DUBs regulate DNA DSBR.
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"5851",leadTitle:null,fullTitle:"Sepsis",title:"Sepsis",subtitle:null,reviewType:"peer-reviewed",abstract:"The book entitled Sepsis will provide a great and up-to-date information in this field to students and researchers involved in sepsis research with its chapters targeting host-pathogen interaction at a metabolic level during sepsis pathogenesis, how age affects sepsis pathogenesis and its outcome in old-age population as compared to young population, sepsis-associated acute organ injury mainly targeting acute kidney injury in sepsis, and kallistatin as host-derived immunomodulatory mechanism during sepsis, along with developments in techniques required for early diagnosis of sepsis and sepsis-associated encephalitis, a devastating medical condition observed during severe sepsis. The book is written by experts in their fields associated with sepsis, a critical condition needing great medical attention.",isbn:"978-953-51-3396-4",printIsbn:"978-953-51-3395-7",pdfIsbn:"978-953-51-4695-7",doi:"10.5772/65611",price:119,priceEur:129,priceUsd:155,slug:"sepsis",numberOfPages:160,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"140438644d49079e214fd82e9fe5e5ac",bookSignature:"Vijay Kumar",publishedDate:"August 23rd 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5851.jpg",numberOfDownloads:11241,numberOfWosCitations:5,numberOfCrossrefCitations:2,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:6,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:13,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 12th 2016",dateEndSecondStepPublish:"November 2nd 2016",dateEndThirdStepPublish:"January 29th 2017",dateEndFourthStepPublish:"April 29th 2017",dateEndFifthStepPublish:"June 28th 2017",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"63844",title:"Dr.",name:"Vijay",middleName:null,surname:"Kumar",slug:"vijay-kumar",fullName:"Vijay Kumar",profilePictureURL:"https://mts.intechopen.com/storage/users/63844/images/system/63844.jpg",biography:"Dr. Vijay Kumar Ph.D. has more than 16 years of research experience in the field of bacterial infections, including sepsis and pneumonia, innate immunity, immunopharmacology, immunomodulation, and inflammation. He obtained his Ph.D. in June 2009 from the Department of Microbiology, Panjab University, Chandigarh, India. Dr. Kumar is the recipient of the prestigious Piero Periti review article award for 2008, awarded by the Journal of Chemotherapy in the field of immunomodulation and antimicrobials for the article titled Innate Immunity in Sepsis Pathogenesis and Its Modulation: New Immunomodulatory Targets Revealed. He was the recipient of junior research and senior research fellowship (2004–2009) offered by the Indian Council of Medical Research (ICMR), New Delhi, India. He has been awarded 17 international travel awards to attend various international conferences in the field of infection and immunity. So far, he has published 70 publications in peer-reviewed international journals in this field. To date, he has achieved more than 2 100 citations and h-index 21 (Google scholar). He has contributed several articles on inflammation and immunity as invited contribution as well as in special issues of the journals, including the Journal of Leukocyte Biology, EXCLI Journal, and Frontiers in Immunology. He is serving as an associate editor for Frontiers in Immunology (Inflammation section), executive guest editor for the journal called Coronaviruses, and editorial board member of Frontiers in Biosciences along with other journals. He is also serving as an invited reviewer for several immunology journals, such as Scientific Reports, British Journal of Pharmacology, Pharmacological Reports, Frontiers in Immunology, Frontiers in Medicine, Journal of Inflammation Research, Cellular and Molecular Immunology, Immunology, Innate Immunity, etc.",institutionString:"Stanley S. Scott cancer Center, School of Medicine Department of Interdisciplinary Oncology Louisiana State University Health Science Center (LSUHSC), New Orleans, LA",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"University of Tennessee Health Science Center",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1009",title:"Pre-Hospital Emergency Medicine",slug:"emergency-medicine-pre-hospital-emergency-medicine"}],chapters:[{id:"56127",title:"Interaction of Host‐Microbial Metabolism in Sepsis",doi:"10.5772/68046",slug:"interaction-of-host-microbial-metabolism-in-sepsis",totalDownloads:1769,totalCrossrefCites:2,totalDimensionsCites:4,hasAltmetrics:0,abstract:"The majority of species of the human gut microbiota is not cultivated on artificial nutrient media, but they are included in the functioning of microbial metabolic conveyor. Between the numerous gut bacteria (transmitter) and billions of intracellular mitochondria (receiver), the function of signaling molecules performs aromatic metabolites. Sepsis destroys the coordinated work of the indigenous anaerobic microflora. This leads to the imbalance of aromatic microbial metabolites (AMM). We hypothesized and proved diagnostic and pathogenic significance of this. First, deficiency of the end products of microbial metabolism—lipophilic AMM (PhPA and derivatives‐cinnamic and benzoic acids) in sepsis, and second, excessive accumulation in blood of intermediate products named, “sepsis‐associated” AMM—both lead to the development of mitochondrial dysfunction. Particularly, the total suppressed production of mROS can manifest by “hibernate‐like state” of cells and lead to MOF. The participation of aromatic metabolites in the development of septic shock can be explained by the inhibition of tyrosine hydroxylase and impaired synthesis of catecholamines. In clinical research, the high levels of “sepsis‐associated” AMM (p‐HPhAA, p‐HPhLA, and PhLA) correlate with the severity according to APACHE II, Sepsis-related Organ Failure Assessments (SOFA) score and mortality. To improve the survival of ICU patients, requires more attention to the role of imbalance of microbial metabolites in sepsis.",signatures:"Beloborodova Natalia Vladimirovna",downloadPdfUrl:"/chapter/pdf-download/56127",previewPdfUrl:"/chapter/pdf-preview/56127",authors:[{id:"199461",title:"Prof.",name:"Natalia V.",surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova"}],corrections:null},{id:"54619",title:"Septic Shock in Older People",doi:"10.5772/68080",slug:"septic-shock-in-older-people",totalDownloads:1161,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Sepsis is a complex condition that is initiated by infection. The incidence of sepsis and its severity are higher at an older age (mean age of approximately 65 years). Clinical manifestations of sepsis are derived from systemic inflammatory response syndrome. Age‐related defects in immunity are shown by changes in cellular and humoral immunity. Recent studies have shown significant changes in the innate response (e.g., changes in toll‐like receptor expression, abnormal activation of mitogen-activated protein kinases, and production of reactive oxygen species) in older people. Transcriptomic analysis on a large scale has provided interesting information showing that specific groups of patients actually have singular profiles for inflammatory responses. Findings from our research group have identified major molecular pathways that are particularly affected in older people during sepsis. Oxidative phosphorylation pathways and mitochondrial dysfunction are altered the most in older people with sepsis compared with younger patients with sepsis. These pathways might have a pivotal role in worsening clinical outcomes compared with younger people with sepsis. The mechanisms leading to specific dysfunction of several signaling pathways in the immune response of older people are complex and appear to involve multiple factors, including environmental factors, microRNAs, and epigenetic changes.",signatures:"Mike Yoshio Hamasaki, Marcel Cerqueira César Machado and\nFabiano Pinheiro da Silva",downloadPdfUrl:"/chapter/pdf-download/54619",previewPdfUrl:"/chapter/pdf-preview/54619",authors:[{id:"171281",title:"Prof.",name:"Marcel",surname:"Machado",slug:"marcel-machado",fullName:"Marcel Machado"},{id:"200926",title:"Prof.",name:"Fabiano",surname:"Pinheiro Da Silva",slug:"fabiano-pinheiro-da-silva",fullName:"Fabiano Pinheiro Da Silva"},{id:"200928",title:"MSc.",name:"Mike",surname:"Hamasaki",slug:"mike-hamasaki",fullName:"Mike Hamasaki"}],corrections:null},{id:"55046",title:"Kallistatin in Sepsis: Protective Actions and Potential Therapeutic Applications",doi:"10.5772/67988",slug:"kallistatin-in-sepsis-protective-actions-and-potential-therapeutic-applications",totalDownloads:1326,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Sepsis is a systemic inflammatory response to infection, leading to multiorgan injury and mortality. Kallistatin is an endogenous protein expressed in the liver and tissues relevant to cardiovascular function. Kallistatin levels are markedly reduced in patients with sepsis and liver disease and in lipopolysaccharide (LPS)-induced septic mice. Kallistatin administration attenuates inflammation, multiorgan damage, and lethality in septic mice with LPS treatment, group A streptococcal, or polymicrobial infection. Importantly, kallistatin treatment not only prevents but also reverses organ injury and lethality in septic mice. Kallistatin decreases sepsis-induced inflammatory responses and tissue damage by modulating differential signaling pathways, including: (1) stimulating endothelial nitric oxide (eNOS) and sirtuin 1 (SIRT) synthesis, and NO formation; (2) increasing suppressor of cytokine signaling-3 (SOCS3) expression; (3) antagonizing tumor necrosis factor-α (TNF-α) and high mobility group box 1 (HMGB1)-mediated oxidative stress and inflammatory gene expression; and (4) displaying bactericidal effects by stimulating superoxide formation. Therefore, kallistatin's multifactorial activities provide effective protection during septic shock in animal models. As kallistatin displays no apparent cytotoxicity, kallistatin therapy may provide a promising approach for the treatment of sepsis in humans.",signatures:"Julie Chao, Pengfei Li and Lee Chao",downloadPdfUrl:"/chapter/pdf-download/55046",previewPdfUrl:"/chapter/pdf-preview/55046",authors:[{id:"200172",title:"Prof.",name:"Julie",surname:"Chao",slug:"julie-chao",fullName:"Julie Chao"}],corrections:null},{id:"54744",title:"The Role of Fish Oil Feeding Rich in ω‐3 Polyunsaturated Fatty Acids in Patients with Sepsis and Septic Shock",doi:"10.5772/68041",slug:"the-role-of-fish-oil-feeding-rich-in-3-polyunsaturated-fatty-acids-in-patients-with-sepsis-and-septi",totalDownloads:1175,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Different clinical studies have demonstrated that fish oil, rich in the very‐long‐chain ω‐3 polyunsaturated fatty acids (PUFAs), has immunomodulatory effects, suppressing the production of pro‐inflammatory cytokines in diverse groups of critically ill patients. Moreover, such compounds have been found to attenuate the inflammatory response within 2–3 days upon parenteral administration. Recent experimental data suggest that activation of the cholinergic anti‐inflammatory pathway constitutes a novel mechanism of such immune‐regulatory effects. Since enhanced vagal tone has been associated with decreased cytokine secretion, novel monitoring tools of its activity at the bedside are needed, in order to evaluate nutritional manipulation of inflammatory response in the critically ill. The present chapter provides an overview of the mechanisms of action through which ω‐3 PUFA modulates immune response in critically ill patients suffering from sepsis and septic shock. Furthermore, it summarizes the current evidence regarding clinical effects from administration of fish oil rich in ω‐3 PUFAs in septic patients. Finally, it presents data that suggest the existence of a continuous interrelation between immune status and autonomic nervous system during systemic inflammation and proposes novel tools of autonomic nervous system monitoring at the bedside, in order to assess pharmacological manipulation of immune response by ω‐3 PUFAs in acute illness.",signatures:"Vasilios Papaioannou",downloadPdfUrl:"/chapter/pdf-download/54744",previewPdfUrl:"/chapter/pdf-preview/54744",authors:[{id:"147093",title:"Prof.",name:"Vasilios",surname:"Papaioannou",slug:"vasilios-papaioannou",fullName:"Vasilios Papaioannou"}],corrections:null},{id:"56058",title:"Sepsis-associated Acute Kidney Injury",doi:"10.5772/intechopen.69612",slug:"sepsis-associated-acute-kidney-injury",totalDownloads:2460,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Sepsis is a life-threatening condition caused by a dysregulated immune response to infection. Interestingly, sepsis mortality increases with acute kidney injury (AKI) and patients with AKI worsen with sepsis. It is interesting to note that most of the clinical trials on sepsis treatment that derived from the results of translational researches are a failure. This is, in part, because of the complexity of human sepsis in comparison with animal models. Another reason for the failure-translation might be the improper matching of the animal models to the individual patient. It is possible that the main mechanism of sepsis induction in each patient with the variety causes of sepsis might be different. Indeed, immune response to sepsis depends on genetic background, route of immune activation, and organisms. Thus, sepsis treatment classified by “mechanistic approach” to individual patient might be more proper than the classification with “sepsis severity”. Specific treatment of sepsis in individual patient according to the specific immune response characteristic might be a more proper translational strategy. Indeed, the understanding in immune response pattern of sepsis and sepsis pathophysiology is necessary for “sepsis mechanistic approach”. Then, we conclude most of the topics and our hypothesis regarding SA-AKI in this review.",signatures:"Wiwat Chancharoenthana, Asada Leelahavanichkul and Somchai\nEiam-Ong",downloadPdfUrl:"/chapter/pdf-download/56058",previewPdfUrl:"/chapter/pdf-preview/56058",authors:[{id:"49591",title:"Dr.",name:"Somchai",surname:"Eiam-Ong",slug:"somchai-eiam-ong",fullName:"Somchai Eiam-Ong"},{id:"200624",title:"Dr.",name:"Wiwat",surname:"Chancharoenthana",slug:"wiwat-chancharoenthana",fullName:"Wiwat Chancharoenthana"},{id:"200625",title:"Dr.",name:"Asada",surname:"Leelahavanichkul",slug:"asada-leelahavanichkul",fullName:"Asada Leelahavanichkul"}],corrections:null},{id:"54731",title:"Clinical Assays in Sepsis: Prognosis, Diagnosis, Outcomes, and the Genetic Basis of Sepsis",doi:"10.5772/67985",slug:"clinical-assays-in-sepsis-prognosis-diagnosis-outcomes-and-the-genetic-basis-of-sepsis",totalDownloads:1842,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Sepsis is the most widespread medical disorder of the intensive care unit (ICU) and the most common cause of death in hospitalized patients. Several endothelium-related molecules have been investigated as potential biomarkers for early diagnosis and/or prognosis of sepsis, providing different results depending on study designs. Therefore, it seems that we are still far from the right combination of sepsis markers to be used in clinical practice. It is more probable that a panel of diverse biomarkers will be more efficient in clinical practice. More recently, the potential use of genetic biomarkers for prognostic purposes started emerging for sepsis, in the form of genome-wide association studies. The successful use of modern molecular diagnostics could enable rapid identification of particularly susceptible or less susceptible individuals, leading to tailored therapeutic treatments.",signatures:"Alice Georgia Vassiliou, Stylianos E. Orfanos and Anastasia\nKotanidou",downloadPdfUrl:"/chapter/pdf-download/54731",previewPdfUrl:"/chapter/pdf-preview/54731",authors:[{id:"200406",title:"Dr.",name:"Alice",surname:"Vassiliou",slug:"alice-vassiliou",fullName:"Alice Vassiliou"},{id:"200411",title:"Dr.",name:"Anastasia",surname:"Kotanidou",slug:"anastasia-kotanidou",fullName:"Anastasia Kotanidou"},{id:"200416",title:"Dr.",name:"Stylianos E.",surname:"Orfanos",slug:"stylianos-e.-orfanos",fullName:"Stylianos E. Orfanos"}],corrections:null},{id:"54786",title:"In Vivo Imaging of Septic Encephalopathy",doi:"10.5772/67983",slug:"in-vivo-imaging-of-septic-encephalopathy",totalDownloads:1509,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Septic encephalopathy is a devastating symptom of severe sepsis. Many studies have been performed to uncover the pathophysiological mechanisms of septic encephalopathy; however, novel technical approaches are still required to overcome this complex symptom. Because patients are suffering from severe cognitive impairment, coma, or delirium, which burden not only patients but also caregivers, overcoming septic encephalopathy is still a major social problem worldwide, especially in the intensive care. Septic encephalopathy seems to be caused by cytokine invasion and/or oxidative stress into the brain, and this pathological state leads to imbalance of neurotransmitters. In addition to this pathophysiology, septic encephalopathy causes complicated symptoms (e.g., ischemic stroke, edema, and aberrant sensory function). For these pathophysiological mechanisms, electrophysiology using animal models, positron emission tomography (PET), computed tomography, and magnetic resonance imaging for septic patients has provided important clues. However, the research for septic encephalopathy is currently confronted with the difficulty of complex symptoms. To overcome this situation, in this chapter, we introduce our novel methods for in vivo imaging of septic encephalopathy using near infrared (NIR) nanoparticles, quantum dots. In addition to our recent progress, we propose a strategy for the future approach to in vivo imaging of septic encephalopathy.",signatures:"Yukio Imamura, Yuki Murakami, Naoya Matsumoto, Hisatake\nMatsumoto, Satoko Mitani, Kentaro Shimizu, Hiroshi Ogura,\nTakeshi Shimazu and Takashi Jin",downloadPdfUrl:"/chapter/pdf-download/54786",previewPdfUrl:"/chapter/pdf-preview/54786",authors:[{id:"104157",title:"Dr.",name:"Yukio",surname:"Imamura",slug:"yukio-imamura",fullName:"Yukio Imamura"},{id:"107971",title:"Dr.",name:"Naoya",surname:"Matsumoto",slug:"naoya-matsumoto",fullName:"Naoya Matsumoto"},{id:"107974",title:"Dr.",name:"Hiroshi",surname:"Ogura",slug:"hiroshi-ogura",fullName:"Hiroshi Ogura"},{id:"107975",title:"Dr.",name:"Takeshi",surname:"Shimazu",slug:"takeshi-shimazu",fullName:"Takeshi Shimazu"},{id:"132233",title:"Dr.",name:"Takashi",surname:"Jin",slug:"takashi-jin",fullName:"Takashi Jin"},{id:"204865",title:"Dr.",name:"Yuki",surname:"Murakami",slug:"yuki-murakami",fullName:"Yuki Murakami"},{id:"204866",title:"Dr.",name:"Hisatake",surname:"Matsumoto",slug:"hisatake-matsumoto",fullName:"Hisatake Matsumoto"},{id:"204867",title:"Dr.",name:"Kentaro",surname:"Shimizu",slug:"kentaro-shimizu",fullName:"Kentaro Shimizu"},{id:"204869",title:"Dr.",name:"Satoko",surname:"Mitani",slug:"satoko-mitani",fullName:"Satoko Mitani"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"8079",title:"Vaccines",subtitle:"the History and Future",isOpenForSubmission:!1,hash:"4ea35b9b32335ffbe19c7682f38c29cd",slug:"vaccines-the-history-and-future",bookSignature:"Vijay Kumar",coverURL:"https://cdn.intechopen.com/books/images_new/8079.jpg",editedByType:"Edited by",editors:[{id:"63844",title:"Dr.",name:"Vijay",surname:"Kumar",slug:"vijay-kumar",fullName:"Vijay Kumar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10426",title:"Inflammation in the 21st Century",subtitle:null,isOpenForSubmission:!1,hash:"73637d19c1b71e285a3483d6df1c2e0f",slug:"inflammation-in-the-21st-century",bookSignature:"Vijay Kumar, Alexandro Aguilera Salgado and Seyyed Shamsadin Athari",coverURL:"https://cdn.intechopen.com/books/images_new/10426.jpg",editedByType:"Edited by",editors:[{id:"63844",title:"Dr.",name:"Vijay",surname:"Kumar",slug:"vijay-kumar",fullName:"Vijay Kumar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10535",title:"SARS-CoV-2 Origin and COVID-19 Pandemic Across the Globe",subtitle:null,isOpenForSubmission:!1,hash:"043fa3e57c1448a9cf8155587a8cac3d",slug:"sars-cov-2-origin-and-covid-19-pandemic-across-the-globe",bookSignature:"Vijay Kumar",coverURL:"https://cdn.intechopen.com/books/images_new/10535.jpg",editedByType:"Edited by",editors:[{id:"63844",title:"Dr.",name:"Vijay",surname:"Kumar",slug:"vijay-kumar",fullName:"Vijay Kumar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5202",title:"Extracorporeal Membrane Oxygenation",subtitle:"Advances in Therapy",isOpenForSubmission:!1,hash:"f7c8f9c0cf1cf50455fba7e2607e9268",slug:"extracorporeal-membrane-oxygenation-advances-in-therapy",bookSignature:"Michael S. 