\r\n\tIt has been established that energy/nutrient depletion, calcium flux injury, or oxidative stress disrupt endoplasmic reticulum homeostasis and even induce accumulation of misfolded/unfolded proteins leading to endoplasmic reticulum stress. Under endoplasmic reticulum stress conditions, an adaptive mechanism of coordinated signaling pathways, defined unfolded protein response (UPR), is activated to return the endoplasmic reticulum to its healthy functioning state. The aging causes a decrease of the protective adaptive response of the UPR and an increase of the pro-apoptotic pathway together with endoplasmic reticulum ultrastructural injury. Controlling endoplasmic reticulum stress response, maintaining the appropriate endoplasmic reticulum ultrastructure and homeostasis, and retaining mitochondria interplay are crucial aspects for cellular health.
\r\n
\r\n\tThis book presents a comprehensive overview of endoplasmic reticulum, including, but not limited to, endoplasmic reticulum ultrastructural anatomy, MAMs, endoplasmic reticulum stress, and their implication in health and diseases. Additionally, identifying perturbations in the endoplasmic reticulum stress response could lead to early detection of age-related disease and may help develop therapeutic approaches.
",isbn:"978-1-80356-228-5",printIsbn:"978-1-80356-227-8",pdfIsbn:"978-1-80356-229-2",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"5d7d49bd80f53dad3761f78de4a862c6",bookSignature:"Dr. Gaia Favero",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",keywords:"Metabolism, Aging, Neurodegenerative Diseases, Endoplasmic Reticulum, Microscopy, Metabolic Stress, Ultrastructural Anatomy, Cellular Stress, Contactology, Mitochondria, Cellular Stress, Endoplasmic Reticulum Response",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 9th 2022",dateEndSecondStepPublish:"May 6th 2022",dateEndThirdStepPublish:"July 5th 2022",dateEndFourthStepPublish:"September 23rd 2022",dateEndFifthStepPublish:"November 22nd 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"19 days",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Human anatomy researcher involved in crucial topics on morphology, anatomy, and molecular medicine - working on innovative approaches to aging-related pathopsychological processes at the University of Brescia.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"238047",title:"Dr.",name:"Gaia",middleName:null,surname:"Favero",slug:"gaia-favero",fullName:"Gaia Favero",profilePictureURL:"https://mts.intechopen.com/storage/users/238047/images/system/238047.jpg",biography:'Dr. Gaia Favero is a prominent scientist in the field of life sciences. She is currently engaged as a researcher for the Scientific-Disciplinary Sector BIO/16 Human Anatomy at the Anatomy and Pathophysiology Division, Department of Clinical and Experimental Sciences, University of Brescia (Italy).\r\nDr. Favero focuses on aging-related morphological dysfunctions as the prelude to various pathophysiological processes in her research programs. The central hypothesis is that natural antioxidants and, in particular, melatonin may act as molecular "switches" that modulate cells and tissues by suppressing, at various levels, oxidative stress and inflammatory signalling cascades. These research approaches represent powerful tools for developing innovative preventive strategies and identifying novel prognostic biomarkers for several diseases. The above-reported research activity determined more than 120 scientific publications and an h-index of 25.',institutionString:"University of Brescia",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Brescia",institutionURL:null,country:{name:"Italy"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"6",title:"Biochemistry, Genetics and Molecular Biology",slug:"biochemistry-genetics-and-molecular-biology"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"278926",firstName:"Ivana",lastName:"Barac",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/278926/images/8058_n.jpg",email:"ivana.b@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"6694",title:"New Trends in Ion Exchange Studies",subtitle:null,isOpenForSubmission:!1,hash:"3de8c8b090fd8faa7c11ec5b387c486a",slug:"new-trends-in-ion-exchange-studies",bookSignature:"Selcan Karakuş",coverURL:"https://cdn.intechopen.com/books/images_new/6694.jpg",editedByType:"Edited by",editors:[{id:"206110",title:"Dr.",name:"Selcan",surname:"Karakuş",slug:"selcan-karakus",fullName:"Selcan Karakuş"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2270",title:"Fourier Transform",subtitle:"Materials Analysis",isOpenForSubmission:!1,hash:"5e094b066da527193e878e160b4772af",slug:"fourier-transform-materials-analysis",bookSignature:"Salih Mohammed Salih",coverURL:"https://cdn.intechopen.com/books/images_new/2270.jpg",editedByType:"Edited by",editors:[{id:"111691",title:"Dr.Ing.",name:"Salih",surname:"Salih",slug:"salih-salih",fullName:"Salih Salih"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"16788",title:"Gene Regulatable Lentiviral Vector System",doi:"10.5772/18155",slug:"gene-regulatable-lentiviral-vector-system",body:'
1. Introduction
The basic principle of current gene therapy is to deliver genetic material to a population of cells in the body, thereby preventing a disease or improving the clinical status of a patient. One of key factors for successful gene therapy is the development of effective delivery. To date, a plethora of gene delivery systems, termed “vectors”, have been developed, and these fall into two broad categories: nonviral and viral vectors. Basically, the nonviral vector systems involve delivery of naked DNA or RNA into target cells with the aid of physical or chemical mediators such as cationic lipids. In terms of their simplicity, producibility, and immunogenicity, nonviral vector systems hold advantages over viral vector systems. However, in terms of the efficiency of gene delivery and expression, the viral vector systems are considered as more ideal (Goverdhana et al., 2005; Verma & Weitzman, 2005).
Although a variety of gene-transfer vectors based on RNA and DNA viruses have been adapted to deliver foreign genes to target cells in vitro and in vivo, most viral vectors are derived from adenoviruses and retroviruses. Adenoviruses are DNA viruses that are characterized by a nonenveloped icosahedral virion containing a double-stranded linear DNA genome of 30-36 kb (Berk, 2007). The virus enters the target cell by endocytosis via interactions between the fiber protein on the virion and the adenoviral receptor on the cell surface followed by the subsequent binding of a second virion protein, penton, to a cellular integrin protein. Inside the cell, uncoating of virions takes place in the cytoplasm where the viral DNA genome remains associated with a core-derived protein that promotes efficient nuclear entry of the viral genome. Within the nucleus, viral DNA exists as an episome, consequently replication of the viral genome takes place in the nucleus (Leopold et al., 1998). Adenovirus genes are mainly divided into two classes, early and late, based on the time of expressions during the replication. Many of the recombinant adenovirus vectors used in gene transfer have been generated by the deletion and/or mutation of the early genes which are mostly involved in the activation of other viral genes, replication of the viral DNA genome, modulation of host immune responses, and inhibition of host cell apoptosis (Armentano et al., 1995; Armentano et al., 1999; Bett et al., 1994; Brough et al., 1997; Danthinne& Imperiale, 2000; Fallaux et al., 1996; Flint & Shenk, 1997; Gao et al., 1996; Graham et al., 1977; Imler et al., 1996; Wang et al., 1995; Yeh et al., 1996). More recently, the helper-dependent adenoviral vectors, so-called “gutted” vectors, have been created by removing most of the viral genes from adenoviral genome (Kochanek et al., 1996; Lowenstein et al., 2002; Ng et al., 2001; Parks et al., 1996; Umana et al., 2001). Although the gutted vectors need to employ a helper virus that provides all the viral proteins necessary for vector production (Kochanek et al., 1996; Lowenstein et al., 2002; Ng et al., 2001; Parks et al., 1996; Umana et al., 2001), defect of all the viral-coding sequences theoretically allows the cloning of large DNA fragments up to 36 kb (Goverdhana et al., 2005). Although their tropism for the airway epithelial cells meant that adenovirus-based vectors were originally developed for the treatment of genetic lung diseases such as cystic fibrosis (Flotte et al., 2007), one of the major advantages of adenoviral vectors is that they are able to infect a wide variety of cells in a cell-cycle independent manner (Bergelson et al., 1997; Cullen, 2001; Tomko et al., 1997; Whittaker et al., 2000). However, one limitation is the persistence of transgene expression; adenoviral vector-mediated gene expression is short-term, ranging from two weeks to a few months. Thus, this vector is more appropriate for use in treatment of diseases that require high and transient gene expression (Robbins & Ghivizzani, 1998).
In contrast with adenoviral vectors, retroviruses have a substantial advantage as vectors for the sustained expression of a transgene in target cells (Verma & Weitzman, 2005). Retroviruses are enveloped RNA viruses belonging to the Retroviridae family. The retroviral particle contains two copies of linear, positive sense, single-stranded RNA of 7-13 kb in length. All members of the Retroviridae family harbors at the minimum three essential genes: gag for structural proteins, pol for enzymes, and env for envelope. In the retroviral genome, the gag gene is positioned upstream of the pol gene, and the Pol polyprotein is generated as a fusion protein with the Gag polyprotein (Gag-Pol). As we shall see in the next section, the viral RNA genome is converted into a double-stranded DNA copy by reverse transcriptase (RT), a processing product of Pol, soon after the entry into the target cell (reverse transcription). Subsequently, the viral DNA is transported to the nucleus and covalently joined with cellular chromatin. This joining step is called integration and it is catalyzed by integrase (IN), another processing product of Pol. The integration step as well as the reverse transcription is hallmark of retroviral infection. Once integrated, the viral DNA serves as a template for the transcription of viral genes, enabling sustained gene expression in infected cells. The integrated viral DNA also contains cis-acting sequences termed the long terminal repeat (LTR) at its termini, which consist of 3’ unique elements (U3), repeat elements (R), and 5’ unique elements (U5). The 5’ LTR sequence functions as the promoter sequence for gene expression, in which viral RNA transcription is initiated at the U3-R, and the transcripts are polyadenylated at the R-U5 boundary of the 3’ LTR. The development of retrovirus as a gene transfer vector was first achieved with oncoretroviruses in the 1980s (Mann et al., 1983; Miller & Rosman, 1989; Shimotohno & Temin, 1981; Tabin et al., 1982; Watanabe & Temin, 1983; Wei et al., 1981); nowadays Moloney murine leukemia virus (MoMLV), one of the well characterized oncoretroviruses, is commonly used for therapeutic applications (Anderson et al., 1990; Blaese et al., 1993; Guild et al., 1988; Levine& Friedmann, 1991; Miller, 1992a, b). However, the important limitation of the MoMLV-derived vector is its cell cycle dependency: this virus lacks the ability to infect non-dividing cells (Harel et al., 1981; Hatziioannou & Goff, 2001; Lewis & Emerman, 1994; Miller et al., 1990; Roe et al., 1993). Unlike the MoMLV, lentiviruses, a separate genus of the Retroviridae family including human immunodeficiency virus type-1 (HIV-1), can infect both dividing and non-dividing cells (Bukrinsky et al., 1992; Hatziioannou & Goff, 2001; Lewis et al., 1992; Lewis & Emerman, 1994). The ability to infect non-dividing cells is not restricted to in vitro cell culture as lentivirus-derived vectors are capable of transducing certain quiescent or terminally differentiated cells such as macrophages and microglia (Miyake et al., 1998; Naldini et al., 1996; Weinberg et al., 1991). This property makes the lentivirus an attractive choice for gene transfer vector (Suzuki & Craigie, 2007).
It is well known that HIV-1 is the causative agent for acquired immunodeficiency syndrome (AIDS). Currently, the standard AIDS treatment, termed highly active antiretroviral therapy (HAART), is to use cocktail of antiretroviral drugs that targets different HIV-1 enzymes including reverse transcriptase and protease. However, although it successfully causes suppression of HIV-1 RNA detected in plasma for a prolonged period of time and dramatic decrease of patient mortality (Palella et al., 1998; Volberding & Deeks, 2010), this pharmacological therapy is facing problems such as drug resistance and side effects in administrated individuals (Meadows & Gervay-Hague, 2006; Richman, 2001). Hence, viral vector-based gene therapy should offer a new approach to supplement the need for current drug regimens for the treatment of HIV/AIDS (Poluri et al., 2003; Strayer et al., 2005). Genetic modification of HIV-susceptible cells or hematopoietic stem cells (HSCs) by expressing anti-HIV transgenes should be one of the goals of the HIV gene therapy (Kitchen et al., 2011). In this regard, the lentiviral vector has the potential advantage for transduction because of its ability to infect quiescent cells including HSC (Miyoshi et al., 1999). However, incorporation of anti-HIV genes into an HIV-based lentiviral vector can create problems for production of the vector itself; expression of the anti-HIV trans gene in the producer cells can interfere with vector production (Banerjea et al., 2003; Li et al., 2003; Mautino & Morgan, 2002c). One way to avoid this difficulty is to introduce a gene regulatable system in which the target transgene is kept silent during vector production and expression is subsequently induced on following infection of the vector in target cells.
Several regulatable gene expression systems have been developed and applied to viral vectors including lentiviral vectors (Goverdhana et al., 2005; Weber & Fussenegger, 2004). In this chapter, we focus on recent development of the gene-regulatable lentiviral vectors and discuss the suitability of the vectors for anti-HIV therapy.
2. Biology of HIV-1 replication
2.1. Genomic organization and gene expression
Lentiviruses, as represented by HIV-1, are also called complex retroviruses, which are characterized by a set of additional regulatory and accessory genes encoded in the viral genome (Cullen, 1991; Frankel & Young, 1998). In the case of HIV-1, the DNA genome converted from the RNA genome is about 9.7 kb and contains nine ORFs; in addition to the gag, pol, and env genes that are typical of all retroviruses, there are two regulatory (tat and rev) and four accessory (vif, vpr, vpu, and nef) genes (Fig. 1). These protein-coding regions are flanked by 5’ and 3’ LTR that are required for reverse transcription, integration, and gene expression steps.
