\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
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",isbn:"978-1-80356-516-3",printIsbn:"978-1-80356-515-6",pdfIsbn:"978-1-80356-517-0",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"b3249deb4cc255484aac878ab8309ded",bookSignature:"Prof. Julia Fedotova",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11639.jpg",keywords:"Vitamin D, SARS-CoV-2, Pharmacotherapy, Post-COVID Syndrome, Rehabilitation, Therapy, Vitamin D Deficiency, Schizophrenia, Prenatal Period, Mechanisms of Schizophrenia, Vitamin D Analogs, Pharmacocorrection",numberOfDownloads:33,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 8th 2022",dateEndSecondStepPublish:"May 12th 2022",dateEndThirdStepPublish:"July 11th 2022",dateEndFourthStepPublish:"September 29th 2022",dateEndFifthStepPublish:"November 28th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"3 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Dr. Julia Fedotova is a leader of several major projects including a grant from the Russian Scientific Foundation RSF 16-15-10053 and RSF 16-15-10053. She is a Member of the St.Petersburg branch of the Russian Pharmacology Society, a Member of the St. Petersburg branch of the Russian Physiologists, biochemists, and pharmacologists, and a Member of the International Society of Dietary Supplements and Phytotherapy.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"269070",title:"Prof.",name:"Julia",middleName:null,surname:"Fedotova",slug:"julia-fedotova",fullName:"Julia Fedotova",profilePictureURL:"https://mts.intechopen.com/storage/users/269070/images/system/269070.jfif",biography:"Julia O. Fedotova, MD, PhD habil., Doc. Biol. Sci was born in St. Petersburg (Russia), in 1973. She graduated and received her Diploma of Pharmacist, from Pharmaceutical Faculty, St. Petersburg State Chemical-Pharmaceutical Academy in 1996. She received her\nPh.D. in Experimental and Clinical Pharmacology and\nPhysiology of Humans and Animals in 1999. She attended the Medical\nSchool, Department of Pharmacology, University of Catania in\n2002, and the Institute of Physiology, Medical School, University of Pecs. She graduated from the special doctoral course in neuropharmacology at the Department\nof Neuropharmacology in the Institute for Experimental Medicine of the Russian\nAcademy of Medical Sciences and she received her Doctor of Biological Sciences degree\n(Ph.D. habil.) in 2008. She is currently a professor at the ITMO University and the\nleading researcher at the I.P. Pavlov Institute of Physiology. She has more than 200 publications (mostly in Russian), 2 patents, and 4 journal articles in collaboration, as well as 6 chapters in journals.\nShe is head of the project “The studying of Vitamin D3 role in the development of\naffective-related disorders in women in the climacteric period, the search of ways for\npharmacorrection”, from the prestigious Russian Scientific Foundation.",institutionString:"ITMO University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"ITMO University",institutionURL:null,country:{name:"Russia"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"5",title:"Agricultural and Biological Sciences",slug:"agricultural-and-biological-sciences"}],chapters:[{id:"82474",title:"Vitamin D Deficiency in Childhood Obesity: Behavioral Factors or Altered Metabolism?",slug:"vitamin-d-deficiency-in-childhood-obesity-behavioral-factors-or-altered-metabolism",totalDownloads:21,totalCrossrefCites:0,authors:[{id:"53819",title:"Prof.",name:"Teodoro",surname:"Durá-Travé",slug:"teodoro-dura-trave",fullName:"Teodoro Durá-Travé"},{id:"60541",title:"Dr.",name:"Fidel",surname:"Gallinas-Victoriano",slug:"fidel-gallinas-victoriano",fullName:"Fidel Gallinas-Victoriano"}]},{id:"82475",title:"Pharmacological Efficacy and Mechanism of Vitamin D in the Treatment of “Kidney-Brain” Disorders",slug:"pharmacological-efficacy-and-mechanism-of-vitamin-d-in-the-treatment-of-kidney-brain-disorders",totalDownloads:12,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"347259",firstName:"Karmen",lastName:"Daleta",middleName:null,title:"Ms.",imageUrl:"//cdnintech.com/web/frontend/www/assets/author.svg",email:"karmen@intechopen.com",biography:null}},relatedBooks:[{type:"book",id:"7038",title:"Vitamin D Deficiency",subtitle:null,isOpenForSubmission:!1,hash:"ba24f0913341357b0779ff9529c4bbfc",slug:"vitamin-d-deficiency",bookSignature:"Julia Fedotova",coverURL:"https://cdn.intechopen.com/books/images_new/7038.jpg",editedByType:"Edited by",editors:[{id:"269070",title:"Prof.",name:"Julia",surname:"Fedotova",slug:"julia-fedotova",fullName:"Julia Fedotova"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6418",title:"Hyperspectral Imaging in Agriculture, Food and Environment",subtitle:null,isOpenForSubmission:!1,hash:"9005c36534a5dc065577a011aea13d4d",slug:"hyperspectral-imaging-in-agriculture-food-and-environment",bookSignature:"Alejandro Isabel Luna