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The pure equilibrium state can be established in an isolated system, in which neither mass nor heat is transferred between the system and the environment. Most engineering transport analyses are based on the semi-, quasi-, or local equilibrium assumptions, which assume that any infinitesimal volume can be treated as a box of equilibrium. This book includes various aspects of non-equilibrium or irreversible statistical mechanics and their relationships with engineering applications. I hope that this book contributes to expanding the predictability of holistic engineering consisting of thermo-, fluid, and particle dynamics.",isbn:"978-1-83968-078-6",printIsbn:"978-1-83968-077-9",pdfIsbn:"978-1-83968-079-3",doi:"10.5772/intechopen.78729",price:119,priceEur:129,priceUsd:155,slug:"non-equilibrium-particle-dynamics",numberOfPages:196,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"2c3add7639dcd1cb442cb4313ea64e3a",bookSignature:"Albert S. 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Kim",profilePictureURL:"https://mts.intechopen.com/storage/users/21045/images/system/21045.jpeg",biography:"Dr. Albert S. Kim earned his physics degree of BS from Kyung Hee University and MS from Yonsei University, South Korea. He received his MS (1997) and Ph.D. (2000) in Civil and Environmental Engineering from the University of California at Los Angeles, USA. He joined the Department of Civil and Environmental Engineering at the University of Hawaii at Manoa in 2001. \r\nDr. Kim’s scientific accomplishments include the US National Science Foundation Faculty Early Career (CAREER) Award (2005), the University of Hawaii Regents’ Medal for Excellence in Research (2006) and the Medal for Excellence in Teaching (2017). Professor Kim has published almost 60 peer-reviewed journal papers and four book chapters. He researches on computational environmental physics for engineering purposes.",institutionString:"University of Hawaii at Manoa",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"6",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"University of Hawaii at Manoa",institutionURL:null,country:{name:"United States of America"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"954",title:"Thermodynamics",slug:"thermodynamics"}],chapters:[{id:"66815",title:"Nonequilibrium Statistical Operator",slug:"nonequilibrium-statistical-operator",totalDownloads:769,totalCrossrefCites:1,authors:[{id:"260373",title:"Prof.",name:"Gerd",surname:"Roepke",slug:"gerd-roepke",fullName:"Gerd Roepke"}]},{id:"67626",title:"The Boundary Element Method for Fluctuating Active Colloids",slug:"the-boundary-element-method-for-fluctuating-active-colloids",totalDownloads:958,totalCrossrefCites:0,authors:[{id:"279308",title:"Prof.",name:"William",surname:"Uspal",slug:"william-uspal",fullName:"William Uspal"}]},{id:"67796",title:"Fundamentals of Irreversible Thermodynamics for Coupled Transport",slug:"fundamentals-of-irreversible-thermodynamics-for-coupled-transport",totalDownloads:1265,totalCrossrefCites:0,authors:[{id:"21045",title:"Prof.",name:"Albert S.",surname:"Kim",slug:"albert-s.-kim",fullName:"Albert S. 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DNA double-strand break (DSB) is a fatal alteration in the chemical structure of DNA; if it has not been repaired in time, it may destroy the stability of genome and lead to a series of human diseases. Usually, they result from a variety of causes including abnormal metabolic process, ionizing radiation, ultraviolet radiation, and active oxygen damage factors [1, 2]. In organism, DNA double-strand break repair (DSBR), a complex reaction system consisting of nonhomologous end-joining (NHEJ) and homologous recombination (HR) pathway, can repair DSBs [3, 4]. Accumulating evidence has demonstrated that ubiquitination and deubiquitination modification play a vital role in controlling the capacity of DSBR via regulating the action and stability of DNA repair enzymes involving in DSBR pathway. In the past decades, there has been great advance in the role of deubiquitinases (DUBs) in DNA damage repair. Here, we reviewed ubiquitination/deubiquitination modification of DSBR genes, the role of DUBs in DSBR and corresponding mechanisms, and the potential effects of this modification on human diseases.
Ubiquitin is an important single-chain polypeptide consisting of 76 amino acid residues and ubiquitously exists in almost all eukaryotic cells and tissues [5, 6]. This polypeptide is characterized by highly conserved protein from yeast to human [6] and is invariant in higher plants and differs by only three residues from animals [7]. Structurally, ubiquitin polypeptide chain appears to be a highly compact β-grasp fold with an α-helix in the cavity formed by a five-strand mixed β-sheet and a marked hydrophobic core formed between the β-sheet and the α-helix [8]. A flexible six-residue tail in the C-terminal of ubiquitin protrudes from β-grasp fold and is requested for forming the bond between ubiquitin and its substrate [9].
Ubiquitination is defined as the process that ubiquitin attaches to its target proteins via catalysis of enzymes. This process is a reversible posttranslational modification that can regulate various processes including cell proliferation, apoptosis, transcription, protein stability and translocation, and DNA damage repair [10, 11, 12]. Ubiquitination process is an ATP-dependent enzymatic cascade reaction [13, 14]. During cascades reaction, C-terminal of ubiquitin is first adenylated by ubiquitin-activating enzyme (E1) via forming a bond between the adenosine monophosphate (AMP) and the C-terminal glycine carboxyl group of ubiquitin, and subsequently, the E1 cysteine side chain directly binds to C-terminal and results in the formation of a thiol-ester linkage. Then, the activated ubiquitin is presented to the active cysteine in a ubiquitin-conjugating enzyme (E2). The E2 delivers the ubiquitin to its substrate cooperating with ubiquitin ligases (E3), which plays a role in substrate recognition. Finally, the C-terminal glycine of the ubiquitin binds to a lysine residue of the substrate with an isopeptide bond. After multiple cycles of cascade reaction, substrate will bind one or more polyubiquitin chains that are formed between the lysine side of one ubiquitin and the C-terminal carboxyl group of another ubiquitin [13, 14]. The 26S proteasome can specifically recognize these target proteins with ubiquitination modification and lead them into ubiquitin-proteasome pathway (UPP) for inducting protein degradation, a key role of ubiquitination. However, UPP is not the only role of ubiquitination. Ubiquitination can also regulate protein activity and the interaction among proteins [13, 14].
Deubiquitination is the reverse process of ubiquitination and regulated by deubiquitinases (DUBs). DUBs, also known as deubiquitinating enzymes, can cleave the bonds between substrate and polyubiquitin chains and improve the stability of substrate. They can also remove single ubiquitin molecule from polyubiquitin chains. Until now, approximately 561 DUBs have been identified in the human genome [15], and most of them are cysteine proteases. According to the difference in their structure and function, DUBs are divided into six classes: ubiquitin-specific proteases (USPs), ubiquitin carboxy-terminal hydrolases (UCHs), ovarian tumor proteases (OTUs), Machado-Joseph disease protein domain proteases (MJDs), JAMM/MPN domain-associated metallopeptidases (JAMMs), and the monocyte chemotactic protein-induced protein (MCPIP) family. These enzymes can stabilize protein and play a crucial role in the life process [13, 14].
DSBs are vital DNA damages caused by a variety of physiological or pathological factors. V(D)J recombination has been identified as the only physiological reason inducing DSBs that result from the recombination of variable (V), diversity (D), and joining (J) gene segments. It often appears in the early development process of the vertebrate immune system. Evidence has shown that diverse immunoglobulins and T-cell receptors are generated due to this special recombination pathway. During V(D)J recombination, DNA strands are cut by RAG-1 and RAG-2 protein between the recombination signal sequences (RSS) heptamer and the flanking sequence and result in the formation of DSBs [16, 17], whereas the ends of the broken strands are subsequently processed and connected through NHEJ pathway [18].
