-qPCR
quantitative real-time PCR
SILAC
stable isotope labeling with amino acids in cell culture
TCGA
The Cancer Genome Atlas
\n',keywords:"ovarian cancer, ivermectin, anti-cancer effect, therapeutic targets, prognostic assessment, biomarker, predictive preventive personalized medicine",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/74781.pdf",chapterXML:"https://mts.intechopen.com/source/xml/74781.xml",downloadPdfUrl:"/chapter/pdf-download/74781",previewPdfUrl:"/chapter/pdf-preview/74781",totalDownloads:965,totalViews:0,totalCrossrefCites:0,dateSubmitted:"December 14th 2020",dateReviewed:"December 19th 2020",datePrePublished:"January 13th 2021",datePublished:"October 6th 2021",dateFinished:"January 13th 2021",readingETA:"0",abstract:"Ivermectin is an old, common, and classic anti-parasite drug, which has been found to have a broad-spectrum anti-cancer effect on multiple human cancers. This chapter will focus on the anti-cancer effects of ivermectin on ovarian cancer. First, ivermectin was found to suppress cell proliferation and growth, block cell cycle progression, and promote cell apoptosis in ovarian cancer. Second, drug pathway network, qRT-PCR, and immunoaffinity blot analyses found that ivermectin acts through molecular networks to target the key molecules in energy metabolism pathways, including PFKP in glycolysis, IDH2 and IDH3B in Kreb’s cycle, ND2, ND5, CYTB, and UQCRH in oxidative phosphorylation, and MCT1 and MCT4 in lactate shuttle, to inhibit ovarian cancer growth. Third, the integrative analysis of TCGA transcriptomics and mitochondrial proteomics in ovarian cancer revealed that 16 survival-related lncRNAs were mediated by ivermectin, SILAC quantitative proteomics analysis revealed that ivermectin extensively inhibited the expressions of RNA-binding protein EIF4A3 and 116 EIF4A3-interacted genes including those key molecules in energy metabolism pathways, and also those lncRNAs regulated EIF4A3-mRNA axes. Thus, ivermectin mediated lncRNA-EIF4A3-mRNA axes in ovarian cancer to exert its anticancer capability. Further, lasso regression identified the prognostic model of ivermectin-related three-lncRNA signature (ZNRF3-AS1, SOS1-IT1, and LINC00565), which is significantly associated with overall survival and clinicopathologic characteristics in ovarian cancer patients. These ivermectin-related molecular pattern alterations benefit for prognostic assessment and personalized drug therapy toward 3P medicine practice in ovarian cancer.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/74781",risUrl:"/chapter/ris/74781",signatures:"Xianquan Zhan and Na Li",book:{id:"10342",type:"book",title:"Ovarian Cancer",subtitle:"Updates in Tumour Biology and Therapeutics",fullTitle:"Ovarian Cancer - Updates in Tumour Biology and Therapeutics",slug:"ovarian-cancer-updates-in-tumour-biology-and-therapeutics",publishedDate:"October 6th 2021",bookSignature:"Gwo-Yaw Ho and Kate Webber",coverURL:"https://cdn.intechopen.com/books/images_new/10342.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83968-744-0",printIsbn:"978-1-83968-743-3",pdfIsbn:"978-1-83968-745-7",isAvailableForWebshopOrdering:!0,editors:[{id:"297757",title:null,name:"Gwo-Yaw",middleName:null,surname:"Ho",slug:"gwo-yaw-ho",fullName:"Gwo-Yaw Ho"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",fullName:"Xianquan Zhan",slug:"xianquan-zhan",email:"yjzhan2011@gmail.com",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",institution:null},{id:"438269",title:"Dr.",name:"Na",middleName:null,surname:"Li",fullName:"Na Li",slug:"na-li",email:"dummy.321487902897532@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Methods",level:"1"},{id:"sec_2_2",title:"2.1 Ovarian cancer cell biological behaviors affected by ivermectin",level:"2"},{id:"sec_3_2",title:"2.2 Ivermectin-mediated pathway network predicted by ingenuity pathway analysis",level:"2"},{id:"sec_4_2",title:"2.3 Ivermectin-mediated target molecule changes in energy metabolism pathways verified at the mRNA and protein levels",level:"2"},{id:"sec_5_2",title:"2.4 Ivermectin-mediated proteome changes in ovarian cancer identified by SILAC-based quantitative proteomics",level:"2"},{id:"sec_6_2",title:"2.5 Transcriptomics and clinical data of ovarian cancer patients extracted from TCGA database",level:"2"},{id:"sec_7_2",title:"2.6 Ivermectin-related lncRNAs verified with qRT-PCR",level:"2"},{id:"sec_8_2",title:"2.7 LncRNA-based prognostic signature optimized with lasso regression for ovarian cancers",level:"2"},{id:"sec_9_2",title:"2.8 Statistical significance",level:"2"},{id:"sec_11",title:"3. Results and discussion",level:"1"},{id:"sec_11_2",title:"3.1 Effects of ivermectin on biological behaviors of ovarian cancers",level:"2"},{id:"sec_12_2",title:"3.2 Effects of ivermectin on cell cycle and apoptosis in ovarian cancers",level:"2"},{id:"sec_13_2",title:"3.3 Effect of ivermectin on cell migration in ovarian cancers",level:"2"},{id:"sec_14_2",title:"3.4 Pharmaceutic molecular network predicted the association of ivermectin with ROS and energy metabolism",level:"2"},{id:"sec_15_2",title:"3.5 SILAC quantitative proteomics revealed the effects of ivermectin on key proteins in energy metabolism pathways in ovarian cancer cells",level:"2"},{id:"sec_16_2",title:"3.6 RT-qPCR and Western blot confirmed the effects of ivermectin on the key molecules in energy metabolism pathways at the mRNA and protein levels",level:"2"},{id:"sec_17_2",title:"3.7 Ivermectin regulated lncRNA-EIF4A3-mRNA axis in ovarian cancer cells",level:"2"},{id:"sec_18_2",title:"3.8 The prognostic model of ivermectin-related three-lncRNA signature for ovarian cancers identified and optimized by lasso regression",level:"2"},{id:"sec_20",title:"4. Conclusions",level:"1"},{id:"sec_21",title:"Acknowledgments",level:"1"},{id:"sec_24",title:"Conflict of interest",level:"1"},{id:"sec_21",title:"Author’s contributions",level:"1"},{id:"sec_24",title:"Acronyms and abbreviations",level:"1"}],chapterReferences:[{id:"B1",body:'Burg RW, Miller BM, Baker EE, et al. Avermectins, new family of potent anthelmintic agents: producing organism and fermentation. Antimicrob Agents Chemother 1979; 15(3): 361–367'},{id:"B2",body:'Crump A. Ivermectin: enigmatic multifaceted \'wonder\' drug continues to surprise and exceed expectations. J Antibiot (Tokyo) 2017; 70(5): 495–505'},{id:"B3",body:'Laing R, Gillan V, Devaney E. Ivermectin—old drug, new tricks? Trends Parasitol 2017; 33(6): 463–472'},{id:"B4",body:'Li N, Zhan X. Anti-parasite drug ivermectin can suppress ovarian cancer by regulating lncRNA-EIF4A3-mRNA axes. EPMA J 2020; 11(2): 289–309'},{id:"B5",body:'Li N, Zhao L, Zhan X. Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol 2020. DOI: 10.1002/jcp.30055'},{id:"B6",body:'Liu J, Zhang K, Cheng L, Zhu H, Xu T. Progress in understanding the molecular mechanisms underlying the antitumour effects of ivermectin. Drug Des Devel Ther 2020; 14: 285–296'},{id:"B7",body:'Juarez M, Schcolnik-Cabrera A, Duenas-Gonzalez A. The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug. Am J Cancer Res 2018; 8(2): 317–331'},{id:"B8",body:'Kobayashi Y, Banno K, Kunitomi H, Tominaga E, Aoki D. Current state and outlook for drug repositioning anticipated in the field of ovarian cancer. J Gynecol Oncol 2019; 30(1): e10'},{id:"B9",body:'Triarico S, Capozza MA, Mastrangelo S, Attinà G, Maurizi P, Ruggiero A. Gynecological cancer among adolescents and young adults (AYA). Ann Transl Med 2020; 8(6): 397'},{id:"B10",body:'Li N, Zhan X. Mass spectrometry-based mitochondrial proteomics in human ovarian cancer. Mass Spectrom Rev 2020; 39(5–6): 471–498'},{id:"B11",body:'Li N, Zhan X. Signaling pathway network alterations in human ovarian cancers identified with quantitative mitochondrial proteomics. EPMA J 2019; 10(2): 153–172'},{id:"B12",body:'Li N, Li H, Cao L, Zhan X. Quantitative analysis of the mitochondrial proteome in human ovarian carcinomas. Endocr Relat Cancer 2018; 25(10): 909–931'},{id:"B13",body:'Li N, Li J, Desiderio DM, Zhan X. SILAC quantitative proteomics analysis of vermectin-related proteomic profiling and molecular network alterations in human ovarian cancer cells. J Mass Spectrom 2020; e4659. DOI: 10.1002/jms.4659'},{id:"B14",body:'Zhang X, Qin T, Zhu Z, et al. Ivermectin augments the in vitro and in vivo efficacy of cisplatin in epithelial ovarian cancer by suppressing Akt/mTOR signaling. Am J Med Sci 2020; 359(2): 123–129'},{id:"B15",body:'Hashimoto H, Messerli SM, Sudo T, Maruta H. Ivermectin inactivates the kinase PAK1 and blocks the PAK1-dependent growth of human ovarian cancer and NF2 tumor cell lines. Drug Discov Ther 2009; 3(6): 243–246'},{id:"B16",body:'Dou Q, Chen HN, Wang K, et al. Ivermectin induces cytostatic autophagy by blocking the PAK1/Akt axis in breast cancer. Cancer Res 2016; 76(15): 4457–4469'},{id:"B17",body:'Song D, Liang H, Qu B, et al. Ivermectin inhibits the growth of glioma cells by inducing cell cycle arrest and apoptosis in vitro and in vivo. J Cell Biochem 2019; 120(1): 622–633'},{id:"B18",body:'Nambara S, Masuda T, Nishio M, et al. Antitumor effects of the antiparasitic agent ivermectin via inhibition of Yes-associated protein 1 expression in gastric cancer. Oncotarget 2017; 8(64): 107666–107677'},{id:"B19",body:'Melotti A, Mas C, Kuciak M, Lorente-Trigos A, Borges I, Ruiz i Altaba A. The river blindness drug ivermectin and related macrocyclic lactones inhibit WNT-TCF pathway responses in human cancer. EMBO Mol Med 2014; 6(10): 1263–1278'},{id:"B20",body:'Slade L, Pulinilkunnil T. The MiTF/TFE family of transcription tactors: master regulators of organelle signaling, metabolism, and stress adaptation. Mol Cancer Res 2017; 15(12):1637–1643'},{id:"B21",body:'Li N, Li H, Wang Y, Cao L, Zhan X. Quantitative proteomics revealed energy metabolism pathway alterations in human epithelial ovarian carcinoma and their regulation by the antiparasite drug ivermectin: data interpretation in the context of 3P medicine. EPMA J 2020; 11: 661–694'},{id:"B22",body:'Guzzo CA, Furtek CI, Porras AG, Chen C, Tipping R, Clineschmidt CM, Lasseter KC. Safety, tolerability, and pharmacokinetics of escalating high doses of ivermectin in healthy adult subjects. J Clin Pharmacol. 2002; 42(10): 1122–1133'},{id:"B23",body:'Li N, Zhan X, Zhan X. The lncRNA SNHG3 regulates energy metabolism of ovarian cancer by an analysis of mitochondrial proteomes. Gynecol Oncol. 2018; 150: 343–354'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Xianquan Zhan",address:"yjzhan2011@gmail.com",affiliation:'
University Creative Research Initiatives Center, Shandong First Medical University, China
Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, China
University Creative Research Initiatives Center, Shandong First Medical University, China
Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, China