The complexity of HIV-1 is also characterized by its specific pattern of viral gene regulation (Kingsman & Kingsman, 1996). The HIV-1 LTR harbors several cis-acting sequences required for the initiation of viral RNA expression. The U3 region of the LTR is composed of a series of control elements that recruit a variety of transcription factors (Brady & Kashanchi, 2005), and consequently, transcription of viral RNA initiates at the U3-R junction. However, the transcription activity of the U3 is basically low, and trans-acting proteins are required to enhance the viral RNA synthesis from the 5’ LTR. Viral regulatory protein, Tat is one of these transactivators (Brady & Kashanchi, 2005). Tat interacts not with DNA, but with an RNA bulge of a stem-loop structure formed at the 5’ end of nascent transcripts, which is known as the transactivation response region (TAR) (Berkhout et al., 1989; Feng & Holland, 1988). Binding of Tat to the TAR then recruits an active transcription elongation complex consisting of cyclin T1 (CycT1), CDK9, and some other factors (Brady & Kashanchi, 2005). Subsequently, CDK9 leads the hyperphosphorylation of the C-terminal domain of RNA polymerase II, in turn resulting in a dramatic stimulation of transcriptional processivity (Brady & Kashanchi, 2005).
More than 30 species of RNA are transcribed from the integrated HIV-1 DNA; these fall into three size classes of mRNA based on the pattern of splicing: unspliced, partially spliced, and multiply spliced RNAs. (Kingsman & Kingsman, 1996; Purcell & Martin, 1993; Schwartz et al., 1990). The unspliced transcript is full-length RNA (about 9 kb) that is packaged as the viral genome into new viral particles but it also functions as mRNA to produce Gag and Gag-Pol polyproteins. The partially spliced transcripts (about 4 kb) encode Vif, Vpr, Vpu, and Env proteins. At early times after infection, however, the multiply spliced RNAs are predominant, and their encoded proteins, Tat, Rev, and Nef are highly produced (Kim et al., 1989).
Figure 1.
Organization of the HIV-1 genome.
2.2. Replication cycle
HIV-1 infection begins with the binding of the viral envelope (Env) glycoprotein gp120 (surface envelope protein: SU) to the CD4 receptor molecule on the surface of host cells. Consequently, the main target cells for HIV-1 infection are the CD4+ subset of helper T cells and monocyte/macrophage lineages (Dalgleish et al., 1984; Landau et al., 1988; Stevenson, 2003). The gp120-CD4 interaction triggers a conformational change in the gp120 that facilitates subsequent binding to a secondary cellular receptor (coreceptor). While most HIV-1 strains use either the α-chemokine receptor CXCR4 or the β-chemokine receptor CCR5 as the coreceptor, other chemokine receptors or related proteins have been reported to serve as coreceptors for HIV-1 infection (Berger et al., 1999). This coreceptor usage is the basis for the differential cell-type tropism of HIV-1 strains. Formation of the gp120-CD4-coreceptor complex then induces refolding of the gp41 subunit of the Env (transmembrane envelope protein: TM), which allows the membrane fusion process between the virus and target cell (Melikyan, 2008).
After penetrating the cell membrane, the viral nucleoprotein core, which contains genomic RNA, is released into the cytoplasm, followed by the uncoating of the viral core that is required for the formation of the reverse transcription complex (RTC) (Arhel, 2010; Bukrinskaya et al., 1998; Fassati & Goff, 2001). Reverse transcription, one of the defining steps of retrovirus infection, takes place in the RTC and it is initiated from the 3’ end of the tRNALys3 that is annealed to the primer binding site (PBS) near the 5’ end of the viral RNA genome. During the reverse transcription reaction, RT firstly synthesizes the minus-strand DNA along with the concomitant degradation of the RNA template by its RNase H activity (Basu et al., 2008). Subsequent synthesis of plus-strand DNA involves priming from two polyprine tracts (PPT), short RNA segments resistant to RNase H digestion, at the 3’ terminus (3’ PPT) and the center (central PPT: cPPT) of the HIV-1 genome. Once the 3’ end of the plus-strand DNA reaches the 5’ end of the cPPT, DNA synthesis proceeds by displacing the existing DNA fragments and stops at a central termination sequence (CTS) in the minus-strand DNA, resulting in a 99 bp triple-strand DNA structure in the center of the HIV-1 DNA (Arhel, 2010; Charneau et al., 1992; Charneau et al., 1994).
The newly synthesized full-length viral DNA remains associated with viral and cellular proteins in a large nucleoprotein complex called the preintegration complex (PIC) (Engelman, 2003). The HIV-1 PIC has been shown to contain RT, IN, matrix (MA), nucleocapsid (NC), and Vpr proteins (Lewinski & Bushman, 2005; Suzuki & Craigie, 2007). In addition to viral proteins, several cellular proteins have been reported as components of the HIV PIC (Suzuki & Craigie, 2007). As mentioned above, unlike many oncoretroviruses, HIV-1 is able to infect non-dividing cells. Thus, the HIV-1 PIC is believed to carry karyophilic signals that direct transport across an intact nuclear membrane in non-dividing cells. Although the molecular mechanisms underlying the active transport of HIV-1 PIC into the nucleus is still poorly understood, several viral and cellular factors have been shown to be implicated in the nuclear import of the HIV-1 PIC (Fassati, 2006; Suzuki & Craigie, 2007; Yamashita & Emerman, 2006). Cell cycle-independent infection of HIV-1 is particularly important in the pathogenesis of the virus and the development of HIV-1-based lentiviral vectors (Blankson et al., 2002; Kaul et al., 2001; Somia & Verma, 2000).
Following nuclear transport of the PIC, integration of viral DNA into the host chromatin takes place. IN is a key component of the PIC that catalyzes the integration. This reaction proceeds via three coordinated steps: 3’ end processing of the viral DNA, joining to the target DNA, and repairing of the gaps between viral DNA and target DNA. IN is responsible for the 3’ end processing and DNA joining steps, but the gap repair step is likely to be carried out by yet-to-be-identified cellular enzymes (Engelman, 2003) (Fig. 2).
The integrated DNA, called the provirus, is acted upon by cellular transcription factors to express viral genes. Early populations of the transcripts are the multiply spliced class of mRNA that encodes Tat, Rev, and Nef proteins (Kingsman & Kingsman, 1996). Tat enhances production of viral mRNAs by more than two log via interaction with TAR and a cellular elongation complex (Brady & Kashanchi, 2005). There is then an increase in the partially spiced and unspliced mRNAs along with a concomitant decrease in the multiply spliced mRNAs, which is caused by the accumulation of Rev protein. Rev is also required for the nuclear export of partially spliced and unspliced mRNAs. These classes of viral RNAs contain a highly structured cis-acting element termed Rev response element (RRE) that is located in the env coding region. Rev bears a leucine-rich nuclear export signal (NES) and, via association with the RRE, mediates nuclear-to-cytoplasmic transport of the partially spliced and unspliced RNAs, resulting in production of Gag, Gag-Pol, Env, and accessory proteins (Pollard & Malim, 1998).
Following the synthesis of the full-length viral RNA genome and the viral proteins, these components are assembled together to produce new viruses. In HIV-1, the assembly process takes place at the plasma membrane (Ono, 2010). Gag protein plays a central role in the formation of virions; this protein is synthesized as a 55 kDa precursor protein for matrix (MA), capsid (CA)), and nucleocapsid (NC) proteins. The Gag precursor proteins are rapidly targeted to the plasma membrane where they multimerize. Although the multimerization of the Gag is sufficient to give rise to virus like particles, incorporation of Gag-Pol proteins is integral to the formation of infectious virions (Wu et al., 1997). Gag-Pol is a 160 kDa multidomain protein consisting of RT, IN, and protease (PR), and it too relocates to the plasma membrane, where Gag and Gag-Pol are assembled into virus particles. In the HIV-1 genome, Gag and Pol are encoded by overlapping ORF; Gag-Pol is generated by a ribosomal frameshifting during translation of the gag gene. This translation mechanism limits intracellular synthesis of Gag-Pol at 10- to 20-fold-lower than Gag (Haraguchi et al., 2010). Env glycoprotein, which is synthesized in the rough endoplasmic reticulum (ER), reaches the cell surface and is incorporated into virus particles. The MA domain of Gag has been suggested to be important for the recruitment of Env into virions (Ono, 2010). Encapsidation of the viral genomic RNA is directed by an interaction between the NC domain of Gag and the packaging signal (or ψ-site located in the 5’ region of the gag initiation codon. The ψ sequence also acts as a dimerization signal for the viral RNA genome. Eventually, the virus particle is pinched off the host cell membrane (budding). Recent evidence has revealed that a number of cellular proteins in the vacuolar protein sorting (VPS) pathway are involved in the HIV-1 budding process. After release from the plasma membrane, virus particles undergo a maturation step, in which Gag and Gag-Pol precursor proteins are cleaved by the viral PR to yield the functional mature proteins of infectious HIV-1 (Vogt, 1996) (Fig. 2).
Accessory proteins (i.e. Vif, Vpr, Vpu, and Nef) are dispensable for viral replication in many in vitro cell culture systems, but these proteins are likely to be required for efficient replication and pathogenicity of HIV-1 in vivo (Malim & Emerman, 2008).
3. Development of HIV-1-derived lentiviral vectors
Although retrovirus vectors derived from oncoretroviruses were introduced first, in recent years, attention of the viral vector research has been focused on lentiviruses such as HIV-1 and equine infectious anemia virus (EIAV) due to their ability to infect non-dividing cells. In particular, HIV-1 should be one of the most practical gene transfer vectors for gene therapy applications because this is the best studied retrovirus. However, HIV-1 is a human pathogen that causes destruction the of CD4+ helper T lymphocytes and the subsequent loss of immune competence (Forsman & Weiss, 2008). Therefore, considerable efforts have been devoted to develop efficient HIV-1-derived lentiviral vectors with improved biosafety features.
So far, three different generations of HIV-1-based lentiviral vectors have been established, which is based on the level of safety improvements in viral vector production (Fig. 3).
Figure 2.
Schematic representation of HIV-1 replication. HIV-1 enters target cells by first binding to the CD4 receptor and a coreceptor (CCR5 or CXCR4), this allows fusion between the cellular and viral membranes. After entry, the viral nucleoprotein core containing the genomic RNA is released into cytoplasm. Reverse transcription takes place in a nucleoprotein complex termed the RTC. The synthesis of full-length viral DNA produces an integration-competent nucleoprotein complex called the PIC and this nucleoprotein complex mediates integration of viral DNA into chromatin. Integrated viral DNA, called the provirus, serves as a transcription template for the synthesis of viral mRNA and genomic RNA. Following the synthesis of viral proteins, the viral components are assembled together to produce new virions, the virus particles then undergo a maturation step to generate infectious HIV-1.
3.1. First-generation lentiviral vectors
One of the key safety concerns in the use of HIV-derived vectors is the generation of replication competent lentiviruses (RCL). Earlier development of lentiviral vectors was achieved by transient transfection of human embryonic kidney (HEK293T) cells with three separate plasmid DNAs encoding i) the lentiviral vector genome which was composed of the wild-type 5’ and 3’ LTR, a part of the gag gene corresponding to the ψ sequence, a part of the env gene containing the RRE, an internal promoter, and the desired gene (transfer vector plasmid), ii) the HIV-1 genome containing all viral genes with the exception of the env gene (packaging plasmid), and iii) the vesicular stomatitis virus G protein (VSV-G) that improves the stability and broadens the cellular tropism of lentiviral vectors (Burns et al., 1993; Naldini et al., 1996). However, in this vector production system, there is a potential risk for the generation of RCL; a recombination event would occur during subsequent reverse transcription in transduced cells between two RNAs that are derived from the transfer vector plasmid and the packaging plasmid and incidentally copackaged within the same virion (Fig. 3A).
Figure 3.
Schematic representation of HIV-1-derived lentiviral vector packaging constructs. The first-generation lentiviral vectors (A) are produced by three separate plasmid DNAs encoding the vector genome, all HIV-1 genes except for env gene, and Env protein (VSV-G). To reduce the potential risk of the generation of replication competent viruses, all accessory genes (vif, vpr, vpu, and nef) are removed from (or mutated in) the packaging plasmids in second-generation lentiviral vectors (B). In third-generation lentiviral vectors, the enhancer/promoter unit is deleted from the U3 region of the 3’ LTR (ΔU3) in transfer vector plasmids (SIN vector). Additionally the U3 region of the 5’ LTR is replaced with the CMV promoter, enabling Tat-independent production of the lentiviral vectors (C). LTR, long terminal repeat; ψ, packaging signal; RRE, Rev response element.
3.2. Second-generation lentiviral vectors
The second-generation lentiviral vectors basically employ a similar three-plasmid system as the first generation vectors. Yet, in order to overcome the safety issue attributable to the first-generation vectors, the second-generation lentiviral vectors were generated without production of all accessory proteins (Vif, Vpr, Vpu, and Nef) via mutation or deletion of these genes from the packaging plasmid (Gasmi et al., 1999; Kim et al., 1998; Zufferey et al., 1997) (Fig. 3B).