For pathological factors, reactive oxygen species (ROSs) resulting from cellular oxidation are one main source of pathological DSBs. Studies have shown that about one percent of the oxygen that we breathe is converted into oxidative free radicals and ultimately can cause DSBs in different degrees [19]. Pathological DSBs can also arise from DNA replication across a nick that is caused by exogenous or endogenous sources. Such ionizing radiation as X-rays and gamma rays may produce free radicals and induce the formation of DSBs [20]. This type of DSBs only occurs in the S phase and is repaired through HR pathway. Additionally, one unusual cause producing DSBs is the topoisomerase II poisons that can lead to DSBs formation, apoptotic cell death, and genomic instability via stabilizing the DNA topoisomerase II cleavable complexes [21]. Another unusual cause is physical stress on the DNA duplex, which may be from the mitotic spindle on chromosomal fusions or telomere failures [22].
Studies have shown that DSBs can induce DNA damage response, and such E3 ligases as ring finger protein (RNF8) subsequently accumulate around the lesions. After that, RNF8-recruiting RNF168 promotes histone H2A Lys13,15 mono-ubiquitination (H2AK13, 15ub). Therefore, the accumulation of DNA-repair regular factors, such as receptor-association protein (RAP80) and TP53 binding protein (53BP1), is allowed [23, 24, 25, 26]. Finally, the ataxia telangiectasia mutated (ATM) and ATM/rad3-related (ATR) kinases, a central regulator of DSB response, are activated and induce the activation of Chk1 and Chk2 kinases and TP53 protein. The activated Chk1 and Chk2 kinases arrest cell cycle to obtain sufficient time for DNA repair, while activate TP53 induces cell death [27, 28].
Merely one DSB that triggers apoptosis or destroys a critical gene is enough to lead a cell to death [29], whereas losing ability to repair DSBs can also lead to genome rearrangement and cellular transformation [30]. In organism, the two primary pathways to correct DSBs are known as HR pathway and NHEJ pathway. For NHEJ pathway, it can repair DSBs with nonhomological damaged ends and is the primary DSBR pathway in mammalian cells. This pathway consists of classical-NHEJ (C-NHEJ) and alternative-NHEJ (A-NHEJ). In C-NHEJ, Ku heterodimer (Ku70 and Ku80 subunits) recognizes and binds to the ends of a DSB to prevent the free ends from degradation. Subsequently, DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is recruited and then binds to Ku heterodimer to recruit XRCC4 and DNA ligase 4 (LIG4). XRCC4 and LIG4 form a complex with XLF to ligate the broken ends [31, 32]. Until now, although the detailed mechanism of NHEJ is poorly understood, a recent study has partly revealed the mechanism about how the complex of XRCC4, LIG4, and XLF connects the fragments of broken DNA [33]. It has shown that XRCC4-XLF complex first bridges the two DNA molecules generated by DSBs, and the bridge can slide along the DNA. Then, the ends of broken DNA are rapidly reconnected. Evidence from molecular epidemiological and genetical studies displays that low or losing capacity of NEEJ pathway is positively associated with the deficiency of immune reaction [34, 35]. For example, about 15% of human severe combined immune deficiency (SCID) has been observed to feature low NHEJ capacity caused by null mutations of Artemis gene [34, 35]. Patients carrying the mutations in the DNA ligase IV gene that is crucial in NHEJ pathway presented some NBS-like features; however, cancers were not observed on these patients [36].
For HR pathway, it was first illuminated in
Except for above-mentioned directly regulated proteins, DSB response factors (including ATM/ATR and BRCA1/BRCA2) can indirectly regulate the capacity of HR pathway [42, 43, 44, 45, 46]. The defects of ATM may alter kinetics of radiation-induced RAD51 formation and the hallmark of RAD51 activation [42]. ATM/ATR can also mediate the phosphorylation of PALB2 to promote the formation of RAD51 nucleofilaments [43]. However, roles of ATM and ATR in HR pathway are still poorly understood. BRCA1 is a protein with 1863 amine acids encoded by breast cancer susceptibility gene and can target DSB lesion through its N-terminal RING domain binding to BRCA1-associated RING domain 1 (BARD1) [44]. BRCA1 can also promote HR pathway via cooperating with RAD51 and forming the complex of BRCA1-PALB2-BRCA2-RAD51 (BRCC) [44]. Surprisingly, BRCA1 can also prevent HR pathway by its incorporating into the complex of BRCA1-Abraxas-RAP80-MERIT40 (BRCA1-A). This may be because BRCA1-A can limit DNA end-resection or sequester BRCA1 away from HR sites by binding to RNF8/RNF168-ubiquitylated chromatin [45, 46]. Studies have shown that low or lost capacity of HR pathway resulting from these causes may cause a series of cancer-prone diseases, including ataxia telangiectasia (AT), Nijmegen breakage syndrome (NBS), Bloom syndrome, Werner syndrome, and Fanconi anemia, reviewed by Thompson and Schild [47].
USPs, the largest subfamily of DUBs with approximately 100 members and the most divers structures, belong to cysteine protease family (clan CA, family C19) and were first identified in
USP1 contains 785 amino acids, and its catalytic domain is one of the largest among all USPs. Although two insertions between boxes 2 and 3 and between boxes 5 and 6 have been identified to locate away from the ubiquitin binding site of USP1, it is still not clear whether these insertions can reach the active site [52]. As USP1 has been reported to overexpress in osteosarcoma and non–small cell lung cancer, inhibitors of USP1 are supposed to have anti-cancer potential [54, 55]. Interestingly, USP1 can be stabilized by USP1-associated factor 1 (UAF1) that can increase the catalytic activity of USP1 [56]. This indicates that USP1 need to form a complex with UAF1 to carry out its functions. A recent study has further proved that three cell clones, USP1−/−, UAF1−/−/−, and USP1−/− UAF1−/−/− double-knockout cells, showed hypersensitivity to both camptothecin and poly (ADP-ribose) polymerase (PARP), suggesting that the USP1/UAF1 complex can promote HR capacity. Moreover, the USP1/UAF1 complex promoting HR capacity is at least in part associated with the suppression of NHEJ, although corresponding mechanisms still need to be further researched [57].
USP3 is a nuclear protein that presents in the chromatin fraction and is also a chromatin-associated DUB [58]. In 1999, Sloper-Mold
Except for USP3, several other USPs (including USP6, USP51, USP29, and USP44) can also deubiquitinate H2A [26, 62, 63]. Among these USPs, USP51 acts as a DUB for histone H2B mono-ubiquitination (H2Bub1), and the depletion of USP51 will suppress DSB reaction and tumor growth [64].
USP4, also named as ubiquitous nuclear protein (UNP), was initially found to promote carcinogenesis of lung and act as an oncogene [65, 66]. The following studies showed that USP4 is overexpressed in several types of human cancers such as hepatocellular carcinoma and plays a crucial role in the progression of tumorigenesis [67, 68]. Growing evidence has exhibited that USP4 affecting tumorigenesis may be correlated with abnormal DSBR capacity [67]. During DSBR pathway, USP4 may display its regulation functions on DSBR in several different processes, including DSB response and HR capacity. It has been identified to act as an important TP53 regulator that can decrease TP53 by deubiquitinating and stabilizing ARF-BP1, a ubiquitin ligase for p53 degradation [67]. During HR pathway, USP4 is required for CtIP recruitment to DNA damage site. It also regulates the resection of DNA DSBs via interacting with CtIP and the MRE11-RAD50-NBS1 (MRN) complex. The depletion of USP4 may abolish DNA end resection [69]. In addition, USP4 is ubiquitinated on multiple sites, and auto-deubiquitination of USP4 can promote CtIP recruitment and affect HR capacity [70].
USP11 and USP15 are two paralogs of USP4, and all of them share a common functional domain consisting of two ubiquitin-like (UBL) and a motif with ubiquitin-specific protease (DUSP) activity [71, 72]. USP11 is identified as a component of HR pathway, but the molecular mechanism is not clear [73], while USP15 is a DUB for murine double minute-2 (Mdm2), one of the E3 ligases that play a major role in regulating TP53 [74]. Thus, cell apoptosis induced by TP53 in DSB response may be inhibited by USP15 via deubiquitinating and stabilizing Mdm2. Except for USP15, USP26 can also deubiquitinate Mdm2 and play the same role as USP15 regulating TP53 [75]. Furthermore, USP26 and USP37 have been shown to inhibit the formation of BRCA1-A and promote the formation of BRCC. This function may involve in HR pathway [76]. However, further studies are needed to elucidate how USP26 and USP37 regulate HR pathway.