Maldonado, Humberto Rodríguez Fuentes and Juan Antonio Vidales Contreras",coverURL:"https://cdn.intechopen.com/books/images_new/6418.jpg",editedByType:"Edited by",editors:[{id:"105774",title:"Prof.",name:"Alejandro Isabel",surname:"Luna Maldonado",slug:"alejandro-isabel-luna-maldonado",fullName:"Alejandro Isabel Luna Maldonado"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10359",title:"Landraces",subtitle:"Traditional Variety and Natural Breed",isOpenForSubmission:!1,hash:"0600836fb2c422f7b624363d1e854f68",slug:"landraces-traditional-variety-and-natural-breed",bookSignature:"Amr Elkelish",coverURL:"https://cdn.intechopen.com/books/images_new/10359.jpg",editedByType:"Edited by",editors:[{id:"231337",title:"Dr.",name:"Amr",surname:"Elkelish",slug:"amr-elkelish",fullName:"Amr Elkelish"}],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. 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The Rho family proteins share a high degree of homology with the Ras proto-oncogene, and indeed were first identified as a result of this similarity (
Although united by homology and function as regulators of the actin cytoskeleton, each of RhoA, Rac1 and Cdc42 has a distinct role in the organization of actin structures (Figure 1). RhoA is principally involved with the production of actin-myosin bundles and the generation of actomyosin contractile force. Rac1 contributes to the formation of actin meshworks that result in the emergence of large protrusive structures that lead to spreading or, if occurring in a polarized manner, will contribute to motility. Cdc42 promotes the formation of actin-rich filopodia. Together, coordinated programs of RhoA, Rac1 and Cdc42 activation/inactivation play prominent roles in processes such as endocytosis/exocytosis, adhesion and motility, which may subsequently impact upon proliferation and death/survival. Recent advances in the development of activation-state sensitive fluorescent probes have allowed temporal and spatial analysis of Rho protein activation, which has added significantly to our appreciation of Rho regulation and function (Hodgson et al. 2010). Much of the early research on Rho protein function relied upon over-expression of dominant-negative mutants that reduced affinity for GTP and constitutively-active mutants that reduced GTP hydrolysis; however, more refined analysis has become possible with the rise of RNAi and knockout methodologies (Heasman and Ridley 2008).
The study of Rho family proteins has historically focused on their roles as molecular switches acting downstream of cell surface receptors to regulate the actin cytoskeleton (Jaffe and Hall 2005). Significant effort has gone into classifying signaling from Rho proteins into
Diagram of actin structures regulated by RhoA, Rac1 and Cdc42.
linear cascades, similarly to the classical Ras/Raf/MEK/ERK kinase cascade. However, recently a greater appreciation of the role of mechanical forces as fundamental influences in biology has emerged (Puceat et al. 2003). As central regulators of the actin-myosin cytoskeleton, an emerging concept is that many of the activities of Rho proteins may not be attributable to simple linear pathways, but instead are the product of modulating contraction and relaxation at the cellular and subcellular levels, with consequent effects on development and function at the tissue and organismal levels.
Pluripotent stem cells were first isolated from testicular teratocarcinoma (Pierce and Dixon 1959), a germ cell tumor type containing a population of pluripotent stem cells together with embryonic and extra-embryonic tissues that arise from these stem cells. Pluripotent stem cells of testicular teratocarcinomas are termed Embryonal Carcinoma (EC) cells and can give rise to collections of tumor cells having morphological characteristics of each of the three embryonic germ layers. In mice, EC cells have been demonstrated to be capable of contributing to every germ layer including the germ-line when injected into host blastocysts (Brinster 1974; Mintz and Illmensee 1975; Illmensee and Mintz 1976). Interestingly, under these conditions, EC cells are non-malignant, and chimeric mice containing tissues differentiated from EC cells are generally healthy. These observations formed the basis for the isolation of Embryonic Stem (ES) cells, which were derived from the pre-implantation embryo, arising when cells constituting the inner cell mass (ICM) of the pre-implantation blastocyst or the epiblast of the post-implantation blastocyst were placed in 2D-culture (Evans and Kaufman 1981; Martin 1981). Like EC cells, ES cells are pluripotent, being capable of giving rise to all tissues of the adult organism originating from the three germ layers, upon injection into a host blastocyst (Bradley et al. 1984). The great similarities observed between EC cells and ES cells led to an appreciation of the importance of the tissue microenvironment in informing cell behavior and fate.
