TALEN DNA binding repeat and its simple code scheme
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More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:{caption:"IntechOpen Maintains",originalUrl:"/media/original/113"}},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"169",leadTitle:null,fullTitle:"Remote Sensing of Biomass - Principles and Applications",title:"Remote Sensing of Biomass",subtitle:"Principles and Applications",reviewType:"peer-reviewed",abstract:"The accurate measurement of ecosystem biomass is of great importance in scientific, resource management and energy sectors. In particular, biomass is a direct measurement of carbon storage within an ecosystem and of great importance for carbon cycle science and carbon emission mitigation. Remote Sensing is the most accurate tool for global biomass measurements because of the ability to measure large areas. Current biomass estimates are derived primarily from ground-based samples, as compiled and reported in inventories and ecosystem samples. By using remote sensing technologies, we are able to scale up the sample values and supply wall to wall mapping of biomass. Three separate remote sensing technologies are available today to measure ecosystem biomass: passive optical, radar, and lidar. There are many measurement methodologies that range from the application driven to the most technologically cutting-edge. The goal of this book is to address the newest developments in biomass measurements, sensor development, field measurements and modeling. The chapters in this book are separated into five main sections.",isbn:null,printIsbn:"978-953-51-0313-4",pdfIsbn:"978-953-51-6177-6",doi:"10.5772/696",price:139,priceEur:155,priceUsd:179,slug:"remote-sensing-of-biomass-principles-and-applications",numberOfPages:336,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"c93637da5d1c8fcd07eda02777afab83",bookSignature:"Temilola Fatoyinbo",publishedDate:"March 28th 2012",coverURL:"https://cdn.intechopen.com/books/images_new/169.jpg",numberOfDownloads:38236,numberOfWosCitations:118,numberOfCrossrefCitations:55,numberOfCrossrefCitationsByBook:4,numberOfDimensionsCitations:141,numberOfDimensionsCitationsByBook:6,hasAltmetrics:1,numberOfTotalCitations:314,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 12th 2010",dateEndSecondStepPublish:"November 9th 2010",dateEndThirdStepPublish:"March 16th 2011",dateEndFourthStepPublish:"April 15th 2011",dateEndFifthStepPublish:"June 14th 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"11875",title:"Dr.",name:"Lola",middleName:null,surname:"Fatoyinbo",slug:"lola-fatoyinbo",fullName:"Lola Fatoyinbo",profilePictureURL:"https://mts.intechopen.com/storage/users/11875/images/system/11875.jpg",biography:"Research Physical Scientist, Biospheric Sciences Laboratory, NASA GSFC \n\nDr. Lola Fatoyinbo studies forest ecology and ecosystem structure at the NASA Goddard Space Flight Center. Dr. Fatoyinbo’s current research focus is the fusion of optical, Synthetic Aperture Radar and lidar data to quantify forest structure, biomass, extent and degradation. Dr. Fatoyinbo has carried out extensive field and remote sensing research in tropical forest ecosystems of continental Africa, Madagascar and Latin America. She received her Bachelors in Biology in 2003 and her PhD in Environmental Sciences in 2008 from the University of Virginia. She then completed a NASA Postdoctoral Fellow within the Radar Science and Engineering Section at the Caltech - Jet Propulsion Laboratory, where her primary research focus was on using interferometric SAR data to quantify tropical forest extent, height and biomass through the development of radar-lidar fusion algorithms. Dr Fatoyinbo is now a research physical scientist at the NASA Goddard Space Flight Center in the Biospheric Sciences Laboratory.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"793",title:"Sustainable Energy Engineering",slug:"sustainable-energy-engineering"}],chapters:[{id:"33849",title:"Lidar Remote Sensing for Biomass Assessment",doi:"10.5772/17479",slug:"lidar-remote-sensing-for-biomass-assessment",totalDownloads:3010,totalCrossrefCites:4,totalDimensionsCites:12,hasAltmetrics:0,abstract:null,signatures:"Jacqueline Rosette, Juan Suárez, Ross Nelson, Sietse Los, Bruce Cook and Peter North",downloadPdfUrl:"/chapter/pdf-download/33849",previewPdfUrl:"/chapter/pdf-preview/33849",authors:[{id:"28463",title:"Dr.",name:"Jacqueline",surname:"Rosette",slug:"jacqueline-rosette",fullName:"Jacqueline Rosette"},{id:"39879",title:"Dr.",name:"Juan",surname:"Suárez",slug:"juan-suarez",fullName:"Juan Suárez"},{id:"39880",title:"Dr.",name:"Sietse",surname:"Los",slug:"sietse-los",fullName:"Sietse Los"},{id:"40828",title:"Dr.",name:"Peter",surname:"North",slug:"peter-north",fullName:"Peter North"},{id:"92404",title:"Dr.",name:"Ross",surname:"Nelson",slug:"ross-nelson",fullName:"Ross Nelson"},{id:"92405",title:"Dr.",name:"Bruce",surname:"Cook",slug:"bruce-cook",fullName:"Bruce Cook"}],corrections:null},{id:"33850",title:"Forest Structure Retrieval from Multi-Baseline SARs",doi:"10.5772/18650",slug:"forest-structure-retrieval-from-multi-baseline-sars",totalDownloads:2267,totalCrossrefCites:6,totalDimensionsCites:8,hasAltmetrics:0,abstract:null,signatures:"Stefano Tebaldini",downloadPdfUrl:"/chapter/pdf-download/33850",previewPdfUrl:"/chapter/pdf-preview/33850",authors:[{id:"32113",title:"Dr.",name:"Stefano",surname:"Tebaldini",slug:"stefano-tebaldini",fullName:"Stefano Tebaldini"}],corrections:null},{id:"33851",title:"Biomass Prediction in Tropical Forests: The Canopy Grain Approach",doi:"10.5772/17185",slug:"biomass-prediction-in-tropical-forest-the-canopy-grain-approach",totalDownloads:2407,totalCrossrefCites:6,totalDimensionsCites:20,hasAltmetrics:0,abstract:null,signatures:"Christophe Proisy, Nicolas Barbier, Michael Guéroult, Raphael Pélissier, Jean-Philippe Gastellu-Etchegorry, Eloi Grau and Pierre Couteron",downloadPdfUrl:"/chapter/pdf-download/33851",previewPdfUrl:"/chapter/pdf-preview/33851",authors:[{id:"27521",title:"Dr.",name:"Christophe",surname:"Proisy",slug:"christophe-proisy",fullName:"Christophe Proisy"},{id:"39750",title:"Dr.",name:"Nicolas",surname:"Barbier",slug:"nicolas-barbier",fullName:"Nicolas Barbier"},{id:"39751",title:"Dr.",name:"Pierre",surname:"Couteron",slug:"pierre-couteron",fullName:"Pierre Couteron"},{id:"39752",title:"Prof.",name:"Jean Philippe",surname:"Gastellu-Etchegorry",slug:"jean-philippe-gastellu-etchegorry",fullName:"Jean Philippe Gastellu-Etchegorry"},{id:"76888",title:"MSc.",name:"Michael",surname:"Guéroult",slug:"michael-gueroult",fullName:"Michael Guéroult"},{id:"95714",title:"Dr.",name:"Raphael",surname:"Pélissier",slug:"raphael-pelissier",fullName:"Raphael Pélissier"},{id:"111697",title:"MSc.",name:"Eloi",surname:"Grau",slug:"eloi-grau",fullName:"Eloi Grau"}],corrections:null},{id:"33852",title:"Remote Sensing of Biomass in the Miombo Woodlands of Southern Africa: Opportunities and Limitations for Research",doi:"10.5772/16608",slug:"remote-sensing-of-biomass-in-the-miombo-woodlands-of-southern-africa-opportunities-and-limitations-f",totalDownloads:3453,totalCrossrefCites:2,totalDimensionsCites:6,hasAltmetrics:0,abstract:null,signatures:"Natasha Ribeiro, Micas Cumbana, Faruk Mamugy and Aniceto Chaúque",downloadPdfUrl:"/chapter/pdf-download/33852",previewPdfUrl:"/chapter/pdf-preview/33852",authors:[{id:"25757",title:"Prof.",name:"Natasha",surname:"Ribeiro",slug:"natasha-ribeiro",fullName:"Natasha Ribeiro"},{id:"117104",title:"BSc.",name:"Aniceto",surname:"Chaúque",slug:"aniceto-chauque",fullName:"Aniceto Chaúque"},{id:"117105",title:"BSc.",name:"Faruk",surname:"Mamugy",slug:"faruk-mamugy",fullName:"Faruk Mamugy"},{id:"117106",title:"BSc.",name:"Micas",surname:"Cumbana",slug:"micas-cumbana",fullName:"Micas Cumbana"}],corrections:null},{id:"33897",title:"Ocean Color Remote Sensing of Phytoplankton Functional Types",doi:"10.5772/17174",slug:"remote-sensing-of-marine-phytoplankton-biomass",totalDownloads:4116,totalCrossrefCites:2,totalDimensionsCites:11,hasAltmetrics:0,abstract:null,signatures:"Tiffany A.H. 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by",editors:[{id:"187893",title:"Dr.",name:"Maria Jose",surname:"Hernández-Serrano",slug:"maria-jose-hernandez-serrano",fullName:"Maria Jose Hernández-Serrano"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"49756",title:"Application of Genome Editing Technology to MicroRNA Research in Mammalians",doi:"10.5772/64330",slug:"application-of-genome-editing-technology-to-microrna-research-in-mammalians",body:'