'}],corrections:null},book:{id:"10342",type:"book",title:"Ovarian Cancer",subtitle:"Updates in Tumour Biology and Therapeutics",fullTitle:"Ovarian Cancer - Updates in Tumour Biology and Therapeutics",slug:"ovarian-cancer-updates-in-tumour-biology-and-therapeutics",publishedDate:"October 6th 2021",bookSignature:"Gwo-Yaw Ho and Kate Webber",coverURL:"https://cdn.intechopen.com/books/images_new/10342.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83968-744-0",printIsbn:"978-1-83968-743-3",pdfIsbn:"978-1-83968-745-7",isAvailableForWebshopOrdering:!0,editors:[{id:"297757",title:null,name:"Gwo-Yaw",middleName:null,surname:"Ho",slug:"gwo-yaw-ho",fullName:"Gwo-Yaw Ho"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"257819",title:"Dr.",name:"Gary",middleName:null,surname:"Liu",email:"gary_liu@dynexsemi.com",fullName:"Gary Liu",slug:"gary-liu",position:null,biography:null,institutionString:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"1",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:{name:"Dynex Semiconductor (United Kingdom)",institutionURL:null,country:{name:"United Kingdom"}}},booksEdited:[],chaptersAuthored:[{id:"62648",title:"High-Performance Packaging Technology for Wide Bandgap Semiconductor Modules",slug:"high-performance-packaging-technology-for-wide-bandgap-semiconductor-modules",abstract:"The properties of wide band gap (WBG) semiconductors are beneficial to power electronics applications ranging from consumer electronics and renewable energy to electric vehicles and high-power traction applications like high-speed trains. WBG devices, properly integrated, will allow power electronics systems to be smaller, lighter, operate at higher temperatures, and at higher frequencies than previous generations of Si-based systems. These will contribute to higher efficiency, and therefore, lower lifecycle costs and lower CO2 emissions. Over 20 years have been spent developing WBG materials, low-defect-density wafers, epitaxy, and device fabrication and processing technology. In power electronics applications, devices are normally packaged into large integrated modules with electrical, mechanical and thermal connection to the system and control circuit. The first generations of WBG device have used conventional or existing module designs to allow drop-in replacement of Si devices; this approach limits the potential benefit. To realize the full potential of WBG devices, especially the higher operating temperatures and faster switching frequency, a new generation of packaging design and technology concepts must be widely implemented.",signatures:"Paul Mumby-Croft, Daohui Li, Xiaoping Dai and Guoyou Liu",authors:[{id:"249439",title:"Dr.",name:"Paul",surname:"Mumby-Croft",fullName:"Paul Mumby-Croft",slug:"paul-mumby-croft",email:"paul_mumby-croft@dynexsemi.com"},{id:"257818",title:"Dr.",name:"Daohui",surname:"Li",fullName:"Daohui Li",slug:"daohui-li",email:"daohui_li@dynexsemi.com"},{id:"257819",title:"Dr.",name:"Gary",surname:"Liu",fullName:"Gary Liu",slug:"gary-liu",email:"gary_liu@dynexsemi.com"},{id:"257820",title:"Dr.",name:"Andy",surname:"Dai",fullName:"Andy Dai",slug:"andy-dai",email:"andy_dai@dynexsemi.com"}],book:{id:"6625",title:"Disruptive Wide Bandgap Semiconductors, Related Technologies, and Their Applications",slug:"disruptive-wide-bandgap-semiconductors-related-technologies-and-their-applications",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"234009",title:"Mr.",name:"Aaron",surname:"Cai",slug:"aaron-cai",fullName:"Aaron Cai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"235675",title:"Ph.D.",name:"Anup",surname:"Bhalla",slug:"anup-bhalla",fullName:"Anup Bhalla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"United Silicon Carbide (United States)",institutionURL:null,country:{name:"United States of America"}}},{id:"236488",title:"Dr.",name:"Neophytos",surname:"Lophitis",slug:"neophytos-lophitis",fullName:"Neophytos Lophitis",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Coventry University",institutionURL:null,country:{name:"United Kingdom"}}},{id:"237104",title:"Dr.",name:"Yaqi",surname:"Wang",slug:"yaqi-wang",fullName:"Yaqi Wang",position:"Director of Operations",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"237878",title:"Dr.",name:"Fan",surname:"Li",slug:"fan-li",fullName:"Fan Li",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Warwick",institutionURL:null,country:{name:"United Kingdom"}}},{id:"242660",title:"Prof.",name:"Liter",surname:"Siek",slug:"liter-siek",fullName:"Liter Siek",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Nanyang Technological University",institutionURL:null,country:{name:"Singapore"}}},{id:"247344",title:"Dr.",name:"Marina",surname:"Antoniou",slug:"marina-antoniou",fullName:"Marina Antoniou",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Cambridge",institutionURL:null,country:{name:"United Kingdom"}}},{id:"247347",title:"Mr.",name:"Anastasios",surname:"Arvanitopoulos",slug:"anastasios-arvanitopoulos",fullName:"Anastasios Arvanitopoulos",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Coventry University",institutionURL:null,country:{name:"United Kingdom"}}},{id:"247349",title:"Mr.",name:"Samuel",surname:"Perkins",slug:"samuel-perkins",fullName:"Samuel Perkins",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Coventry University",institutionURL:null,country:{name:"United Kingdom"}}},{id:"261885",title:"Dr.",name:"Mike",surname:"Jennings",slug:"mike-jennings",fullName:"Mike Jennings",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Warwick",institutionURL:null,country:{name:"United Kingdom"}}}]},generic:{page:{slug:"publishing-process-steps",title:"Publishing Process Steps and Descriptions",intro:"
This is a brief overview of the main steps involved in publishing with IntechOpen Compacts, Monographs and Edited Books. Once you submit your proposal you will be appointed a Author Service Manager who will be your single point of contact and lead you through all the described steps below.
",metaTitle:"Publishing Process Steps and Descriptions",metaDescription:"This is a brief overview of the main steps involved in publishing with InTechOpen Compacts, Monographs and Edited Books. Once you submit your proposal you will be appointed a Publishing Process Manager who will be your single point of contact and lead you through all the described steps below.",metaKeywords:null,canonicalURL:"page/publishing-process-steps",contentRaw:'[{"type":"htmlEditorComponent","content":"
1. SEND YOUR PROPOSAL
\\n\\n
Please complete the publishing proposal form. The completed form should serve as an overview of your future Compacts, Monograph or Edited Book. Once submitted, your publishing proposal will be sent for evaluation, and a notice of acceptance or rejection will be sent within 10 to 30 working days from the date of submission.
\\n\\n
2. SUBMIT YOUR MANUSCRIPT
\\n\\n
After approval, you will proceed in submitting your full-length manuscript. 50-130 pages for compacts, 130-500 for Monographs & Edited Books.Your full-length manuscript must follow IntechOpen's Author Guidelines and comply with our publishing rules. Once the manuscript is submitted, but before it is forwarded for peer review, it will be screened for plagiarism.
\\n\\n
3. PEER REVIEW RESULTS
\\n\\n
External reviewers will evaluate your manuscript and provide you with their feedback. You may be asked to revise your draft, or parts of your draft, provide additional information and make any other necessary changes according to their comments and suggestions.
\\n\\n
4. ACCEPTANCE AND PRICE QUOTE
\\n\\n
If the manuscript is formally accepted after peer review you will receive a formal Notice of Acceptance, and a price quote.
\\n\\n
The Open Access Publishing Fee of your IntechOpen Compacts, Monograph or Edited Book depends on the volume of the publication and includes: project management, editorial and peer review services, technical editing, language copyediting, cover design and book layout, book promotion and ISBN assignment.
\\n\\n
We will send you your price quote and after it has been accepted (by both the author and the publisher), both parties will sign a Statement of Work binding them to adhere to the agreed upon terms.
\\n\\n
At this step you will also be asked to accept the Copyright Agreement.
\\n\\n
5. LANGUAGE COPYEDITING, TECHNICAL EDITING AND TYPESET PROOF
\\n\\n
Your manuscript will be sent to Straive, a leader in content solution services, for language copyediting. You will then receive a typeset proof formatted in XML and available online in HTML and PDF to proofread and check for completeness. The first typeset proof of your manuscript is usually available 10 days after its original submission.
\\n\\n
After we receive your proof corrections and a final typeset of the manuscript is approved, your manuscript is sent to our in house DTP department for technical formatting and online publication preparation.
\\n\\n
Additionally, you will be asked to provide a profile picture (face or chest-up portrait photograph) and a short summary of the book which is required for the book cover design.
\\n\\n
6. INVOICE PAYMENT
\\n\\n
The invoice is generally paid by the author, the author’s institution or funder. The payment can be made by credit card from your Author Panel (one will be assigned to you at the beginning of the project), or via bank transfer as indicated on the invoice. We currently accept the following payment options:
\\n\\n
\\n\\t
Credit Card
\\n\\t
PayPal
\\n\\t
Bank Transfer
\\n
\\n\\n
IntechOpen will help you complete your payment safely and securely, keeping your personal, professional and financial information safe.
\\n\\n
7. ONLINE PUBLICATION, PRINT AND DELIVERY OF THE BOOK
\\n\\n
IntechOpen authors can choose whether to publish their book online only or opt for online and print editions. IntechOpen Compacts, Monographs and Edited Books will be published on www.intechopen.com. If ordered, print copies are delivered by DHL within 12 to 15 working days.
\\n\\n
If you feel that IntechOpen Compacts, Monographs or Edited Books are the right publishing format for your work, please fill out the publishing proposal form. For any specific queries related to the publishing process, or IntechOpen Compacts, Monographs & Edited Books in general, please contact us at book.department@intechopen.com
Please complete the publishing proposal form. The completed form should serve as an overview of your future Compacts, Monograph or Edited Book. Once submitted, your publishing proposal will be sent for evaluation, and a notice of acceptance or rejection will be sent within 10 to 30 working days from the date of submission.
\n\n
2. SUBMIT YOUR MANUSCRIPT
\n\n
After approval, you will proceed in submitting your full-length manuscript. 50-130 pages for compacts, 130-500 for Monographs & Edited Books.Your full-length manuscript must follow IntechOpen's Author Guidelines and comply with our publishing rules. Once the manuscript is submitted, but before it is forwarded for peer review, it will be screened for plagiarism.
\n\n
3. PEER REVIEW RESULTS
\n\n
External reviewers will evaluate your manuscript and provide you with their feedback. You may be asked to revise your draft, or parts of your draft, provide additional information and make any other necessary changes according to their comments and suggestions.
\n\n
4. ACCEPTANCE AND PRICE QUOTE
\n\n
If the manuscript is formally accepted after peer review you will receive a formal Notice of Acceptance, and a price quote.
\n\n
The Open Access Publishing Fee of your IntechOpen Compacts, Monograph or Edited Book depends on the volume of the publication and includes: project management, editorial and peer review services, technical editing, language copyediting, cover design and book layout, book promotion and ISBN assignment.
\n\n
We will send you your price quote and after it has been accepted (by both the author and the publisher), both parties will sign a Statement of Work binding them to adhere to the agreed upon terms.
\n\n
At this step you will also be asked to accept the Copyright Agreement.
\n\n
5. LANGUAGE COPYEDITING, TECHNICAL EDITING AND TYPESET PROOF
\n\n
Your manuscript will be sent to Straive, a leader in content solution services, for language copyediting. You will then receive a typeset proof formatted in XML and available online in HTML and PDF to proofread and check for completeness. The first typeset proof of your manuscript is usually available 10 days after its original submission.
\n\n
After we receive your proof corrections and a final typeset of the manuscript is approved, your manuscript is sent to our in house DTP department for technical formatting and online publication preparation.
\n\n
Additionally, you will be asked to provide a profile picture (face or chest-up portrait photograph) and a short summary of the book which is required for the book cover design.
\n\n
6. INVOICE PAYMENT
\n\n
The invoice is generally paid by the author, the author’s institution or funder. The payment can be made by credit card from your Author Panel (one will be assigned to you at the beginning of the project), or via bank transfer as indicated on the invoice. We currently accept the following payment options:
\n\n
\n\t
Credit Card
\n\t
PayPal
\n\t
Bank Transfer
\n
\n\n
IntechOpen will help you complete your payment safely and securely, keeping your personal, professional and financial information safe.
\n\n
7. ONLINE PUBLICATION, PRINT AND DELIVERY OF THE BOOK
\n\n
IntechOpen authors can choose whether to publish their book online only or opt for online and print editions. IntechOpen Compacts, Monographs and Edited Books will be published on www.intechopen.com. If ordered, print copies are delivered by DHL within 12 to 15 working days.