3.3. Third-generation lentiviral vectors
The second-generation vectors, however, still carry the transcriptionally active LTR elements that could induce the homologous recombination between the vector genome and wild-type HIV-1. This would be particularly problematic if the lentiviral vectors are used for gene therapy of HIV/AIDS. Thus, further improvements were made in the third-generation lentiviral vectors. To minimize the transcriptional activity of the LTR in transduced cells, the enhancer/promoter unit was deleted from the U3 region of the 3’ LTR in transfer vector plasmids. During reverse transcription in the transduced cells, this deletion is transferred to the 5’ LTR of the lentiviral DNA, thereby reducing promoter activity of the integrated provirus (self-inactivating [SIN] vector) (Miyoshi et al., 1998; Zufferey et al., 1998). Additionally, the U3’region of the 5’ LTR in the transfer vector plasmid was replaced with the cytomegalovirus (CMV) promoter, which enabled Tat-independent transcription of the lentiviral vector genome in producer cells (Dull et al., 1998; Miyoshi et al., 1998). In these SIN vectors, there is no compete HIV-1 U3 sequence. Moreover, expression of Rev protein is directed by a separate plasmid, but not by the packaging plasmid encoding gag and pol genes (Wagner et al., 2000) (Fig. 3C). Currently, third-generation SIN lentiviral vector system offers the best safety profile in terms of generation of RCL because this vector requires only three HIV-1 genes (gag, pol, and rev) for production, however safety improvement in the design of HIV-1-derived lentiviral vectors is still one of the challenging areas in gene therapy study
4. Incorporation of regulatable gene expression systems in HIV-1-derived lentiviral vectors
Lentiviral vectors hold great promise for a gene therapy approach to inherited and acquired diseases. In these particular clinical settings, it would be more beneficial to reversibly control transgene expression in a dose and time dependent manner as illustrated in the field of angiogenesis and Parkinson’s disease (Ma et al., 2002; Yancopoulos et al., 2000). To meet the standards required for clinical applications, a number of regulatable gene expression systems have been developed, and some of them are indeed incorporated into viral vectors including HIV-1-derived lentiviral vectors (reviewed in Goverdhana et al., 2005).
Although early development of the regulatable gene expression systems was based on naturally occurring inducible cellular promoters that respond to exogenous signals, these types of systems had limitations due to the pleiotropic effects of the inducer, high levels of “leaky” background expression and poor performance in inducibility. Therefore, recent efforts have been mostly focused on the development of chimeric gene regulatable systems derived from prokaryotic, eukaryotic, and viral elements, which are designed to enhance specificity and activity of transgene expression (Fussenegger, 2001).
4.1. Tetracycline-regulated system
The most widely used inducible system in lentiviral vectors is the tetracycline (Tet)-regulated system. This system was originally based on binding of the Tet-controlled repressor (tetR), a 23.6 kDa protein of Escherichia coli (E. coli), to the operator sequence of E. coli Tet resistance gene (Baron & Bujard, 2000), but further developed to be operated in mammalian cells by the generation of a chimeric protein in which tetR is fused with herpes simplex virus (HSV) VP16 protein, a eukaryotic transactivator (Tet-controlled transactivator: tTA) (Gossen & Bujard, 1992). In the absence of Tet or its derivatives such as doxycycline (Dox), the tTA binds the Tet-response element (TRE) that is composed of seven tandem copies of Tet operator (tetO) sequences and placed upstream of the CMV minimal promoter (Baron & Bujard, 2000). This type of original Tet-regulated system, called Tet-off system, has been incorporated into HIV-1-derived lentiviral vectors (Gascon et al., 2008; Haack et al., 2004; Kafri et al., 2000; Vigna et al., 2002) (Fig. 4A). In the first study that employed the Tet-off system in the context of a lentiviral vector, transgene induction by the withdrawal of Dox resulted in a more than 500-fold increase in the expression level of a GFP reporter gene (Kafri et al., 2000). Of note, the Dox-dependent regulation of GFP expression was also confirmed in the brain cells of rats that had been transduced by the lentiviral vector and then administered Dox through drinking water, indicating applicability of the gene regulatable lentiviral vectors in vivo (Kafri et al., 2000). However, even in the presence of Dox, high levels of basal GFP expression was observed, which would be attributed to the transcriptional interference arising from the neighboring CMV promoter or the wild-type HIV-1 LTR.
In addition to the background activity in the repressed state, the major limitation of the Tet-off system is the requirement of continuous administration of Tet or Dox to suppress transgene expression. To overcome this limitation, another type of Tet-controlled gene expression system was established by introduction of several permutations in the tTA protein of the Tet-off system. The mutant tTA binds the tetO sequences only in the presence of Tet/Dox: it exhibits opposite function (Gossen et al., 1995). Because this modified version of regulatable system, the so-called Tet-on system, shows rapid kinetics of gene upregulation compared to Tet-off system, several HIV-1-derived lentiviral vectors have been constructed using the Tet-on system as well (Johansen et al., 2002; Koponen et al., 2003; Pluta et al., 2005; Reiser et al., 2000; Vogel et al., 2004) (Fig. 4B).
One more approach to permit tight control of transgenes in the context of a lentiviral vector is demonstrated in the Tet-regulated system that employs a chimeric tetR fused with the Krüppel-associated box (KRAB) domain, a transcriptional regulator found in many DNA binding zinc-finger proteins (Szulc et al., 2006; Wiznerowicz & Trono, 2003). Binding of the KRAB domain-containing repressor protein to DNA recruits various heterochromatin-inducing factors, thereby suppressing activity of cellular RNA polymerases (RNAPs) II and III. This transcriptional silencing can be exerted no farther than 2-3 kb away from the repressor binding site. In the new design of Tet-regulated lentiviral vector system, the tetO site was inserted upstream of the RNAP III promoter-driven small hairpin RNA (shRNA) expression cassette which was located in the U3 region of lentiviral vector genome, and the activity of tetO-linked shRNA expression unit was tightly suppressed in the presence of KRAB-fused tTA and in the absence of Dox. The KRAB-fused tTA/Dox-dependent inhibition of transcriptional activity was also observed in the internal RNAP II promoter for a reporter transgene within the same vector genome. However, when the transduced cells were treated with Dox, shRNA was produced to achieve RNA interference, which was correlated with the expression of the reporter transgene (Szulc et al., 2006; Wiznerowicz & Trono, 2003).
One drawback of the Tet-regulated system is that there is a requirement to deliver two distinct expression units into a target cell: one is for transactivator (e.g. tTA) expression and the other is for transgene expression. In a binary lentiviral vector approach in which tTA and transgene expression cassettes are cloned into separate vectors, a population cells that is singly transduced with either tTA or transgene would be produced, resulting in low inducibility as a whole. This can be a bottleneck, particularly in relevant applications of the Tet-regulated lentiviral vector systems in clinical use. Single vector systems that contain the entire regulatable component in a unique vector is one of the solutions to guarantee simultaneous expression of the two expression units in the target gene, and these have indeed been established (Gascon et al., 2008; Kafri et al., 2000; Szulc et al., 2006; Vogel et al., 2004).
4.2. Mifepristone-inducible system
This gene regulatable system (also called GeneSwitch system) is based on a mutated human progesterone receptor that responds to the synthetic progestin antagonist but fails to bind natural progestins or other steroids (Burcin et al., 1999; Wang et al., 1994). Similar to Tet-regulated system, this system requires two components: the regulator (transactivator) protein and the inducible promoter sequence that drives transgene expression. The regulator is a hybrid protein consisting of a GAL4 DNA-binding domain from Saccharomyces cerevisiae, a ligand-binding domain of mutant progesterone receptor, and an activation domain of the p65 subunit of human NF-κB (Burcin et al., 1999). The inducible transgene expression unit contains six copies of the GAL4 upstream activating sequences (UAS) and the TATA box sequence in its promoter (Abruzzese et al., 1999). The progestin antagonist commonly used as an inducer for the GeneSwitch system is mifepristone (MFP, RU486). The regulator protein initially exists as an inactive monomeric form. However, in the presence of MFP, it binds to the MFP and undergoes a conformational change, causing the regulator protein to become an active homodimer. The active form of the regulator is able to bind to GAL4 UAS and induce transgene expression (Nordstrom, 2003) (Fig. 4C).
Sirin and Park have incorporated the MFP-inducible gene expression system into HIV-1-derived lentiviral vectors (Sirin & Park, 2003). In their design, two different SIN lentiviral vectors were constructed, in which either the regulator protein expression unit or the inducible transgene expression unit was cloned. When human cell lines (HeLa and Huh7 cells) were infected with both lentiviral vectors, up to a 275-fold increase in the number of reporter fluorescent protein-positive cells was observed at 48 hours following MFP treatment. Similar effective induction was also detected in cells transduced by a lentiviral vector expressing the human α1-antitrypsin (hAAT) with an extremely low level of basal hAAT expression (Sirin & Park, 2003).
Although an in vitro study using adenovirus vector expressing the chloramphenicol acetyl transferase (CAT) as a reporter transgene gene demonstrates that induction level of the GeneSwitch system is lower than that of the Tet-regulated (Tet-on) system (Molin et al., 1998), the GeneSwitch system holds some advantages in its application to human gene therapy. The majority of components of the regulator protein are derived from human proteins, which has less impact on cell viability and immunogenicity. In addition, MFP has been approved by the Food and Drug Administration (FDA) for use in humans (Ulmann et al., 1995), and the concentration of MFP need for transgene induction is significantly lower than the concentration for its anti-progesterone effect (Nordstrom, 2003).
Figure 4.
Diagrams of two regulatable gene expression systems. The Tetracycline-regulated system is the most widely used inducible system in lentiviral vectors. In a Tet-off system (A), the Tet-controlled transactivator (tTA), a chimeric protein of E. Coli Tet-controlled repressor (tetR) and HSV VP16, binds the Tet-response element (TRE) upstream of the CMV promoter in the absence of Tet or Dox. On the other hand, in the Tet-on system (B), several mutations are introduced into the tTA (rtTA) so that this transactivator binds the TRE in the presence of Dox. The Mifepristone-inducible system (GeneSwitch) has been also incorporated into HIV-1-derived lentiviral vectors. In this system, the transactivator is a chimeric protein that comprises the GAL4 DNA-binding domain from Saccharomyces cerevisiae fused to the ligand-binding domain of a mutant progesterone receptor (hPR LBD Δ19) and the activation domain of the p65 subunit of human NF-kB. In the presence of mifepristone (MFP), the chimeric transactivator binds to the six copies of GAL4 upstream of the activating sequences and induce transgene expression (C). TATA, TATA box sequence.
4.3. Ecdysone-regulated system
The Drosophila melanogaster ecdysone receptor (EcR)-based gene regulatable system has been adapted to lentiviral vectors (Galimi et al., 2005). EcR is a member of the nuclear receptor superfamily that mediates a cascade of morphological changes in Drosophila, triggered by the steroid hormone ecdysone. Ecdysone regulates gene expressions by interacting with the functional EcR, which in turn induces binding of the EcR to DNA regulatory elements EcREs) near target genes (No et al., 1996). The ecdysone-regulated gene expression system incorporated into lentiviral vectors employed two elements: i) the dimeric regulator protein of the EcR fused with HSV VP16 activation domain (VgEcR) and the retinoid X receptor (RXR), and ii) the hybrid promoter between the glucocorticoid response element and that of type II nuclear receptors (E/GRE) (Galimi et al., 2005). Upon exposure to ecdysone or synthetic analogues such as ponasterone A, the VgECR/RXR heterodimer binds to the E/GRE, resulting in induction of transgene expression (Saez et al., 2000). One advantage of the ecdysone-regulated gene expression system is the pharmacological profile of the inducer that allows for fast distribution and clearance after administration in vivo (Saez et al., 2000). Additionally, the inducible promoter is not responsive to natural nuclear receptors (No et al., 1996).
In the single vector approach, the inducible GFP expression cassette containing E/GRE as well as a CNV promoter-driven bicistronic unit for VgEcR and RXR expressions were cloned into an HIV-1-derived SIN lentiviral vector. However, this ecdysone-regulated system was also applicable to the binary vector system, in which the VgEcR/RXR expression unit was in one lentiviral vector and the inducible transgene expression unit was in the second vector. The latter approach would be of value in deliver of longer transgene. These lentiviral vectors have been shown to successfully deliver the ponA-inducible GFP expression units in vitro and ex vivo (Galimi et al., 2005).
4.4. Other regulatable systems
Besides the Tet- MFP-, and ecdysone-regulated systems, different types of inducible lentiviral vectors have been generated based on the other chimeric regulatable systems, which include streptogramin-adjustable expression system derived from Streptomyces coelicolor (Mitta et al., 2004) and gaseous acetaldehyde-inducible expression system derived from Aspergillus nidulans (Hartenbach & Fussenegger, 2005). Although some endogenous cellular elements that respond to exogenous signals or stress have been adapted to HIV-1- and EIAV-derived lentiviral vectors (Beutelspacher et al., 2005; Hurttila et al., 2008; Parker et al., 2009), the pleiotropic effects exerted by the inducing agent would be a drawback in a human therapeutic context (Fussenegger, 2001).
5. Application of a gene regulatable lentiviral vector for HIV-1 inhibition
Lentiviral vector-mediated gene therapy has the potential to improve the clinical state of a patient with HIV-1. This goal would be accomplished by ex vivo transduction of anti-HIV genes into CD4+ virus target cells such as helper T cells and macrophages or CD34+ progenitor cells (HSCs), making them resistant to HIV-1 infection (intracellular immunization approach) (Baltimore, 1988; Kitchen et al., 2011). So far, various studies have reported the delivery of anti-HIV genes by HIV-1-based lentiviral vectors in vitro and in vivo, and the anti-HIV genes can be categorized as either RNA- or protein-based (Mukhtar et al., 2000) (Banerjea et al., 2003; Dropulic et al., 1996; Klimatcheva et al., 2001; Li et al., 2003; Mautino et al., 2001; Mautino & Morgan, 2002a, b, c). Among the RNA-based anti-HIV genes include a ribozyme that cleaves the U5 region of HIV-1 RNA by its enzymatic activity (Dropulic et al., 1996), an antisense RNA that hybridizes the transcripts of HIV-1 env gene to inhibit translation of Env (Mautino & Morgan, 2002a, c), and small interfering RNA (siRNA) that induces sequence-specific degradation of HIV-1 RNA (Banerjea et al., 2003). In the protein-based approach, the transdominant negative mutant of Rev (TdRev) is best described as an anti-HIV gene used in the setting of lentiviral vectors (Klimatcheva et al., 2001; Mautino et al., 2001; Mautino & Morgan, 2002c; Mukhtar et al., 2000). The TdReV named RevM10 is a derivative of HIV-1 Rev in which two amino acid mutations are introduced in the C-terminus activation domain, and hampers nuclear export of HIV-1 mRNAs via the formation of inactive multimers with WT Rev (Hope et al., 1992; Malim et al., 1989). It should be noted that RevM10 has been already tested in phase I clinical trials to treat HIV infection via transduction of the gene into CD34+ cells with MoMLV-derived retroviral vectors (Kang et al., 2002; Kitchen et al., 2011; Podsakoff et al., 2005).