A major attraction of murine ESC (mESC) research stemmed from the realization that mutations introduced into the mESC genome would be readily transmitted through the germ-line, enabling the establishment of strains of mice harboring specific genetic mutations (Capecchi 1989), thereby facilitating the elegant functional characterization of virtually any gene of interest. The first gene to be targeted and inactivated in mES cells was the X-linked gene
ES cells express markers of their undifferentiated state such as the octamer binding protein 4 (Oct4) (Rosner et al. 1990; Scholer et al. 1990), the SRY-related HMG-box gene 2 (Sox2) (Yuan et al. 1995), signal transducer and activator of transcription 3 (Stat3) (Niwa et al. 1998), the homeobox protein Nanog (Chambers et al. 2003; Mitsui et al. 2003) and alkaline phosphatase (AP) (Hahnel et al. 1990) that denote their capacity for both self-renewal and pluripotency. Of these, Oct4 and Sox2 have key roles in the maintenance of ES cell self-renewing capacity such that their expression is essential for the maintenance of pluripotency and their ectopic expression in somatic cells contributes to the generation of induced pluripotent (iPS) cells (Takahashi and Yamanaka 2006; Yu et al. 2007; Nakagawa et al. 2008).
Oct4 is a POU-domain transcription factor also termed POU5F1 and is indispensable for plutipotency. Oct4 deficient embryos develop to the morula stage, but are unable to form an ICM (Nichols et al. 1998) and in vitro culture of Oct4 deficient embryos failed to yield ES cells (Nichols et al. 1998). These observations are further elaborated by more recent work showing that selective deletion of the Oct4 gene in primordial germ cells (PGC) results in their death by apoptosis (Kehler et al. 2004). Oct4 expression is very tightly regulated and its transient increase and decrease during early stages of embryonic development have been termed the totipotent cycle (Yeom et al. 1996). While evidence for the absolute requirement for Oct4 in the maintenance of ES cells is very strong, there is controversy on whether it is required for the maintenance of adult stem cells. Although there are numerous reports of Oct4 expression in adult stem cells including in hematopoietic and mesenchymal stem cells and stem cells of epithelial tissues such as the pancreas, kidney, breast, uterus, lung and skin, a recent study in which its expression was systematically abrogated in several of these tissues has revealed that Oct4 is required for neither the maintenance of adult stem cells nor for wound healing (Lengner et al. 2007).
Sox2 is a HMG-box containing transcription factor closely related to the Y-chromosome located sex determining gene SRY. Its main role in the maintenance of pluripotency is thought to be closely related to the regulation of Oct4 transcription. Indeed Sox2 and Oct4 can jointly bind regulatory chromosomal regions associated with both the
Since the initial isolation of ICM-derived mESCs in the early 1980s (Evans and Kaufman 1981; Martin 1981), conditions for the culture of ESCs have been developed and progressively refined. mESCs are propagated on a feeder layer of murine embryonic fibroblasts (MEFs) or in media containing leukemia inhibitory factor (LIF), under which conditions they maintain a pluripotent state (Williams et al. 1988). Withdrawal of LIF or culture in the absence of fibroblasts results in spontaneous differentiation of mESCs into a variety of lineages (Evans and Kaufman 1981; Martin 1981; Williams et al. 1988). The dependence of mES cells on LIF is thought to be related to LIF mediated activation of STAT3 signaling (Smith et al. 1988) which together with Oct4/Sox2, has a possible role in the regulation of Nanog expression.
Human ESCs (hESCs), which have been isolated from the epiblasts of human blastocysts (Thomson et al. 1998; Reubinoff et al. 2000) are also propagated on a feeder layer of MEFs, but LIF has no role in maintaining their pluripotency (Thomson et al. 1998; Reubinoff et al. 2000). Instead, a balance between Tgfβ/activin/nodal signaling and suppression of BMP signaling together with the FGF signaling pathway are important for self-renewal and the maintenance of pluripotency in this system (James et al. 2005; Vallier et al. 2005; Xu et al. 2005). However, as yet no reliable defined medium has been developed to enable the culture of hES cells in the absence of feeder cells. Like mESCs, hESCs spontaneously differentiate if cultured in the absence of a feeder layer, but unlike mESCs they undergo blebbing and apoptosis when maintained in a dissociated state (Watanabe et al. 2007).
hESCs are not only a valuable tool for the study of human development, but also have applications in regenerative medicine, toxicology and the development of new drugs to target human disease (Murry and Keller 2008). mESCs and hESCs are thus examples of the two major types of pluripotent stem cells, derived as they are from the ICM and the epiblast respectively.