\n\n
If you feel that IntechOpen Compacts, Monographs or Edited Books are the right publishing format for your work, please fill out the publishing proposal form. For any specific queries related to the publishing process, or IntechOpen Compacts, Monographs & Edited Books in general, please contact us at book.department@intechopen.com
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{},profiles:[],filtersByRegion:[{group:"region",caption:"North America",value:1,count:13389},{group:"region",caption:"Middle and South America",value:2,count:11662},{group:"region",caption:"Africa",value:3,count:4168},{group:"region",caption:"Asia",value:4,count:22333},{group:"region",caption:"Australia and Oceania",value:5,count:2019},{group:"region",caption:"Europe",value:6,count:33644}],offset:0,limit:12,total:null},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{hasNoEditors:"0",sort:"dateEndThirdStepPublish",topicId:"16,19,25"},books:[{type:"book",id:"11027",title:"Basics of Hypoglycemia",subtitle:null,isOpenForSubmission:!0,hash:"98ebc1e36d02be82c204b8fd5d24f97a",slug:null,bookSignature:"Dr. Alok Raghav",coverURL:"https://cdn.intechopen.com/books/images_new/11027.jpg",editedByType:null,editors:[{id:"334465",title:"Dr.",name:"Alok",surname:"Raghav",slug:"alok-raghav",fullName:"Alok Raghav"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11814",title:"Liposomes - Recent Advances, New Perspectives and Applications",subtitle:null,isOpenForSubmission:!0,hash:"62d8542d18b8cddcf507f7948b2ae74b",slug:null,bookSignature:"Dr. Rajeev K. Tyagi",coverURL:"https://cdn.intechopen.com/books/images_new/11814.jpg",editedByType:null,editors:[{id:"269120",title:"Dr.",name:"Rajeev",surname:"Tyagi",slug:"rajeev-tyagi",fullName:"Rajeev Tyagi"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11709",title:"Type 1 Diabetes Mellitus",subtitle:null,isOpenForSubmission:!0,hash:"cc0e61f864a2a8a9595f4975ce301f70",slug:null,bookSignature:"Dr. Shilpa Mehta and Dr. Resmy Palliyil Gopi",coverURL:"https://cdn.intechopen.com/books/images_new/11709.jpg",editedByType:null,editors:[{id:"342545",title:"Dr.",name:"Shilpa",surname:"Mehta",slug:"shilpa-mehta",fullName:"Shilpa Mehta"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11889",title:"Sexual Disorders and Dysfunctions",subtitle:null,isOpenForSubmission:!0,hash:"b988fda30a4e2364ee9d47e417bd0ba9",slug:null,bookSignature:"Dr. Dhastagir Sultan Sheriff",coverURL:"https://cdn.intechopen.com/books/images_new/11889.jpg",editedByType:null,editors:[{id:"167875",title:"Dr.",name:"Dhastagir Sultan",surname:"Sheriff",slug:"dhastagir-sultan-sheriff",fullName:"Dhastagir Sultan Sheriff"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11867",title:"Echocardiography",subtitle:null,isOpenForSubmission:!0,hash:"d9159ce31733bf78cc2a79b18c225994",slug:null,bookSignature:"Dr. Gabriel Cismaru",coverURL:"https://cdn.intechopen.com/books/images_new/11867.jpg",editedByType:null,editors:[{id:"191888",title:"Dr.",name:"Gabriel",surname:"Cismaru",slug:"gabriel-cismaru",fullName:"Gabriel Cismaru"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11591",title:"The Wounds of Our Mother Psychoanalysis - New Models for a Psychoanalysis in Crisis",subtitle:null,isOpenForSubmission:!0,hash:"c6a104ee38fec8d9ba8aa139a33003ce",slug:null,bookSignature:"Dr. Paolo Azzone",coverURL:"https://cdn.intechopen.com/books/images_new/11591.jpg",editedByType:null,editors:[{id:"324882",title:"Dr.",name:"Paolo",surname:"Azzone",slug:"paolo-azzone",fullName:"Paolo Azzone"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"12107",title:"Contemporary Topics in Patient Safety - Volume 2",subtitle:null,isOpenForSubmission:!0,hash:"3fe674b93710773f0db746ca96d6e048",slug:null,bookSignature:"Dr. Philip Salen and Dr. Stanislaw P. Stawicki",coverURL:"https://cdn.intechopen.com/books/images_new/12107.jpg",editedByType:null,editors:[{id:"217603",title:"Dr.",name:"Philip",surname:"Salen",slug:"philip-salen",fullName:"Philip Salen"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11894",title:"Advances in Muscular Dystrophy Research - From Cellular and Molecular Basis to Therapies",subtitle:null,isOpenForSubmission:!0,hash:"8438d4a2b753a62d529eb68d6ade6597",slug:null,bookSignature:"Dr. Gisela Gaina",coverURL:"https://cdn.intechopen.com/books/images_new/11894.jpg",editedByType:null,editors:[{id:"242747",title:"Dr.",name:"Gisela",surname:"Gaina",slug:"gisela-gaina",fullName:"Gisela Gaina"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11855",title:"Diabetic Foot - Recent Advances",subtitle:null,isOpenForSubmission:!0,hash:"9803b17d7d00c8eab822a0ab53d209b0",slug:null,bookSignature:"Dr. Alok Raghav",coverURL:"https://cdn.intechopen.com/books/images_new/11855.jpg",editedByType:null,editors:[{id:"334465",title:"Dr.",name:"Alok",surname:"Raghav",slug:"alok-raghav",fullName:"Alok Raghav"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"12105",title:"E-cigarettes and Health",subtitle:null,isOpenForSubmission:!0,hash:"3f372f37c421b5fc9a01f31341d478c7",slug:null,bookSignature:"Dr. Victor Hoe and Dr. Li Ping Wong",coverURL:"https://cdn.intechopen.com/books/images_new/12105.jpg",editedByType:null,editors:[{id:"267448",title:"Dr.",name:"Victor",surname:"Hoe",slug:"victor-hoe",fullName:"Victor Hoe"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11883",title:"Cardio-Oncology - Diagnosis and Therapy",subtitle:null,isOpenForSubmission:!0,hash:"93375c2f76319e1e9b5dbd4e8b3a0320",slug:null,bookSignature:"Dr. Haitao Zhu and Prof. Dongqing Wang",coverURL:"https://cdn.intechopen.com/books/images_new/11883.jpg",editedByType:null,editors:[{id:"138467",title:"Dr.",name:"Haitao",surname:"Zhu",slug:"haitao-zhu",fullName:"Haitao Zhu"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"12101",title:"Healthcare Access - New Threats, New Approaches",subtitle:null,isOpenForSubmission:!0,hash:"da4020a2f408a62e168c093b7d5bdf4a",slug:null,bookSignature:"Prof. Ayse Emel Onal",coverURL:"https://cdn.intechopen.com/books/images_new/12101.jpg",editedByType:null,editors:[{id:"25840",title:"Prof.",name:"Ayse Emel",surname:"Onal",slug:"ayse-emel-onal",fullName:"Ayse Emel Onal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:22},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:6},{group:"topic",caption:"Business, Management and Economics",value:7,count:4},{group:"topic",caption:"Chemistry",value:8,count:15},{group:"topic",caption:"Computer and Information Science",value:9,count:18},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:8},{group:"topic",caption:"Engineering",value:11,count:37},{group:"topic",caption:"Environmental Sciences",value:12,count:5},{group:"topic",caption:"Immunology and Microbiology",value:13,count:8},{group:"topic",caption:"Materials Science",value:14,count:15},{group:"topic",caption:"Mathematics",value:15,count:8},{group:"topic",caption:"Medicine",value:16,count:62},{group:"topic",caption:"Nanotechnology and Nanomaterials",value:17,count:2},{group:"topic",caption:"Neuroscience",value:18,count:2},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:7},{group:"topic",caption:"Physics",value:20,count:5},{group:"topic",caption:"Psychology",value:21,count:5},{group:"topic",caption:"Robotics",value:22,count:2},{group:"topic",caption:"Social Sciences",value:23,count:8},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:2}],offset:12,limit:12,total:71},popularBooks:{featuredBooks:[{type:"book",id:"7827",title:"Interpersonal Relationships",subtitle:null,isOpenForSubmission:!1,hash:"ebf41f4d17c75010eb3294cc8cac3d47",slug:"interpersonal-relationships",bookSignature:"Martha Peaslee Levine",coverURL:"https://cdn.intechopen.com/books/images_new/7827.jpg",editors:[{id:"186919",title:"Dr.",name:"Martha",middleName:null,surname:"Peaslee Levine",slug:"martha-peaslee-levine",fullName:"Martha Peaslee Levine"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10808",title:"Current Concepts in Dental Implantology",subtitle:"From Science to Clinical Research",isOpenForSubmission:!1,hash:"4af8830e463f89c57515c2da2b9777b0",slug:"current-concepts-in-dental-implantology-from-science-to-clinical-research",bookSignature:"Dragana Gabrić and Marko Vuletić",coverURL:"https://cdn.intechopen.com/books/images_new/10808.jpg",editors:[{id:"26946",title:"Prof.",name:"Dragana",middleName:null,surname:"Gabrić",slug:"dragana-gabric",fullName:"Dragana Gabrić"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10796",title:"Extracellular Vesicles",subtitle:"Role in Diseases, Pathogenesis and Therapy",isOpenForSubmission:!1,hash:"eb5407fcf93baff7bca3fae5640153a2",slug:"extracellular-vesicles-role-in-diseases-pathogenesis-and-therapy",bookSignature:"Manash K. Paul",coverURL:"https://cdn.intechopen.com/books/images_new/10796.jpg",editors:[{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10908",title:"Advances in Decision Making",subtitle:null,isOpenForSubmission:!1,hash:"126486f7f91e18e2e3539a32c38be7b1",slug:"advances-in-decision-making",bookSignature:"Fausto Pedro García Márquez",coverURL:"https://cdn.intechopen.com/books/images_new/10908.jpg",editors:[{id:"22844",title:"Prof.",name:"Fausto Pedro",middleName:null,surname:"García Márquez",slug:"fausto-pedro-garcia-marquez",fullName:"Fausto Pedro García Márquez"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"95",title:"Applications and Experiences of Quality Control",subtitle:null,isOpenForSubmission:!1,hash:"4bcb22b1eee68210a977a97d5a0f363a",slug:"applications-and-experiences-of-quality-control",bookSignature:"Ognyan Ivanov",coverURL:"https://cdn.intechopen.com/books/images_new/95.jpg",editors:[{id:"22230",title:"Prof.",name:"Ognyan",middleName:null,surname:"Ivanov",slug:"ognyan-ivanov",fullName:"Ognyan Ivanov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"2160",title:"MATLAB",subtitle:"A Fundamental Tool for Scientific Computing and Engineering Applications - Volume 1",isOpenForSubmission:!1,hash:"dd9c658341fbd264ed4f8d9e6aa8ca29",slug:"matlab-a-fundamental-tool-for-scientific-computing-and-engineering-applications-volume-1",bookSignature:"Vasilios N. Katsikis",coverURL:"https://cdn.intechopen.com/books/images_new/2160.jpg",editors:[{id:"12289",title:"Prof.",name:"Vasilios",middleName:"N.",surname:"Katsikis",slug:"vasilios-katsikis",fullName:"Vasilios Katsikis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"3560",title:"Advances in Landscape Architecture",subtitle:null,isOpenForSubmission:!1,hash:"a20614517ec5f7e91188fe8e42832138",slug:"advances-in-landscape-architecture",bookSignature:"Murat Özyavuz",coverURL:"https://cdn.intechopen.com/books/images_new/3560.jpg",editors:[{id:"93073",title:"Dr.",name:"Murat",middleName:null,surname:"Ozyavuz",slug:"murat-ozyavuz",fullName:"Murat Ozyavuz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10739",title:"Global Decline of Insects",subtitle:null,isOpenForSubmission:!1,hash:"543783652b9092962a8fa4bed38eeb17",slug:"global-decline-of-insects",bookSignature:"Hamadttu Abdel Farag El-Shafie",coverURL:"https://cdn.intechopen.com/books/images_new/10739.jpg",editors:[{id:"192142",title:"Dr.",name:"Hamadttu",middleName:null,surname:"Abdel Farag El-Shafie",slug:"hamadttu-abdel-farag-el-shafie",fullName:"Hamadttu Abdel Farag El-Shafie"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10911",title:"Higher Education",subtitle:"New Approaches to Accreditation, Digitalization, and Globalization in the Age of Covid",isOpenForSubmission:!1,hash:"223a02337498e535e967174c1f648fbc",slug:"higher-education-new-approaches-to-accreditation-digitalization-and-globalization-in-the-age-of-covid",bookSignature:"Lee Waller and Sharon Waller",coverURL:"https://cdn.intechopen.com/books/images_new/10911.jpg",editors:[{id:"263301",title:"Dr.",name:"Lee",middleName:null,surname:"Waller",slug:"lee-waller",fullName:"Lee Waller"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"3568",title:"Recent Advances in Plant in vitro Culture",subtitle:null,isOpenForSubmission:!1,hash:"830bbb601742c85a3fb0eeafe1454c43",slug:"recent-advances-in-plant-in-vitro-culture",bookSignature:"Annarita Leva and Laura M. R. Rinaldi",coverURL:"https://cdn.intechopen.com/books/images_new/3568.jpg",editors:[{id:"142145",title:"Dr.",name:"Annarita",middleName:null,surname:"Leva",slug:"annarita-leva",fullName:"Annarita Leva"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"3737",title:"MATLAB",subtitle:"Modelling, Programming and Simulations",isOpenForSubmission:!1,hash:null,slug:"matlab-modelling-programming-and-simulations",bookSignature:"Emilson Pereira Leite",coverURL:"https://cdn.intechopen.com/books/images_new/3737.jpg",editors:[{id:"12051",title:"Prof.",name:"Emilson",middleName:null,surname:"Pereira Leite",slug:"emilson-pereira-leite",fullName:"Emilson Pereira Leite"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"1770",title:"Gel Electrophoresis",subtitle:"Principles and Basics",isOpenForSubmission:!1,hash:"279701f6c802cf02deef45103e0611ff",slug:"gel-electrophoresis-principles-and-basics",bookSignature:"Sameh Magdeldin",coverURL:"https://cdn.intechopen.com/books/images_new/1770.jpg",editors:[{id:"123648",title:"Dr.",name:"Sameh",middleName:null,surname:"Magdeldin",slug:"sameh-magdeldin",fullName:"Sameh Magdeldin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:4797},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"7827",title:"Interpersonal