Although a promising approach for HIV gene therapy, constitutive expression of anti-HIV genes in the context of HIV-1-derived lentiviral vectors could encounter a problem of self-inhibition of the vector particle production, resulting in significant decrease of viral infectious titer (Mautino & Morgan, 2002b). This problem of self-inhibition can be solved by several means. If the anti-HIV gene targets specific sequences in the HIV-1 RNA, one strategy to avoid the self-inhibition would be to engineer nucleotide sequences of lentiviral vector genome and packaging genes in order that anti-HIV gene will exclusively recognize wild-type virus in transduced cells. As for TdRev, the inhibition of vector production could be overcome by replacement of the HIV-1 Rev-dependent nuclear export element (e.g. RRE) with the one derived from another lentiviruses, conferring Rev-independent property on the lentiviral vectors (Mautino et al., 2001; Taylor et al., 2008). But, if the anti-HIV genes are designed to target HIV-1 at more fundamental process such as virion formation and budding processes, an ideal strategy would be the incorporation of regulatable transgene expression system into lentiviral vectors, in which expression of the anti-HIV gene is “OFF” during vector production and turned “ON” in the target cells.
In order to assess the availability of gene regulatable systems in inhibition of HIV-1, we have generated HIV-1-derived lentiviral vectors harboring the MFP-inducible transgene expression unit (Shinoda et al., 2009). In the study, two SIN lentiviral vectors were designed to incorporate the MFP-inducible unit in either the forward or the reverse orientation with respect to the direction of transfer vector genome (designated as forward and reverse vectors, respectively), since it has been reported that promoter activity of the internal gene expression unit could be affected by its orientation and/or the presence of adjacent LTR (Chen et al., 1992; Reiser et al., 2000; Sirin & Park, 2003). When firefly luciferase gene, which does not interfere with HIV-1 production, was inserted into the MFP-inducible lentiviral vectors, substantial levels of infectious vectors could be yielded from the forward and reverse vector systems by co-transfection with packaging plasmid DNAs in HEK293T cells. However, the infectious titer obtained by the forward vector was more than 10-fold higher than reverse vector, and even in the absence of transactivator and inducer, significant level of the leaky expression of luciferase was observed in the forward vector plasmid transfected-cells, but not in the reverse vector-transfected cells (Shinoda et al., 2009). It can be speculated that the higher background activity in the forward vector was due to the enhancement of gene expression by orientation-dependent cis-acting element such as the woodchuck post-regulatory element (WPRE) and/or the weak promoter activity of the 5’ LTR. Importantly, this tight suppression of inducible unit in the reverse vector was reflected in its ability to produce infectious vectors when a transdominant negative mutant of human VPS4B protein in the VPS pathway, which inhibits budding process of HIV-1, was used as a transgene. Transfection of the reverse vector plasmid containing VPS4B dominant-negative mutant yielded infectious lentiviral vector, transfection of the forward vector could not generate infectious vectors, demonstrating the self-inhibition by the leaky expression of VPS4B dominant-negative mutant from the forward vector plasmid in vector producing cells (Shinoda et al., 2009). As expected, subsequent transduction of the transactivator-expressing cells with the infectious reverse vector bearing the VPS4B mutant resulted in significant inhibition of wild-type HIV-1 production only in the presence of MFP (Shinoda et al., 2009). Thus, this previous study demonstrates that the gene regulatable lentiviral vector system has the capability to transduce anti-HIV gene and subsequently block HIV-1 budding without the problem of self-inhibition during vector production.
6. Conclusion and future direction
Lentiviral vectors derived from HIV-1 are attractive gene delivery vehicles in terms of stable and long-term transgene expression in dividing and non-dividing cells. Although strong promoters used to achieve high levels of transgene expression are put into general use in the lentiviral vectors, incorporation of regulatable gene expression system confers transcriptional flexibility to the vector, which expands the potential of the lentiviral vectors for a wide array of gene transfer applications, particularly when undesired side effect would be expected by the constitutive expression of transgene. Nevertheless, many obstacles must be overcome for the clinical application of gene regulatable lentiviral vectors in gene therapy. One of the obstacles is that all the components of a regulatory system should be incorporated into a single vector, limiting the cloning capacity for transgene. Another issue is that there is no gene regulatory system approved by the FDA for clinical use. However, if their safety and efficacy are validated, development of gene regulatable lentiviral vector systems will be a next promising step toward achieving successful gene therapy for otherwise incurable diseases.
Acknowledgments
We are grateful Wei Xin Chin for proofreading and comments on the manuscript.
\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/16788.pdf",chapterXML:"https://mts.intechopen.com/source/xml/16788.xml",downloadPdfUrl:"/chapter/pdf-download/16788",previewPdfUrl:"/chapter/pdf-preview/16788",totalDownloads:4412,totalViews:718,totalCrossrefCites:2,totalDimensionsCites:4,totalAltmetricsMentions:0,impactScore:3,impactScorePercentile:84,impactScoreQuartile:4,hasAltmetrics:0,dateSubmitted:"October 26th 2010",dateReviewed:"April 2nd 2011",datePrePublished:null,datePublished:"July 20th 2011",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/16788",risUrl:"/chapter/ris/16788",book:{id:"500",slug:"viral-gene-therapy"},signatures:"Yasutsugu Suzuki and Youichi Suzuki",authors:[{id:"30581",title:"Dr.",name:"Youichi",middleName:null,surname:"Suzuki",fullName:"Youichi Suzuki",slug:"youichi-suzuki",email:"micys@nus.edu.sg",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"43634",title:"Mr",name:"Yasutsugu",middleName:null,surname:"Suzuki",fullName:"Yasutsugu Suzuki",slug:"yasutsugu-suzuki",email:"yasuzuki@virus.kyoto-u.ac.jp",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Biology of HIV-1 replication",level:"1"},{id:"sec_2_2",title:"2.1. Genomic organization and gene expression",level:"2"},{id:"sec_3_2",title:"2.2. Replication cycle",level:"2"},{id:"sec_5",title:"3. Development of HIV-1-derived lentiviral vectors",level:"1"},{id:"sec_5_2",title:"3.1. First-generation lentiviral vectors",level:"2"},{id:"sec_6_2",title:"3.2. Second-generation lentiviral vectors",level:"2"},{id:"sec_7_2",title:"3.3. Third-generation lentiviral vectors",level:"2"},{id:"sec_9",title:"4. Incorporation of regulatable gene expression systems in HIV-1-derived lentiviral vectors",level:"1"},{id:"sec_9_2",title:"4.1. Tetracycline-regulated system",level:"2"},{id:"sec_10_2",title:"4.2. Mifepristone-inducible system",level:"2"},{id:"sec_11_2",title:"4.3. Ecdysone-regulated system",level:"2"},{id:"sec_12_2",title:"4.4. Other regulatable systems",level:"2"},{id:"sec_14",title:"5. Application of a gene regulatable lentiviral vector for HIV-1 inhibition",level:"1"},{id:"sec_15",title:"6. Conclusion and future direction",level:"1"},{id:"sec_16",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'AbruzzeseR. V.GodinD.BurcinM.MehtaV.FrenchM.LiY.O’MalleyB. W.NordstromJ. L.\n\t\t\t\t\t1999\n\t\t\t\t\tLigand-dependent regulation of plasmid-based transgene expression in vivo. Hum. Gene Ther.,\n\t\t\t\t\t10\n\t\t\t\t\t9\n\t\t\t\t\t14991507\n\t\t\t'},{id:"B2",body:'AndersonW. F.BlaeseR. M.CulverK.\n\t\t\t\t\t1990\n\t\t\t\t\tThe ADA human gene therapy clinical protocol: Points to Consider response with clinical protocol, July 6, 1990.\n\t\t\t\t\tHum. Gene Ther.,\n\t\t\t\t\t1\n\t\t\t\t\t3\n\t\t\t\t\t331362\n\t\t\t'},{id:"B3",body:'ArhelN.\n\t\t\t\t\t2010\n\t\t\t\t\tRevisiting HIV-1 uncoating.\n\t\t\t\t\tRetrovirology, 7\n\t\t\t\t\t96\n\t\t\t'},{id:"B4",body:'ArmentanoD.SookdeoC. C.HehirK. M.GregoryR. J.StGeorge. J. A.PrinceG. A.WadsworthS. C.SmithA. E.\n\t\t\t\t\t1995\n\t\t\t\t\tCharacterization of an adenovirus gene transfer vector containing an E4 deletion. Hum. Gene Ther.,\n\t\t\t\t\t6\n\t\t\t\t\t10\n\t\t\t\t\t13431353\n\t\t\t'},{id:"B5",body:'ArmentanoD.SmithM. P.SookdeoC. C.ZabnerJ.PerriconeM. A.StGeorge. J. A.WadsworthS. C.GregoryR. J.\n\t\t\t\t\t1999\n\t\t\t\t\tE4ORF3 requirement for achieving long-term transgene expression from the cytomegalovirus promoter in adenovirus vectors.\n\t\t\t\t\tJ. Virol.,\n\t\t\t\t\t73\n\t\t\t\t\t8\n\t\t\t\t\t70317034\n\t\t\t'},{id:"B6",body:'BaltimoreD.\n\t\t\t\t\t1988 Gene therapy. Intracellular immunization. Nature,\n\t\t\t\t\t335\n\t\t\t\t\t6189\n\t\t\t\t\t395396\n\t\t\t'},{id:"B7",body:'BanerjeaA.LiM. J.BauerG.RemlingL.LeeN. S.RossiJ.AkkinaR.\n\t\t\t\t\t2003\n\t\t\t\t\tInhibition of HIV-1 by lentiviral vector-transduced siRNAs in T lymphocytes differentiated in SCID-hu mice and CD34+ progenitor cell-derived macrophages.