One of the most interesting recent developments in ES research is the revelation that signaling through RhoA plays a key role in the survival of human embryonic stem cells. This was first appreciated in 2007, following a cell-based screen of biologically active compounds that promoted survival and proliferation of dissociated hESCs that identified Y27632, a selective inhibitor of the Rho-effector protein ROCK (Watanabe et al. 2007). The ROCK1 and ROCK2 serine/threonine kinases are central and critical regulators of actomyosin contractility (Coleman et al. 2001). Typically, these kinases are activated by association with active GTP-bound Rho proteins. Active ROCK promotes actomyosin contractility through a dual mechanism of simultaneously phosphorylating and activating the contractile force-generating regulatory myosin light chain (MLC) and the LIM kinases (Sugihara et al. 1998), which modulate filamentous actin stability. In contrast to hESC, mES cells do not require ROCK inhibition for survival even when disaggregated to a single cell suspension. Since that initial study, subsequent screens have identified additional ROCK selective inhibitors that promote the survival of hESC (Andrews et al. 2010; Pakzad et al. 2010) and neural stem cells (Xu et al. 2010), thereby independently validating the role of ROCK as a key regulator of ESC survival. The addition of Y27632 to the culture media is now standard practice and has greatly improved the reliability of hES cell survival (Olson 2008; Krawetz et al. 2009). The addition of Y-27632 can be directly to the cell culture medium or into the extracellular matrix upon which the hESCs are plated (Danovi et al. 2010). ROCK inhibitors have also been shown to improve recovery of cryopreserved ESC (Scott and Olson 2007; Wickman et al. 2010) and increase the efficiency of adenovirus-mediated gene transfer (Patwari and Lee 2008).
Recently, it has become clear that the actomyosin machinery downstream of Rho activation is essential for the blebbing and apoptosis that follow dissociation of hESCs (Martin 1981; Chen et al. 2010; Ohgushi et al. 2010), as inhibition of the myosin heavy chain ATPase with Blebbistatin, the use of actin disruption drugs or selective knock-down of ROCK1, ROCK2 or the myosin heavy and light chains all prolong survival of dissociated hESCs. Rho activation, coupled with Rac inhibition, was determined to be the driver of dissociation-induced hESC apoptosis via ROCK-mediated myosin light chain phosphorylation (Ohgushi et al. 2010). Activation of ROCK1 by caspase-mediated cleavage (Buecker et al. 2010) does not appear to contribute to apoptosis induced in this manner (Ohgushi et al. 2010). Overexpression of an active form of Ezrin, which strengthens the physical coupling between the plasma membrane and cortical actin cytoskeleton, was sufficient to block blebbing but not the dissociation-induced cell death, indicating that apoptosis was not caused by blebbing itself but the result of actomyosin contraction (Ohgushi et al. 2010). Although the dissociation-induced cell death was linked back to mitochondrial depolarization and cytochrome c release, further study will be required to determine how actomyosin contractility is coupled to the mitochondrial pathway of apoptosis (Ohgushi et al. 2010). It is also becoming clear that the particular sub-embryonic origin of the embryonic stem cell line determines whether Rho signaling is detrimental to survival on dissociation. While epiblast-derived hESCs are acutely sensitive to Rho signaling following dissociation, ICM-derived mESC have the capacity to survive dissociation without the need for inhibition of the actomyosin machinery (Ohgushi et al. 2010), a characteristic they share with human induced pluripotent stem cells (hiPSC), which display mESC-like morphological features (Evans and Kaufman 1981). On the other hand, epiblast-derived murine epiblast stem cells (mEpiSC) or mESCs differentiated into epiblast-like cells acquire a dependence on ROCK-inhibition in order to survive dissociation (Ohgushi et al. 2010). One theoretical possibility to account for these observations is that external pulling forces from adjacent cells in an epithelial sheet counteract the internal actomyosin contractile forces within individual cells such that the internal and external mechanical forces become balanced in all directions along the epithelial plane, thereby limiting their pro-apoptotic effects. Since mESCs are derived from the ICM prior to differentiation into epithelial-type cells and grow in disorganized three-dimensional cell collectives similar to the
The pro-apoptotic effect of Rho signaling in dissociated hESC is strongly counteracted by signaling through Rac. Indeed it has been shown that Rac1 is required for the survival of epiblast cells within the blastocyst during morphogenesis of the murine peri-implantation egg cylinder (He et al. 2010). During this process, the apoptosis mediated clearance of cells that are not in contact with the basement membrane (known as cavitation) is counteracted by signaling through Rac in those cells that remain apposed to the basement membrane (BM). In the absence of Rac1, cells in contact with the BM undergo apoptosis despite the survival signals that it normally provides (Kim et al. 2011). It is these BM-associated cells that give rise to the epiblast (He et al. 2010). Activation of Rac in the epiblast is mediated by the recruitment of the Crk adaptor protein and DOCK180 GEF (He et al. 2010). In turn, active Rac signals via PI3K and Akt to promote survival (He et al. 2010). Interestingly, a single dual-function protein, Abr, acts as Rho-GEF and Rac-GAP within dissociated hES cells in culture, simultaneously activating Rho and inactivating Rac upon cell dissociation, in a manner dependent on cell-cell interactions involving E-cadherin (Martin 1981; Ohgushi et al. 2010). The role of E-cadherin in hESC survival was also revealed in a chemical biology screen for small molecules that affected survival (Pakzad et al. 2010). One compound increased the survival of dissociated cells by reducing E-cadherin endocytosis, thus increasing the levels of cell-surface E-cadherin and consequently promoting cell-cell adhesions. In agreement with these