USP7, also called herpesvirus-associated ubiquitin-specific protease (HAUSP), is identified to act as a factor that promotes viral lytic growth, because it is associated with a herpesvirus protein ICP0 that is crucial for the viral lytic cycle [77, 78]. Substrates of USP7 are widespread, and a large part of them are tumor suppressors or oncogenes, such as TP53, PTEN, Chk1, Mdm2, and FOXO [79]. USP7 can regulate these tumor suppressors and play a key role in DSB response [80, 81, 82]. For example, USP7 directly deubiquitinates Chk1
DUB | Substrates | Process | Reference |
---|---|---|---|
USP1 | Unclear | Promote HR and partly suppress NHEJ | [57] |
USP3 | H2A, γH2AX | Suppress DNA DSB response | [61] |
USP4 | ARF-BP1, USP4 | Suppress p53-dependent apoptosis in DSB response | [67, 70] |
USP6 | H2A | Suppress DNA DSB response | [26] |
USP7 | Chk1, p53, Mdm2 | Promote p53-dependent apoptosis in DSB response | [81, 82, 83] |
USP10 | p53 | Promote p53-dependent apoptosis in DSB response | [84] |
USP11 | unclear | Promote HR | [73] |
USP15 | Mdm2 | Suppress p53-dependent apoptosis in DSB response | [74] |
USP20 | Claspin | Promote DNA DSB response | [80] |
USP26 | Mdm2 | Suppress p53-dependent apoptosis in DSB response and promote HR | [75, 76] |
USP29 | H2A, p53 | Suppress DNA DSB response and promote p53-dependent apoptosis in DSB response | [63, 85] |
USP37 | Unclear | Promote HR | [76] |
USP42 | p53 | Promote p53-dependent apoptosis in DSB response or promote DSB response | [86] |
USP44 | H2A | Suppress DNA DSB response | [63] |
USP51 | H2A, H2B | Suppress DNA DSB response | [62, 64] |
OTUB1 | p53 | Promote p53-dependent apoptosis in DSB response not via its catalytic ability | [87, 88] |
OTUD5 | p53 | Promote p53-dependent apoptosis in DSB response | [89] |
POH1 | K63 | Promote HR but not via deubiquitinating K63 | [90] |
DUBs regulate DNA DSBR.
OTUs are divided into three subclasses: Otubians, A20-like OTUs, and other OTUs [91]. Otubians consist of OTUB 1 and OTUB 2 that are the first two proteins identified to display the DUB activity
JAMMs, the important members of metalloproteinase (MMP), contain JAMM/MPN domain-associated metallopeptidases sequences. These sequences include three conserved residues (two His and one Asp) that make up of catalytic center with two zinc ions [101]. The 26S proteasome-associated PAD1 homolog 1 (POH1) is a representative member of JAMMs and plays a key role in DSBR pathway. POH1 has been shown to be required for HR, which was supposed to associate with its ability to restrict 53BP1 through cleaving ubiquitin from the polyubiquitin chains of K63 protein. However, the result from another study showed that POH1-regulating HR process was independent of 53BP1 [90]. Thus, further studies are needed to elucidate detailed regulative mechanisms.
DSBR is a crucial DNA repair pathway and requests a series of DNA repair enzymes, whose activation is usually controlled via the post-translational modification regulation. In the regulation of DSBR capacity, DUBs play a vital role via deubiquitinating key proteins involving in DSBR pathway and/or enhance DSB response. However, there are several issues to be noted. First, although DUBs are a large posttranslational modification factor, only small part of them have functionally been identified. Second, despite DUBs that regulate DSBR capacity via increasing the stability and activation of DSBR enzymes, the detailed mechanisms are still unclear. Finally, some other signal pathways may affect DSBR, and it is not clear whether DUBs regulate these signal pathways. Thus, further studies are needed to solve more detailed molecular mechanisms of DUBs regulating DSBR.
This study was supported in part by the National Natural Science Foundation of China (Nos. 81760502, 81572353, 81372639, 81472243, 81660495, and 81460423), the Innovation Program of Guangxi Municipal Education Department (Nos. 201204LX674 and 201204LX324), Innovation Program of Guangxi Health Department (No. Z2013781), the Natural Science Foundation of Guangxi (Nos. 2017GXNSFGA198002, 2017GXNSFAA198002, 2016GXNSFDA380003, 2015GXNSFAA139223, 2013GXNSFAA019251, 2014GXNSFDA118021, and 2014GXNSFAA118144), Research Program of Guangxi “Zhouyue Scholar” (No. 2017-38), Research Program of Guangxi Specially-invited Expert (No. 2017-6th), Research Program of Guangxi Clinic Research Center of Hepatobiliary Diseases (No. AD17129025), and Open Research Program from Molecular Immunity Study Room Involving in Acute & Severe Diseases in Guangxi Colleges and Universities (Nos. kfkt20160062 and kfkt20160063).
AMP | adenosine monophosphate |
DSB | DNA double-strand break |
DSBR | double-strand break repair |
DUB | deubiquitinase |
HR | homologous recombination |
MCPIP | the monocyte chemotactic protein-induced protein |
MJD | Machado-Joseph disease protein domain protease |
NHEJ | non-homologous end-joining |
OUT | ovarian tumor protease |
ROS | reactive oxygen species |
RSS | recombination signal sequence |
UCH | ubiquitin carboxy-terminal hydrolase |
UPP | ubiquitin-proteasome pathway |
USP | ubiquitin-specific protease |
Nepal is an agrarian country and 60.4% of its population is dependent on agriculture and it contributes to 26.8% of national GDP [1, 2]. Commercialization of agriculture is needed to accelerate the economic growth in the country, which is largely subsistence type. Since Nepal has entered World Trade Organization (WTO) as a member country in 2004, it is necessary to exploit the globalized trade for the nation [3]. Most of the people who are engaged in agriculture are rural dwellings and they are the prime driver of the agriculture of the country, Nepal. However, the commercialization of agriculture demands high-value inputs, which are often associated with higher use of improved, and hybrid cultivars, machinery, fertilizers, pesticides, etc.
Pesticides are those chemical substances that are used to control pests of an agricultural and urban setting. These substances include fungicides, insecticides, rodenticides, herbicides, molluscicides, nematicides, miticides, avicides, etc. Insecticides are used for a very long time to deter, minimize, and manage insect pests in an agricultural field, forest land, and in human settlements. In agricultural crop production only, insects and other pests cause around 35% yield decline [4].
The role of insecticides to reduce the insect pests attack on various crops, damage to the health of humans and livestock is crucial. Due to the advantage of the rapid action of these chemicals over target organisms, these are widely being used all over the world. Nepal could not be an exception regarding the use of chemical insecticides. Insecticides encompass a broad range of chemicals that are toxic not only to insects but also to other organisms. These chemicals often lead to pesticide resistance, the resurgence of insect pests, and the decline of beneficial organisms, along with the detrimental impact on human health and the environment [5]. Unscientific use of pesticides is of major concern to the farmers of the developing countries and Nepal could not be the exception, which further exacerbates the situation.
Phytophagous insects only do the damage to grown crops, on average of 35–40%. Sometimes, it exceeds more than that based on the severity of the pest [6]. Commercial growers mainly depend on various insecticides to get rid of the various insect pests. But, the exact amount of import of these insecticides, their use, and the effect on human health and the environment is of major concern to Nepalese agriculture [7].
A rigorous and thorough study was done to collect and synthesize information on the topic of the review. Different research papers, review articles, reports, governmental websites, and their publications were studied and screened for data compilations. Gathered data were coded in the MS-Excel and subsequent tabulation and column graphs were generated.
The use of insecticides started in Nepal in early 1950s with intention of control of malaria, especially to eradicate the disease transmitted by mosquitoes for the Gandaki Hydropower Project [8]. First introduced chemicals to Nepal were Paris green, gramaxone, nicotine sulfates, Dichloro-diphenyl –trichloroethane (DDT), and these all were brought from the USA. These chemicals were followed by other organochlorines, organophosphates, carbamates, and synthetic pyrethroids [8, 9]. In the agricultural field, pesticides were started to use in the early sixties. This is the era of the green revolution where farmers were instructed to get maximum yield from a crop by using higher inputs such as improved seeds, chemical fertilizers, pesticides, etc. Until that period, farmers were unaware of the chemicals and insecticides to manage the various insect pests of agricultural crops. At the time, farmers have a preference over broad-spectrum pesticides due to the effective work to knock down the pests [10]. Nepal does not produce any insecticides till now but imported primarily from six countries, that is, India, China, Malaysia, Singapore, Italy, and Japan [3]. Till now, 54 types of insecticides were introduced to Nepal with 14 bio-pesticides, which are depicted in Tables 1 and 2. Organochlorines and some other highly toxic chemical pesticides were banned in Nepal, which are shown in Table 3. Insecticides were registered in 1787 commercial names by Plant Quarantine and Pesticide Management Center (PQPMC) under the Department of Agriculture, Nepal. In Nepal, there are altogether 16,110 retailers, 5 pesticide formulators, 37 pesticide applicators, and 286 pesticide importers [11]. Traders of pesticides are mainly concentrated in the commercial agricultural areas such as in plain regions, in the valley, and in and around the major cities of the country. Still, pesticide business has not penetrated the mid-hills, hills, and larger rural areas of the country.