\n\t\t\t\t\tMol. Ther.,\n\t\t\t\t\t8\n\t\t\t\t\t1\n\t\t\t\t\t6271\n\t\t\t'},{id:"B8",body:'BaronU.BujardH.\n\t\t\t\t\t2000\n\t\t\t\t\tTet repressor-based system for regulated gene expression in eukaryotic cells: principles and advances.\n\t\t\t\t\tMethods Enzymol.,\n\t\t\t\t\t327\n\t\t\t\t\t401421\n\t\t\t'},{id:"B9",body:'BasuV. P.SongM.GaoL.RigbyS. T.HansonM. N.BambaraR. A.\n\t\t\t\t\t2008\n\t\t\t\t\tStrand transfer events during HIV-1 reverse transcription.\n\t\t\t\t\tVirus Res.,\n\t\t\t\t\t134\n\t\t\t\t\t1-2 , 1938\n\t\t\t'},{id:"B10",body:'BergelsonJ. M.CunninghamJ. A.DroguettG.Kurt-JonesE. A.KrithivasA.HongJ. S.HorwitzM. S.CrowellR. L.FinbergR. W.\n\t\t\t\t\t1997\n\t\t\t\t\tIsolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science, 275\n\t\t\t\t\t5304\n\t\t\t\t\t13201323\n\t\t\t'},{id:"B11",body:'BergerE. A.MurphyP. M.FarberJ. M.\n\t\t\t\t\t1999\n\t\t\t\t\tChemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease.\n\t\t\t\t\tAnnu. Rev. Immunol.,\n\t\t\t\t\t17\n\t\t\t\t\t657700\n\t\t\t'},{id:"B12",body:'BerkA. J.\n\t\t\t\t\t2007\n\t\t\t\t\tAdenoviridae: The Viruses and Their Replication, In Fields Virology, Knipe, D.M.; Howley, P.M., 2\n\t\t\t\t\t2355 Lippincott Williams & Wilkins, Philadelphia'},{id:"B13",body:'BerkhoutB.SilvermanR. H.JeangK. T.\n\t\t\t\t\t1989\n\t\t\t\t\tTat trans-activates the human immunodeficiency virus through a nascent RNA target.\n\t\t\t\t\tCell, 59\n\t\t\t\t\t2\n\t\t\t\t\t273282\n\t\t\t'},{id:"B14",body:'BettA. J.HaddaraW.PrevecL.GrahamF. L.\n\t\t\t\t\t1994\n\t\t\t\t\tAn efficient and flexible system for construction of adenovirus vectors with insertions or deletions in early regions 1 and 3.\n\t\t\t\t\tProc. Natl. Acad. Sci. USA,\n\t\t\t\t\t91\n\t\t\t\t\t19\n\t\t\t\t\t88028806\n\t\t\t'},{id:"B15",body:'BeutelspacherS. C.ArdjomandN.TanP. H.PattonG. S.LarkinD. F.GeorgeA. J.Mc ClureM. O.\n\t\t\t\t\t2005\n\t\t\t\t\tComparison of HIV-1 and EIAV-based lentiviral vectors in corneal transduction.\n\t\t\t\t\tExp. Eye Res.,\n\t\t\t\t\t80\n\t\t\t\t\t6\n\t\t\t\t\t787794\n\t\t\t'},{id:"B16",body:'BlaeseR. M.CulverK. W.ChangL.AndersonW. F.MullenC.NienhuisA.CarterC.DunbarC.LeitmanS.BergerM.et al.\n\t\t\t\t\t1993 Treatment of severe combined immunodeficiency disease (SCID) due to adenosine deaminase deficiency with CD34+ selected autologous peripheral blood cells transduced with a human ADA gene. Amendment to clinical research project, Project 90-C-195, January 10, 1992. Hum. Gene Ther.,\n\t\t\t\t\t4\n\t\t\t\t\t4\n\t\t\t\t\t521527\n\t\t\t'},{id:"B17",body:'BlanksonJ. N.PersaudD.SilicianoR. F.\n\t\t\t\t\t2002\n\t\t\t\t\tThe challenge of viral reservoirs in HIV-1 infection.\n\t\t\t\t\tAnnu. Rev. Med.,\n\t\t\t\t\t53 No. 557593\n\t\t\t'},{id:"B18",body:'BradyJ.KashanchiF.\n\t\t\t\t\t2005 Tat gets the "green" light on transcription initiation. Retrovirology\n\t\t\t\t\t2\n\t\t\t\t\t69\n\t\t\t'},{id:"B19",body:'BroughD. E.HsuC.KulesaV. A.LeeG. M.CantolupoL. J.LizonovaA.KovesdiI.\n\t\t\t\t\t1997\n\t\t\t\t\tActivation of transgene expression by early region 4 is responsible for a high level of persistent transgene expression from adenovirus vectors in vivo.\n\t\t\t\t\tJ. Virol.\n\t\t\t\t\t71\n\t\t\t\t\t12\n\t\t\t\t\t92069213\n\t\t\t'},{id:"B20",body:'BukrinskayaA.BrichacekB.MannA.StevensonM.\n\t\t\t\t\t1998\n\t\t\t\t\tEstablishment of a functional human immunodeficiency virus type 1 (HIV-1) reverse transcription complex involves the cytoskeleton.\n\t\t\t\t\tJ. Exp. Med.,\n\t\t\t\t\t188\n\t\t\t\t\t11\n\t\t\t\t\t21132125\n\t\t\t'},{id:"B21",body:'BukrinskyM. I.SharovaN.DempseyM. P.StanwickT. L.BukrinskayaA. G.HaggertyS.StevensonM.\n\t\t\t\t\t1992\n\t\t\t\t\tActive nuclear import of human immunodeficiency virus type 1 preintegration complexes.\n\t\t\t\t\tProc. Natl. Acad. Sci. USA,\n\t\t\t\t\t89\n\t\t\t\t\t14\n\t\t\t\t\t65806584\n\t\t\t'},{id:"B22",body:'BurcinM. M.SchiednerG.KochanekS.TsaiS. Y.O’MalleyB. W.\n\t\t\t\t\t1999\n\t\t\t\t\tAdenovirus-mediated regulable target gene expression in vivo. Proc. Natl. Acad. Sci. USA,\n\t\t\t\t\t96\n\t\t\t\t\t2\n\t\t\t\t\t355360\n\t\t\t'},{id:"B23",body:'BurnsJ. C.FriedmannT.DrieverW.BurrascanoM.YeeJ. K.\n\t\t\t\t\t1993\n\t\t\t\t\tVesicular stomatitis virus G glycoprotein pseudotyped retroviral vectors: concentration to very high titer and efficient gene transfer into mammalian and nonmammalian cells.\n\t\t\t\t\tProc. Natl. Acad. Sci. USA,\n\t\t\t\t\t90\n\t\t\t\t\t17\n\t\t\t\t\t80338037\n\t\t\t'},{id:"B24",body:'CharneauP.AlizonM.ClavelF.\n\t\t\t\t\t1992\n\t\t\t\t\tA second origin of DNA plus-strand synthesis is required for optimal human immunodeficiency virus replication.\n\t\t\t\t\tJ. Virol.,\n\t\t\t\t\t66\n\t\t\t\t\t5\n\t\t\t\t\t28142820\n\t\t\t'},{id:"B25",body:'CharneauP.MirambeauG.RouxP.PaulousS.BucH.ClavelF.\n\t\t\t\t\t1994\n\t\t\t\t\tHIV-1 reverse transcription. A termination step at the center of the genome. J. Mol. Biol.,\n\t\t\t\t\t241\n\t\t\t\t\t5\n\t\t\t\t\t651662\n\t\t\t'},{id:"B26",body:'ChenB. F.HsiehC. L.ChenD. S.HwangL. H.\n\t\t\t\t\t1992\n\t\t\t\t\tImproved gene expression by a U3-based retroviral vector.\n\t\t\t\t\tBiochem. Biophys. Res. Commun.,\n\t\t\t\t\t184\n\t\t\t\t\t1\n\t\t\t\t\t330337\n\t\t\t'},{id:"B27",body:'CullenB. R.\n\t\t\t\t\t1991\n\t\t\t\t\tHuman immunodeficiency virus as a prototypic complex retrovirus.\n\t\t\t\t\tJ. Virol.,\n\t\t\t\t\t65\n\t\t\t\t\t3\n\t\t\t\t\t10531056\n\t\t\t'},{id:"B28",body:'CullenB. R.\n\t\t\t\t\t2001\n\t\t\t\t\tJourney to the center of the cell.\n\t\t\t\t\tCullenB. R. (2001). Journey to the center of the cell. Cell, Vol. 105, No. 6, pp. 697-700, 105\n\t\t\t\t\t6\n\t\t\t\t\t697700\n\t\t\t'},{id:"B29",body:'DalgleishA. G.BeverleyP. C.ClaphamP. R.CrawfordD. H.GreavesM. F.WeissR. A.\n\t\t\t\t\t1984\n\t\t\t\t\tThe CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus.\n\t\t\t\t\tNature, 312\n\t\t\t\t\t5996\n\t\t\t\t\t763767\n\t\t\t'},{id:"B30",body:'DanthinneX.ImperialeM. J.\n\t\t\t\t\t2000\n\t\t\t\t\tProduction of first generation adenovirus vectors: a review. Gene Ther.,\n\t\t\t\t\t7\n\t\t\t\t\t20\n\t\t\t\t\t17071714\n\t\t\t'},{id:"B31",body:'DropulicB.HermankovaM.PithaP. M.\n\t\t\t\t\t1996\n\t\t\t\t\tA conditionally replicating HIV-1 vector interferes with wild-type HIV-1 replication and spread. Proc. Natl. Acad. Sci. USA,\n\t\t\t\t\t93\n\t\t\t\t\t20\n\t\t\t\t\t1110311108\n\t\t\t'},{id:"B32",body:'DullT.ZuffereyR.KellyM.MandelR. J.NguyenM.TronoD.NaldiniL.\n\t\t\t\t\t1998\n\t\t\t\t\tA third-generation lentivirus vector with a conditional packaging system.\n\t\t\t\t\tJ. Virol.,\n\t\t\t\t\t72\n\t\t\t\t\t11\n\t\t\t\t\t84638471\n\t\t\t'},{id:"B33",body:'EngelmanA.\n\t\t\t\t\t2003\n\t\t\t\t\tThe roles of cellular factors in retroviral integration.\n\t\t\t\t\tCurr. Top. Microbiol. Immunol.,\n\t\t\t\t\t281\n\t\t\t\t\t209238\n\t\t\t'},{id:"B34",body:'FallauxF. J.KranenburgO.CramerS. J.HouwelingA.Van OrmondtH.HoebenR. C.Van Der EbA. J.\n\t\t\t\t\t1996\n\t\t\t\t\tCharacterization of 911: a new helper cell line for the titration and propagation of early region 1-deleted adenoviral vectors. Hum. Gene Ther.,\n\t\t\t\t\t7\n\t\t\t\t\t2\n\t\t\t\t\t215222\n\t\t\t'},{id:"B35",body:'FassatiA.\n\t\t\t\t\t2006\n\t\t\t\t\tHIV infection of non-dividing cells: a divisive problem.\n\t\t\t\t\tRetrovirology, 3\n\t\t\t\t\t74\n\t\t\t'},{id:"B36",body:'FassatiA.GoffS. P.\n\t\t\t\t\t2001\n\t\t\t\t\tCharacterization of intracellular reverse transcription complexes of human immunodeficiency virus type 1. J. Virol.,\n\t\t\t\t\t75\n\t\t\t\t\t8\n\t\t\t\t\t36263635\n\t\t\t'},{id:"B37",body:'FengS.HollandE. C.\n\t\t\t\t\t1988\n\t\t\t\t\tHIV-1 tat trans-activation requires the loop sequence within tar.\n\t\t\t\t\tNature, 334\n\t\t\t\t\t6178\n\t\t\t\t\t165167\n\t\t\t'},{id:"B38",body:'FlintJ.ShenkT.\n\t\t\t\t\t1997\n\t\t\t\t\tViral transactivating proteins.\n\t\t\t\t\tAnnu. Rev. Genet.,\n\t\t\t\t\t31\n\t\t\t\t\t177212\n\t\t\t'},{id:"B39",body:'FlotteT. R.NgP.DyllaD. E.Mc CrayP. B.Jr WangG.KollsJ. K.HuJ.\n\t\t\t\t\t2007\n\t\t\t\t\tViral vector-mediated and cell-based therapies for treatment of cystic fibrosis.\n\t\t\t\t\tMol. Ther.,\n\t\t\t\t\t15\n\t\t\t\t\t2\n\t\t\t\t\t229241\n\t\t\t'},{id:"B40",body:'ForsmanA.WeissR. A.\n\t\t\t\t\t2008 Why is HIV a pathogen? Trends Microbiol.,\n\t\t\t\t\t16\n\t\t\t\t\t12\n\t\t\t\t\t555560\n\t\t\t'},{id:"B41",body:'FrankelA. D.YoungJ. A.\n\t\t\t\t\t1998\n\t\t\t\t\tHIV-1: fifteen proteins and an RNA.\n\t\t\t\t\tAnnu. Rev. Biochem.,\n\t\t\t\t\t67\n\t\t\t\t\t125\n\t\t\t'},{id:"B42",body:'FusseneggerM.\n\t\t\t\t\t2001\n\t\t\t\t\tThe impact of mammalian gene regulation concepts on functional genomic research, metabolic engineering, and advanced gene therapies.\n\t\t\t\t\tBiotechnol., Prog.\n\t\t\t\t\t17\n\t\t\t\t\t1\n\t\t\t\t\t151\n\t\t\t'},{id:"B43",body:'GalimiF.SummersR. G.van PraagH.VermaI. M.GageF. H.\n\t\t\t\t\t2005\n\t\t\t\t\tA role for bone marrow-derived cells in the vasculature of noninjured CNS.\n\t\t\t\t\tBlood, 105\n\t\t\t\t\t6\n\t\t\t\t\t24002402\n\t\t\t'},{id:"B44",body:'GaoG. P.YangY.WilsonJ. M.\n\t\t\t\t\t1996\n\t\t\t\t\tBiology of adenovirus vectors with E1 and E4 deletions for liver-directed gene therapy.\n\t\t\t\t\tJ. Virol.\n\t\t\t\t\t70\n\t\t\t\t\t12\n\t\t\t\t\t89348943\n\t\t\t'},{id:"B45",body:'GasconS.Paez-GomezJ. A.Diaz-GuerraM.ScheiffeleP.SchollF. G.