observations, ectopic over-expression of E-cadherin was also sufficient to increase survival of dissociated hESCs (Rizzino 2010). However, when dissociated hESCs were grown on E-cadherin coated plates, they still underwent membrane blebbing and had significantly lower survival, indicating that homotypic E-cadherin interactions alone were not sufficient to promote survival (Ohgushi et al. 2010). These observations suggest the existence of a yet uncharacterized sensor that transmits a complementary signal derived from cell-cell adhesion that acts in concert with, or in parallel to, E-cadherin activation to repress actomyosin contractility and consequent cell death. Although mESCs are not sensitive to the same sort of dissociation-induced cell death, constitutive Rac1 deletion was found to induce membrane blebbing and eventual apoptosis of epiblast derived stem cells, possibly due to the lack of Rac1 activity to counter-balance the effect of RhoA activation (Kim et al. 2011). These Rac1 deleted cells also were defective in the formation of actin cytoskeleton structures such as lamellipodia and were significantly slower in migrating on collagen I coated dishes, revealing the critical role played by Rac1 in these biological activities. Similarly, Rac1 was found to be an important contributor to mESC migration on laminin (Li et al. 2010).
Also implicated in murine peri-implantation development is the Cdc42 GTP-binding protein. Mouse embryoid bodies deficient for Cdc42 exhibited polarization defects characterized by aberrant adherens and tight cell-cell junction formation and failure of cavitation (Wu et al. 2007), in a process mediated by the atypical protein kinase C (aPKC) family of kinases. Despite the polarization defects, basement membrane formation, which requires polarized deposition and assembly of basement membrane components at the basal side of a cell layer, was unaffected by deletion of Cdc42 (Wu et al. 2007). Interestingly mES cells lacking Cdc42 had lower levels of active Rac1 although total Rac1 protein levels were unaffected (Wu et al. 2007), suggesting that some of the observed defects could be the result of reduced Rac1 activity. However, unlike Rac1 deficient mES cells that would undergo apoptosis while in contact with the basement membrane (Kim et al. 2011), deletion of Cdc42 still allowed survival of cells in contact with the BM (Wu et al. 2007). Additional defects in PIP2-induced actin polymerization and cytoskeletal organization were likely to also contribute to defective adhesion and migration of mESC deleted of Cdc42 (Chambers et al. 2003; Wu et al. 2007). The motility of mESC plated on plated on laminin also were dependent on Cdc42 as revealed by siRNA-mediated knockdown (Li et al. 2010). These morphological, polarization and motility defects almost certainly contributed to early embryonic lethality in Cdc42 deficient mice (Chambers et al. 2003). These tantalizing observations point to complementary functions for Rho, Rac and Cdc42 during the processes of cavitation and the appearance of the epiblast, and underscore the importance of these proteins in appropriately mediating the survival or apoptotic clearance of cells during early morphogenesis. It therefore appears that the activity of the Rho family GTPases crucially determines the fate of pluripotent stem cells within the early developing embryo.
An interesting aspect of ESC is that under the right conditions, such as hanging drop suspension leading to the formation of embryoid bodies (Kurosawa 2007), differentiation results in the production of cardiomyocytes that spontaneously contact and relax (beating) as they would in an intact heart (Wobus et al. 1991). Human ESC can also be differentiated into cardiomyocytes, which has generated considerable excitement in the field because of their value in examining the role of specific proteins in cardiac disease phenotypes, and also due to the eventual possibility that they might have therapeutic utility (Brinster 1974). To examine the role of Rac1 in the differentiation of mESC into cardiomyocytes, ectopic expression of constitutively-active Rac 1 deficient in GTPase activity (Rac1V12) or dominant-negative Rac1 with reduced affinity for GTP (Rac1N17 was used to elucidate the consequences of Rac1 gain-of-function and loss-of-function, respectively (Puceat et al. 2003). Expression of active Rac1V12 blocked the characteristic beating of embryoid bodies, due to a differentiation defect as indicated by reduced expression of cardiomyocyte differentiation markers such as MEF2C and ventricular myosin light chain 2 (MLCv2). In contrast, expression of a constitutively active form of RhoA did not block cardiomyocyte differentiation. Previous research had revealed that Rac1 regulates the activity of the NADPH oxidase that generates reactive oxygen species (ROS) (Di-Poi et al. 2001), and when H2O2 was added to embryoid bodies for up to 7 days the effect on blocking cardiomyocyte differentiation by active Rac1V12 was mimicked, while the ROS scavenger catalase reduced the differentiation block induced by active Rac1V12 (Puceat et al. 2003). Consistent with this conclusion, expression of a point-mutant form of Rac1 that does not activate the NADPH oxidase (Rac1V12D38) did not block cardiomyocyte differentiation. Expression of the dominant-negative Rac1N17 to examine loss-of-function did not affect differentiation but did impair beating by interfering with the organization of sarcomeric units required for contraction (Puceat et al. 2003). In contrast to what occurred when Rac1 was expressed early, when the MLCv2 promoter was used to express active Rac1 in differentiated cardiomyocytes, increased beating was observed due to a facilitation of differentiation and prolonged proliferation (Puceat et al. 2003). Expression of dominant-negative Rac1N17 from the MLCv2 promoter had a similar effect as early expression on the organization of sarcomeric units. These results revealed that the role of Rac1 in cardiac differentiation is likely dependent on the developmental stage. Given the availability of mESC in which Rac1 can be conditionally deleted (Yuan et al. 1995), more refined analysis of the role of Rac1 in cardiac differentiation and disease should be possible.