Relationships",subtitle:null,isOpenForSubmission:!1,hash:"ebf41f4d17c75010eb3294cc8cac3d47",slug:"interpersonal-relationships",bookSignature:"Martha Peaslee Levine",coverURL:"https://cdn.intechopen.com/books/images_new/7827.jpg",publishedDate:"July 27th 2022",numberOfDownloads:7175,editors:[{id:"186919",title:"Dr.",name:"Martha",middleName:null,surname:"Peaslee Levine",slug:"martha-peaslee-levine",fullName:"Martha Peaslee Levine"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10808",title:"Current Concepts in Dental Implantology",subtitle:"From Science to Clinical Research",isOpenForSubmission:!1,hash:"4af8830e463f89c57515c2da2b9777b0",slug:"current-concepts-in-dental-implantology-from-science-to-clinical-research",bookSignature:"Dragana Gabrić and Marko Vuletić",coverURL:"https://cdn.intechopen.com/books/images_new/10808.jpg",publishedDate:"July 27th 2022",numberOfDownloads:1981,editors:[{id:"26946",title:"Prof.",name:"Dragana",middleName:null,surname:"Gabrić",slug:"dragana-gabric",fullName:"Dragana Gabrić"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10796",title:"Extracellular Vesicles",subtitle:"Role in Diseases, Pathogenesis and Therapy",isOpenForSubmission:!1,hash:"eb5407fcf93baff7bca3fae5640153a2",slug:"extracellular-vesicles-role-in-diseases-pathogenesis-and-therapy",bookSignature:"Manash K. Paul",coverURL:"https://cdn.intechopen.com/books/images_new/10796.jpg",publishedDate:"July 20th 2022",numberOfDownloads:2308,editors:[{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10908",title:"Advances in Decision Making",subtitle:null,isOpenForSubmission:!1,hash:"126486f7f91e18e2e3539a32c38be7b1",slug:"advances-in-decision-making",bookSignature:"Fausto Pedro García Márquez",coverURL:"https://cdn.intechopen.com/books/images_new/10908.jpg",publishedDate:"July 27th 2022",numberOfDownloads:1473,editors:[{id:"22844",title:"Prof.",name:"Fausto Pedro",middleName:null,surname:"García Márquez",slug:"fausto-pedro-garcia-marquez",fullName:"Fausto Pedro García Márquez"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"95",title:"Applications and Experiences of Quality Control",subtitle:null,isOpenForSubmission:!1,hash:"4bcb22b1eee68210a977a97d5a0f363a",slug:"applications-and-experiences-of-quality-control",bookSignature:"Ognyan Ivanov",coverURL:"https://cdn.intechopen.com/books/images_new/95.jpg",publishedDate:"April 26th 2011",numberOfDownloads:318571,editors:[{id:"22230",title:"Prof.",name:"Ognyan",middleName:null,surname:"Ivanov",slug:"ognyan-ivanov",fullName:"Ognyan Ivanov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"2160",title:"MATLAB",subtitle:"A Fundamental Tool for Scientific Computing and Engineering Applications - Volume 1",isOpenForSubmission:!1,hash:"dd9c658341fbd264ed4f8d9e6aa8ca29",slug:"matlab-a-fundamental-tool-for-scientific-computing-and-engineering-applications-volume-1",bookSignature:"Vasilios N. Katsikis",coverURL:"https://cdn.intechopen.com/books/images_new/2160.jpg",publishedDate:"September 26th 2012",numberOfDownloads:271836,editors:[{id:"12289",title:"Prof.",name:"Vasilios",middleName:"N.",surname:"Katsikis",slug:"vasilios-katsikis",fullName:"Vasilios Katsikis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"3560",title:"Advances in Landscape Architecture",subtitle:null,isOpenForSubmission:!1,hash:"a20614517ec5f7e91188fe8e42832138",slug:"advances-in-landscape-architecture",bookSignature:"Murat Özyavuz",coverURL:"https://cdn.intechopen.com/books/images_new/3560.jpg",publishedDate:"July 1st 2013",numberOfDownloads:243450,editors:[{id:"93073",title:"Dr.",name:"Murat",middleName:null,surname:"Ozyavuz",slug:"murat-ozyavuz",fullName:"Murat Ozyavuz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10739",title:"Global Decline of Insects",subtitle:null,isOpenForSubmission:!1,hash:"543783652b9092962a8fa4bed38eeb17",slug:"global-decline-of-insects",bookSignature:"Hamadttu Abdel Farag El-Shafie",coverURL:"https://cdn.intechopen.com/books/images_new/10739.jpg",publishedDate:"July 20th 2022",numberOfDownloads:1582,editors:[{id:"192142",title:"Dr.",name:"Hamadttu",middleName:null,surname:"Abdel Farag El-Shafie",slug:"hamadttu-abdel-farag-el-shafie",fullName:"Hamadttu Abdel Farag El-Shafie"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10911",title:"Higher Education",subtitle:"New Approaches to Accreditation, Digitalization, and Globalization in the Age of Covid",isOpenForSubmission:!1,hash:"223a02337498e535e967174c1f648fbc",slug:"higher-education-new-approaches-to-accreditation-digitalization-and-globalization-in-the-age-of-covid",bookSignature:"Lee Waller and Sharon Waller",coverURL:"https://cdn.intechopen.com/books/images_new/10911.jpg",publishedDate:"July 13th 2022",numberOfDownloads:2082,editors:[{id:"263301",title:"Dr.",name:"Lee",middleName:null,surname:"Waller",slug:"lee-waller",fullName:"Lee Waller"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"3568",title:"Recent Advances in Plant in vitro Culture",subtitle:null,isOpenForSubmission:!1,hash:"830bbb601742c85a3fb0eeafe1454c43",slug:"recent-advances-in-plant-in-vitro-culture",bookSignature:"Annarita Leva and Laura M. R. Rinaldi",coverURL:"https://cdn.intechopen.com/books/images_new/3568.jpg",publishedDate:"October 17th 2012",numberOfDownloads:256294,editors:[{id:"142145",title:"Dr.",name:"Annarita",middleName:null,surname:"Leva",slug:"annarita-leva",fullName:"Annarita Leva"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"10808",title:"Current Concepts in Dental Implantology",subtitle:"From Science to Clinical Research",isOpenForSubmission:!1,hash:"4af8830e463f89c57515c2da2b9777b0",slug:"current-concepts-in-dental-implantology-from-science-to-clinical-research",bookSignature:"Dragana Gabrić and Marko Vuletić",coverURL:"https://cdn.intechopen.com/books/images_new/10808.jpg",editedByType:"Edited by",publishedDate:"July 27th 2022",editors:[{id:"26946",title:"Prof.",name:"Dragana",middleName:null,surname:"Gabrić",slug:"dragana-gabric",fullName:"Dragana Gabrić"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11328",title:"Botulinum Toxin",subtitle:"Recent Topics and Applications",isOpenForSubmission:!1,hash:"7dd05a316001cef143e209eda51387a7",slug:"botulinum-toxin-recent-topics-and-applications",bookSignature:"Suna Sabuncuoglu",coverURL:"https://cdn.intechopen.com/books/images_new/11328.jpg",editedByType:"Edited by",publishedDate:"July 27th 2022",editors:[{id:"270856",title:"Associate Prof.",name:"Suna",middleName:null,surname:"Sabuncuoglu",slug:"suna-sabuncuoglu",fullName:"Suna Sabuncuoglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11085",title:"Polycystic Ovary Syndrome",subtitle:"Functional Investigation and Clinical Application",isOpenForSubmission:!1,hash:"3066dd3ff29e1fac072fd60b08d4d3e7",slug:"polycystic-ovary-syndrome-functional-investigation-and-clinical-application",bookSignature:"Zhengchao Wang",coverURL:"https://cdn.intechopen.com/books/images_new/11085.jpg",editedByType:"Edited by",publishedDate:"July 27th 2022",editors:[{id:"204883",title:"Dr.",name:"Zhengchao",middleName:null,surname:"Wang",slug:"zhengchao-wang",fullName:"Zhengchao Wang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10833",title:"Tumor Angiogenesis and Modulators",subtitle:null,isOpenForSubmission:!1,hash:"f29b575c46128b2da061ef7f9bd1070b",slug:"tumor-angiogenesis-and-modulators",bookSignature:"Ke Xu",coverURL:"https://cdn.intechopen.com/books/images_new/10833.jpg",editedByType:"Edited by",publishedDate:"July 27th 2022",editors:[{id:"59529",title:"Dr.",name:"Ke",middleName:null,surname:"Xu",slug:"ke-xu",fullName:"Ke Xu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11356",title:"Molecular Cloning",subtitle:null,isOpenForSubmission:!1,hash:"671c629dd86e97f0fb467b9e70e92296",slug:"molecular-cloning",bookSignature:"Sadık Dincer, Hatice Aysun Mercimek Takcı and Melis Sumengen Ozdenef",coverURL:"https://cdn.intechopen.com/books/images_new/11356.jpg",editedByType:"Edited by",publishedDate:"July 27th 2022",editors:[{id:"188141",title:"Prof.",name:"Sadik",middleName:null,surname:"Dincer",slug:"sadik-dincer",fullName:"Sadik Dincer"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7827",title:"Interpersonal Relationships",subtitle:null,isOpenForSubmission:!1,hash:"ebf41f4d17c75010eb3294cc8cac3d47",slug:"interpersonal-relationships",bookSignature:"Martha Peaslee Levine",coverURL:"https://cdn.intechopen.com/books/images_new/7827.jpg",editedByType:"Edited by",publishedDate:"July 27th 2022",editors:[{id:"186919",title:"Dr.",name:"Martha",middleName:null,surname:"Peaslee Levine",slug:"martha-peaslee-levine",fullName:"Martha Peaslee Levine"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10908",title:"Advances in Decision Making",subtitle:null,isOpenForSubmission:!1,hash:"126486f7f91e18e2e3539a32c38be7b1",slug:"advances-in-decision-making",bookSignature:"Fausto Pedro García Márquez",coverURL:"https://cdn.intechopen.com/books/images_new/10908.jpg",editedByType:"Edited by",publishedDate:"July 27th 2022",editors:[{id:"22844",title:"Prof.",name:"Fausto Pedro",middleName:null,surname:"García Márquez",slug:"fausto-pedro-garcia-marquez",fullName:"Fausto Pedro García Márquez"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10669",title:"Corrosion",subtitle:"Fundamentals and Protection Mechanisms",isOpenForSubmission:!1,hash:"4a76d54f8a40fc2e7002a8d13fd617c1",slug:"corrosion-fundamentals-and-protection-mechanisms",bookSignature:"Fahmina Zafar, Anujit Ghosal and Eram Sharmin",coverURL:"https://cdn.intechopen.com/books/images_new/10669.jpg",editedByType:"Edited by",publishedDate:"July 27th 2022",editors:[{id:"89672",title:"Dr.",name:"Fahmina",middleName:null,surname:"Zafar",slug:"fahmina-zafar",fullName:"Fahmina Zafar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10677",title:"Advanced Topics of Topology",subtitle:null,isOpenForSubmission:!1,hash:"bf964c52f9e653fac20a7fcab58070e5",slug:"advanced-topics-of-topology",bookSignature:"Francisco Bulnes",coverURL:"https://cdn.intechopen.com/books/images_new/10677.jpg",editedByType:"Edited by",publishedDate:"July 27th 2022",editors:[{id:"92918",title:"Dr.",name:"Francisco",middleName:null,surname:"Bulnes",slug:"francisco-bulnes",fullName:"Francisco Bulnes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11195",title:"Recent Advances in Biometrics",subtitle:null,isOpenForSubmission:!1,hash:"2d32e33e0f499cb5241734bb75dd2a83",slug:"recent-advances-in-biometrics",bookSignature:"Muhammad Sarfraz",coverURL:"https://cdn.intechopen.com/books/images_new/11195.jpg",editedByType:"Edited by",publishedDate:"July 27th 2022",editors:[{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"228",title:"Optics and Lasers",slug:"optics-and-lasers",parent:{id:"20",title:"Physics",slug:"physics"},numberOfBooks:77,numberOfSeries:0,numberOfAuthorsAndEditors:2175,numberOfWosCitations:3299,numberOfCrossrefCitations:1444,numberOfDimensionsCitations:3248,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicId:"228",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"10672",title:"Nonlinear Optics",subtitle:"Nonlinear Nanophotonics and Novel Materials for Nonlinear Optics",isOpenForSubmission:!1,hash:"cfe87b713a8bee22c19361b86b03d506",slug:"nonlinear-optics-nonlinear-nanophotonics-and-novel-materials-for-nonlinear-optics",bookSignature:"Boris I. Lembrikov",coverURL:"https://cdn.intechopen.com/books/images_new/10672.jpg",editedByType:"Edited by",editors:[{id:"2359",title:"Dr.",name:"Boris I.",middleName:"I.",surname:"Lembrikov",slug:"boris-i.