\n\t\t\t\t\t2008\n\t\t\t\t\tDual-promoter lentiviral vectors for constitutive and regulated gene expression in neurons. J. Neurosci. Methods,\n\t\t\t\t\t168\n\t\t\t\t\t1\n\t\t\t\t\t104112\n\t\t\t'},{id:"B46",body:'GasmiM.GlynnJ.JinM. J.JollyD. J.YeeJ. K.ChenS. T.\n\t\t\t\t\t1999\n\t\t\t\t\tRequirements for efficient production and transduction of human immunodeficiency virus type 1-based vectors.\n\t\t\t\t\tJ. Virol.,\n\t\t\t\t\t73\n\t\t\t\t\t3\n\t\t\t\t\t18281834\n\t\t\t'},{id:"B47",body:'GossenM.BujardH.\n\t\t\t\t\t1992\n\t\t\t\t\tTight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc. Natl. Acad. Sci. USA,\n\t\t\t\t\t89\n\t\t\t\t\t12\n\t\t\t\t\t55475551\n\t\t\t'},{id:"B48",body:'GossenM.FreundliebS.BenderG.MullerG.HillenW.BujardH.\n\t\t\t\t\t1995\n\t\t\t\t\tTranscriptional activation by tetracyclines in mammalian cells. Science, 268\n\t\t\t\t\t5218\n\t\t\t\t\t17661769\n\t\t\t'},{id:"B49",body:'GoverdhanaS.PuntelM.XiongW.ZirgerJ. M.BarciaC.CurtinJ. F.SofferE. B.MondkarS.KingG. D.HuJ.SciasciaS. A.CandolfiM.GreengoldD. S.LowensteinP. R.CastroM. G.\n\t\t\t\t\t2005\n\t\t\t\t\tRegulatable gene expression systems for gene therapy applications: progress and future challenges.\n\t\t\t\t\tMol. Ther.,\n\t\t\t\t\t12\n\t\t\t\t\t2\n\t\t\t\t\t189211\n\t\t\t'},{id:"B50",body:'GrahamF. L.SmileyJ.RussellW. C.NairnR.\n\t\t\t\t\t1977\n\t\t\t\t\tCharacteristics of a human cell line transformed by DNA from human adenovirus type 5.\n\t\t\t\t\tJ. Gen. Virol.,\n\t\t\t\t\t36\n\t\t\t\t\t1\n\t\t\t\t\t5974\n\t\t\t'},{id:"B51",body:'GuildB. C.FinerM. H.HousmanD. E.MulliganR. C.\n\t\t\t\t\t1988\n\t\t\t\t\tDevelopment of retrovirus vectors useful for expressing genes in cultured murine embryonal cells and hematopoietic cells in vivo.\n\t\t\t\t\tJ. Virol.,\n\t\t\t\t\t62\n\t\t\t\t\t10\n\t\t\t\t\t37953801\n\t\t\t'},{id:"B52",body:'HaackK.CockrellA. S.MaH.IsraeliD.HoS. N.Mc CownT. J.KafriT.\n\t\t\t\t\t2004\n\t\t\t\t\tTransactivator and structurally optimized inducible lentiviral vectors.\n\t\t\t\t\tMol. Ther.,\n\t\t\t\t\t10\n\t\t\t\t\t3\n\t\t\t\t\t585596\n\t\t\t'},{id:"B53",body:'HaraguchiH.SudoS.NodaT.MomoseF.KawaokaY.MorikawaY.\n\t\t\t\t\t2010\n\t\t\t\t\tIntracellular localization of human immunodeficiency virus type 1 Gag and GagPol products and virus particle release: relationship with the Gag-to-GagPol ratio.\n\t\t\t\t\tMicrobiol. Immunol.,\n\t\t\t\t\t54\n\t\t\t\t\t12\n\t\t\t\t\t734746\n\t\t\t'},{id:"B54",body:'HarelJ.RassartE.JolicoeurP.\n\t\t\t\t\t1981\n\t\t\t\t\tCell cycle dependence of synthesis of unintegrated viral DNA in mouse cells newly infected with murine leukemia virus.\n\t\t\t\t\tVirology, 110\n\t\t\t\t\t1\n\t\t\t\t\t202207\n\t\t\t'},{id:"B55",body:'HartenbachS.FusseneggerM.\n\t\t\t\t\t2005\n\t\t\t\t\tAutoregulated, bidirectional and multicistronic gas-inducible mammalian as well as lentiviral expression vectors.\n\t\t\t\t\tJ. Biotechnol.,\n\t\t\t\t\t120\n\t\t\t\t\t1\n\t\t\t\t\t8398\n\t\t\t'},{id:"B56",body:'HatziioannouT.GoffS. P.\n\t\t\t\t\t2001\n\t\t\t\t\tInfection of nondividing cells by Rous sarcoma virus. J. Virol.,\n\t\t\t\t\t75\n\t\t\t\t\t19\n\t\t\t\t\t95269531\n\t\t\t'},{id:"B57",body:'HopeT. J.KleinN. P.ElderM. E.ParslowT. G.\n\t\t\t\t\t1992\n\t\t\t\t\ttrans-dominant inhibition of human immunodeficiency virus type 1 Rev occurs through formation of inactive protein complexes.\n\t\t\t\t\tJ. Virol.,\n\t\t\t\t\t66\n\t\t\t\t\t4\n\t\t\t\t\t18491855\n\t\t\t'},{id:"B58",body:'HurttilaH.KoponenJ. K.KansanenE.JyrkkanenH. K.KivelaA.KylatieR.Yla-HerttualaS.LevonenA. L.\n\t\t\t\t\t2008\n\t\t\t\t\tOxidative stress-inducible lentiviral vectors for gene therapy. Gene Ther.,\n\t\t\t\t\t15\n\t\t\t\t\t18\n\t\t\t\t\t12711279\n\t\t\t'},{id:"B59",body:'ImlerJ. L.ChartierC.DreyerD.DieterleA.Sainte-MarieM.FaureT.PaviraniA.MehtaliM.\n\t\t\t\t\t1996\n\t\t\t\t\tNovel complementation cell lines derived from human lung carcinoma A549 cells support the growth of E1-deleted adenovirus vectors.\n\t\t\t\t\tGene Ther.,\n\t\t\t\t\t3\n\t\t\t\t\t1\n\t\t\t\t\t7584\n\t\t\t'},{id:"B60",body:'JohansenJ.RosenbladC.AndsbergK.MollerA.LundbergC.BjorlundA.JohansenT. E.\n\t\t\t\t\t2002\n\t\t\t\t\tEvaluation of Tet-on system to avoid transgene down-regulation in ex vivo gene transfer to the CNS.\n\t\t\t\t\tGene Ther.,\n\t\t\t\t\t9\n\t\t\t\t\t19\n\t\t\t\t\t12911301\n\t\t\t'},{id:"B61",body:'KafriT.van PraagH.GageF. H.VermaI. M.\n\t\t\t\t\t2000\n\t\t\t\t\tLentiviral vectors: regulated gene expression. Mol. Ther.,\n\t\t\t\t\t1\n\t\t\t\t\t6\n\t\t\t\t\t516521\n\t\t\t'},{id:"B62",body:'KangE. M.De WitteM.MalechH.MorganR. A.CarterC.LeitmanS. F.ChildsR.BarrettA. J.LittleR.TisdaleJ. F.\n\t\t\t\t\t2002\n\t\t\t\t\tGene therapy-based treatment for HIV-positive patients with malignancies. J. Hematother. Stem Cell Res.,\n\t\t\t\t\t11\n\t\t\t\t\t5\n\t\t\t\t\t809816\n\t\t\t'},{id:"B63",body:'KaulM.GardenG. A.LiptonS. A.\n\t\t\t\t\t2001\n\t\t\t\t\tPathways to neuronal injury and apoptosis in HIV-associated dementia.\n\t\t\t\t\tNature, 410\n\t\t\t\t\t6831\n\t\t\t\t\t988994\n\t\t\t'},{id:"B64",body:'KimS. Y.ByrnR.GroopmanJ.BaltimoreD.\n\t\t\t\t\t1989\n\t\t\t\t\tTemporal aspects of DNA and RNA synthesis during human immunodeficiency virus infection: evidence for differential gene expression.\n\t\t\t\t\tJ. Virol.,\n\t\t\t\t\t63\n\t\t\t\t\t9\n\t\t\t\t\t37083713\n\t\t\t'},{id:"B65",body:'KimV. N.MitrophanousK.KingsmanS. M.KingsmanA. J.\n\t\t\t\t\t1998\n\t\t\t\t\tMinimal requirement for a lentivirus vector based on human immunodeficiency virus type 1. J. Virol.,\n\t\t\t\t\t72\n\t\t\t\t\t1\n\t\t\t\t\t811816\n\t\t\t'},{id:"B66",body:'KingsmanS. M.KingsmanA. J.\n\t\t\t\t\t1996\n\t\t\t\t\tThe regulation of human immunodeficiency virus type-1 gene expression. Eur. J. Biochem.,\n\t\t\t\t\t240\n\t\t\t\t\t3\n\t\t\t\t\t491507\n\t\t\t'},{id:"B67",body:'KitchenS. G.ShimizuS.AnD. S.\n\t\t\t\t\t2011\n\t\t\t\t\tStem cell-based anti-HIV gene therapy. Virology, 411\n\t\t\t\t\t2\n\t\t\t\t\t260272\n\t\t\t'},{id:"B68",body:'KlimatchevaE.PlanellesV.DayS. L.FulreaderF.RendaM. J.RosenblattJ.\n\t\t\t\t\t2001\n\t\t\t\t\tDefective lentiviral vectors are efficiently trafficked by HIV-1 and inhibit its replication. Mol. Ther.,\n\t\t\t\t\t3\n\t\t\t\t\t6\n\t\t\t\t\t928939\n\t\t\t'},{id:"B69",body:'KochanekS.ClemensP. R.MitaniK.ChenH. H.ChanS.CaskeyC. T.\n\t\t\t\t\t1996\n\t\t\t\t\tA new adenoviral vector: Replacement of all viral coding sequences with 28 kb of DNA independently expressing both full-length dystrophin and beta-galactosidase.\n\t\t\t\t\tProc. Natl. Acad. Sci. USA,\n\t\t\t\t\t93\n\t\t\t\t\t12\n\t\t\t\t\t57315736\n\t\t\t'},{id:"B70",body:'KoponenJ. K.KankkonenH.KannastoJ.WirthT.HillenW.BujardH.Yla-HerttualaS.\n\t\t\t\t\t2003\n\t\t\t\t\tDoxycycline-regulated lentiviral vector system with a novel reverse transactivator rtTA2S-M2 shows a tight control of gene expression in vitro and in vivo.\n\t\t\t\t\tGene Ther.,\n\t\t\t\t\t10\n\t\t\t\t\t6\n\t\t\t\t\t459466\n\t\t\t'},{id:"B71",body:'LandauN. R.WartonM.LittmanD. R.\n\t\t\t\t\t1988\n\t\t\t\t\tThe envelope glycoprotein of the human immunodeficiency virus binds to the immunoglobulin-like domain of CD4.\n\t\t\t\t\tNature, 334\n\t\t\t\t\t6178\n\t\t\t\t\t159162\n\t\t\t'},{id:"B72",body:'LeopoldP. L.FerrisB.GrinbergI.WorgallS.HackettN. R.CrystalR. G.\n\t\t\t\t\t1998\n\t\t\t\t\tFluorescent virions: dynamic tracking of the pathway of adenoviral gene transfer vectors in living cells. Hum. Gene Ther.,\n\t\t\t\t\t9\n\t\t\t\t\t3\n\t\t\t\t\t367378\n\t\t\t'},{id:"B73",body:'LevineF.FriedmannT.\n\t\t\t\t\t1991\n\t\t\t\t\tGene therapy techniques.\n\t\t\t\t\tCurr. Opin. Biotechnol.,\n\t\t\t\t\t2\n\t\t\t\t\t6\n\t\t\t\t\t840844\n\t\t\t'},{id:"B74",body:'LewinskiM. K.BushmanF. D.\n\t\t\t\t\t2005\n\t\t\t\t\tRetroviral DNA integration--mechanism and consequences.\n\t\t\t\t\tAdv. Genet.,\n\t\t\t\t\t55\n\t\t\t\t\t147181\n\t\t\t'},{id:"B75",body:'LewisP.HenselM.EmermanM.\n\t\t\t\t\t1992\n\t\t\t\t\tHuman immunodeficiency virus infection of cells arrested in the cell cycle.\n\t\t\t\t\tEMBO J.,\n\t\t\t\t\t11\n\t\t\t\t\t8\n\t\t\t\t\t30533058\n\t\t\t'},{id:"B76",body:'LewisP.EmermanM.\n\t\t\t\t\t1994\n\t\t\t\t\tPassage through mitosis is required for oncoretroviruses but not for the human immunodeficiency virus.\n\t\t\t\t\tJ. Virol.,\n\t\t\t\t\t68\n\t\t\t\t\t1\n\t\t\t\t\t510516\n\t\t\t'},{id:"B77",body:'LiM. J.BauerG.MichienziA.YeeJ. K.LeeN. S.KimJ.LiS.CastanottoD.ZaiaJ.RossiJ. J.\n\t\t\t\t\t2003\n\t\t\t\t\tInhibition of HIV-1 infection by lentiviral vectors expressing Pol III-promoted anti-HIV RNAs.\n\t\t\t\t\tMol. Ther.,\n\t\t\t\t\t8\n\t\t\t\t\t2\n\t\t\t\t\t196206\n\t\t\t'},{id:"B78",body:'LowensteinP. R.ThomasC. E.UmanaP.GerdesC. A.VerakisT.BoyerO.TondeurS.KlatzmannD.CastroM. G.\n\t\t\t\t\t2002\n\t\t\t\t\tHigh-capacity, helper-dependent, "gutless" adenoviral vectors for gene transfer into brain.\n\t\t\t\t\tMethods Enzymol.,\n\t\t\t\t\t346\n\t\t\t\t\t292311\n\t\t\t'},{id:"B79",body:'MaY.FeiginA.DhawanV.FukudaM.ShiQ.GreeneP.BreezeR.FahnS.FreedC.EidelbergD.\n\t\t\t\t\t2002\n\t\t\t\t\tDyskinesia after fetal cell transplantation for parkinsonism: a PET study.\n\t\t\t\t\tAnn. Neurol.,\n\t\t\t\t\t52\n\t\t\t\t\t5\n\t\t\t\t\t628634\n\t\t\t'},{id:"B80",body:'MalimM. H.BohnleinS.HauberJ.CullenB. R.\n\t\t\t\t\t1989\n\t\t\t\t\tFunctional dissection of the HIV-1 Rev trans-activator--derivation of a trans-dominant repressor of Rev function.\n\t\t\t\t\tCell, 58\n\t\t\t\t\t1\n\t\t\t\t\t205214\n\t\t\t'},{id:"B81",body:'MalimM. H.EmermanM.