Mechanical forces are increasingly appreciated as major influences in embryonic development. External mechanical forces can be produced by physical alterations to the microenvironment. These external forces are sensed by cells, leading to responses that allow the cell to adapt to the changed environmental circumstances. One way that cells respond to mechanical force is via integrin-mediated activation of Rho and ROCK resulting in increased cellular stiffness via increased actomyosin contracility, which is also known as reinforcement (Guilluy et al. 2011). There is considerable evidence that suppression of
Mechanism of conditional activation of ROCK. 1: Diagram of ROCK domains, RBD = Rho Binding Domain, PH = Pleckstrin Homology domain, CRD = Cysteine-Rich Domain. 2: Kinase domain of ROCK2 was fused to Enhanced Green Fluorescent Protein (EGFP) and the hormone-binding domain of Estrogen Receptor (ER) to create conditionally regulated ROCK:ER. 3: In the absence of ligand, Heat Shock Protein 90 (Hsp90) binds to the ER domain and represses catalytic activity. 4: Upon binding of estrogen analogues such as 4-hydroxytamoxifen (4HT), 5: Hsp90 is displaced thereby allowing for ROCK catalytic activity.
actomyosin contractility by inhibition of ROCK promotes the survival and continued proliferation of epiblast-derived hES cells. It is suggested, however, that this signaling axis is less important in ICM-derived mES cells. We therefore decided to take advantage of a system to conditionally activate ROCK within mES cells to determine whether ROCK activation and consequent actomyosin contractility had a role in their proliferation, survival and/or maintenance of pluripotency. Accordingly, we transduced G4 mES cells (George et al. 2007) with a pBabe-Puro retroviral vector (Morgenstern and Land 1990) encoding a conditionally-active version of ROCK fused to the hormone-binding domain of the estrogen receptor (Figure 2) (Croft and Olson 2006) to establish the pBabe-Puro-ROCK:ER mES cell line in which ROCK activity could be elicited by treatment with the estrogen analog 4-hydroxytamoxifen (4HT). As a negative control, cells were transduced with pBabe-Puro encoding a kinase-dead counterpart (KD:ER) to produce control pBabe-Puro-KD:ER mES cells that express of catalytically inactive control ROCK protein.
When maintained in 4HT, pBabe-Puro-ROCK:ER mES cells exhibited robust growth and a large number of colonies exhibiting a refractive colony morphology under transmitted light and fewer colonies exhibiting a differentiated morphology, consistent with a high degree of pluripotency (Figure 3). Consistent with this observation, 4HT treated pBabe-Puro-ROCK:ER mES cells express significantly higher levels of the pluripotency marker alkaline phosphatase (ALP) than 4HT treated pBabe-Puro-KD:ER mES cells or vehicle treated pBabe-Puro-ROCK:ER
Conditional ROCK activation in mES cells elicits a highly refractive colony morphology. Panels show brightfield images of pBabe-Puro-ROCK:ER and pBabe-Puro-KD:ER mES cells treated with Vehicle or 4HT. Flat colonies containing mainly differentiated cells (purple arrows) and raised colonies containing mainly undifferentiated cells (white arrows) are indicated. Scale bar denotes 500µm.
and pBabe-Puro-KD:ER mES cells (Figure 4A). To determine whether the increased ALP activity observed upon ROCK activation correlated with an increase in stemness, we then assessed the expression of two classical markers of pluripotency, Oct4 and Nanog. 4HT treated pBabe-Puro-ROCK:ER mES cells express significantly higher levels of Oct4 and Nanog than 4HT treated pBabe-Puro-KD:ER mES cells or vehicle treated pBabe-Puro-ROCK:ER and pBabe-Puro-KD:ER mES cells (Figure 4B). Consistent with this effect being mediated by the activity of ROCK, co-treatment of pBabe-Puro-ROCK:ER mES cells with 4HT and the selective ROCK inhibitor Y-27632 failed to induce Oct4 or Nanog expression (Figure 4B).