-lembrikov",fullName:"Boris I. Lembrikov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9655",title:"Bioluminescence",subtitle:"Technology and Biology",isOpenForSubmission:!1,hash:"26b9e7dade717a5ffdc2dbcfaa1ea43d",slug:"bioluminescence-technology-and-biology",bookSignature:"Hirobumi Suzuki and Katsunori Ogoh",coverURL:"https://cdn.intechopen.com/books/images_new/9655.jpg",editedByType:"Edited by",editors:[{id:"185746",title:"Dr.",name:"Hirobumi",middleName:null,surname:"Suzuki",slug:"hirobumi-suzuki",fullName:"Hirobumi Suzuki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10767",title:"Fiber Optics",subtitle:"Technology and Applications",isOpenForSubmission:!1,hash:"f6624b8ef72a4a369383a4b719bba2a4",slug:"fiber-optics-technology-and-applications",bookSignature:"Guillermo Huerta-Cuellar",coverURL:"https://cdn.intechopen.com/books/images_new/10767.jpg",editedByType:"Edited by",editors:[{id:"237167",title:"Dr.",name:"Guillermo",middleName:null,surname:"Huerta-Cuellar",slug:"guillermo-huerta-cuellar",fullName:"Guillermo Huerta-Cuellar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10017",title:"Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"e20f25706d03f0c52ac852f7fa2375e7",slug:"optoelectronics",bookSignature:"Mike Haidar Shahine",coverURL:"https://cdn.intechopen.com/books/images_new/10017.jpg",editedByType:"Edited by",editors:[{id:"102474",title:"Dr.",name:"Mike Haidar",middleName:null,surname:"Shahine",slug:"mike-haidar-shahine",fullName:"Mike Haidar Shahine"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10075",title:"Nonlinear Optics",subtitle:"From Solitons to Similaritons",isOpenForSubmission:!1,hash:"b034b2a060292c8511359aec0db1002c",slug:"nonlinear-optics-from-solitons-to-similaritons",bookSignature:"İlkay Bakırtaş and Nalan Antar",coverURL:"https://cdn.intechopen.com/books/images_new/10075.jpg",editedByType:"Edited by",editors:[{id:"186388",title:"Prof.",name:"İlkay",middleName:null,surname:"Bakırtaş",slug:"ilkay-bakirtas",fullName:"İlkay Bakırtaş"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9211",title:"Single Photon Manipulation",subtitle:null,isOpenForSubmission:!1,hash:"567ddcc14b68fa14e54df3bce2f51acc",slug:"single-photon-manipulation",bookSignature:"Keyu Xia",coverURL:"https://cdn.intechopen.com/books/images_new/9211.jpg",editedByType:"Edited by",editors:[{id:"210723",title:"Prof.",name:"Keyu",middleName:null,surname:"Xia",slug:"keyu-xia",fullName:"Keyu Xia"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7965",title:"Liquid Crystals and Display Technology",subtitle:null,isOpenForSubmission:!1,hash:"eb83772cea6200bdd685b8a1b93ee35d",slug:"liquid-crystals-and-display-technology",bookSignature:"Morteza Sasani Ghamsari and Irina Carlescu",coverURL:"https://cdn.intechopen.com/books/images_new/7965.jpg",editedByType:"Edited by",editors:[{id:"64949",title:"Prof.",name:"Morteza",middleName:null,surname:"Sasani Ghamsari",slug:"morteza-sasani-ghamsari",fullName:"Morteza Sasani Ghamsari"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8527",title:"Luminescence",subtitle:"OLED Technology and Applications",isOpenForSubmission:!1,hash:"dbdf51e72104f9e570cc0f1ea6c02a9e",slug:"luminescence-oled-technology-and-applications",bookSignature:"Sergei Pyshkin",coverURL:"https://cdn.intechopen.com/books/images_new/8527.jpg",editedByType:"Edited by",editors:[{id:"43016",title:"Prof.",name:"Sergei",middleName:"L.",surname:"Pyshkin",slug:"sergei-pyshkin",fullName:"Sergei Pyshkin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8873",title:"Optical Coherence Tomography and Its Non-medical Applications",subtitle:null,isOpenForSubmission:!1,hash:"04048c4d925e4a7256014a26cf19c40c",slug:"optical-coherence-tomography-and-its-non-medical-applications",bookSignature:"Michael R. Wang",coverURL:"https://cdn.intechopen.com/books/images_new/8873.jpg",editedByType:"Edited by",editors:[{id:"6356",title:"Dr.",name:"Michael",middleName:null,surname:"Wang",slug:"michael-wang",fullName:"Michael Wang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9272",title:"Optical Fiber Applications",subtitle:null,isOpenForSubmission:!1,hash:"dd156cc0568d8a4204d9f13609d8ff9e",slug:"optical-fiber-applications",bookSignature:"Guillermo Huerta-Cuellar and Roghayeh Imani",coverURL:"https://cdn.intechopen.com/books/images_new/9272.jpg",editedByType:"Edited by",editors:[{id:"237167",title:"Dr.",name:"Guillermo",middleName:null,surname:"Huerta-Cuellar",slug:"guillermo-huerta-cuellar",fullName:"Guillermo Huerta-Cuellar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7515",title:"Photonic Crystals",subtitle:"A Glimpse of the Current Research Trends",isOpenForSubmission:!1,hash:"1dcab6021cb88bdb66e9588e2fc24d19",slug:"photonic-crystals-a-glimpse-of-the-current-research-trends",bookSignature:"Pankaj Kumar Choudhury",coverURL:"https://cdn.intechopen.com/books/images_new/7515.jpg",editedByType:"Edited by",editors:[{id:"205744",title:"Dr.",name:"Pankaj",middleName:null,surname:"Kumar Choudhury",slug:"pankaj-kumar-choudhury",fullName:"Pankaj Kumar Choudhury"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7682",title:"Holographic Materials and Applications",subtitle:null,isOpenForSubmission:!1,hash:"ca1b913a04397b7c3477135969230103",slug:"holographic-materials-and-applications",bookSignature:"Manoj Kumar",coverURL:"https://cdn.intechopen.com/books/images_new/7682.jpg",editedByType:"Edited by",editors:[{id:"191886",title:"Dr.",name:"Manoj",middleName:null,surname:"Kumar",slug:"manoj-kumar",fullName:"Manoj Kumar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:77,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"49652",doi:"10.5772/61720",title:"Sample Preparations for Scanning Electron Microscopy – Life Sciences",slug:"sample-preparations-for-scanning-electron-microscopy-life-sciences",totalDownloads:8761,totalCrossrefCites:37,totalDimensionsCites:84,abstract:"Sample preparations are essential in scanning electron microscopy. Flawed sample preparations can undermine the quality of results and lead to false conclusions. Thus, the aim of this chapter is to equip researchers, post graduate students and technicians with essential knowledge required to prepare samples for scanning electron microscopy (SEM) investigations in the life sciences.",book:{id:"5075",slug:"modern-electron-microscopy-in-physical-and-life-sciences",title:"Modern Electron Microscopy in Physical and Life Sciences",fullTitle:"Modern Electron Microscopy in Physical and Life Sciences"},signatures:"Mogana Das Murtey and Patchamuthu Ramasamy",authors:[{id:"176330",title:"Dr.",name:"Mogana",middleName:"Das",surname:"Murtey",slug:"mogana-murtey",fullName:"Mogana Murtey"},{id:"181159",title:"Mr.",name:"Patchamuthu",middleName:null,surname:"Ramasamy",slug:"patchamuthu-ramasamy",fullName:"Patchamuthu Ramasamy"}]},{id:"26791",doi:"10.5772/28067",title:"Optical Vortices in a Fiber: Mode Division Multiplexing and Multimode Self-Imaging",slug:"optical-vortices-in-a-fiber-mode-division-multiplexing-and-multimode-self-reproducing",totalDownloads:4552,totalCrossrefCites:30,totalDimensionsCites:49,abstract:null,book:{id:"2018",slug:"recent-progress-in-optical-fiber-research",title:"Recent Progress in Optical Fiber Research",fullTitle:"Recent Progress in Optical Fiber Research"},signatures:"S.N. Khonina, N.L. Kazanskiy and V.A. Soifer",authors:[{id:"72613",title:"Prof.",name:"Svetlana",middleName:null,surname:"Khonina",slug:"svetlana-khonina",fullName:"Svetlana Khonina"}]},{id:"30963",doi:"10.5772/34176",title:"Microstructural and Mineralogical Characterization of Clay Stabilized Using Calcium-Based Stabilizers",slug:"microstructural-and-mineralogical-characterization-of-clay-stabilized-using-calcium-based-stabilizer",totalDownloads:6804,totalCrossrefCites:29,totalDimensionsCites:48,abstract:null,book:{id:"1505",slug:"scanning-electron-microscopy",title:"Scanning Electron Microscopy",fullTitle:"Scanning Electron Microscopy"},signatures:"Pranshoo Solanki and Musharraf Zaman",authors:[{id:"20942",title:"Prof.",name:"Pranshoo",middleName:null,surname:"Solanki",slug:"pranshoo-solanki",fullName:"Pranshoo Solanki"},{id:"20945",title:"Prof.",name:"Musharraf",middleName:null,surname:"Zaman",slug:"musharraf-zaman",fullName:"Musharraf Zaman"}]},{id:"42033",doi:"10.5772/53897",title:"Photonic Crystals for Optical Sensing: A Review",slug:"photonic-crystals-for-optical-sensing-a-review",totalDownloads:6050,totalCrossrefCites:24,totalDimensionsCites:43,abstract:null,book:{id:"3486",slug:"advances-in-photonic-crystals",title:"Advances in Photonic Crystals",fullTitle:"Advances in Photonic Crystals"},signatures:"Benedetto Troia, Antonia Paolicelli, Francesco De Leonardis and Vittorio M. N. Passaro",authors:[{id:"83905",title:"Prof.",name:"Vittorio",middleName:"M. N.",surname:"Passaro",slug:"vittorio-passaro",fullName:"Vittorio Passaro"}]},{id:"38543",doi:"10.5772/48331",title:"Application of FTIR Spectroscopy in Environmental Studies",slug:"application-of-ftir-spectroscopy-in-environmental-studies",totalDownloads:27703,totalCrossrefCites:10,totalDimensionsCites:43,abstract:null,book:{id:"2397",slug:"advanced-aspects-of-spectroscopy",title:"Advanced Aspects of Spectroscopy",fullTitle:"Advanced Aspects of Spectroscopy"},signatures:"Claudia Maria Simonescu",authors:[{id:"142381",title:"Dr.",name:"Claudia Maria",middleName:null,surname:"Simonescu",slug:"claudia-maria-simonescu",fullName:"Claudia Maria Simonescu"}]}],mostDownloadedChaptersLast30Days:[{id:"52164",title:"An Overview on Quantum Cascade Lasers: Origins and Development",slug:"an-overview-on-quantum-cascade-lasers-origins-and-development",totalDownloads:3255,totalCrossrefCites:2,totalDimensionsCites:11,abstract:"This chapter presents an introductory review on quantum cascade lasers (QCLs). An overview is prefaced, including a brief description of their beginnings and operating basics. Materials used, as well as growth methods, are also described. The possibility of developing GaN-based QCLs is also shown. Summarizing, the applications of these structures cover a broad range, including spectroscopy, free-space communication, as well as applications to near-space radar and chemical/biological detection. Furthermore, a number of state-of-the-art applications are described in different fields, and finally a brief assessment of the possibilities of volume production and the overall state of the art in QCLs research are elaborated.",book:{id:"5389",slug:"quantum-cascade-lasers",title:"Quantum Cascade Lasers",fullTitle:"Quantum Cascade Lasers"},signatures:"Raúl Pecharromán-Gallego",authors:[{id:"188866",title:"Dr.",name:"Raúl",middleName:null,surname:"Pecharromán-Gallego",slug:"raul-pecharroman-gallego",fullName:"Raúl Pecharromán-Gallego"}]},{id:"49526",title:"Focused Ion Beams (FIB) — Novel Methodologies and Recent Applications for Multidisciplinary Sciences",slug:"focused-ion-beams-fib-novel-methodologies-and-recent-applications-for-multidisciplinary-sciences",totalDownloads:4325,totalCrossrefCites:5,totalDimensionsCites:11,abstract:"Considered as the newest field of electron microscopy, focused ion beam (FIB) technologies are used in many fields of science for site-specific analysis, imaging, milling, deposition, micromachining, and manipulation. Dual-beam platforms, combining a high-resolution scanning electron microscope (HR-SEM) and an FIB column, additionally equipped with precursor-based gas injection systems (GIS), micromanipulators, and chemical analysis tools (such as energy-dispersive spectra (EDS) or wavelength-dispersive spectra (WDS)), serve as multifunctional tools for direct lithography in terms of nano-machining and nano-prototyping, while advanced specimen preparation for transmission electron microscopy (TEM) can practically be carried out with ultrahigh precision. Especially, when hard materials and material systems with hard substrates are concerned, FIB is the only technique for site-specific micro- and nanostructuring. Moreover, FIB sectioning and sampling techniques are frequently used for revealing the structural and morphological distribution of material systems with three-dimensional (3D) network at micro-/nanoscale.This book chapter includes many examples on conventional and novel processes of FIB technologies, ranging from analysis of semiconductors to electron tomography-based imaging of hard materials such as nanoporous ceramics and composites. In addition, recent studies concerning the active use of dual-beam platforms are mentioned",book:{id:"5075",slug:"modern-electron-microscopy-in-physical-and-life-sciences",title:"Modern Electron Microscopy in Physical and Life Sciences",fullTitle:"Modern Electron Microscopy in Physical and Life Sciences"},signatures:"Meltem Sezen",authors:[{id:"176338",title:"Associate Prof.",name:"Meltem",middleName:null,surname:"Sezen",slug:"meltem-sezen",fullName:"Meltem Sezen"}]},{id:"50866",title:"Effects of Different Laser Pulse Regimes (Nanosecond, Picosecond and Femtosecond) on the Ablation of Materials for Production of Nanoparticles in Liquid Solution",slug:"effects-of-different-laser-pulse-regimes-nanosecond-picosecond-and-femtosecond-on-the-ablation-of-ma",totalDownloads:6112,totalCrossrefCites:11,totalDimensionsCites:36,abstract:"Ultra-short laser pulse interaction with materials has received much attention from researchers in micro- and nanomachining, especially for the generation of nanoparticles in liquid environments, because of the straightforward method and direct application for organic solvents. In addition, the colloidal nanoparticles produced by laser ablation have very high purity—they are free from surfactants and reaction products or by-products. In this chapter, nanosecond, picosecond and femtosecond laser pulse durations are compared in laser material processing. Due to the unique properties of the short and ultra-short laser pulse durations in material processing, they are more apparent in the production of precision material processing and generation of nanoparticles in liquid environments.",book:{id:"5236",slug:"high-energy-and-short-pulse-lasers",title:"High Energy and Short Pulse Lasers",fullTitle:"High Energy and Short Pulse Lasers"},signatures:"Abubaker Hassan Hamad",authors:[{id:"183494",title:"Dr.",name:"Abubaker",middleName:"Hassan",surname:"Hamad",slug:"abubaker-hamad",fullName:"Abubaker Hamad"}]},{id:"49537",title:"Electron Diffraction",slug:"electron-diffraction",totalDownloads:10155,totalCrossrefCites:11,totalDimensionsCites:32,abstract:"Electron microscopes are usually supplied with equipment for obtaining diffraction patterns and micrographs from the same area of a specimen and the best results are attained if the complete use is to be made of these combined facilities. Electron diffraction patterns are used to obtain quantitative data including phase identification, orientation relationship and crystal defects in materials, etc. At first, a general introduction including a geometrical and quantitative approach to electron diffraction from a crystalline specimen, the reciprocal lattice and electron diffraction in the electron microscope are