Recent achievements in genome editing have resulted in progress beyond any imagination decades ago. This new technology provides tools for fast and precise alterations into genome with unprecedented efficiency and specificity. For instance, a group of targeted nucleases have been successfully used to modify genomic sequences in a wide variety of cells and organisms, including mammalians.[1-4] This modification is realized by the combination of conventional gene knockout technology with genome editing, empowering the researchers to make any desired changes in a given gene or its regulatory elements to establish casual linkage between genetic variations and biological phenotypes. This new methodology completes a framework for studying gene function and regulation
Mammalian genomes contain billions of DNA bases and are difficulty to manipulate.[5-7] Conventional genome editing is inefficient and must undergo a number of complicated and time-consuming procedures to obtain double knockouts. Because this technology had been built upon homologous recombination (HR), the targeted gene modifications occur at an extremely low frequency (1 in 106 ~ 109 cells).[8] This is the reason why this conventional approach is mainly used for producing knockout mice, for which a large amount of high quality embryonic stem cells is available. Although knockout mice have provided great insights into the fundamentals of developmental biology and physiology; the pathological roles of genes have yet to be addressed in relevant disease models or human samples.
To overcome limitations of conventional gene knockout technology, a number of nuclease-based methods have been developed in the past decade.[9-12] These novel technologies exploit the ability of endonucleases to induce double-stranded DNA breaks (DSBs) and stimulate subsequent damage repair mechanisms in mammalian cells.[11, 13-17] Remarkably, this nuclease-induced DSBs not only make sequence changes at the break points but also enhance HR rate to an astonish frequency of 1-40%.[7, 18] This approach provides a simple and effective way to streamline the genome editing with the potential to generate double knockout models in both cell lines and animals. Because of this technical breakthrough, nuclease-based methods quickly gain popularity for gene editing in variety of cell types and species. To date, four major classes of targeted nucleases are prominent: meganucleases derived from microbial mobile elements, zinc finger nuclease (ZFN) based on eukaryotic transcription factor DNA binding motif, transcription activator-like effector nuclease (TALEN) derived from a plan-invasive bacterial protein and most recently the bacterial type II clustered, regularly interspaced, short palindromic repeat-associated nuclease Cas (CRISPRE-Cas).[19] These technologies are collectively termed as targeted nucleases because they all have more or less a programmable DNA binding domain for specific genome targeting. The first three nucleases all recognize specific DNA sequences through protein-DNA interaction, whereas the last CRISPRE-Cas is targeted by a short guide RNA that recognizes the unwind DNA via Watson-Crick base pairing. The purpose of the nuclease is to make localized DSBs. These DSBs will invoke powerful non-homologous end-joining as well as homologous-direct recombination repair pathway for the versatile and precise modification of complicated mammalian genome.[14, 18, 20-32]
Large fraction of the genome is transcribed without protein coding potential. [33, 34] These non-coding transcripts can be broadly categorized into short and long non-coding RNAs, in which the arbitrary size delineation is at ~ 200 bases in length. Short non-coding RNAs are less 200 bases including microRNA, tRNAs and snoRNAs. An abundant class of small regulatory RNAs are termed microRNAs (miRNAs) that have been identified to play major roles in gene regulation.[35-38] Like coding mRNAs, miRNAs are transcribed by polymerase II and processed into ~ 22 nucleotide non-coding transcripts, which repress translation by binding to target sites within the 3’ untranslated region of mRNA.[39-41] Recent genomic studies have discovered over 1000 miRNAs in human and mouse genome.[34] It is estimated that up to 80% of human genes are regulated by miRNAs.[36, 42] Some mRNAs are clustered in polycistronic transcripts and allow coordinated regulation, while others are expressed in a tissue-specific and developmental stage-specific manner.[35, 40] The roles of miRNAs have been extensively studied at molecular and cellular levels in a number of species including mammals.[43, 44] Furthermore, their roles in physiology and development in animals have been established by conditional knockins and knockouts.[45-47] In fact, miRNAs are expressed across genome, and many of them show spatial and temporal expression. Similar to transcription factors, miRNAs may function as master regulators of embryonic pluripotency, differentiation, and tissue/organ formation.[37] Recently, increasing evidence suggests that miRNAs are implicated in numerous disease states as well. For instance, miR-21 was found to be overexpressed in virtually all types of human cancers and thus has emerged as an important therapeutic target in cancer treatment.[45, 48, 49] Additionally, miR-21 and other miRNAs have been shown to play crucial regulatory roles in basic cell functions such as cell growth, proliferation and apoptosis.[48, 49] Their pathological roles in multiple human diseases such as autoimmune, cardiovascular and neurological disorders and obesity are emerging.[50, 51]
MicroRNA genes have a great diversity in mammalian genomes. They are located in either introns of annotated protein-coding genes or outside the context of an annotated genes.[34] Gemone analysis studies reveal that up to 42% of human miRNAs are in clusters of two or more with pairwise chromosome distance of at most 3000 nucleotides. This pattern of clustering allows similar levels of expression and coordinated regulation. Examples of the two most famous clusters are miR-17~92 and miR-302~367. While the deletion of miR-17~92 cluster causes skeletal and growth defects, overexpression of miR-302-367 cluster enhances somatic reprogramming to pluripotent status. These clustered miRNAs appear to function together; therefore alteration of a specific member may not result in expected changes in physiology.