Taken together, these results strongly suggest that ROCK activation in mES cells promotes stemness and facilitates proliferation and survival. These observations are consistent with a previous report that inhibition of ROCK activity or silencing of ROCK expression in mESC causes a reduction in stem like properties including alkaline phosphatase activity and Oct3/4 expression, and increased expression of differentiation markers SOX-1, nestin and MAP2c when grown at high seeding densities (Chang et al. 2010). Interestingly, the effects of ROCK inhibition on morphology and colony formation were reversible if cells had been
Conditional ROCK activation in mES cells increases stemness. (A) Histogram shows alkaline phosphatase activity in pBabe-Puro-ROCK:ER and pBabe-Puro-KD:ER mES cells treated with Vehicle or 4HT. (B) Histograms show expression at the mRNA level of the stem cell markers Oct4 and Nanog in pBabe-Puro-ROCK:ER and pBabe-Puro-KD:ER mES cells treated with Vehicle or 4HT. All values are expressed as mean ± SD. P values were calculated using the Student’s t-test.
grown at low initial densities where the reduction in stem like properties were not observed. However, at high cell densities where ROCK inhibition had repressed stem cell properties the effects were not reversible, suggesting that epigenetic reprogramming had occurred. It would be very interesting to determine whether the effects of ROCK activation on the maintenance of stemness would persist upon removal of tamoxifen and return of actomyosin contractility to basal levels.
There have been significant recent advances in our understanding of the requirement for specific Rho GTPases and downstream signaling pathways in ES cells from gene knockouts, RNAi and small molecule inhibitors. However, what has been missing is an understanding of where and when Rho proteins are activated and inactivated, for example during adhesion or differentiation. Activation-state sensitive fluorescent probes have been developed and used to characterize the temporal and spatial patterns of Rho activation during tumor cell migration and invasion (Vega et al. 2011). One exciting complementary area of research will be the determination of Rho protein activation with spatial and temporal resolution during ES cell growth and differentiation, ultimately through progressive developmental stages
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Almost all the parts of this plant, that are, fruit, leaves, flower bud, trunk, and pseudo-stem, can be utilized. This chapter deals with the fiber extracted from the pseudo-stem of the banana plant. It discusses the production of banana pseudo-stem fiber, which includes plantation and harvesting; extraction of banana pseudo-stem fiber; retting; and degumming of the fiber. It also deals with the characteristics of the banana pseudo-stem fiber, such as morphological, physical and mechanical, durability, degradability, thermal, chemical, and antibacterial properties. 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So, air and water can potentially become polluted everywhere. Little is known about changes in pollution rates. The increase in water-related diseases provides a real assessment of the degree of pollution in the environment. This chapter summarizes water quality parameters from an ecological perspective not only for humans but also for other living things. According to its quality, water can be classified into four types. Those four water quality types are discussed through an extensive review of their important common attributes including physical, chemical, and biological parameters. 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Accordingly, 80 medicinal plant species were reviewed; leaves and roots are the main parts of the plants used for preparation of traditional medicines. The local practitioners provided various traditional medications to their patients’ diseases such as stomachaches, asthma, dysentery, malaria, evil eyes, cancer, skin diseases, and headaches. The uses of medicinal plants for human and animal treatments are practiced from time immemorial. Stream/riverbanks, cultivated lands, disturbed sites, bushlands, forested areas and their margins, woodlands, grasslands, and home gardens are major habitats of medicinal plants. Generally, medicinal plants used for traditional medicine play a significant role in the healthcare of the majority of the people in Ethiopia. The major threats to medicinal plants are habitat destruction, urbanization, agricultural expansion, investment, road construction, and deforestation. Because of these, medicinal plants are being declined and lost with their habitats. Community- and research-based conservation mechanisms could be an appropriate approach for mitigating the problems pertinent to the loss of medicinal plants and their habitats and for documenting medicinal plants. Chromatography; electrophoretic, macroscopic, and microscopic techniques; and pharmaceutical practice are mainly used for quality control of herbal medicines.",book:{id:"8502",slug:"plant-science-structure-anatomy-and-physiology-in-plants-cultured-in-vivo-and-in-vitro",title:"Plant Science",fullTitle:"Plant Science - Structure, Anatomy and Physiology in Plants Cultured in Vivo and in Vitro"},signatures:"Admasu Moges and Yohannes Moges",authors:[{id:"249746",title:"Ph.D.",name:"Admasu",middleName:null,surname:"Moges",slug:"admasu-moges",fullName:"Admasu Moges"},{id:"297761",title:"MSc.",name:"Yohannes",middleName:null,surname:"Moges",slug:"yohannes-moges",fullName:"Yohannes Moges"}]},{id:"29764",title:"Underlying Causes of Paresthesia",slug:"underlying-causes-of-paresthesia",totalDownloads:193348,totalCrossrefCites:3,totalDimensionsCites:7,abstract:null,book:{id:"1069",slug:"paresthesia",title:"Paresthesia",fullTitle:"Paresthesia"},signatures:"Mahdi Sharif-Alhoseini, Vafa Rahimi-Movaghar and Alexander R. 