presented. The scattering process by an individual atom as well as a crystal, the Bragg law, Laue conditions and structure factor are also discussed. Types of diffraction patterns such as ring pattern, spot pattern and Kikuchi pattern, and general and unique indexing diffraction patterns are explained. The procedure for indexing simple, complicated and imperfect patterns as well as Kikuchi lines and a combination of Kikuchi lines and spots is outlined. The known and unknown materials are identified by indexing patterns. Practical comparisons between various methods of analysing diffraction patterns are also described. The basic diffraction patterns and the fine structure in the patterns including specimen tilting experiments, orientation relationship determination, phase identification, twinning, second phases, crystallographic information, dislocation, preferred orientation and texture, extra spots and streaks are described in detail. Finally, electron diffraction patterns of new materials are investigated.",book:{id:"5075",slug:"modern-electron-microscopy-in-physical-and-life-sciences",title:"Modern Electron Microscopy in Physical and Life Sciences",fullTitle:"Modern Electron Microscopy in Physical and Life Sciences"},signatures:"Mohsen Asadi Asadabad and Mohammad Jafari Eskandari",authors:[{id:"176352",title:"Dr.",name:"Mohsen",middleName:null,surname:"Asadi Asadabad",slug:"mohsen-asadi-asadabad",fullName:"Mohsen Asadi Asadabad"},{id:"177600",title:"Dr.",name:"Mohammad",middleName:null,surname:"Jafari Eskandari",slug:"mohammad-jafari-eskandari",fullName:"Mohammad Jafari Eskandari"}]},{id:"38543",title:"Application of FTIR Spectroscopy in Environmental Studies",slug:"application-of-ftir-spectroscopy-in-environmental-studies",totalDownloads:27699,totalCrossrefCites:10,totalDimensionsCites:43,abstract:null,book:{id:"2397",slug:"advanced-aspects-of-spectroscopy",title:"Advanced Aspects of Spectroscopy",fullTitle:"Advanced Aspects of Spectroscopy"},signatures:"Claudia Maria Simonescu",authors:[{id:"142381",title:"Dr.",name:"Claudia Maria",middleName:null,surname:"Simonescu",slug:"claudia-maria-simonescu",fullName:"Claudia Maria Simonescu"}]}],onlineFirstChaptersFilter:{topicId:"228",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},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:108,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:141,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:124,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:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,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. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"August 2nd, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:33,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:42,paginationItems:[{id:"82914",title:"Glance on the Critical Role of IL-23 Receptor Gene Variations in Inflammation-Induced Carcinogenesis",doi:"10.5772/intechopen.105049",signatures:"Mohammed El-Gedamy",slug:"glance-on-the-critical-role-of-il-23-receptor-gene-variations-in-inflammation-induced-carcinogenesis",totalDownloads:15,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Chemokines Updates",coverURL:"https://cdn.intechopen.com/books/images_new/11672.jpg",subseries:{id:"18",title:"Proteomics"}}},{id:"82875",title:"Lipidomics as a Tool in the Diagnosis and Clinical Therapy",doi:"10.5772/intechopen.105857",signatures:"María Elizbeth Alvarez Sánchez, Erick Nolasco Ontiveros, Rodrigo Arreola, Adriana Montserrat Espinosa González, Ana María García Bores, Roberto Eduardo López Urrutia, Ignacio Peñalosa Castro, María del Socorro Sánchez Correa and Edgar Antonio Estrella Parra",slug:"lipidomics-as-a-tool-in-the-diagnosis-and-clinical-therapy",totalDownloads:9,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82440",title:"Lipid Metabolism and Associated Molecular Signaling Events in Autoimmune Disease",doi:"10.5772/intechopen.105746",signatures:"Mohan Vanditha, Sonu Das and Mathew John",slug:"lipid-metabolism-and-associated-molecular-signaling-events-in-autoimmune-disease",totalDownloads:17,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82483",title:"Oxidative Stress in Cardiovascular Diseases",doi:"10.5772/intechopen.105891",signatures:"Laura Mourino-Alvarez, Tamara Sastre-Oliva, Nerea Corbacho-Alonso and Maria G. Barderas",slug:"oxidative-stress-in-cardiovascular-diseases",totalDownloads:10,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Importance of Oxidative Stress and Antioxidant System in Health and Disease",coverURL:"https://cdn.intechopen.com/books/images_new/11671.jpg",subseries:{id:"15",title:"Chemical Biology"}}}]},overviewPagePublishedBooks:{paginationCount:33,paginationItems:[{type:"book",id:"7006",title:"Biochemistry and Health Benefits of Fatty Acids",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7006.jpg",slug:"biochemistry-and-health-benefits-of-fatty-acids",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Viduranga Waisundara",hash:"c93a00abd68b5eba67e5e719f67fd20b",volumeInSeries:1,fullTitle:"Biochemistry and Health Benefits of Fatty Acids",editors:[{id:"194281",title:"Dr.",name:"Viduranga Y.",middleName:null,surname:"Waisundara",slug:"viduranga-y.-waisundara",fullName:"Viduranga Y. Waisundara",profilePictureURL:"https://mts.intechopen.com/storage/users/194281/images/system/194281.jpg",biography:"Dr. Viduranga Waisundara obtained her Ph.D. in Food Science\nand Technology from the Department of Chemistry, National\nUniversity of Singapore, in 2010. She was a lecturer at Temasek Polytechnic, Singapore from July 2009 to March 2013.\nShe relocated to her motherland of Sri Lanka and spearheaded the Functional Food Product Development Project at the\nNational Institute of Fundamental Studies from April 2013 to\nOctober 2016. She was a senior lecturer on a temporary basis at the Department of\nFood Technology, Faculty of Technology, Rajarata University of Sri Lanka. She is\ncurrently Deputy Principal of the Australian College of Business and Technology –\nKandy Campus, Sri Lanka. She is also the Global Harmonization Initiative (GHI)",institutionString:"Australian College of Business & Technology",institution:{name:"Kobe College",institutionURL:null,country:{name:"Japan"}}}]},{type:"book",id:"6820",title:"Keratin",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6820.jpg",slug:"keratin",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Miroslav Blumenberg",hash:"6def75cd4b6b5324a02b6dc0359896d0",volumeInSeries:2,fullTitle:"Keratin",editors:[{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}}]},{type:"book",id:"7978",title:"Vitamin A",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7978.jpg",slug:"vitamin-a",publishedDate:"May 15th 2019",editedByType:"Edited by",bookSignature:"Leila Queiroz Zepka, Veridiana Vera de Rosso and Eduardo Jacob-Lopes",hash:"dad04a658ab9e3d851d23705980a688b",volumeInSeries:3,fullTitle:"Vitamin A",editors:[{id:"261969",title:"Dr.",name:"Leila",middleName:null,surname:"Queiroz Zepka",slug:"leila-queiroz-zepka",fullName:"Leila Queiroz Zepka",profilePictureURL:"https://mts.intechopen.com/storage/users/261969/images/system/261969.png",biography:"Prof. Dr. Leila Queiroz Zepka is currently an associate professor in the Department of Food Technology and Science, Federal University of Santa Maria, Brazil. She has more than fifteen years of teaching and research experience. She has published more than 550 scientific publications/communications, including 15 books, 50 book chapters, 100 original research papers, 380 research communications in national and international conferences, and 12 patents. She is a member of the editorial board of five journals and acts as a reviewer for several national and international journals. Her research interests include microalgal biotechnology with an emphasis on microalgae-based products.",institutionString:"Universidade Federal de Santa Maria",institution:{name:"Universidade Federal de Santa Maria",institutionURL:null,country:{name:"Brazil"}}}]},{type:"book",id:"7953",title:"Bioluminescence",subtitle:"Analytical Applications and Basic Biology",coverURL:"https://cdn.intechopen.com/books/images_new/7953.jpg",slug:"bioluminescence-analytical-applications-and-basic-biology",publishedDate:"September 25th 2019",editedByType:"Edited by",bookSignature:"Hirobumi Suzuki",hash:"3a8efa00b71abea11bf01973dc589979",volumeInSeries:4,fullTitle:"Bioluminescence - Analytical Applications and Basic Biology",editors:[{id:"185746",title:"Dr.",name:"Hirobumi",middleName:null,surname:"Suzuki",slug:"hirobumi-suzuki",fullName:"Hirobumi Suzuki",profilePictureURL:"https://mts.intechopen.com/storage/users/185746/images/system/185746.png",biography:"Dr. Hirobumi Suzuki received his Ph.D. in 1997 from Tokyo Metropolitan University, Japan, where he studied firefly phylogeny and the evolution of mating systems. He is especially interested in the genetic differentiation pattern and speciation process that correlate to the flashing pattern and mating behavior of some fireflies in Japan. He then worked for Olympus Corporation, a Japanese manufacturer of optics and imaging products, where he was involved in the development of luminescence technology and produced a bioluminescence microscope that is currently being used for gene expression analysis in chronobiology, neurobiology, and developmental biology. Dr. Suzuki currently serves as a visiting researcher at Kogakuin University, Japan, and also a vice president of the Japan Firefly Society.",institutionString:"Kogakuin University",institution:null}]}]},openForSubmissionBooks:{paginationCount:2,paginationItems:[{id:"11474",title:"Quality of Life Interventions - Magnitude of Effect and Transferability",coverURL:"https://cdn.intechopen.com/books/images_new/11474.jpg",hash:"5a6bcdaf5ee144d043bcdab893ff9e1c",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"July 7th 2022",isOpenForSubmission:!0,editors:[{id:"245319",title:"Ph.D.",name:"Sage",surname:"Arbor",slug:"sage-arbor",fullName:"Sage Arbor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11473",title:"Social Inequality - Structure and Social Processes",coverURL:"https://cdn.intechopen.com/books/images_new/11473.jpg",hash:"cefab077e403fd1695fb2946e7914942",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"July 13th 2022",isOpenForSubmission:!0,editors:[{id:"313341",title:"Ph.D.",name:"Yaroslava",surname:"Robles-Bykbaev",slug:"yaroslava-robles-bykbaev",fullName:"Yaroslava Robles-Bykbaev"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},onlineFirstChapters:{paginationCount:49,paginationItems:[{id:"83087",title:"Role of Cellular Responses in Periodontal Tissue Destruction",doi:"10.5772/intechopen.106645",signatures:"Nam Cong-Nhat Huynh",slug:"role-of-cellular-responses-in-periodontal-tissue-destruction",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Periodontology - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11566.jpg",subseries:{id:"1",title:"Oral Health"}}},{id:"83073",title:"Dental and Orofacial Trauma Impacts on Oral-Health-Related—Quality of Life in Children: Low- and Middle-Income Countries",doi:"10.5772/intechopen.105845",signatures:"Yolanda Malele-Kolisa, Nazia Khan, Mpho P. Molete, Maphefo D. Thekiso and Mzubanzi Mabongo",slug:"dental-and-orofacial-trauma-impacts-on-oral-health-related-quality-of-life-in-children-low-and-middl",totalDownloads:9,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Dental Trauma",coverURL:"https://cdn.intechopen.com/books/images_new/11567.jpg",subseries:{id:"2",title:"Prosthodontics and Implant Dentistry"}}},{id:"82938",title:"Trauma from Occlusion: Practical Management Guidelines",doi:"10.5772/intechopen.105960",signatures:"Prashanth Shetty, Shweta Hegde, Shubham Chelkar, Rahul Chaturvedi, Shruti Pochhi, Aakanksha Shrivastava, Dudala Lakshmi, Shreya Mukherjee, Pankaj Bajaj and Shahzada Asif Raza",slug:"trauma-from-occlusion-practical-management-guidelines",totalDownloads:14,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Dental Trauma",coverURL:"https://cdn.intechopen.com/books/images_new/11567.jpg",subseries:{id:"2",title:"Prosthodontics and Implant Dentistry"}}},{id:"82654",title:"Atraumatic Restorative Treatment: More than a Minimally Invasive Approach?",doi:"10.5772/intechopen.105623",signatures:"Manal A. Ablal",slug:"atraumatic-restorative-treatment-more-than-a-minimally-invasive-approach",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Dental Caries - The Selection of Restoration Methods and Restorative Materials",coverURL:"https://cdn.intechopen.com/books/images_new/11565.jpg",subseries:{id:"1",title:"Oral Health"}}},{id:"82608",title:"Early Management of Dental Trauma in the Era of COVID-19",doi:"10.5772/intechopen.105992",signatures:"Khairul Bariah Chi Adam, Haszelini Hassan, Pram Kumar Subramaniam, Izzati Nabilah Ismail, Nor Adilah Harun and Naziyah Shaban Mustafa",slug:"early-management-of-dental-trauma-in-the-era-of-covid-19",totalDownloads:3,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Dental Trauma",coverURL:"https://cdn.intechopen.com/books/images_new/11567.jpg",subseries:{id:"2",title:"Prosthodontics and Implant Dentistry"}}},{id:"82767",title:"Teeth Avulsion",doi:"10.5772/intechopen.105846",signatures:"Manal Abdalla Eltahir, Randa Fath Elrahman