S. No. | Insecticide chemical group (in use) | Common names |
---|---|---|
1 | Organophosphate | Acephate, Azamethiphos, Chlorantraniliprole, Chlorpyrifos, Dimethoate, Ethion, Malathion, Phenthoate, Profenofos, Quinalphos, Temephos |
2 | Carbamates | Propoxur, Thiodicarb |
3 | Synthetic pyrethroids | Cypermethrin, Permthrin, Alphacypermethrin, Alphamethrin, Bifenthrin, Beta-cyfluthrin, Cyfluthrin, Etofenprox, Fenvalerate, Flumethrin, Lambda Cyhalothrin |
4 | Nicotinoid | Acetamiprid, Dinotefuran, Imidacloprid, Nitenpyram, Thiacloprid, Thiamethoxam |
5 | Avermectin | Abamectin, Emamectin benzoate |
6 | Methyl | Amitrazz |
7 | Organic thiophosphate | Azamethiphos |
8 | Nereistoxin analogue | Cartap hydrochloride |
9 | Halogenated pyrroles | Chlorfenapyr |
10 | Thioureas | Diafenthiuron |
11 | Benzoylurea | Diflubenzuron |
12 | Pyrazole | Fipronil |
13 | Pyridine compound | Flonicamid, Pymetrozin |
14 | Diamide | Flubendiamide |
15 | Isoxazoline | Fluralaner |
16 | Oxadiazine | Indoxacarb |
17 | Spinosyns | Spinosad |
18 | Tetronic acid | Spriomesifen |
19 | Tetramic acid | Spriotetreamat |
20 | Insect growth regulator | Novaluron, Lufenuron, Cyromazine, Chlorfluazuron, Buprofezin |
21 | Dazomet | — |
Registered pesticides in Nepal till 14 July, 2020.
S. No. | Common name | Origin |
---|---|---|
1 | Neem based | |
2 | Bacteria | |
3 | Bacteria | |
4 | Bacteria | |
5 | Bacteria | |
6 | Fungus | |
7 | Fungus | |
8 | Fungus | |
9 | Fungus | |
10 | Fungus | |
11 | Fungus | |
12 | Fungus | |
13 | Nematode | |
14 | Nuclear polyhedrosis virus | Virus |
List of bio-pesticides registered in Nepal.
S. No. | Banned pesticides | Decision year | S. No. | Banned pesticides | Decision year |
---|---|---|---|---|---|
1 | DDT | 2001 | 13 | Monocrotophus | 2006 |
2 | BHC | 2001 | 14 | Methyl Parathion | 2006 |
3 | Aldrin | 2001 | 15 | Endosulphan | 2012 |
4 | Dieldrin | 2001 | 16 | Phorate | 2015 |
5 | Endrin | 2001 | 17 | Carbofuran | 2019 |
6 | Heptachlor | 2001 | 18 | Dichlorvos | 2019 |
7 | Chlordane | 2001 | 19 | Triazophos | 2019 |
8 | Mirex | 2001 | 20 | Carbaryl | 2019 |
9 | Phosphamidon | 2001 | 21 | Benomyl | 2019 |
10 | Organo Murcuric Fungicides | 2001 | 22 | Carbosulphan | 2019 |
11 | Lindane | 2001 | 23 | Dicofol | 2019 |
12 | Toxapheone | 2001 | 24 | Aluminium Phosphide 56% | 2019 |
Banned pesticides in Nepal.
In average, consumption of pesticide inactive ingredient is very low, that is, 0.396 kg/ha compared to other countries such as India (0. 481 kg/ha), China (2.0–2.5 kg/ha), Japan (10.8 kg/ha), Europe (1.9 kg/ha) and USA (1.5 kg/ha) [12]. But, in highly commercial agricultural areas have much higher use of pesticides than the national average.
Since insecticides are imported highly from foreign countries based on higher demand, farmers are using those chemicals in their fields injudiciously. Comparatively use of insecticides and other pesticides used in Nepal are lower than in developed countries, but the real problem is in the commercial pocket areas where growers are using exceedingly higher than they needed. There is a wider perception to the farmers that they have got the only chemical measures to control insect pests. Lack of awareness and knowledge of farmers, lack of alternatives of insect pests’ management other than chemicals, lack of governmental regulation and monitoring policies and actions for pesticide use are some of the reasons for improper and excessive use of insecticides in Nepal [13]. Insecticide use is reported much higher in vegetables compared to cereal crops and others. Since the vegetable growers are commercial, they tend to use insecticides more often. One study reported that more than 85% of insecticides imported were used in vegetable crops to deter various insect pests and oftentimes farmers are using insecticides even the insects are not at a damaging level. It is reported that a higher concentration of insecticides residues, that is, Cypermethrin than the permissible limit was detected in tomato and brinjal. The same study also showed that the concentration of Deltamethrin was higher in cowpea and was followed by cauliflower, tomato, and brinjal [14]. The residues of carbamate and organophosphate group of insecticides were observed in the vegetables sampled from the leading vegetable market of Nepal located in the heart of the capital city, Kathmandu. Tomato and cowpea were having higher residues of insecticides and these were grown in the commercial pocket of vegetables of Nepal, that is, Sarlahi and Kavre districts. The same study has revealed that 21.38% of tomato samples and 18.75% of cowpea samples were of sub-standard quality among the samples which were tested positive in pesticide residue analysis using the reagent kit method were [15]. The trend of insecticide use is increasing in Nepal by 10–20% per year and this signifies the prevailing crisis of Nepalese agriculture not only in terms of economic losses but also of associated detrimental effects [16].
It is reported that 25% of farmers of plain regions, 9% of mid-hills, and 7% of mountains use pesticides in their fields, and their usage in these ecological zones of Nepal is depicted inFigure 1 [17]. It is also reported that insecticides application is significantly higher in cotton and tea plantation in Nepal and it is worthwhile to mention that, compared to the cereal crops, use of insecticides and other pesticides is significantly higher in vegetables and other commercial/cash crops, as shown in Figure 2 [11]. In Kavrepalanchok district, near to the capital city, farmers were using insecticides 1–3 times whereas the same farmers were using 2–15 times in vegetables such as cabbage, potato, tomato, bitter gourd, cucumber, etc. It is even comparable to the share of pesticides in the production of various crops. Wheat has no pesticide application whereas, pesticide application in bitter gourd accounts for an 8.41% share in crop production [18] Farmers have reported the use of a cocktail spray of insecticides. Some farmers have also malpractice of dipping green vegetables in insecticide solutions such as malathion, mancozeb, etc. for a shiny and fresh look to fetch a good price in the market [12]. Farmers are very unaware and they hardly care for the waiting period to pick their harvest before they take it to the market. And, these products are purchased by the consumer and immediately taken for their food requirement and this makes the case more worsen [15].
Crop wise pesticide use (a. i. gm/ha) in Nepal (Source: PQPMC, 2021).
Ecological scenario of pesticide use in Nepal (Source: PQPMC, 2021).
Farmers of Nepal are very unaware of pesticide risk and it is the case of the area where people are engaged in conventional agriculture. In one survey conducted in Gaidahawa Rural Municipality of Rupandehi district, about 73% of the vegetable farmers have the practice of reusing the leftover pesticides. In the farmers’ field, researchers have reported that farmers have left the pesticide containers and packets in the open field, without thinking about the risk those containers possess [19]. Among the various pesticides reported in the area, chlorpyrifos was with higher concentration, that is, 177 μg/kg from the soil samples collected from three different depths of soil, that is, 0–5 cm, 15–20 cm, and 35–40 cm. DDT although banned in Nepal from 2001, its residues were found at all depths of the soil, which shows its persistent nature in the environment [19, 20]. The DDT mean concentration at 35–40 cm soil depth from the above-mentioned research area was found higher than 10 μg/kg, which is more than the threshold value for the safety of various soil organisms. Other insecticides such as Profenofos and imidacloprid were also found in the soil samples abundantly at different soil samples and found to be toxic to different soil organisms [19].
Insecticides can be used in a variety of forms, including liquid, concentrated, powder, dust, particle, aerosol, and fog, to control various insect pests of various crops. Those chemicals sprayed in a crop’s field will move and transfer to the environment via water, wind, and absorption. It can be transferred to long distances and in various forms. A large part of the most commonly used insecticides do not reach their target insect and may be affecting non-target organisms or polluting the environment. Non-target organisms include not only other insects, but also vertebrates such as wildlife, humans, and domestic animals. Insecticides can enter non-target habitats or ecosystems and affect non-target organisms [20]. Since food is a basic need and the practices of insecticide use do have a greater impact on human health. The most contaminated insecticides group, that is, carbamate and organophosphates are neurotoxic and are acetylcholinesterase inhibitors. These insecticides belong to the toxicity categories I and II. These are categorized under the most dangerous insecticides to the non-target organisms including humans and the environment [21]. These chemical insecticides may have contaminate on the environment such as soil, water (surface and ground), various flora and fauna, etc.
Since the import of pesticides including insecticides is increasing every year. The import of pesticides in the year 2013/14 was 454 tons but now, in the year 2019/20, import has been increased to 681 tons as shown in Figure 3 [11]. The residues of those chemicals on the soil and water are accumulating every year. One research has highlighted the moderate risk of cancer to the public where the soil is contaminated with organochlorine residues such as DDT and endosulfan [22]. This signifies not only the impending to the human health but also to the rich flora and fauna of the country itself. This sort of unsustainable practices in agriculture could be the cause of the loss of rich fauna which includes 17,097 species [23]. Various biotas inhabiting the soil such as bacteria, fungi, nematodes, earthworms, soil-inhabiting insects, and other arthropods with the presence of other organisms help to maintain the quality of soil and provide major ecosystem services for maintaining soil health and ultimately the quality of food production. The malpractices of insecticides along with other hazardous pesticides could have a detrimental effect on those organisms and ultimately deteriorate the quality and quantity of food production [19]. Another research conducted at Biratnagar of Nepal reported the presence of DDT and endosulfan in soil. The research also suggested that the use of DDT is still ongoing in the region but endosulfan residues were of past use [22].