Although the exact mechanism of the regulation of each miRNA remains to be determined, the biogenesis of miRNA is becoming more apparent. From their gene loci, miRANs are initially transcribed by RNA polymerase II as long primary transcripts, which are processed into approximately 70-nucleotide precursors by the RNAse III enzyme Drosha in the nucleus.[52] These highly structured precursors are termed pre-miRNAs and subsequently transported from the nucleus to the cytoplasm by an Exportin-5 protein shuttler.[40] In cytoplasm, these pre-miRNAs are further cleaved by another RNase III enzyme, Dicer, resulting in imperfect miRNA:miRNA duplexes of about 18 ~ 24 bp in length.[53, 54] Although either strand of the duplex may potentially mature as a functional miRNA, only one strand is usually chosen and subsequently incorporated into the RNA-induced silence complex (RISC) where the miRNA and its mRNA target interact.[55, 56]
Despite their fundamental importance, the exact role of miRNAs in the context of human development and disease processes remain largely unknown. This is partly due to lack of effective methods for completely abolishing their expression in human cells and disease-relevant models. Although miRNA knockdown by short-interfering RNAs (siRNAs) provides a rapid and inexpensive tool to study most protein-coding genes, it cannot be used to reduce mature miRNAs in a sensible way at the cellular level. Other alternatives include small molecule inhibitors, antisense oligo-nucleotides, anti-miR vectors and miRNA sponges.[57, 58] However, the major limitations of these methods are transient nature of their effects and a high risk of off-target effects as well as toxicity. It is no surprise to see reports on discrepancies between the effects of miRNA inhibitors and genetic knockouts. With the completion of the genome sequencing, genome-wide gene targeting knockout of miRNA have been taken.[59] As a result, resources for the conditional ablation of miRNAs in mouse have been attempted.[60] In one study, generation of 162 miRNA targeting vectors and 46 germline-transmitted miRNA knockout mice was reported.[60] However, this homologous donor based knockout technology is expected to have tremendous hurdles to apply to other mammalian species such as rat, pig and monkeys. These larger animals are more close to humans; however, they all lack large scale culture of high quality embryonic cells to make use of this conventional technology. Nevertheless, the work in mice will provide an important basis for elucidating the physiological roles of certain miRNAs in at least one animal species.
Programmable DNA-binding proteins have emerged as an exciting platform for engineering targeted nucleases for precise genome editing.[61] The key component of these engineered nucleases is the DNA recognition domain that is capable of directing the nucleases to the specific genome loci therefore generating DNA double-strand breaks (DSBs) near or at the target sites.[62] In mammalian cells, these DSBs are repaired by one of two mechanisms, non-homologous end-joining (NHEJ) or homologous recombination (HR).[18] Repair by NHEJ is error-prone and often results in small insertions or deletion mutations, termed indels, at the break point. At the same time, DSBs can also greatly stimulate high-fidelity HDR repair mechanism in fast dividing cells. In mammalian cells, NHEJ is dominant over HR, but the frequency of latter can be substantially increased when large amount of exogenous homologous donors are co-delivered into cells.[25]
With these strategies, various methods, including meganucleases, ZFNs, TALENs and CRISPRE-Cas have been reported for genome editing in a wide variety of mammalian species.[63-70] For these methods, a DNA endonuclease enzyme for generating DSBs is brought in place by a guide molecule. In the first three scenarios, the guider is a protein, whereas the last (CRESPRE-Cas) is a short stretch of RNA. Figure 1 illustrates the action of targeted nucleases and the binding mode of guide molecules. In general, the protein guider is more specific than the RNA guider, where degeneration is governed by hybridization mechanism. The pros and cons as well as their features of four main technologies are discussed below.
Action of the Targeted Nucleases and Their DNA Binding Mode. Genomic DNA is shown horizontally in black and double stranded, with the site of DNA cleavage indicated by arrowheads. For meganuclease, the holoenzyme binds and cleaves the target DNA. For ZFN and TALENs, they function as a pair; with one zinc finger DNA binding domain (ZF) binding to the upper strand while the other ZF binding to the lower strand. Once this fused FokI enzyme (purple oval) is oriented to form a homodimer, it is activated to cut DNA. For CRISPR-Cas, the Cas9 holoenzyme (orange oval) is directed to the target site by the guide RNA and cleave the DNA at the position close to the PAM motif (grey arrow).
Meganucleases are endonucleases with a large DNA recognition site of 12 ~ 45 bp in length.[71] As a result, this site may occur only once in most mammalian genome.[6] Although Meganuclease possesses high degree precision and low toxicity, its target range is limited. Moreover, the intertwined DNA-binding domain and nuclease domain restrict its capacity to reprogram for other targets, and the probability of finding a meganuclease for cutting a desired locus is extremely slim.[72] For example, the phiC31 integrase mediates recombination between a donor DNA of two 34 bp sequences, termed as attachment sites (att) and the other in mammalian genome. In the introduction of phage integrase, a phiC31 integrase can insert a plasmid donor DNA of any size and requires no additional co-factors. Other advantages of using phiC31 integrase include non-viral delivery, sustainable transgene expression, and functions in species like bacteria, yeast, plants, frogs, chickens, mice, rats, pigs, cows, and humans.[2, 73] However, potential sites of phiC31-based genome editing are limited. In human genome, of the 106 mapped integration sites of phiC31, ~ 39% are within coding genes and ~ 61% are in the intergenic regions.[74]
First described in 1996, ZFN is a chimeric protein that is composed of two distinctive domains, a programmable DNA binding domain and an endonuclease, FokI.[75] Because of its programmability, ZFN have been successfully employed to modify almost all genome types including bacteria, plants, and animals.[1, 76, 77] In fact, ZFNs have been used for the correction of a number of hereditary diseases such as hemophilia B, sickle cell anaemia, a-1 antitrypsin deficiency and gene therapies for viral infections.[77-80] ZFN-based HIV gene therapy is already under clinical trials, because of its specificity and safety profile.[81, 82] However, the use of ZFNs has been partly hindered by the complex and time-consuming strategies to generate highly specific zinc-finger arrays with sufficient affinity and specificity. It is worthy to note that ZFNs also suffer some constrains in targeting range with about one potential target site every 500 bp.[83] It is conceivable that one may find it difficult to design ZFNs to precisely targeting a smaller gene in genome, such as miRNAs.
Similar to ZFNs, TALENs are also fusion proteins that comprise of a programmable DNA binding domain with an endonuclease, FokI. The DNA-binding domain of TALEN consists of ~34 amino acid repeats, followed by a single half repeat of 20 amino acids.[84] Interestingly, the tandem repeats are nearly identical, except for two amino acid codons at positions 12 and 13, referred to as “repeat variable di-residue” (RVD). [85]Each of the four most common RVDs specifies the binding to one of the four nucleotide bases (Table 1). The natural RVD for G is NN with asparagine at positions 12 and 13. NN binds G with high affinity, but also recognizes and binds A with relative low affinity.[86] Although artificial NH or NK provides good specificity for G, the binding affinity to G is relative low as compared to NN.[86] It is worth to note that TALE proteins bind DNA sequences with an invariable base T in the first position of the target. The corresponding module is not the repeat but the cryptic sequences flanking the repeats. Because the first binding base is invariable, the DAN-binding domain can theatrically be programmed to bind any sequences starting with a “T”. Taking advantage of the simplicity of the coding principle, the DNA-binding domain can be easily designed to allow binding of almost any sequences within genomes. Owing to the repetitive nature of the DNA binding domain, the assembly of the custom TALENs by direct synthesis or traditional cloning is expensive and technically challenging.[87] Realizing the potential of TALEN technology, a number of approaches for TALEN assembly have been devised to allow low ~ medium throughput, or high-throughput with automation. Fortunately, a number of Biotech companies provide either assembly kit and/or service due to its technical difficulty (Table 2). Like ZFN, this genome editing technology has been shown to function in a wide variety of cells and organisms, including bacteria, yeast, plant, insect, zebrafish and mammal.[21, 88-92] Furthermore, unlike meganuclease or ZFN that limit the choice of targets, TALEN can virtually bind any loci in the genome with new design that removes the 5’ first “T” base constrain.
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
\n\t\t\t\t | \n\t\t\tNI | \n\t\t\tA | \n\t\t
\n\t\t\t\t | \n\t\t\tNG | \n\t\t\tT | \n\t\t
\n\t\t\t\t | \n\t\t\tNN(NH*/NK*) | \n\t\t\tG or A | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
TALEN DNA binding repeat and its simple code scheme
*Note: NH and NK favor specificity rather than activity. They bind to G more specifically but with less affinity as compared to NN.