Ibrahim and Hanan Alharbi",slug:"teeth-avulsion",totalDownloads:21,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Dental Trauma",coverURL:"https://cdn.intechopen.com/books/images_new/11567.jpg",subseries:{id:"2",title:"Prosthodontics and Implant Dentistry"}}},{id:"82735",title:"The Influence of Salivary pH on the Prevalence of Dental Caries",doi:"10.5772/intechopen.106154",signatures:"Laura-Cristina Rusu, Alexandra Roi, Ciprian-Ioan Roi, Codruta Victoria Tigmeanu and Lavinia Cosmina Ardelean",slug:"the-influence-of-salivary-ph-on-the-prevalence-of-dental-caries",totalDownloads:12,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Dental Caries - The Selection of Restoration Methods and Restorative Materials",coverURL:"https://cdn.intechopen.com/books/images_new/11565.jpg",subseries:{id:"1",title:"Oral Health"}}},{id:"82288",title:"Dental Emergency and Conditions",doi:"10.5772/intechopen.105495",signatures:"Navneet Kaur",slug:"dental-emergency-and-conditions",totalDownloads:12,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Dental Trauma",coverURL:"https://cdn.intechopen.com/books/images_new/11567.jpg",subseries:{id:"2",title:"Prosthodontics and Implant Dentistry"}}},{id:"81961",title:"Antioxidants as an Adjuncts to Periodontal Therapy",doi:"10.5772/intechopen.105016",signatures:"Sura Dakhil Jassim and Ali Abbas Abdulkareem",slug:"antioxidants-as-an-adjuncts-to-periodontal-therapy",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Dental Trauma",coverURL:"https://cdn.intechopen.com/books/images_new/11567.jpg",subseries:{id:"2",title:"Prosthodontics and Implant Dentistry"}}},{id:"82357",title:"Caries Management Aided by Fluorescence-Based Devices",doi:"10.5772/intechopen.105567",signatures:"Atena Galuscan, Daniela Jumanca and Aurora Doris Fratila",slug:"caries-management-aided-by-fluorescence-based-devices",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Dental Caries - The Selection of Restoration Methods and Restorative Materials",coverURL:"https://cdn.intechopen.com/books/images_new/11565.jpg",subseries:{id:"1",title:"Oral Health"}}}]},subseriesFiltersForOFChapters:[{caption:"Prosthodontics and Implant Dentistry",value:2,count:23,group:"subseries"},{caption:"Oral Health",value:1,count:26,group:"subseries"}],publishedBooks:{paginationCount:33,paginationItems:[{type:"book",id:"10840",title:"Benzimidazole",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/10840.jpg",slug:"benzimidazole",publishedDate:"July 13th 2022",editedByType:"Edited by",bookSignature:"Pravin Kendrekar and Vinayak Adimule",hash:"e28c770013e7a8dd0fc37aea6aa9def8",volumeInSeries:34,fullTitle:"Benzimidazole",editors:[{id:"310674",title:"Dr.",name:"Pravin",middleName:null,surname:"Kendrekar",slug:"pravin-kendrekar",fullName:"Pravin Kendrekar",profilePictureURL:"https://mts.intechopen.com/storage/users/310674/images/system/310674.jpg",institutionString:"Visiting Scientist at Lipid Nanostructures Laboratory, Centre for Smart Materials, School of Natural Sciences, University of Central Lancashire",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"10798",title:"Starch",subtitle:"Evolution and Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/10798.jpg",slug:"starch-evolution-and-recent-advances",publishedDate:"June 28th 2022",editedByType:"Edited by",bookSignature:"Martins Ochubiojo Emeje",hash:"f197f6062c1574a9a90e50a369271bcf",volumeInSeries:33,fullTitle:"Starch - Evolution and Recent Advances",editors:[{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",institutionURL:null,country:{name:"Nigeria"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"11332",title:"Essential Oils",subtitle:"Advances in Extractions and Biological Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11332.jpg",slug:"essential-oils-advances-in-extractions-and-biological-applications",publishedDate:"June 23rd 2022",editedByType:"Edited by",bookSignature:"Mozaniel Santana de Oliveira and Eloisa Helena de Aguiar Andrade",hash:"742e6cae3a35686f975edc8d7f9afa94",volumeInSeries:32,fullTitle:"Essential Oils - Advances in Extractions and Biological Applications",editors:[{id:"195290",title:"Ph.D.",name:"Mozaniel",middleName:null,surname:"Santana De Oliveira",slug:"mozaniel-santana-de-oliveira",fullName:"Mozaniel Santana De Oliveira",profilePictureURL:"https://mts.intechopen.com/storage/users/195290/images/system/195290.png",institutionString:"Museu Paraense Emílio Goeldi",institution:{name:"Museu Paraense Emílio Goeldi",institutionURL:null,country:{name:"Brazil"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"10839",title:"Protein Detection",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/10839.jpg",slug:"protein-detection",publishedDate:"June 23rd 2022",editedByType:"Edited by",bookSignature:"Yusuf Tutar and Lütfi Tutar",hash:"2f1c0e4e0207fc45c936e7d22a5369c4",volumeInSeries:31,fullTitle:"Protein Detection",editors:[{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",institutionString:"University of Health Sciences",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"10797",title:"Cell Culture",subtitle:"Advanced Technology and Applications in Medical and Life Sciences",coverURL:"https://cdn.intechopen.com/books/images_new/10797.jpg",slug:"cell-culture-advanced-technology-and-applications-in-medical-and-life-sciences",publishedDate:"June 15th 2022",editedByType:"Edited by",bookSignature:"Xianquan Zhan",hash:"2c628f4757f9639a4450728d839a7842",volumeInSeries:30,fullTitle:"Cell Culture - Advanced Technology and Applications in Medical and Life Sciences",editors:[{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",institutionString:"Shandong First Medical University",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"10841",title:"Hydrolases",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/10841.jpg",slug:"hydrolases",publishedDate:"June 15th 2022",editedByType:"Edited by",bookSignature:"Sajjad Haider, Adnan Haider and Angel Catalá",hash:"4e868cde273d65a7ff54b1817d640629",volumeInSeries:29,fullTitle:"Hydrolases",editors:[{id:"110708",title:"Dr.",name:"Sajjad",middleName:null,surname:"Haider",slug:"sajjad-haider",fullName:"Sajjad Haider",profilePictureURL:"https://mts.intechopen.com/storage/users/110708/images/system/110708.png",institutionString:"King Saud University",institution:{name:"King Saud University",institutionURL:null,country:{name:"Saudi Arabia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"10803",title:"Reactive Oxygen Species",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/10803.jpg",slug:"reactive-oxygen-species",publishedDate:"April 28th 2022",editedByType:"Edited by",bookSignature:"Rizwan Ahmad",hash:"176adcf090fdd1f93cb8ce3146e79ca1",volumeInSeries:28,fullTitle:"Reactive Oxygen Species",editors:[{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",institutionURL:null,country:{name:"Saudi Arabia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9008",title:"Vitamin K",subtitle:"Recent Topics on the Biology and Chemistry",coverURL:"https://cdn.intechopen.com/books/images_new/9008.jpg",slug:"vitamin-k-recent-topics-on-the-biology-and-chemistry",publishedDate:"March 23rd 2022",editedByType:"Edited by",bookSignature:"Hiroyuki Kagechika and Hitoshi Shirakawa",hash:"8b43add5389ba85743e0a9491e4b9943",volumeInSeries:27,fullTitle:"Vitamin K - Recent Topics on the Biology and Chemistry",editors:[{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",institutionURL:null,country:{name:"Japan"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"10799",title:"Phenolic Compounds",subtitle:"Chemistry, Synthesis, Diversity, Non-Conventional Industrial, Pharmaceutical and Therapeutic Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10799.jpg",slug:"phenolic-compounds-chemistry-synthesis-diversity-non-conventional-industrial-pharmaceutical-and-therapeutic-applications",publishedDate:"February 23rd 2022",editedByType:"Edited by",bookSignature:"Farid A. Badria",hash:"339199f254d2987ef3167eef74fb8a38",volumeInSeries:26,fullTitle:"Phenolic Compounds - Chemistry, Synthesis, Diversity, Non-Conventional Industrial, Pharmaceutical and Therapeutic Applications",editors:[{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",institutionString:"Mansoura University",institution:{name:"Mansoura University",institutionURL:null,country:{name:"Egypt"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9659",title:"Fibroblasts",subtitle:"Advances in Inflammation, Autoimmunity and Cancer",coverURL:"https://cdn.intechopen.com/books/images_new/9659.jpg",slug:"fibroblasts-advances-in-inflammation-autoimmunity-and-cancer",publishedDate:"December 22nd 2021",editedByType:"Edited by",bookSignature:"Mojca Frank Bertoncelj and Katja Lakota",hash:"926fa6446f6befbd363fc74971a56de2",volumeInSeries:25,fullTitle:"Fibroblasts - Advances in Inflammation, Autoimmunity and Cancer",editors:[{id:"328755",title:"Ph.D.",name:"Mojca",middleName:null,surname:"Frank Bertoncelj",slug:"mojca-frank-bertoncelj",fullName:"Mojca Frank Bertoncelj",profilePictureURL:"https://mts.intechopen.com/storage/users/328755/images/system/328755.jpg",institutionString:"BioMed X Institute",institution:{name:"University Hospital of Zurich",institutionURL:null,country:{name:"Switzerland"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"8977",title:"Protein Kinases",subtitle:"Promising Targets for Anticancer Drug Research",coverURL:"https://cdn.intechopen.com/books/images_new/8977.jpg",slug:"protein-kinases-promising-targets-for-anticancer-drug-research",publishedDate:"December 8th 2021",editedByType:"Edited by",bookSignature:"Rajesh Kumar Singh",hash:"6d200cc031706a565b554fdb1c478901",volumeInSeries:24,fullTitle:"Protein Kinases - Promising Targets for Anticancer Drug Research",editors:[{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"8018",title:"Extracellular Matrix",subtitle:"Developments and Therapeutics",coverURL:"https://cdn.intechopen.com/books/images_new/8018.jpg",slug:"extracellular-matrix-developments-and-therapeutics",publishedDate:"October 27th 2021",editedByType:"Edited by",bookSignature:"Rama Sashank Madhurapantula, Joseph Orgel P.R.O. and Zvi Loewy",hash:"c85e82851e80b40282ff9be99ddf2046",volumeInSeries:23,fullTitle:"Extracellular Matrix - Developments and Therapeutics",editors:[{id:"212416",title:"Dr.",name:"Rama Sashank",middleName:null,surname:"Madhurapantula",slug:"rama-sashank-madhurapantula",fullName:"Rama Sashank Madhurapantula",profilePictureURL:"https://mts.intechopen.com/storage/users/212416/images/system/212416.jpg",institutionString:"Illinois Institute of Technology",institution:{name:"Illinois Institute of Technology",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Proteomics",value:18,count:4},{group:"subseries",caption:"Metabolism",value:17,count:6},{group:"subseries",caption:"Cell and Molecular Biology",value:14,count:9},{group:"subseries",caption:"Chemical Biology",value:15,count:14}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:9},{group:"publicationYear",caption:"2021",value:2021,count:7},{group:"publicationYear",caption:"2020",value:2020,count:12},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:2}],authors:{paginationCount:148,paginationItems:[{id:"165328",title:"Dr.",name:"Vahid",middleName:null,surname:"Asadpour",slug:"vahid-asadpour",fullName:"Vahid Asadpour",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/165328/images/system/165328.jpg",biography:"Vahid Asadpour, MS, Ph.D., is currently with the Department of Research and Evaluation, Kaiser Permanente Southern California. He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:{name:"Association for Computing Machinery",country:{name:"United States of America"}}},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"426586",title:"Dr.",name:"Oladunni A.",middleName:null,surname:"Daramola",slug:"oladunni-a.-daramola",fullName:"Oladunni A. Daramola",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Federal University of Technology",country:{name:"Nigeria"}}},{id:"357014",title:"Prof.",name:"Leon",middleName:null,surname:"Bobrowski",slug:"leon-bobrowski",fullName:"Leon Bobrowski",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Bialystok University of Technology",country:{name:"Poland"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"354126",title:"Dr.",name:"Setiawan",middleName:null,surname:"Hadi",slug:"setiawan-hadi",fullName:"Setiawan Hadi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Padjadjaran University",country:{name:"Indonesia"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"332603",title:"Prof.",name:"Kumar S.",middleName:null,surname:"Ray",slug:"kumar-s.