Scenario of yearly pesticide import into Nepal (Source: PQPMC, 2021).
These insecticides exposure to humans causes detrimental health defects such as hormonal imbalance, immune suppression, lower intelligence, reproductive anomaly, damage on kidney, liver, neural regions, and cancer. Farmworkers who have also exposure to insecticides get the symptoms of headache, drowsiness, dizziness, skin irritation, muscular twitching, respiratory discomfort, etc. [24, 25].
It is reported that the estimated health cost of the pesticide user individual who has got exposure to pesticides is Nepalese Rupee (NPR) 287. Of the total household expenditure, pesticide-induced health costs take 0.2% of annual household expenditure and 10.32% of annual health care expenditure [26].
More than the optimal concentration of insecticides also has unprecedented results human health and their expenditure on health care. One unit increase in insecticide concentration, that is, by 1 ml/L of water, would cause increased sickness cases by 6.8% and health costs by nearly NPR 30. Similarly, more hours of insecticide or any other pesticides application would bring unintended results to the health of the farmers and their expenditure [26].
It is also upsetting to mention the intentional or suicidal attempts of pesticide poisoning are common in Nepal. Most of the time, insecticides; mainly organophosphate are used by suicidal attempters. The most commonly used insecticides for self-pesticide poisoning were methyl parathion, dichlorvos, aluminum phosphide, and zinc phosphide [27].
It is speculated that the insecticide reduction will cause a decline in the yield of the crops. But, it is not the case of the countries which are following a reduction in pesticide use because of their focus on the ecology of pests and agro-ecosystem. In that scenario, their production has been affected as speculated. Sweden has reduced pesticide use by 68% and public health poisonings by 77%. Their cutoff to the pesticides did not cause increased crop losses by the various pest species including insects. Indonesia also has reduced pesticide use by 65% and on the contrary, their production of rice has increased by 12%. India is also practicing the same and reducing the use significantly over the past years. But, Nepal is doing the opposite [25]. We are quite increasing the pesticide use for the sake of higher production, but, we are not aware of the fact that we are using unwarranted pesticides. Farmers, the ones who are not trained with the Integrated Pest Management (IPM) practices, are spraying the chemical pesticides more often than the ones who are trained. It is found that the trained farmers are spraying the pesticides 2.7 more times than the optimal whereas; the ones who are not trained are spraying 4.4 times of control [27]. This suggests the need of organizing community-based IPM training and environmental awareness programs about harmful effects of pesticides and sharing the know-how of insect pest management other than chemicals. It is also reported that Nepalese farmers are willing to pay higher prices (53–79%) than the current pesticide costs to mitigate the detrimental effect on their health and environment, and this clearly shows that they are willing to adopt alternative measures of pest management. But, the IPM programs of Nepal do have a contribution to the reduction of pesticide use but do not have a significant contribution to the reduction of health damages associated with the pesticides [25].
For the first time in Nepal’s history, the pesticide act was enacted in 1991, regulations were approved in 1993, and pesticide board was formulated in 1994 [18, 28]. Currently, Pesticides Management Act, 2019 was enacted which provisioned registration of bio-pesticides and also included the provision of facilitating warehouses for storing the date expire, band, and obsoleted pesticides in seven provinces of Nepal. It also included the provision of bringing back the pesticides which are spoiled, banned, or obsolete pesticides. It also included the provincial pesticide committee. Punishment was also provisioned in the act and upon defiance of these laws minimum of 25 thousand Nepalese Rupee (NPR) penalty, one-month prison, and maximum 200 thousand NRS penalty, and one-year prison was provisioned. Overall, the pesticide act regulates the manufacture, import, sale, transport, distribution, and use of pesticides in the country. This enabled the registration of pesticides, monitoring and inspection of pesticides, registration of importers and traders, and banning of highly toxic pesticides to minimize the exposure to humans, livestock, and other associated environmental components [29]. But, there is a great scope for proper inaction of law so that the widespread misuse of chemical pesticides in the country either by the importers, traders, and applicators could be minimized greatly. Since Nepal shares an open border with India, there are unintended pesticide imports to the country and many of them are more toxic, banned, and unregistered. Tracking the trade with India is oftentimes difficult since a porous border gives the opportunity to the persons who are involved in illegal trades.
Nepal is also a signatory country for WHO and follows the rules, regulations, and treaties proposed by them. Recently as directed by WHO, the country has banned 1a and 1b types of extremely hazardous pesticides. As a responsible member, Nepal has signed international treaties like the Basal convention, Stockholm convention, and Rotterdam convention, which have aimed to minimize the use of persistent and toxic pesticides [3].
Since Nepali farmers do not have much more information and knowledge about the methods of pest management other than chemicals. But, the Nepal Government and Department of Agriculture have started to prioritize the IPM program. Integrated Pest Management (IPM) is a pest control strategy that aims to combine various techniques of pest management such as mechanical, physical, cultural, biological, and chemical to minimize the risks possessed by the pest in a given ecosystem [30]. IPM always considers the use of chemicals as a last resort and before using chemicals, it seeks out all the possible alternatives for insect pest management.
Since 1999, the Nepalese government has used the Farmer Field School approach to strengthen farmers for cultivating healthy crops with decisions based on an understanding of the field agroecosystem with having eyes on beneficial organisms such as predators and parasites of insect pests. A Farmer Field School, also known as a school without walls, is a school that teaches basic agroecology and crop management skills. A group of farmers gathers in one of their own fields to observe, discuss, record, and analyze real-world field problems from crop planting to harvest. This field school is based on the concept of “learning by doing” rather than “seeing is believing”. The FFS was specially designed for farmers to learn and adopt IPM practices to their diverse and ever-changing ecological conditions [31]. Several crop season-long FFS have been organized in Nepal in recent years to provide knowledge and know-how on IPM to vegetable farmers in the hope of reducing their use of pesticides [32].
IPM farmer’s field schools in the country have positive impacts on the farmers for using a lesser amount of pesticides. This was evident in the Bhaktapur district of the country, which is also well known for commercial vegetable production, and seasonal and off-seasonal vegetables are produced here. As reported, farmers were using a significantly higher amount of pesticides where mean active ingredient (a.i.) of fungicides and insecticides were 2373 and 1963 g respectively and on average use of pesticide use was 2011 g a.i./ha. Among the used pesticides to cruciferous vegetables, the share of insecticides was more, that is, 76% which was followed by fungicides (19%) and unknown were 5%. The participants of IPM farmer’s field school had reduced significantly lower amounts of pesticides compared to non-participants. It was reported the 36% lesser amount of pesticides due to the effect of participation of IPM farmer’s field school [32]. In another report, pesticide application by the farmers was decreased by 40% upon participation in farmer’s field school [33]. This obviously shows the importance of these programs organized by governmental institutions.
Bio-pesticide could be a viable alternatives for Nepalese farmers since it will not be toxic to humans, other organisms, and the environment at large. There are altogether 14 registered bio-pesticides in Nepal which are effective to manage various insect pests and in some instances, other pests too of various crops. In Nepal, the use of bio-pesticides started commercially roughly after 2000. The share of bio-pesticides in the year 2019/20 is 0.005% of the total quantity of pesticides imported and used. This shows the predominantly higher use of conventional pesticides compared to commercial bio-pesticides. But, the use of locally available plant resources for pest control is a long practiced tradition of the farmers of Nepal. Many plants possess pesticide properties and these are all available all around the country. Three hundred and twenty four species of botanicals are found in Nepal only and among them, 23 species have special importance to the farming community of Nepal. The most common plants used as pesticides are as follows: Neem (
Although Nepal shares larger scope of isolation of different micro-organisms from the soil of Nepal, it offers only the formulation of two funguses, that is,
Nepal, an agrarian country located in Southeast Asia is going to face unprecedented changes in human health, environment, and ecosystems due to more use of insecticides to deter insect pests in the farmer’s field. Large amounts of insecticides are imported from foreign countries. These chemicals certainly have negative impacts on the farming community and the environment at large. The situation seems even worse because of a lack of knowledge and skills related to the safety aspects of the farming community about the use of insecticides and its negative effects not only to the consumers but on them too. Many researches have confirmed the presence of undesirable residues of insecticides in vegetables, fruits, and other agricultural commodities. Incidences of human diseases such as immune dysfunction, kidney failure, cancer, etc. are also increasing in the country which somehow has a direct or indirect relation to the more use of insecticides in the field. Because farmer knowledge and behavior can reduce the ecological risk of pesticides, programs such as IPM training and farmer’s field school (FFS), etc. could be determined to change the status quo. Prioritizing the botanicals by the Nepal government and its respective agricultural agencies to the area where there is no practice of using conventional pesticides has special significance to protect the health of humans, various flora and fauna, and the environment.
The author wishes to appreciate the contribution of all the individuals and organizations who are constantly working on pesticides, their residues, effects, and mitigation in Nepal, and who has helped the author directly and indirectly in preparing this manuscript.