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
Addgene (Cambridge, Massachusetts) | \n\t\t\twww.addgene.org | \n\t\t\tCollections of TALEN assembly kits for multiple organisms | \n\t\t
Cellectis (Paris, France) | \n\t\t\twww.cellectis.com | \n\t\t\tTALEN or meganuclease-based services | \n\t\t
GenCopoea (Rockville, Maryland) | \n\t\t\twww.genecopoeia.com | \n\t\t\tTALEN design and assembly; HR donor design and cloning; Indel detection kits | \n\t\t
GenScript (Piscataway, New Jersey) | \n\t\t\twww.genscript.com | \n\t\t\tTALEN gene synthesis | \n\t\t
Life Technologies (Carlsbad, California) | \n\t\t\twww.lifetechnologies.com | \n\t\t\tTALEN design and assembly services for genome editing; Targeted gene activator/silencer cloning services | \n\t\t
Selected companies with TALEN tool kit and service
Unlike ZFNs or TALENs, CRISPR-Cas needs a short RNA for target site recognition, which is mediated by Watson-Crick DNA base pairing. To form a triplex with genomic DNA, CRISPR-Cas9 also requires a NGG protospacer adjacent motif (PAM) immediately downstream of the hybrid region.
The bacterial CRISPRE-Cas9 system can be reconstituted in mammalian cells using three components: a programmable, specificity-determining CRISPR RNA (crRNA), an auxiliary trans-activating (tracrRNA), and a CRISPRE-associated endonuclease Cas9 (Cas9).[93, 94] In current applications, crRNA and tracrRAN duplexes are fused to generate a chimeric sgRAN that mimics the natural crRNA-tracrRNA hybrid. The single sgRNA has been shown to interact with the holoenzyme Cas9 to generate efficient cleavage.[95] The adaptation of the CRISPR-Cas9 by the research community have been phenomenal, and the system has been used to modify genes in most model species, including drosophila, silkworm, plant, C elegan, zebrafish, Xenopus, rat, mouse, pig, and human.[96-106] The success is mainly due to some significant advantages. First, a single protein Cas9 is required and remains the same. This means no time-consuming protein engineering is required, in contrast to that of meganuclease, ZFN or TALEN. Second, genome targeting depends on an oligonucleotides (20 ~ 30 in length), which are very easy and cheap to produce. Third, among the established programmable DNA-binding domains, CRISPR-Cas9 is most easily to facilitate genome-scale perturbations owing to its one-binding to one target. Last, this is an open system, where most of them are established and can be purchased from the non-profit distributor Addgene in Cambridge Massachusetts. However, the sequence of individual guide RNA makes difference in terms of efficacy and specificity, not all guide RNA provides the same high levels of genome editing activities.[107] Bad guide RAN can elicit off-target effects, causing cyto-toxicity to cells.[108] This can be very problematic for therapeutic applications.
The technologies are still quickly evolving, and tools to better assess both efficiency and specificity will be essential to improve the system. Choosing certain method shall be carefully balanced to serve the need of research. For example, ZFNs, TALENs and CRISPR-Cas9 are reasonable options to target most coding genes. ZFNs and TALENs shall be preferred when specificity and low-toxicity are required. For genome-wide screen or in dealing with multiple targets, CRISCR-Cas9 is more suitable because of its robustness and one molecule for one target. For small gene manipulations, TALENs may be of choice since they have broad rang access in the genome and edit precisely the target with high specificity with much less toxicity and off-target effects as compared to CRISCR-Cas9.
One of the challenges in knocking out a miRNA is that the mature and fully functional miRNA is only ~ 22 nucleotides in length. Therefore, sequence alterations outside this 22-nucleotide region may have little or no effects on function of miRNA. To design useful targeted nucleases, sites have to be carefully chosen so that targeted nucleases are directed to the critical region of miRNA gene loci. To this end, the relative small but highly structured pre-miRNA (~70 bp) appears appropriate since it contains sequences vital for miRNA biogenesis and function.[35, 43] Within pre-miRNA, the seed regions of 5p and 3p as well as the dicer processing sites are of choice (Figure 2). Indeed, a number of reports have used this strategy for miRNA knockouts; studies have shown that small indels targeting these sites are effective to abolish miRNA expression in mammalian cells.[45, 46, 59]
Here, we use miR-21 as an example to illustrate the valid target sites that were successfully used in knockout studies. We choose miR-21 for a number of reasons. First, the human miRNA-21 was one of the first mammalian genes identified. MicroRNA-21 is located on plus strand of chromosome within a protein coding gene TMEM49. It is independently transcribed as a ~3433 nuclotides long primary transcript, where the pre-miR-21 (72 nucleotides) has a typical stem-loop (hairpin) structure similar to other miRNAs.[109] Second, the mature miRNA sequence is typically processed from the 5’-arm of the miR-21 precursor.[110] Last, miR-21 is strongly conserved and its role in physiology and pathology has been extensively explored and firmly established.[45, 48, 49, 109] Together, miR-21 provides general design strategies for miRNA gene editing.
As illustrated in Figure 2, the region corresponding to 1-8 nucleotides of the mature miRNA is the most preferred site of cleavage. This is because a small indel in this seed region is expected to abolish miRNA activity.[111] The second choice would be the adjacent Dicer processing site of the seed region. In principle, the chosen of process sites shall be preferred to the one that close to the seed region, indels involves both process site and seed sequences would most likely results in complete knockout. According to above consideration, the 5’ miRNA seed region and the adjacent Dicer processing site are usually chosen for miR-21 knockout. Similarly, the 3’-arm of the miRNA precursor shall be preferred when the mature miRNA is of 3p miRNA.
MicroRNA knockout strategy and the preferred cleavage sites. The upper panel shows the stem-loop structure of miR-21, with mature miR-21 shown in red and seed region underlined. The middle panel shows the TALEN pair and their binding sequences, separated by a 15-bp spacer. The cleavage site normally falls in the middle of the spacer, where the FokI dimerizes and makes double-strand breaks (DSBs) at the seed and/or Dicer process site. These DSBs can lead to two potential consequences as illustrated in the low panel. The predominant route 1 leads to indels via non-homologous end joining mechanism, where the alternative route 2 may lead to a precise genome editing via homologous recombination. Repair by homologous recombination can be used to bring in any desired changes at the targeted site. For knocking out miRNA-21, replacement of pre-miRNA with selection markers can facilitate the enrichment and selection of edited cells.
Here we introduce the potential sites as a general strategy for miRNA knockout utilizing the dominant NHEJ mechanisms. In fact ZFNs, TALENs and CRISPR-Cas have been used to functionally knockout a number of miRNAs in mammalian cells.[45, 59, 112-116] Among the three types of programmable nucleases, TALENs are suitable for small loci with narrow targetable regions, whereas ZFNs and CRISPR-Cas are limited by availability of binding modules and the requirement of PAM motif respectively. It is important to keep in mind; the binding sites of targeted nucleases may be different from the cleavage sites in terms of design. For ZFNs and TALENs, the cleavage site is situated in the middle of their binding sites of ZFNs or TALENs. For CRSPR-Cas, the cleavage site is within the guider RNA and close to the PAM motif (Figure 2).