\n\t\t\t\t\t2008\n\t\t\t\t\tHIV-1 accessory proteins--ensuring viral survival in a hostile environment. Cell Host Microbe.,\n\t\t\t\t\t3\n\t\t\t\t\t6\n\t\t\t\t\t388398\n\t\t\t'},{id:"B82",body:'MannR.MulliganR. C.BaltimoreD.\n\t\t\t\t\t1983\n\t\t\t\t\tConstruction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus.\n\t\t\t\t\tCell, 33\n\t\t\t\t\t1\n\t\t\t\t\t153159\n\t\t\t'},{id:"B83",body:'MautinoM. R.KeiserN.MorganR. A.\n\t\t\t\t\t2001\n\t\t\t\t\tInhibition of human immunodeficiency virus type 1 (HIV-1) replication by HIV-1-based lentivirus vectors expressing transdominant Rev.\n\t\t\t\t\tJ. Virol.,\n\t\t\t\t\t75\n\t\t\t\t\t8\n\t\t\t\t\t35903599\n\t\t\t'},{id:"B84",body:'MautinoM. R.MorganR. A.\n\t\t\t\t\t2002a\n\t\t\t\t\tEnhanced inhibition of human immunodeficiency virus type 1 replication by novel lentiviral vectors expressing human immunodeficiency virus type 1 envelope antisense RNA. Hum. Gene Ther.,\n\t\t\t\t\t13\n\t\t\t\t\t9\n\t\t\t\t\t10271037\n\t\t\t'},{id:"B85",body:'MautinoM. R.MorganR. A.\n\t\t\t\t\t2002b\n\t\t\t\t\tGene therapy of HIV-1 infection using lentiviral vectors expressing anti-HIV-1 genes. AIDS Patient Care STDS,\n\t\t\t\t\t16\n\t\t\t\t\t1\n\t\t\t\t\t1126\n\t\t\t'},{id:"B86",body:'MautinoM. R.MorganR. A.\n\t\t\t\t\t2002c\n\t\t\t\t\tInhibition of HIV-1 replication by novel lentiviral vectors expressing transdominant Rev and HIV-1 env antisense. Gene Ther.,\n\t\t\t\t\t9\n\t\t\t\t\t7\n\t\t\t\t\t421431\n\t\t\t'},{id:"B87",body:'MeadowsD. C.Gervay-HagueJ.\n\t\t\t\t\t2006\n\t\t\t\t\tCurrent developments in HIV chemotherapy.\n\t\t\t\t\tChemMedChem, 1\n\t\t\t\t\t1\n\t\t\t\t\t1629\n\t\t\t'},{id:"B88",body:'MelikyanG. B.\n\t\t\t\t\t2008\n\t\t\t\t\tCommon principles and intermediates of viral protein-mediated fusion: the HIV-1 paradigm.\n\t\t\t\t\tRetrovirology, 5\n\t\t\t\t\t111\n\t\t\t'},{id:"B89",body:'MillerA. D.RosmanG. J.\n\t\t\t\t\t1989\n\t\t\t\t\tImproved retroviral vectors for gene transfer and expression.\n\t\t\t\t\tBiotechniques\n\t\t\t\t\t7\n\t\t\t\t\t9\n\t\t\t\t\t980990\n\t\t\t'},{id:"B90",body:'MillerA. D.\n\t\t\t\t\t1992a\n\t\t\t\t\tHuman gene therapy comes of age.\n\t\t\t\t\tNature, 357\n\t\t\t\t\t6378\n\t\t\t\t\t455460\n\t\t\t'},{id:"B91",body:'MillerA. D.\n\t\t\t\t\t1992b\n\t\t\t\t\tRetroviral vectors.\n\t\t\t\t\tCurr. Top. Microbiol. Immunol.,\n\t\t\t\t\t158\n\t\t\t\t\t124\n\t\t\t'},{id:"B92",body:'MillerD. G.AdamM. A.MillerA. D.\n\t\t\t\t\t1990\n\t\t\t\t\tGene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection.\n\t\t\t\t\tMol. Cell. Biol.,\n\t\t\t\t\t10\n\t\t\t\t\t8\n\t\t\t\t\t42394242\n\t\t\t'},{id:"B93",body:'MittaB.WeberC. C.RimannM.FusseneggerM.\n\t\t\t\t\t2004\n\t\t\t\t\tDesign and in vivo characterization of self-inactivating human and non-human lentiviral expression vectors engineered for streptogramin-adjustable transgene expression. Nucleic Acids Res.,\n\t\t\t\t\t32\n\t\t\t\t\t12\n\t\t\t\t\te106\n\t\t\t'},{id:"B94",body:'MiyakeK.SuzukiN.MatsuokaH.TohyamaT.ShimadaT.\n\t\t\t\t\t1998\n\t\t\t\t\tStable integration of human immunodeficiency virus-based retroviral vectors into the chromosomes of nondividing cells. Hum. Gene Ther.,\n\t\t\t\t\t9\n\t\t\t\t\t4\n\t\t\t\t\t467475\n\t\t\t'},{id:"B95",body:'MiyoshiH.BlomerU.TakahashiM.GageF. H.VermaI. M.\n\t\t\t\t\t1998\n\t\t\t\t\tDevelopment of a self-inactivating lentivirus vector.\n\t\t\t\t\tJ. Virol.,\n\t\t\t\t\t72\n\t\t\t\t\t10\n\t\t\t\t\t81508157\n\t\t\t'},{id:"B96",body:'MiyoshiH.SmithK. A.MosierD. E.VermaI. M.TorbettB. E.\n\t\t\t\t\t1999\n\t\t\t\t\tTransduction of human CD34+ cells that mediate long-term engraftment of NOD/SCID mice by HIV vectors. Science, 283\n\t\t\t\t\t5402\n\t\t\t\t\t682686\n\t\t\t'},{id:"B97",body:'MolinM.ShoshanM. C.Ohman-ForslundK.LinderS.AkusjarviG.\n\t\t\t\t\t1998\n\t\t\t\t\tTwo novel adenovirus vector systems permitting regulated protein expression in gene transfer experiments. J. Virol.,\n\t\t\t\t\t72\n\t\t\t\t\t10\n\t\t\t\t\t83588361\n\t\t\t'},{id:"B98",body:'MukhtarM.DukeH.BouHamdan. M.PomerantzR. J.\n\t\t\t\t\t2000\n\t\t\t\t\tAnti-human immunodeficiency virus type 1 gene therapy in human central nervous system-based cells: an initial approach against a potential viral reservoir. Hum. Gene Ther.,\n\t\t\t\t\t11\n\t\t\t\t\t2\n\t\t\t\t\t347359\n\t\t\t'},{id:"B99",body:'NaldiniL.BlomerU.GallayP.OryD.MulliganR.GageF. H.VermaI. M.TronoD.\n\t\t\t\t\t1996\n\t\t\t\t\tIn vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science, 272\n\t\t\t\t\t5259\n\t\t\t\t\t263267\n\t\t\t'},{id:"B100",body:'NgP.BeauchampC.EveleghC.ParksR.GrahamF. L.\n\t\t\t\t\t2001\n\t\t\t\t\tDevelopment of a FLP/frt system for generating helper-dependent adenoviral vectors. Mol. Ther.,\n\t\t\t\t\t3\n\t\t\t\t\t5\n\t\t\t\t\t809815\n\t\t\t'},{id:"B101",body:'NoD.YaoT. P.EvansR. M.\n\t\t\t\t\t1996\n\t\t\t\t\tEcdysone-inducible gene expression in mammalian cells and transgenic mice. Proc. Natl. Acad. Sci. USA,\n\t\t\t\t\t93\n\t\t\t\t\t8\n\t\t\t\t\t33463351\n\t\t\t'},{id:"B102",body:'NordstromJ. L.\n\t\t\t\t\t2003\n\t\t\t\t\tThe antiprogestin-dependent GeneSwitch system for regulated gene therapy.\n\t\t\t\t\tSteroids, 68\n\t\t\t\t\t10-13 , 10851094\n\t\t\t'},{id:"B103",body:'OnoA.\n\t\t\t\t\t2010\n\t\t\t\t\tRelationships between plasma membrane microdomains and HIV-1 assembly. Biol. Cell\n\t\t\t\t\t102\n\t\t\t\t\t6\n\t\t\t\t\t335350\n\t\t\t'},{id:"B104",body:'PalellaF. J.Jr DelaneyK. M.MoormanA. C.LovelessM. O.FuhrerJ.SattenG. A.AschmanD. J.HolmbergS. D.\n\t\t\t\t\t1998\n\t\t\t\t\tDeclining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N. Engl. J. Med.,\n\t\t\t\t\t338\n\t\t\t\t\t13\n\t\t\t\t\t853860\n\t\t\t'},{id:"B105",body:'ParkerD. G.BreretonH. M.KlebeS.CosterD. J.WilliamsK. A.\n\t\t\t\t\t2009 A steroid-inducible promoter for the cornea. Br. J. Ophthalmol.,\n\t\t\t\t\t93\n\t\t\t\t\t9\n\t\t\t\t\t12551259\n\t\t\t'},{id:"B106",body:'ParksR. J.ChenL.AntonM.SankarU.RudnickiM. A.GrahamF. L.\n\t\t\t\t\t1996 A helper-dependent adenovirus vector system: removal of helper virus by Cre-mediated excision of the viral packaging signal. Proc. Natl. Acad. Sci. USA,\n\t\t\t\t\t93\n\t\t\t\t\t24\n\t\t\t\t\t1356513570\n\t\t\t'},{id:"B107",body:'PlutaK.LuceM. J.BaoL.Agha-MohammadiS.ReiserJ.\n\t\t\t\t\t2005 Tight control of transgene expression by lentivirus vectors containing second-generation tetracycline-responsive promoters. J. Gene Med.,\n\t\t\t\t\t7\n\t\t\t\t\t6\n\t\t\t\t\t803817\n\t\t\t'},{id:"B108",body:'PodsakoffG. M.EngelB. C.CarbonaroD. A.ChoiC.SmogorzewskaE. M.BauerG.SelanderD.CsikS.WilsonK.BettsM. R.KoupR. A.NabelG. J.BishopK.KingS.SchmidtM.vonKalle. C.ChurchJ. A.KohnD. B.\n\t\t\t\t\t2005 Selective survival of peripheral blood lymphocytes in children with HIV-1 following delivery of an anti-HIV gene to bone marrow CD34(+) cells. Mol. Ther.,\n\t\t\t\t\t12\n\t\t\t\t\t1\n\t\t\t\t\t7786\n\t\t\t'},{id:"B109",body:'PollardV. W.MalimM. H.\n\t\t\t\t\t1998 The HIV-1 Rev protein. Annu. Rev. Microbiol.,\n\t\t\t\t\t52\n\t\t\t\t\t491532\n\t\t\t'},{id:"B110",body:'PoluriA.van MaanenM.SuttonR. E.\n\t\t\t\t\t2003 Genetic therapy for HIV/AIDS. Expert Opin. Biol. Ther.,\n\t\t\t\t\t3\n\t\t\t\t\t6\n\t\t\t\t\t951963\n\t\t\t'},{id:"B111",body:'PurcellD. F.MartinM. A.\n\t\t\t\t\t1993 Alternative splicing of human immunodeficiency virus type 1 mRNA modulates viral protein expression, replication, and infectivity. J. Virol.,\n\t\t\t\t\t67\n\t\t\t\t\t11\n\t\t\t\t\t63656378\n\t\t\t'},{id:"B112",body:'ReiserJ.LaiZ.ZhangX. Y.BradyR. O.\n\t\t\t\t\t2000 Development of multigene and regulated lentivirus vectors. J. Virol.,\n\t\t\t\t\t74\n\t\t\t\t\t22\n\t\t\t\t\t1058910599\n\t\t\t'},{id:"B113",body:'RichmanD. D.\n\t\t\t\t\t2001 HIV chemotherapy. Nature,\n\t\t\t\t\t410\n\t\t\t\t\t6831\n\t\t\t\t\t9951001\n\t\t\t'},{id:"B114",body:'RobbinsP. D.GhivizzaniS. C.\n\t\t\t\t\t1998 Viral vectors for gene therapy. Pharmacol. Ther.,\n\t\t\t\t\t80\n\t\t\t\t\t1\n\t\t\t\t\t3547\n\t\t\t'},{id:"B115",body:'RoeT.ReynoldsT. C.YuG.BrownP. O.\n\t\t\t\t\t1993 Integration of murine leukemia virus DNA depends on mitosis. EMBO J.,\n\t\t\t\t\t12\n\t\t\t\t\t5\n\t\t\t\t\t20992108\n\t\t\t'},{id:"B116",body:'SaezE.NelsonM. C.EshelmanB.BanayoE.KoderA.ChoG. J.EvansR. M.\n\t\t\t\t\t2000 Identification of ligands and coligands for the ecdysone-regulated gene switch. Proc. Natl. Acad. Sci. USA,\n\t\t\t\t\t97\n\t\t\t\t\t26\n\t\t\t\t\t1451214517\n\t\t\t'},{id:"B117",body:'SchwartzS.FelberB. K.BenkoD. M.FenyoE. M.PavlakisG. N.\n\t\t\t\t\t1990 Cloning and functional analysis of multiply spliced mRNA species of human immunodeficiency virus type 1. J. Virol.,\n\t\t\t\t\t64\n\t\t\t\t\t6\n\t\t\t\t\t25192529\n\t\t\t'},{id:"B118",body:'ShimotohnoK.TeminH. M.\n\t\t\t\t\t1981 Formation of infectious progeny virus after insertion of herpes simplex thymidine kinase gene into DNA of an avian retrovirus. Cell,\n\t\t\t\t\t26\n\t\t\t\t\t1\n\t\t\t\t\t6777\n\t\t\t'},{id:"B119",body:'ShinodaY.HiedaK.KoyanagiY.SuzukiY.\n\t\t\t\t\t2009 Efficient transduction of cytotoxic and anti-HIV-1 genes by a gene-regulatable lentiviral vector. Virus Genes\n\t\t\t\t\t39\n\t\t\t\t\t2\n\t\t\t\t\t165175\n\t\t\t'},{id:"B120",body:'SirinO.ParkF.\n\t\t\t\t\t2003 Regulating gene expression using self-inactivating lentiviral vectors containing the mifepristone-inducible system. Gene,\n\t\t\t\t\t323\n\t\t\t\t\t6777\n\t\t\t'},{id:"B121",body:'SomiaN.VermaI. M.