-ray",fullName:"Kumar S. Ray",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Statistical Institute",country:{name:"India"}}},{id:"415409",title:"Prof.",name:"Maghsoud",middleName:null,surname:"Amiri",slug:"maghsoud-amiri",fullName:"Maghsoud Amiri",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Allameh Tabataba'i University",country:{name:"Iran"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}}]}},subseries:{item:{id:"17",type:"subseries",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11413,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,series:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983"},editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",slug:"anca-pantea-stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",slug:"attilio-rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",slug:"yanfei-(jacob)-qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},onlineFirstChapters:{paginationCount:18,paginationItems:[{id:"82875",title:"Lipidomics as a Tool in the Diagnosis and Clinical Therapy",doi:"10.5772/intechopen.105857",signatures:"María Elizbeth Alvarez Sánchez, Erick Nolasco Ontiveros, Rodrigo Arreola, Adriana Montserrat Espinosa González, Ana María García Bores, Roberto Eduardo López Urrutia, Ignacio Peñalosa Castro, María del Socorro Sánchez Correa and Edgar Antonio Estrella Parra",slug:"lipidomics-as-a-tool-in-the-diagnosis-and-clinical-therapy",totalDownloads:9,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82440",title:"Lipid Metabolism and Associated Molecular Signaling Events in Autoimmune Disease",doi:"10.5772/intechopen.105746",signatures:"Mohan Vanditha, Sonu Das and Mathew John",slug:"lipid-metabolism-and-associated-molecular-signaling-events-in-autoimmune-disease",totalDownloads:17,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82709",title:"Fatty Acid Metabolism as a Tumor Marker",doi:"10.5772/intechopen.106072",signatures:"Gatot Nyarumenteng Adhipurnawan Winarno",slug:"fatty-acid-metabolism-as-a-tumor-marker",totalDownloads:10,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82583",title:"Leukaemia: The Purinergic System and Small Extracellular Vesicles",doi:"10.5772/intechopen.104326",signatures:"Arinzechukwu Ude and Kelechi Okeke",slug:"leukaemia-the-purinergic-system-and-small-extracellular-vesicles",totalDownloads:11,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82531",title:"Abnormal Iron Metabolism and Its Effect on Dentistry",doi:"10.5772/intechopen.104502",signatures:"Chinmayee Dahihandekar and Sweta Kale Pisulkar",slug:"abnormal-iron-metabolism-and-its-effect-on-dentistry",totalDownloads:12,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Iron Metabolism - A Double-Edged Sword",coverURL:"https://cdn.intechopen.com/books/images_new/10842.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82409",title:"Purinergic Signaling in Covid-19 Disease",doi:"10.5772/intechopen.105008",signatures:"Hailian Shen",slug:"purinergic-signaling-in-covid-19-disease",totalDownloads:8,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82374",title:"The Potential of the Purinergic System as a Therapeutic Target of Natural Compounds in Cutaneous Melanoma",doi:"10.5772/intechopen.105457",signatures:"Gilnei Bruno da Silva, Daiane Manica, Marcelo Moreno and Margarete Dulce Bagatini",slug:"the-potential-of-the-purinergic-system-as-a-therapeutic-target-of-natural-compounds-in-cutaneous-mel",totalDownloads:12,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82096",title:"An Important Component of Tumor Progression: Fatty Acids",doi:"10.5772/intechopen.105087",signatures:"Jin Wang, Qifei Wang and Guangzhen Wu",slug:"an-important-component-of-tumor-progression-fatty-acids",totalDownloads:9,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81927",title:"Purinergic System in Immune Response",doi:"10.5772/intechopen.104485",signatures:"Yerly Magnolia Useche Salvador",slug:"purinergic-system-in-immune-response",totalDownloads:18,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"80495",title:"Iron in Cell Metabolism and Disease",doi:"10.5772/intechopen.101908",signatures:"Eeka Prabhakar",slug:"iron-in-cell-metabolism-and-disease",totalDownloads:22,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Iron Metabolism - A Double-Edged Sword",coverURL:"https://cdn.intechopen.com/books/images_new/10842.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81799",title:"Cross Talk of Purinergic and Immune Signaling: Implication in Inflammatory and Pathogenic Diseases",doi:"10.5772/intechopen.104978",signatures:"Richa Rai",slug:"cross-talk-of-purinergic-and-immune-signaling-implication-in-inflammatory-and-pathogenic-diseases",totalDownloads:49,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81764",title:"Involvement of the Purinergic System in Cell Death in Models of Retinopathies",doi:"10.5772/intechopen.103935",signatures:"Douglas Penaforte Cruz, Marinna Garcia Repossi and Lucianne Fragel Madeira",slug:"involvement-of-the-purinergic-system-in-cell-death-in-models-of-retinopathies",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81681",title:"Immunomodulatory Effects of a M2-Conditioned Medium (PRS® CK STORM): Theory on the Possible Complex Mechanism of Action through Anti-Inflammatory Modulation of the TLR System and the Purinergic System",doi:"10.5772/intechopen.104486",signatures:"Juan Pedro Lapuente",slug:"immunomodulatory-effects-of-a-m2-conditioned-medium-prs-ck-storm-theory-on-the-possible-complex-mech",totalDownloads:13,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81580",title:"Graft-Versus-Host Disease: Pathogenesis and Treatment",doi:"10.5772/intechopen.104450",signatures:"Shin Mukai",slug:"graft-versus-host-disease-pathogenesis-and-treatment",totalDownloads:39,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"80485",title:"Potential Marker for Diagnosis and Screening of Iron Deficiency Anemia in Children",doi:"10.5772/intechopen.102792",signatures:"Yulia Nadar Indrasari, Siti Nurul Hapsari and Muhamad Robiul Fuadi",slug:"potential-marker-for-diagnosis-and-screening-of-iron-deficiency-anemia-in-children",totalDownloads:67,totalCrossrefCites:0,totalDimensionsCites:1,authors:null,book:{title:"Iron Metabolism - A Double-Edged Sword",coverURL:"https://cdn.intechopen.com/books/images_new/10842.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"79693",title:"Ferroptosis: Can Iron be the Last or Cure for a Cell?",doi:"10.5772/intechopen.101426",signatures:"Asuman Akkaya Fırat",slug:"ferroptosis-can-iron-be-the-last-or-cure-for-a-cell",totalDownloads:109,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Iron Metabolism - A Double-Edged Sword",coverURL:"https://cdn.intechopen.com/books/images_new/10842.jpg",subseries:{id:"17",title:"Metabolism"}}}]},publishedBooks:{paginationCount:1,paginationItems:[{type:"book",id:"11392",title:"Leadership in a Changing World",subtitle:"A Multidimensional Perspective",coverURL:"https://cdn.intechopen.com/books/images_new/11392.jpg",slug:"leadership-in-a-changing-world-a-multidimensional-perspective",publishedDate:"May 11th 2022",editedByType:"Edited by",bookSignature:"Muhammad Mohiuddin, Bilal Khalid, Md. Samim Al Azad and Slimane Ed-dafali",hash:"86a6d33cf601587e591064ce92effc02",volumeInSeries:1,fullTitle:"Leadership in a Changing World - A Multidimensional Perspective",editors:[{id:"418514",title:"Dr.",name:"Muhammad",middleName:null,surname:"Mohiuddin",slug:"muhammad-mohiuddin",fullName:"Muhammad Mohiuddin",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038UqSfQAK/Profile_Picture_2022-05-13T10:39:03.jpg",institutionString:"Université Laval",institution:{name:"Université Laval",institutionURL:null,country:{name:"Canada"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},testimonialsList:[{id:"27",text:"The opportunity to work with a prestigious publisher allows for the possibility to collaborate with more research groups interested in animal nutrition, leading to the development of new feeding strategies and food valuation while being more sustainable with the environment, allowing more readers to learn about the subject.",author:{id:"175967",name:"Manuel",surname:"Gonzalez Ronquillo",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",slug:"manuel-gonzalez-ronquillo",institution:{id:"6221",name:"Universidad Autónoma del Estado de México",country:{id:null,name:"Mexico"}}}},{id:"18",text:"It was great publishing with IntechOpen, the process was straightforward and I had support all along.",author:{id:"71579",name:"Berend",surname:"Olivier",institutionString:"Utrecht University",profilePictureURL:"https://mts.intechopen.com/storage/users/71579/images/system/71579.png",slug:"berend-olivier",institution:{id:"253",name:"Utrecht University",country:{id:null,name:"Netherlands"}}}},{id:"8",text:"I work with IntechOpen for a number of reasons: their professionalism, their mission in support of Open Access publishing, and the quality of their peer-reviewed publications, but also because they believe in equality.",author:{id:"202192",name:"Catrin",surname:"Rutland",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",slug:"catrin-rutland",institution:{id:"134",name:"University of Nottingham",country:{id:null,name:"United Kingdom"}}}}]},submityourwork:{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:108,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:141,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:124,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:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,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}],subseriesList:[{id:"3",title:"Bacterial Infectious Diseases",scope:"
\r\n\tThe era of antibiotics led us to the illusion that the problem of bacterial infection is over. However, bacterial flexibility and adaptation mechanisms allow them to survive and grow in extreme conditions. The best example is the formation of a sophisticated society of bacteria defined as a biofilm. Understanding the mechanism of bacterial biofilm formation has changed our perception of the development of bacterial infection but successfully eradicating biofilm remains a challenge. Considering the above, it is not surprising that bacteria remain a major public health threat despite the development of many groups of antibiotics. Additionally, increasing prevalence of acquired antibiotic resistance forces us to realize that we are far from controlling the development of bacterial infections. On the other hand, many infections are endogenous and result from an unbalanced relationship between the host and the microorganism. The increasing use of immunosuppressants, such as chemotherapy or organ transplantation, increases the incidence of patients highly susceptible to bacterial infections in the population.
\r\n
\r\n\tThis topic will focus on the current challenges and advantages in the diagnosis and treatment of bacterial infections. We will discuss the host-microbiota relationship, the treatment of chronic infections due to biofilm formation, and the development of new diagnostic tools to rapidly distinguish between colonization and probable infection.
",coverUrl:"https://cdn.intechopen.com/series_topics/covers/3.jpg",keywords:"Antibiotics, Biofilm, Antibiotic Resistance, Host-microbiota Relationship, Treatment, Diagnostic Tools"},{id:"4",title:"Fungal Infectious Diseases",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",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment"},{id:"5",title:"Parasitic Infectious Diseases",scope:"Parasitic diseases have evolved alongside their human hosts. In many cases, these diseases have adapted so well that they have developed efficient resilience methods in the human host and can live in the host for years. Others, particularly some blood parasites, can cause very acute diseases and are responsible for millions of deaths yearly. Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. In the current atmosphere of the Coronavirus pandemic, communities around the world, particularly those in different underdeveloped areas, are faced with the growing challenges of the high burden of parasitic diseases. At the same time, they are faced with the Covid-19 pandemic leading to what some authors have called potential syndemics that might worsen the outcome of such infections. Therefore, it is important to conduct studies that examine parasitic infections in the context of the coronavirus pandemic for the benefit of all communities to help foster more informed decisions for the betterment of human and animal health.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",keywords:"Blood Borne Parasites, Intestinal Parasites, Protozoa, Helminths, Arthropods, Water Born Parasites, Epidemiology, Molecular Biology, Systematics, Genomics, Proteomics, Ecology"},{id:"6",title:"Viral Infectious Diseases",scope:"The Viral Infectious Diseases Book Series aims to provide a comprehensive overview of recent research trends and discoveries in various viral infectious diseases emerging around the globe. The emergence of any viral disease is hard to anticipate, which often contributes to death. A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. This series will focus on various crucial factors related to emerging viral infectious diseases, including epidemiology, pathogenesis, host immune response, clinical manifestations, diagnosis, treatment, and clinical recommendations for managing viral infectious diseases, highlighting the recent issues with future directions for effective therapeutic strategies.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",keywords:"Novel Viruses, Virus Transmission, Virus Evolution, Molecular Virology, Control and Prevention, Virus-host Interaction"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:null},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/257819",hash:"",query:{},params:{id:"257819"},fullPath:"/profiles/257819",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()