Free online tools such as TALEN Targeter and SAPTA are available to design DNA binding domain of TALEN that is specific and has a low risk of of-target effects.[117, 118] Similar to ZFNs, TALENS s requires the design of protein pairs, which bind two optimal anchoring positions on opposite strands, usually spaced 15 ~ 25 bp apart to allow for FokI dimerization and cutting.[119] Length of DNA binding sequences may vary, typically ranging from 14 ~ 20 bp. In humans, 20 bp may offer high specificity, considering the genome size. It is worthy to note that longer domains (18 ~ 20) may decrease cell toxicity by reducing the risk of off-target effects.[120]
A number of approaches have been developed for rapid assembly of custom TALENs. With these advances, TALEN pairs can be generated easily and economically in a matter of days.[121] Most of the methods rely on the ability of type IIS restriction enzymes to assemble premade repeats into fully functional TALEN scaffold (Figure 3). A TALEN scaffold is comprised of a number of domains from the N-terminus to the C-terminus, including a nuclear localization signal, part of the N-terminal sequences for the first “T” recognition, flowed by the last half-repeat and part of C-terminal sequences fused with a nuclease FokI. Because the last binding nucleotide can be any one of the four, the TALEN scaffolds normally have four different flavours. To make the TALEN fully functional, an eukaryotic gene promoter is normally placed at 5’ of TALEN coding region and a poly A signal sequences at the 3’ end of TALEN.
Most assembly protocol is based on the Golden Gate method, which relies on the ability of type IIS restriction enzymes to cut outside their recognition site. Type IIS recognition sites arranged in inverse orientation at the 5’ and 3’ end of DNA fragment will be removed upon cleavage, slowing simultaneous restriction and ligation. The continuous re-digestion of unwanted ligation products increases the formation of the desired construct.[122, 123] As type IIS fusion sites can be designed to have different sequences, Golden Gate cloning enables directional and seamless assembly of multiple DNA fragments. Based on this principle, one-step or two-step assembly protocol or kits are developed and commercially available to allow do-it-yourself assembly of TALEN in any molecular biology laboratories.[121]
Golden Gate assembly of TALENs and molecular structure. Two-step assembly strategy can increase the correct joining of monomers into multimers and subsequently into the TALEN scaffold. A TALEN, from its N- to C-terminus, is composed of a nuclear localization signal peptide (NLS), modified N- and C-termini flanking the assembled RVDs, and fused nuclease FokI at C-terminus. CMV (cytomegaloviral) promoter situates at the 5’ of the TALEN and drives its expression in mammalian cells. The polyadenylation signal (Poly A) is to add a poly(A) tail to the TALEN mRNA.
While it is possible to disrupt genes in mammalian genome with TALENs alone, the frequency of gene editing is typically 2 ~ 40%, averaging ~16% for mono-allelic disruptions.[87] Cells carrying bi-allelic disruption are rare and require time-consuming signal cell-derivation and subsequent screening.[5] One strategy is to combine TALENs targeting to the miRNA seed region with a homologous recombination of donor vector carrying a selectable marker.[46, 59, 114] This approach enables convenient positive selection, and the combination of NHEJ with stem-loop deletion results in efficient bi-allelic miRNA gene ablation, which can be as high as >90%.[46]Additionally, by using HR donors, endogenous loci can be potentially modified with custom sequences such as IRES-florescent proteins to allow functional assessment of endogenous miRNA expression and regulation.[124]
All targeted nucleases can be used in mammalians to create miRNA knockouts.[45, 46, 59, 113-116] Success of miRNA gene editing depends largely on the ability to deliver all the reagents efficiently to the cells. For transgenics, direct injection of DNA vector or sometime
Following the delivery, small-scale sequence changes are introduced at the break by NHEJ.[18] These indels are typically assayed by polymerase chain reaction (PCR) amplification of the region, followed by DNA sequencing or by a gel electrophoresis assay using T7E1 endonuclease, or alternatively by high-resolution melting analysis.[131] In addition to detecting changes at genomic level, a reverse transcripts-PCR on the expression can also be performed to confirm the reduced/ablated expression of miRNA at transcript level. PCR-based genotyping can be used to make distinctions between HR and NHEJ events when donor DNA is used.[131]
Targeted nucleases are powerful genome editing tools for uncovering gene functions. Though relatively new, they have been successfully employed in a broad variety of systems and produced exciting results for miRNA research.
To understand the biological and pathological significance of miRNAs, a talen-based knockout library for 274 highly conserved human miRNAs has been established.[59] To demonstrate the genome editing activities of the TALEN library, 66 TALEN pairs against 33 miRNA loci are selected. All TALEN pairs tested induce mutations as assessed by a mismatch-senstivie T7EI assay with a frequency above 0.5%.[132] To gain some insight of functional role miRNAs, the authors conduct detail analysis on members of the miR-200 family.
There are at least two members in the highly conserved miR-200 family, miR-141 and miR-200c.[59] Interestingly, miR-141 and miR-200c have largely indistinguishable activity and differ only in the seed region by one nucleotide. This imposes a great difficulty to use either overexpression or complementary inhibitor-based knockdown to investigate the potential functional divergence without complications. Using TALEN technology, however, the authors can target the seed region of the 5p strand for miR-141 but choose the Drosha processing site in the 3p strand for miR-200c, hence avoid cross-targeting.[52, 110] With this design, both single and double knockout clones were obtained and their corresponding expression of mature miRNAs was confirmed by RT-PCR.[59] Using these cell models, the authors found that miR-141 represses the expression of mRNAs that have miR-141 motif at the 3’-untranslated region. Similarly, miR-200c represses expression of mRNAs that have miR-200c motif. These data indicate the two closely related miRNAs do not cross-react notably and may control largely nonoverlapping group of genes. Together, TALEN-based method may provide unprecedented tools for miRNA research with great precision and specificity.
MicroRNA-21 gene knockout in the cultured human cells was achieved independently by two research groups.[45, 131, 133] The first group used a combination of TALEN pair with a HR donor. TALENs were designed to position the miR-21 seed region in the central portion of the spacer, directing the cleavage to the functionally essential miRNA motif. The HR donor construct was created corresponding to the cleavage location of the TALEN pair and carried 509-bp (5’ arm) and 600-bp (3’ arm) regions of homology to the miR-21 genome sequences. TALEN pair and HR donor were delivered together using transfection protocol. In the case of HR events, the donor replaces the entire miR-21 precursor with two selectable marker genes (red florescent protein and puromycin resistant gene). Clonal population of cells in which an HR event occurred can be easily selected by puromycin treatment. Because NJEJ is the predominant repair mechanism induced by DSBs, selecting for HR events would most likely produce clones that harbour bi-allelic modifications, with the second allele carrying an indel in the seed region. In fact, this approach demonstrated bi-allelic miR-21 gene disruption at very high frequency of 87% in cultured HEK293 cells.[131] Analysis of three independent clones showed a total loss of miR-21expression. Phenotypical examination revealed an increase in miR-21 target gene expression, reduced cell proliferation, and alteration of global miRNA expression profiles, which is in agreement with the role of miR-21 in cancer biology.[45, 48]
To explore the gene specific-function
Targeted knockout of miRNAs in mice by TALEN has also been reported.[113] In this study, microinjection of synthesized mRNA of TALEN was carried out in one cell stage of embryo. Embryos were allowed to develop to two-cell stage and subsequently transferred into pseudopregnant female mice. With optimized protocol, these mice were able to produce 29.6% mono-allelic offspring. Further cross-mating of the heterozygous founder mice with the wild type strain was able to produced heterozygote offspring, suggesting transmittable of the mutated miRNA.
Targeted nuclease technology has become one the most powerful and versatile platforms for engineering biology. The new technology is enabling systematic interrogation of genome, including miRNAs in mammals with high precision and efficacy. It is superb over other technologies by creating null mutations that lead to complete suppression of gene expression. Furthermore, bi-allelic ablation of miRNAs in cultured somatic cells opens new avenue to study the pathological role of miRNAs in relevant disease samples. Knowledge gained from these studies is more likely lead to discovery of novel drug targets, accelerating new therapeutics towards clinic application. In deed, a number of animal studies as well as clinical trials using targeted nucleases already provide encouraging results. In addition to repairing mutations underlying inherited diseases, targeted nucleases can be used to create productive mutations in tissues to combat viral infections or complex diseases such as familial hypercholesterolemia and hypertension.