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Stress is any adverse environmental condition that hampers proper growth of plant. Abiotic stress creates adverse effect on multiple procedures of morphology, biochemistry and physiology that are directly connected with growth and yield of plant. Abiotic stress are quantitative trait hence genes linked to these traits can be identified and used to select desirable alleles responsible for tolerance in plant. Plants can initiate a number of molecular, cellular and physiological modifications to react to and adapt to abiotic stress. Crop productivity is significantly affected by drought, salinity and cold. Abiotic stress reduce water availability to plant roots by increasing water soluble salts in soil and plants suffer from increased osmotic pressure outside the root. Physiological changes include lowering of leaf osmotic potential, water potential and relative water content, creation of nutritional imbalance, enhancing relative stress injury or one or more combination of these factors. Morphological and biochemical changes include changes in root and shoot length, number of leaves, secondary metabolite (glycine betaine, proline, MDA, abscisic acid) accumulation in plant, source and sink ratio. 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It has been demonstrated that an increase in crop yields significantly reduces poverty. Yield, the mass of harvest crop product in a specific area, is influenced by several factors. These factors are grouped in three basic categories known as technological (agricultural practices, managerial decision, etc.), biological (diseases, insects, pests, weeds) and environmental (climatic condition, soil fertility, topography, water quality, etc.). These factors account for yield differences from one region to another worldwide. The current chapter will discuss each of these three basic factors as well as providing some recommendations for overcoming them. In addition, it will provide the importance of climate-smart agriculture in the increase of crop yields while facilitating the achievement of crop production in safe environment. This goes in line with the second goal of 2030 Agenda for Sustainable Development of United Nations in transforming our world formulated as end hunger, achieve food security, improve nutrition and promote sustainable agriculture.",book:{id:"8153",slug:"agronomy-climate-change-food-security",title:"Agronomy",fullTitle:"Agronomy - Climate Change & Food Security"},signatures:"Tandzi Ngoune Liliane and Mutengwa Shelton Charles",authors:[{id:"313819",title:"Dr.",name:"Liliane",middleName:null,surname:"Tandzi",slug:"liliane-tandzi",fullName:"Liliane Tandzi"},{id:"314316",title:"Prof.",name:"Charles Shelton",middleName:null,surname:"Mutengwa",slug:"charles-shelton-mutengwa",fullName:"Charles Shelton Mutengwa"}]},{id:"40178",title:"Molecular Markers and Marker-Assisted Breeding in Plants",slug:"molecular-markers-and-marker-assisted-breeding-in-plants",totalDownloads:23130,totalCrossrefCites:85,totalDimensionsCites:153,abstract:null,book:{id:"3060",slug:"plant-breeding-from-laboratories-to-fields",title:"Plant Breeding from Laboratories to Fields",fullTitle:"Plant Breeding from Laboratories to Fields"},signatures:"Guo-Liang Jiang",authors:[{id:"158810",title:"Dr.",name:"Guo-Liang",middleName:null,surname:"Jiang",slug:"guo-liang-jiang",fullName:"Guo-Liang Jiang"}]},{id:"60074",title:"Pollen Germination in vitro",slug:"pollen-germination-in-vitro",totalDownloads:2812,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Pollen germination in vitro is a reliable method to test the pollen viability. It also addresses many basic questions in sexual reproduction and particularly useful in wide hybridization. Many pollen germination medium ranging from simple sugars to complex one having vitamins, growth regulators, etc. in addition to various minerals have been standardized to germinate pollen artificially. The different media, successful pollen germination methods, procedures from pollen germination studies with wheat, rye, brinjal, pigeonpea and its wild relatives are discussed.",book:{id:"6659",slug:"pollination-in-plants",title:"Pollination in Plants",fullTitle:"Pollination in Plants"},signatures:"Jayaprakash P",authors:[{id:"235465",title:"Dr.",name:"Jayaprakash",middleName:null,surname:"P",slug:"jayaprakash-p",fullName:"Jayaprakash P"}]},{id:"62376",title:"Genotype × Environment Interaction: A Prerequisite for Tomato Variety Development",slug:"genotype-environment-interaction-a-prerequisite-for-tomato-variety-development",totalDownloads:2339,totalCrossrefCites:2,totalDimensionsCites:7,abstract:"Tomato (Solanum lycopersicum L.) is the second most important vegetable crop in the world due to its high level of nutrition particularly in vitamins and antioxidants. It is grown in several ecologies of the world due to its adaptability and ease of cultivation. 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She is now a lecturer at the University of Witwatersrand, South Africa, and a principal researcher at the Health Economics and Epidemiology Research Office (HE2RO), South Africa. Dr. Moolla holds a Ph.D. in Psychology with her research being focused on mental health and resilience. In her professional work capacity, her research has further expanded into the fields of early childhood development, mental health, the HIV and TB care cascades, as well as COVID. She is also a UNESCO-trained International Bioethics Facilitator.",institutionString:"University of the Witwatersrand",institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419588",title:"Ph.D.",name:"Sergio",middleName:"Alexandre",surname:"Gehrke",slug:"sergio-gehrke",fullName:"Sergio Gehrke",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038WgMKQA0/Profile_Picture_2022-06-02T11:44:20.jpg",biography:"Dr. Sergio Alexandre Gehrke is a doctorate holder in two fields. The first is a Ph.D. in Cellular and Molecular Biology from the Pontificia Catholic University, Porto Alegre, Brazil, in 2010 and the other is an International Ph.D. in Bioengineering from the Universidad Miguel Hernandez, Elche/Alicante, Spain, obtained in 2020. In 2018, he completed a postdoctoral fellowship in Materials Engineering in the NUCLEMAT of the Pontificia Catholic University, Porto Alegre, Brazil. He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. In addition, he is also a Collaborating Professor in several Postgraduate programs at different universities all over the world.",institutionString:null,institution:{name:"Universidad Católica San Antonio de Murcia",country:{name:"Spain"}}},{id:"342152",title:"Dr.",name:"Santo",middleName:null,surname:"Grace Umesh",slug:"santo-grace-umesh",fullName:"Santo Grace Umesh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/342152/images/16311_n.jpg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"333647",title:"Dr.",name:"Shreya",middleName:null,surname:"Kishore",slug:"shreya-kishore",fullName:"Shreya Kishore",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333647/images/14701_n.jpg",biography:"Dr. Shreya Kishore completed her Bachelor in Dental Surgery in Chettinad Dental College and Research Institute, Chennai, and her Master of Dental Surgery (Orthodontics) in Saveetha Dental College, Chennai. She is also Invisalign certified. She’s working as a Senior Lecturer in the Department of Orthodontics, SRM Dental College since November 2019. She is actively involved in teaching orthodontics to the undergraduates and the postgraduates. Her clinical research topics include new orthodontic brackets, fixed appliances and TADs. She’s published 4 articles in well renowned indexed journals and has a published patency of her own. Her private practice is currently limited to orthodontics and works as a consultant in various clinics.",institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"323731",title:"Prof.",name:"Deepak M.",middleName:"Macchindra",surname:"Vikhe",slug:"deepak-m.-vikhe",fullName:"Deepak M. Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. His research interests include root canal morphology, functionally graded concept, dental biomaterials, epidemiology and dental education, biomimetic restoration, finite element analysis and endodontic regeneration. Dr. Madfa has numerous international publications, full articles, two patents, a book and a book chapter. Furthermore, he won 14 international scientific awards. Furthermore, he is involved in many academic activities ranging from editorial board member, reviewer for many international journals and postgraduate students' supervisor. Besides, I deliver many courses and training workshops at various scientific events. Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\r\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\r\nHer topics of interest are biomaterials science and cell culture studies. 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Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Orthodontist, Assoc Prof in the Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. After graduating from TED Ankara College in 1986, she attended the Hacettepe University, Faculty of Dentistry in Ankara. \nIn 1993 she attended the Gazi University, Faculty of Dentistry, Department of Orthodontics for her PhD education. After finishing the PhD education, she worked as orthodontist in Ankara Dental Hospital under the Turkish Government, Ministry of Health and in a special Orthodontic Clinic till 2011. Between 2011 and 2016, Dr. Deniz Uzuner worked as a specialist in the Department of Orthodontics, Faculty of Dentistry, Gazi University in Ankara/Turkey. In 2016, she was appointed associate professor. Dr. Deniz Uzuner has authored 23 Journal Papers, 3 Book Chapters and has had 39 oral/poster presentations. She is a member of the Turkish Orthodontic Society. Her knowledge of English is at an advanced level.",institutionString:null,institution:null},{id:"332914",title:"Dr.",name:"Muhammad Saad",middleName:null,surname:"Shaikh",slug:"muhammad-saad-shaikh",fullName:"Muhammad Saad Shaikh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jinnah Sindh Medical University",country:{name:"Pakistan"}}},{id:"315775",title:"Dr.",name:"Feng",middleName:null,surname:"Luo",slug:"feng-luo",fullName:"Feng Luo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sichuan University",country:{name:"China"}}},{id:"344229",title:"Dr.",name:"Sankeshan",middleName:null,surname:"Padayachee",slug:"sankeshan-padayachee",fullName:"Sankeshan Padayachee",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"315727",title:"Ms.",name:"Kelebogile A.",middleName:null,surname:"Mothupi",slug:"kelebogile-a.-mothupi",fullName:"Kelebogile A. 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