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It’s a beautiful fruit with smooth, shining skin. Yellow, red, and purple fruits are available. This fruit contains vitamins, minerals, fiber, and antioxidants. It has a very low-calorie count. Breeding focuses on fruit quality through selection, hybridization, and biotechnological treatments for plantation and post-harvest management. Diseases, pests, viruses, and physiological abnormalities can be treated with plant protection techniques. Like other fruits, it’s edible after harvesting. Made into juices, concentrates, jams, gelatins, and sweets. If processing facilities and transport are available, it can be exported as pulp or concentrate. The tamarillo can diversify sub-tropical fruit production as a high-value cash crop, with excellent fruits commanding premium prices in Europe, North America, and Japan.",book:{id:"11311",title:"Tropical Plant Species",coverURL:"https://cdn.intechopen.com/books/images_new/11311.jpg"},signatures:"Rafiq Ahmad Shah, Parshant Bakshi, Hamidullah Itoo and Gaganpreet Kour"},{id:"83046",title:"Gene Expression and Transcriptome Sequencing: Basics, Analysis, Advances",slug:"gene-expression-and-transcriptome-sequencing-basics-analysis-advances",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.105929",abstract:"Gene expression studies are extremely useful for understanding a broad range of biological, physiological, and molecular responses. The techniques for gene expression reflect differential patterns of gene regulation and have evolved with time from detecting one gene to many genes at a time laterally. Gene expression depends on the spatiotemporal expression in a particular tissue at a given time point and needs critical examination and interpretation. Transcriptome sequencing or RNA-seq using next-generation sequencing (short and long reads) is the most widely deployed technology for accurate quantification of gene expression. According to the biological aim of the experiment, replications, platform, and chemistries, propelling improvement has been demonstrated and documented using RNA-seq in plants, humans, animals, and clinical sciences with respect to gene expression of mRNA, small non-coding, long non-coding RNAs, alternative splice variations, isoform variations, gene fusions, single-nucleotide variants. Integrating transcriptome sequencing with other techniques such as chromatin immunoprecipitation, methylation, genome-wide association studies, manifests insights into genetic and epigenetic regulation. Epi-transcriptome including RNA methylation, modification, and alternative polyadenylation events can also be explored through long-read sequencing. In this chapter, we have presented an account of the basics of gene expression methods, transcriptome sequencing, and the various methodologies involved in the downstream analysis.",book:{id:"11349",title:"Gene Expression",coverURL:"https://cdn.intechopen.com/books/images_new/11349.jpg"},signatures:"Yogesh Shukla, Amol Phule, Harshvardhan Zala, Nakul D. Magar, Priya Shah, K. Harish, Tejas C. Bosamia, Kalyani M. 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The genes that encode citrate synthase and subunits of the succinate dehydrogenase complex are the ones that show the greatest multiplicity, while in the phosphoenolpyruvate-pyruvate-oxaloacetate node, only malic enzymes and pyruvate phosphate dikinase present two copies in some Streptomyces. The extra DNA from these multiple gene copies can be more than 50 kb, and the question arises whether all of these genes are transcribed and translated. As far as we know, there is few information about the transcription of these genes in any of this Streptomyces, nor if any of the activities that are encoded by a single gene could be limiting both for growth and for the formation of precursors of the antibiotics produced by these microorganisms. Therefore, it is important to study the transcription and translation of genes involved in carbon metabolism in antibiotic-producing Streptomyces growing on various sugars.",book:{id:"10893",title:"Actinobacteria",coverURL:"https://cdn.intechopen.com/books/images_new/10893.jpg"},signatures:"Toshiko Takahashi, Jonathan Alanís, Polonia Hernández and María Elena Flores"},{id:"82757",title:"Seed Dormancy: Induction, Maintenance and Seed Technology Approaches to Break Dormancy",slug:"seed-dormancy-induction-maintenance-and-seed-technology-approaches-to-break-dormancy",totalDownloads:8,totalDimensionsCites:0,doi:"10.5772/intechopen.106153",abstract:"Dormancy is the major cause of erratic germination, patchy emergence and uneven seedling establishment in the field. These traits are exceedingly undesirable in crop production as future phases of growth and development are strongly linked to uniform seedling development at early growth phases. 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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. 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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:"18",type:"subseries",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11414,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. 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