Targeted nucleases can be tweaked to carry out other functions, such as modifying DNA associated histones, activating or inhibiting gene transcriptions and monitoring chromatin dynamics in living cells. It becomes increasing apparent that targeted nuclease is a versatile and common platform for elucidating gene function and epigenetic regulation.
However, many challenges still lie ahead. The most prominent issue may be the off-target effect. In this aspect, ZFNs and TALENs appear less problematic owing to the intimate interaction with their binding sites and the requirement of correct binding of two molecules. In contrast, CRISPRE-Cas tends to have higher off-target effects, because it binds DNA via base pairing. One or more mispairings may be tolerated, which may cause detrimental unintended effects.[134] Attempts to solve this issue include improvement of guide RNA scaffold, use of computational algorithms to predict off-targets, and development of high throughput method to assess unintended cuts. The challenge, though, is difficult to detect the off-target cleavage. Hence, one shall interpret the data with caution, and is aware of the potential off-target effects and its related toxicity. Secondly, although nuclease molecule may have high level of activity within cells, one may find that some tissue types are still difficult to deliver into. In this case, multiple delivery methods shall be tried, suitable one shall be optimized. Finally, for further development toward clinical application, it will be essential to thoroughly the safety and toxicity profile using a variety of mammalian models.
Advance in genome engineering technology based on the targeted nucleases are enabling the systematic interrogation of mammalian gene function. Using this system, miRNA gene sequences within mammalian genome can be easily edited with high efficacy and precision. Targeted miRNA editing will empower researcher to reveal the complex regulatory circuits governed by miRNAs and to realize, in the long-term, their full diagnostic and therapeutic potential.
Mycobacterium leprae (
The immunity of the host plays an important role in disease progress and control. Thus, fortunately 95% of patients exposed to
Leprosy has been successfully eliminated as a public health problem in 2000 globally and at the national level in 113 countries out of 122 by 2005 [1]. Elimination of leprosy is defined by World Health Organization as a point prevalence below 1 per 10,000 population [2]. However, the number of new patients diagnosed with leprosy is still significant, at more than 200,000 in 2016 globally. The new case detection rate of the disease (NCDR) is only slowly declining (Figure 1) [3].
Trend in case detection and case detection rate, by WHO region, 2006–2016 [
The long incubation period, silent symptoms, long duration MDT and unavailability of effective vaccine makes this disease difficult to identify, treat and eradicate. To add to the misery the stigma associated with the disease is another challenge. In such circumstances, prevention and control of disease gains utmost importance.
In 2017, 192,713 patients were on treatment globally which makes the prevalence rate of 0.25 per 10,000 population [4]. Total of 210,671 new cases were reported in same year from 150 countries making NCDR of 2.77 per 100,000 population. Figure 2 below shows the trends over the past decade (2008–2017) in new case detection of leprosy cases globally in the reporting countries of World Health Organization (WHO) [4].
Country-wise trends of detection of new leprosy cases from 2008 to 2017 [
The three main goals of control of leprosy are
To detect the pathology early and treat the patient completely.
To prevent the transmission to the others.
To prevent the disabilities and other complications.
Thus the following modalities are adopted to control leprosy:
Medical measures
Social support
Program management
Evaluation
The control of leprosy starts with the estimation of size and magnitude of the problem. Most common epidemiological survey method of collection of data is “Quick random sample survey.” Information about the prevalence of leprosy, age and sex-wise distribution, various forms of leprosy and the health facilities available should be gathered. Roughly the total prevalence of leprosy in an area would be about 4 times that of the cases found among school children [5, 6]. These estimates are essential to plan, implement and to evaluate the results of the control program.
The objective is to detect all the cases as early as possible and to register them. Active case finding is important as the disease is symptomless in the early stages. Cases can be detected by the Contact surveys, Group surveys and Mass surveys. Contact surveys consists of examination of all household contacts with a lepromatous case, particularly children, in areas with prevalence less than 1 per 1000. Contact surveillance of households is recommended for a minimum period of 10 years after case is declared bacteriologically negative, and for 5 years in households with a non-lepromatous case from the time of diagnosis of the index case. Group surveys are done in areas where prevalence of leprosy is more than 1 in 1000 population. This consists of screening certain groups such as school children, slum dwellers, military recruits, industrial workers, etc. through “Skin camps.” Lastly, mass surveys consists of examination of each and every individual by house-to-house visits in hyperendemic areas (prevalence – 10 or more per 1000 population). These are generally carried out by repeated annual examinations of school children which yield better results at relatively low cost [5, 6]. The data of each case is entered in the standardized proforma developed by WHO.
Since an effective vaccine is unavailable for leprosy the secondary prevention (early treatment) becomes more important. Until 1981, Dapsone (Diamino Diphenyl Sulphone—DDS) was used to treat leprosy which resulted in the development of resistance and relapse, making leprosy control difficult.
Multidrug Therapy: In 1982, WHO recommended Multidrug Therapy (MDT) for all leprosy patients. Introduction of MDT has opened a new avenue in the control of leprosy in the world. Aim of MDT is to convert the infectious case into noninfectious as soon as possible, so as to reduce the reservoir of infection in the community.
The main objectives of MDT are:
To ensure early detection of the cases.
To interrupt the transmission of infection.
To prevent drug resistance, relapse and reaction.
The advantages of MDT over dapsone monotherapy are:
Shorter duration of treatment,
Better patient compliance,
High cure rate,
Cost-effectiveness and
Ease in health delivery system.
There are two types of MDT regimens used depending on the symptoms and signs shown by the patients - Paucibacillary (PB) and Multibacillary (MB). Recommended Regimens are discussed below [3, 5, 6, 7]:
i. Multibacillary leprosy:
MDT is recommended for following groups of patients:
All smear positive cases.
Skin lesions more than five in number.
More than one nerve trunk thickening.
All cases of relapse/reactivation and all cases who have been treated with Dapsone monotherapy earlier.
The drugs used in Multibacillary MDT and dosages are:
Rifampicin: 600 mg once monthly, supervised.
Dapsone: 100 mg daily, self administered.
Clofazimine: 300 mg once monthly, supervised and 50 mg daily, self administered.
Duration of treatment for Multibacillary leprosy is 12 months, can be extended to 18 months and continued where possible up to smear negativity. Sometimes LL/BL patients with high bacilli may need 2–3 years or more of MDT for achieving bacteriological negativity.
ii. Paucibacillary leprosy:
The drugs and dose schedule is:
Rifampicin 600 mg once a month for 6 months supervised.
Dapsone 100 mg daily for 6 months self administered.
Paucibacillary leprosy is treated for 6 months.
MDT is not contraindicated in patients with HIV infection.
Each MDT blister pack contains tablets for 4 weeks treatment. For easy identification color coding of the blister pack is done, that is, with different colors for multibacillary and paucibacillary cases both in adults and children.
The treatment in both PB and MB cases varies depending on the age of the patient. The patients between 10 to 14 years are treated as paediatric cases, while >14 years are considered adult. The standard treatment regimen for MB leprosy in adults is given for 12 months. The drugs in each blister pack are (Figure 3):
Two capsules of Rifampicin of 300 mg (600 mg once a month) to be taken as single dose under supervision.
Clofazimine 3 capsules of 100 mg each to be consumed once a month as single dose under supervision and 50 mg daily for next 28 days.
Dapsone 100 mg as single dose and then daily once for 1 month.
MDT for adult MB type of leprosy [
The standard adult treatment regimen for PB leprosy is (Figure 4):
Rifampicin: 600 mg once a month.
Dapsone: 100 mg daily.
Duration: 6 months (6 blister packs of 28 days each).
MDT for adult PB type of leprosy [
Treatment regimen for MB leprosy in children (ages 10–14 years) is (Figure 5):
Rifampicin: 450 mg once a month.
Clofazimine: 150 mg once a month, and 50 mg every other day.
Dapsone: 50 mg daily.
Duration: 12 months (12 blister packs of 28 days each).
MDT for pediatric MB type of leprosy [
Treatment regimen for PB leprosy in children (ages 10–14 years) is (Figure 6):
Rifampicin: 450 mg once a month.
Dapsone: 50 mg daily.
Duration: 6 months (6 blister packs of 28 days each).
MDT for pediatric PB type of leprosy [
MDT is provided free-of-charge globally through an agreement between a pharmaceutical company and WHO. WHO manages distribution of MDT to countries in coordination with national leprosy programs.
Clinical surveillance of the patients after completion of treatment is an important part of MDT to ensure complete cure. For paucibacillary cases follow up for at least once a year for 2 years after completion of treatment and for multibacillary cases at least once a year for 5 years [3, 4, 5].
Early diagnosis of cases, aggressive treatment and proactive measures to avoid complications and disabilities is the backbone for the success of any comprehensive program. In addition to accurate reporting and control measures, effective preventions will be needed to achieve elimination. Search for an effective vaccine either to be used alone or in combination with a drug has been going for a long time.
Presently BCG (Bacillus Calmette-Guerin) is the only vaccine that has shown some protection against
Other variants of vaccination are also suggested.
Another milestone in prevention of leprosy is the discovery of the vaccine candidate, called LepVax. Scientists at Infectious Disease Research Institute (IDRI), along with national and international collaborators including the National Hansen’s Disease Program and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, with financial support from American Leprosy Missions, have developed this leprosy vaccine. Based on the preclinical studies, the LepVax, has progressed to Phase I clinical testing in the United States, the first stage of safety testing in human volunteers. The clinical trial is focused not only on safety but also evaluates the immune response of the individual to the vaccine.
Chemoprophylaxis alone provides two-year protective window while effective immunization will provide a much broader protective window. Thus many studies and research is going on to provide both chemoprophylaxis and immunization for immediate and short-term protection and longer-term protection respectively. This strategy could have better impact and distinct appeal in controlling and preventing leprosy. Such trials could also provide a gateway for the assessment and implementation of new emerging vaccines (Figure 7).
Locations of leprosy vaccine testing.
Chemoprohylaxis using effective antibiotics focuses on providing protection to people at risk such as close contacts – family members, neighbors, co-workers, health care providers for lepers etc. Due to the stigma of disease the leprosy cases are found in clusters in all endemic regions, rather than being evenly dispersed over the whole area. Thus these high risk people can be identified and prophylaxis provided along with secondary prevention strategies. The process includes focused surveillance, contact tracing, early diagnosis and treatment. This helps in reducing the incidence and breaking the chain of transmission.
Chemoprophylaxis, as recommended by WHO Guideline Development Group (GDG), is done using single dose rifampicin (SDR) for contacts of leprosy patients both in adults and children of 2 years of age and above. Before starting the drug leprosy and TB disease are to be excluded. There should be no contraindications also for the use of rifampicin.
Other important considerations for the implementation of this chemoprophylaxis by programs are:
Adequate management of contacts.
Consent of the index case to disclose his/her disease.
An RCT found that SDR reduces risk of leprosy over 5–6 years in leprosy contacts. For every 1000 contacts treated with SDR, there were four leprosy cases prevented after 1–2 years and three cases prevented after 5–6 years.
Recommended dosage schedules for SDR are given in Table 1.
Age/weight | Rifampicin single dose |
---|---|
Adults (≥15 years) | 600 mg |
10–14 years | 450 mg |
Children 6–9 years (weight ≥ 20 kg) | 300 mg |
Children <20 kg (≥2 years) | 10–15 mg/kg |
Rifampicin dose for chemoprophylaxis [3].
The limitations of this approach are:
The protection is approximately for only 2 years.
High bacillary load cannot be eliminated using single dose.
Specific screening test needed to distinguish between contacts with high and low bacillary load.
Among communicable diseases, leprosy remains a leading cause of peripheral neuropathy and disability in the world, despite extensive efforts to reduce the disease burden. It is an important aspect of leprosy control. It means the medical, surgical, social, educational, and vocational restoration as far as possible of treated patients to normal activity so that they resume their place in the home, in society and industry [5, 6, 7]. Early treatment helps in disability limitation.
Rehabilitation: WHO has defined rehabilitation as “the combined and coordinated use of medical, social, educational and vocational measures for training and retraining the individual to the highest possible level of functional ability.”
Preventive rehabilitation consists of prevention of development of disabilities in a leprosy patient by early diagnosis and prompt treatment. But once the patient becomes handicapped and suffers from the damage caused, should be trained and retrained to the maximum functional ability so that the patient becomes useful to self, to the family and to community at large by various measures such as medical (physical), surgical, psychological, vocational and social rehabilitation (Flow chart 20.10).
Health education is given to the patient, to the family and to the community at large about leprosy. The education should be directed to ensure general public and patients help them develop their own actions and efforts to change the perception about the disease and seeking professional help whenever required. Early recognition of symptoms, prompt diagnosis, health seeking behavior, personal care, treatment adherence and rehabilitation are important aspects of health education. The key messages included are about the cause of disease and the complete cure available to encourage people for early diagnosis and treatment. It also aims at helping people to change their attitude and behavior by removing the misunderstandings and misconceptions. Mass Health education also helps to eradicate social stigma, social ostracism and social prejudice associated with leprosy which is the biggest hindrance for the eradication of disease.
The complications of the disease cause disfigurement and disabilities which in turn gives way to the stigma and strong discrimination of these patients. This results not only in physical and social isolation also financial dependency, ultimately forcing the leprosy patients to beg on streets for their survival. To address this issue WHO introduced the strategy of community-based rehabilitation (CBR). This intended to enhance the quality of life for lepers with disabilities through community initiatives. Community participation and using local resources to support the rehabilitation of people with disabilities within their own communities is the foundation of this concept [9, 10].
“Enhanced Global Strategy for Further Reducing the Disease Burden due to Leprosy for 2011–2015” was launched in 2009 by the World Health Organization. The target of the program was to reduce Grade 2 Disability rate (G2DR) in leprosy patients by at least 35% by the end of 2015 (G2DR is the number of new cases with grade 2 disability per 100,000 population). Since the elimination of leprosy in 2005, the prevalence is very less and thus G2DR has been proposed as an indicator. The advantage of G2DR as indicator is that, it is less susceptible to operational factors such as detection delay and is a more robust marker for mapping cases of leprosy in any country. This will also help the program implementers to focus on interventions that reduce visible deformities by enhancing early detection and treatment of leprosy patients and ultimately reduce the number of new leprosy cases in the population. However by the end of 2015, only Thailand was able to achieve this target [11].
In 2016, WHO launched the “Global Leprosy Strategy 2016–2020: Accelerating towards a leprosy-free world” [9].
The program aims to reinvigorate efforts to control leprosy and avert disabilities, especially among children still affected by the disease in endemic countries.
The strategy is built around three major pillars:
Strengthen government ownership and partnerships;
Stop leprosy and its complications; and
Stop discrimination and promote inclusion.
The strategy of this program is:
To sustain expertise and increase the number of skilled leprosy staff;
To improve the participation of affected persons in leprosy services;
To reduce visible deformities and stigma associated with the disease;
To call for renewed political commitment and enhanced coordination among partners;
To highlight the importance of research and improved data collection and analysis.
The key interventions needed to achieve these targets include:
Early case detection especially in children before visible disabilities occur thus reduce transmission;
In highly endemic areas or communities detection of disease among higher risk groups through campaigns;
Improving health care coverage and access for marginalized populations such as poor patients, patients in the difficult to reach areas and the areas of conflicts.
Customization of the strategic interventions in endemic countries is permitted to suit the national plans to meet the new targets. E.g. Screening all close contacts of persons affected by leprosy; initiating a shorter and uniform treatment regimen; and incorporating specific interventions against stigmatization and discrimination.
Its ultimate goal of this program is to further reduce the global and local leprosy burden, that is, (a) zero disabilities in children with leprosy-affected, (b) G2DR less than one per million population and (c) repeal of laws that discriminate leprosy patients of their rights.
Author declares no conflict of interest.
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',metaTitle:"Horizon 2020 Compliance",metaDescription:"General requirements for Open Access to Horizon 2020 research project outputs are found within Guidelines on Open Access to Scientific Publication and Research Data in Horizon 2020. The guidelines, in their simplest form, state that if you are a Horizon 2020 recipient, you must ensure open access to your scientific publications by enabling them to be downloaded, printed and read online. Additionally, said publications must be peer reviewed. ",metaKeywords:null,canonicalURL:null,contentRaw:'[{"type":"htmlEditorComponent","content":"Publishing with IntechOpen means that your scientific publications already meet these basic requirements. It also means that through our utilization of open licensing, our publications are also able to be copied, shared, searched, linked, crawled, and mined for text and data, optimizing our authors' compliance as suggested by the European Commission.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. 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germination and subsequent seedling establishment. Salt negatively effects the crop production worldwide. Because most of the cultivated plants are salt-sensitive glycophytes. Salt stress affects the seed germination and seedling establishment through osmotic stress, ion toxicity, and oxidative stress. Salinity may adversely influence seed germination by decreasing the amounts of seed germination stimulants such as GAs, enhancing ABA amounts, and altering membrane permeability and water behavior in the seed. Rapid seed germination and subsequent seedling establishment are important factors affecting crop production under salinity conditions. Seed priming is one of the useful physiological approaches for adaptation of glycophyte species to saline conditions during germination and subsequent seedling establishment. In seed priming, seeds are exposed to an eliciting solution for a certain period that allows partial hydration without radicle protrusion. Seed priming is a simple, low cost, and powerful biotechnological tool used to overcome the salinity problem in agricultural lands.",book:{id:"10363",slug:"abiotic-stress-in-plants",title:"Abiotic Stress in Plants",fullTitle:"Abiotic Stress in Plants"},signatures:"Cüneyt Uçarlı",authors:[{id:"189302",title:"Dr.",name:"Cüneyt",middleName:null,surname:"Uçarlı",slug:"cuneyt-ucarli",fullName:"Cüneyt Uçarlı"}]},{id:"67884",title:"Adaptation of Halophytes to Different Habitats",slug:"adaptation-of-halophytes-to-different-habitats",totalDownloads:1649,totalCrossrefCites:6,totalDimensionsCites:13,abstract:"In recent years, global climate change has been altering environmental (severe drought, soil salinization, irregular precipitation, etc.), around world, decreasing crop yield and upsetting the balance of ecosystems. Nonetheless, a group of plants known as halophytes have the ability to survive and develop in saline soils (wetlands, deserts or temperate zones), may be used in agriculture as a possible alternative to crops (salt-sensitive), as well as for fodder, energy production, medicinal purposes, and desalination of salt-affected areas (phytoremediation). This chapter provides a comprehensive summary of the adaptive strategies used by the annual and perennial halophytes on ecophysiological perspectives, to survive in diverse habitats. The results show a great diverse strategies, such as heteromorphism, seed banks, dormancy, rapid germination, and recovery capacity, from saline shock, favoring the chances of seed survival, although these mechanisms depend on light, moisture, temperature, and the type of salt, in which seeds germinate. In addition, it has been included some molecular, and biochemical aspects, discovered in last years, that might improve our understanding of physiology of these plants. It can conclude that halophytes may be as a possible alternative to ease pressure on cropping systems, restored lands degraded, or confer stress tolerance trough gene transfer.",book:{id:"8033",slug:"seed-dormancy-and-germination",title:"Seed Dormancy and Germination",fullTitle:"Seed Dormancy and Germination"},signatures:"Milagros Bueno González",authors:[{id:"298374",title:"Prof.",name:"Milagros",middleName:null,surname:"Bueno",slug:"milagros-bueno",fullName:"Milagros Bueno"}]},{id:"52387",title:"Plant Pathogens",slug:"plant-pathogens",totalDownloads:4584,totalCrossrefCites:5,totalDimensionsCites:9,abstract:"Plants cover the most area of the earth’s living environment as trees, grasses, flowers, and so on. Plants play different important roles in the environment such as ecosystem balance and food supplement for animals and humans. Moreover, wild or cultivated plants are considered the powerful biofertilizers for the soil, where the plant debris after death and degradation provides the soil with sufficient organic matters. Accordingly, plant care is a great duty and hard mission, which must be constantly improved. The study of plant pathogens belongs to the branch of biology known as plant pathology. The latter is also concerned to overcome the plant diseases arising from the biotic and/or abiotic origin. Biotic (infectious) diseases are developed owing to microbial infection, while abiotic (noninfectious) diseases are developed due to environmental factors. In this chapter, we are concerned with plant pathogens or phytopathogenic microbes such as bacteria, viruses, fungi, mollicutes, and so on.",book:{id:"5363",slug:"plant-growth",title:"Plant Growth",fullTitle:"Plant Growth"},signatures:"Waleed M. Abdulkhair and Mousa A. 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It is commonly a moderately salt-sensitive crop. Salinity stress is the main abiotic factor that arrests the physiological characteristics and plant growth of a maize plant. It causes the osmotic effect, associated with an increase in phytotoxic ions, oxidative stress by increased reactive oxygen species (ROS) production, and ionic effect in the cytosol. These salinity effects hinder the maize plant’s physiological processes such as respiration, photosynthesis, transpiration, stomatal functioning, hormone regulation, and functioning, seed germination, and dormancy and water relation with plants and ultimately reduce the plant growth and yield. However, the physiology of maize subjected to salinity shows various responses that depend on the genetic responses and growth stages. Maize plant undergoes many physiological changes and adapts some mechanism internally to cope with salinity stress. Numerous mitigating strategies such as application of chemicals, application of plant growth-promoting rhizobacteria (PGPR), application of hormones, and use of genetic and molecular techniques are used to handle salinity. This chapter will cover the effect of salinity on maize growth, its physiology, and physiological adaptations of maize plants with management strategies.",book:{id:"10118",slug:"plant-stress-physiology",title:"Plant Stress Physiology",fullTitle:"Plant Stress Physiology"},signatures:"Shazia Iqbal, Sajid Hussain, Muhammad Abdul Qayyaum, Muhammad Ashraf and Saifullah",authors:[{id:"307063",title:"Dr.",name:"Muhammad",middleName:null,surname:"Ashraf",slug:"muhammad-ashraf",fullName:"Muhammad Ashraf"},{id:"316789",title:"Dr.",name:"Hussain",middleName:null,surname:"Sajid",slug:"hussain-sajid",fullName:"Hussain Sajid"},{id:"320035",title:"Dr.",name:"Shazia",middleName:null,surname:"Iqbal",slug:"shazia-iqbal",fullName:"Shazia Iqbal"},{id:"320037",title:"Dr.",name:"Muhammad Abdul",middleName:null,surname:"Qayyaum",slug:"muhammad-abdul-qayyaum",fullName:"Muhammad Abdul Qayyaum"},{id:"320728",title:"Dr.",name:"Saifullah",middleName:null,surname:null,slug:"saifullah",fullName:"Saifullah null"}]}],onlineFirstChaptersFilter:{topicId:"375",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:106,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. 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Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. 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He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. 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He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. 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Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. 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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. 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