\n\t\t\t\t\t2000 Gene therapy: trials and tribulations. Nat. Rev. Genet.,\n\t\t\t\t\t1\n\t\t\t\t\t2\n\t\t\t\t\t9199\n\t\t\t'},{id:"B122",body:'StevensonM.\n\t\t\t\t\t2003 HIV-1 pathogenesis. Nat. Med.,\n\t\t\t\t\t9\n\t\t\t\t\t7\n\t\t\t\t\t853860\n\t\t\t'},{id:"B123",body:'StrayerD. S.AkkinaR.BunnellB. A.DropulicB.PlanellesV.PomerantzR. J.RossiJ. J.ZaiaJ. A.\n\t\t\t\t\t2005 Current status of gene therapy strategies to treat HIV/AIDS. Mol. Ther.,\n\t\t\t\t\t11\n\t\t\t\t\t6\n\t\t\t\t\t823842\n\t\t\t'},{id:"B124",body:'SuzukiY.CraigieR.\n\t\t\t\t\t2007 The road to chromatin- nuclear entry of retroviruses. Nat. Rev. Microbiol.,\n\t\t\t\t\t5\n\t\t\t\t\t3\n\t\t\t\t\t187196\n\t\t\t'},{id:"B125",body:'SzulcJ.WiznerowiczM.SauvainM. O.TronoD.AebischerP.\n\t\t\t\t\t2006 A versatile tool for conditional gene expression and knockdown. Nat. Methods,\n\t\t\t\t\t3\n\t\t\t\t\t2\n\t\t\t\t\t109116\n\t\t\t'},{id:"B126",body:'TabinC. J.HoffmannJ. W.GoffS. P.WeinbergR. A.\n\t\t\t\t\t1982 Adaptation of a retrovirus as a eucaryotic vector transmitting the herpes simplex virus thymidine kinase gene. Mol. Cell. Biol.,\n\t\t\t\t\t2\n\t\t\t\t\t4\n\t\t\t\t\t426436\n\t\t\t'},{id:"B127",body:'TaylorJ. A.VojtechL.BahnerI.KohnD. B.LaerD. V.RussellD. W.RichardR. E.\n\t\t\t\t\t2008 Foamy virus vectors expressing anti-HIV transgenes efficiently block HIV-1 replication. Mol. Ther.,\n\t\t\t\t\t16\n\t\t\t\t\t1\n\t\t\t\t\t4651\n\t\t\t'},{id:"B128",body:'TomkoR. P.XuR.PhilipsonL.\n\t\t\t\t\t1997 HCAR and MCAR: the human and mouse cellular receptors for subgroup C adenoviruses and group B coxsackieviruses. Proc. Natl. Acad. Sci. USA,\n\t\t\t\t\t94\n\t\t\t\t\t7\n\t\t\t\t\t33523356\n\t\t\t'},{id:"B129",body:'UlmannA.PeyronR.SilvestreL.\n\t\t\t\t\t1995 Clinical uses of mifepristone (MFP). Ann. N. Y. Acad. Sci.,\n\t\t\t\t\t761\n\t\t\t\t\t248260\n\t\t\t'},{id:"B130",body:'UmanaP.GerdesC. A.StoneD.DavisJ. R.WardD.CastroM. G.LowensteinP. R.\n\t\t\t\t\t2001 Efficient FLPe recombinase enables scalable production of helper-dependent adenoviral vectors with negligible helper-virus contamination. Nat. Biotechnol.,\n\t\t\t\t\t19\n\t\t\t\t\t6\n\t\t\t\t\t582585\n\t\t\t'},{id:"B131",body:'VermaI. M.WeitzmanM. D.\n\t\t\t\t\t2005 Gene therapy: twenty-first century medicine. Annu. Rev. Biochem.,\n\t\t\t\t\t74\n\t\t\t\t\t711738\n\t\t\t'},{id:"B132",body:'VignaE.CavalieriS.AillesL.GeunaM.LoewR.BujardH.NaldiniL.\n\t\t\t\t\t2002 Robust and efficient regulation of transgene expression in vivo by improved tetracycline-dependent lentiviral vectors. Mol. Ther.,\n\t\t\t\t\t5\n\t\t\t\t\t3\n\t\t\t\t\t252261\n\t\t\t'},{id:"B133",body:'VogelR.AmarL.ThiA. D.SaillourP.MalletJ.\n\t\t\t\t\t2004 A single lentivirus vector mediates doxycycline-regulated expression of transgenes in the brain. Hum. Gene Ther.,\n\t\t\t\t\t15\n\t\t\t\t\t2\n\t\t\t\t\t157165\n\t\t\t'},{id:"B134",body:'VogtV. M.\n\t\t\t\t\t1996 Proteolytic processing and particle maturation. Curr. Top. Microbiol. Immunol.,\n\t\t\t\t\t214\n\t\t\t\t\t95131\n\t\t\t'},{id:"B135",body:'VolberdingP. A.DeeksS. G.\n\t\t\t\t\t2010 Antiretroviral therapy and management of HIV infection. Lancet,\n\t\t\t\t\t376\n\t\t\t\t\t9734\n\t\t\t\t\t4962\n\t\t\t'},{id:"B136",body:'WagnerR.GrafM.BielerK.WolfH.GrunwaldT.FoleyP.UberlaK.\n\t\t\t\t\t2000 Rev-independent expression of synthetic gag-pol genes of human immunodeficiency virus type 1 and simian immunodeficiency virus: implications for the safety of lentiviral vectors. Hum. Gene Ther.,\n\t\t\t\t\t11\n\t\t\t\t\t17\n\t\t\t\t\t24032413\n\t\t\t'},{id:"B137",body:'WangQ.JiaX. C.FinerM. H.\n\t\t\t\t\t1995 A packaging cell line for propagation of recombinant adenovirus vectors containing two lethal gene-region deletions. Gene Ther.,\n\t\t\t\t\t2\n\t\t\t\t\t10\n\t\t\t\t\t775783\n\t\t\t'},{id:"B138",body:'WangY.O’MalleyB. W.Jr TsaiS. Y.O’MalleyB. W.\n\t\t\t\t\t1994 A regulatory system for use in gene transfer. Proc. Natl. Acad. Sci. USA,\n\t\t\t\t\t91\n\t\t\t\t\t17\n\t\t\t\t\t81808184\n\t\t\t'},{id:"B139",body:'WatanabeS.TeminH. M.\n\t\t\t\t\t1983 Construction of a helper cell line for avian reticuloendotheliosis virus cloning vectors. Mol. Cell. Biol.,\n\t\t\t\t\t3\n\t\t\t\t\t12\n\t\t\t\t\t22412249\n\t\t\t'},{id:"B140",body:'WeberW.FusseneggerM.\n\t\t\t\t\t2004 Approaches for trigger-inducible viral transgene regulation in gene-based tissue engineering. Curr. Opin. Biotechnol.\n\t\t\t\t\t15\n\t\t\t\t\t5\n\t\t\t\t\t383391\n\t\t\t'},{id:"B141",body:'WeiC. M.GibsonM.SpearP. G.ScolnickE. M.\n\t\t\t\t\t1981 Construction and isolation of a transmissible retrovirus containing the src gene of Harvey murine sarcoma virus and the thymidine kinase gene of herpes simplex virus type 1. J. Virol.,\n\t\t\t\t\t39\n\t\t\t\t\t3\n\t\t\t\t\t935944\n\t\t\t'},{id:"B142",body:'WeinbergJ. B.MatthewsT. J.CullenB. R.MalimM. H.\n\t\t\t\t\t1991 Productive human immunodeficiency virus type 1 (HIV-1) infection of nonproliferating human monocytes. J. Exp. Med.,\n\t\t\t\t\t174\n\t\t\t\t\t6\n\t\t\t\t\t14771482\n\t\t\t'},{id:"B143",body:'WhittakerG. R.KannM.HeleniusA.\n\t\t\t\t\t2000 Viral entry into the nucleus. Annu. Rev. Cell Dev. Biol.\n\t\t\t\t\t16\n\t\t\t\t\t627651\n\t\t\t'},{id:"B144",body:'WiznerowiczM.TronoD.\n\t\t\t\t\t2003 Conditional suppression of cellular genes: lentivirus vector-mediated drug-inducible RNA interference. J. Virol.,\n\t\t\t\t\t77\n\t\t\t\t\t16\n\t\t\t\t\t89578961\n\t\t\t'},{id:"B145",body:'WuX.LiuH.XiaoH.ConwayJ. A.HunterE.KappesJ. C.\n\t\t\t\t\t1997 Functional RT and IN incorporated into HIV-1 particles independently of the Gag/Pol precursor protein. EMBO J.,\n\t\t\t\t\t16\n\t\t\t\t\t16\n\t\t\t\t\t51135122\n\t\t\t'},{id:"B146",body:'YamashitaM.EmermanM.\n\t\t\t\t\t2006 Retroviral infection of non-dividing cells: old and new perspectives. Virology,\n\t\t\t\t\t344\n\t\t\t\t\t1\n\t\t\t\t\t8893\n\t\t\t'},{id:"B147",body:'YancopoulosG. D.DavisS.GaleN. W.RudgeJ. S.WiegandS. J.HolashJ.\n\t\t\t\t\t2000 Vascular-specific growth factors and blood vessel formation. Nature,\n\t\t\t\t\t407\n\t\t\t\t\t6801\n\t\t\t\t\t242248\n\t\t\t'},{id:"B148",body:'YehP.DedieuJ. F.OrsiniC.VigneE.DenefleP.PerricaudetM.\n\t\t\t\t\t1996 Efficient dual transcomplementation of adenovirus E1 and E4 regions from a 293-derived cell line expressing a minimal E4 functional unit. J. Virol.,\n\t\t\t\t\t70\n\t\t\t\t\t1\n\t\t\t\t\t559565\n\t\t\t'},{id:"B149",body:'ZuffereyR.DullT.MandelR. J.BukovskyA.QuirozD.NaldiniL.TronoD.\n\t\t\t\t\t1998 Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery. J. Virol.,\n\t\t\t\t\t72\n\t\t\t\t\t12\n\t\t\t\t\t98739880\n\t\t\t'},{id:"B150",body:'ZuffereyR.NagyD.MandelR. J.NaldiniL.TronoD.\n\t\t\t\t\t1997 Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo. Nat. Biotechnol.,\n\t\t\t\t\t15\n\t\t\t\t\t9\n\t\t\t\t\t871875\n\t\t\t'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Yasutsugu Suzuki",address:null,affiliation:'
Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Graduate School of Biostudies, Kyoto University, Japan
Yong Loo Lin School of Medicine, National University of Singapore, Singapore
'}],corrections:null},book:{id:"500",type:"book",title:"Viral Gene Therapy",subtitle:null,fullTitle:"Viral Gene Therapy",slug:"viral-gene-therapy",publishedDate:"July 20th 2011",bookSignature:"Ke Xu",coverURL:"https://cdn.intechopen.com/books/images_new/500.jpg",licenceType:"CC BY-NC-SA 3.0",editedByType:"Edited by",isbn:null,printIsbn:"978-953-307-539-6",pdfIsbn:"978-953-51-6438-8",reviewType:"peer-reviewed",numberOfWosCitations:45,isAvailableForWebshopOrdering:!0,editors:[{id:"59529",title:"Dr.",name:"Ke",middleName:null,surname:"Xu",slug:"ke-xu",fullName:"Ke Xu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1050"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"16775",type:"chapter",title:"Retroviral Vectors in Gene Therapy: Mechanism of Integration, Successes in Gene Therapy Trials, Emerging Problems and Potential Solutions",slug:"retroviral-vectors-in-gene-therapy-mechanism-of-integration-successes-in-gene-therapy-trials-emergin",totalDownloads:2871,totalCrossrefCites:0,signatures:"Ahmed F. Salem, Johanna Smith, Michael Lisanti and Rene Daniel",reviewType:"peer-reviewed",authors:[{id:"50210",title:"Dr.",name:"Rene",middleName:null,surname:"Daniel",fullName:"Rene Daniel",slug:"rene-daniel"},{id:"73148",title:"Dr.",name:"Ahmed F.",middleName:null,surname:"Salem",fullName:"Ahmed F. Salem",slug:"ahmed-f.-salem"},{id:"73149",title:"MSc.",name:"Johanna",middleName:null,surname:"Smith",fullName:"Johanna Smith",slug:"johanna-smith"},{id:"73151",title:"Dr.",name:"Michael",middleName:null,surname:"Lisanti",fullName:"Michael Lisanti",slug:"michael-lisanti"}]},{id:"16776",type:"chapter",title:"Production of Retroviral and Lentiviral Gene Therapy Vectors: Challenges in the Manufacturing of Lipid Enveloped Virus",slug:"production-of-retroviral-and-lentiviral-gene-therapy-vectors-challenges-in-the-manufacturing-of-lipi",totalDownloads:9312,totalCrossrefCites:6,signatures:"Ana Rodrigues, Paula M. Alves and Ana Coroadinha",reviewType:"peer-reviewed",authors:[{id:"32017",title:"Dr.",name:"Ana",middleName:null,surname:"Coroadinha",fullName:"Ana Coroadinha",slug:"ana-coroadinha"},{id:"45242",title:"Mrs.",name:"Ana",middleName:null,surname:"Rodrigues",fullName:"Ana Rodrigues",slug:"ana-rodrigues"},{id:"88272",title:"Prof.",name:"Paula M.",middleName:null,surname:"Alves",fullName:"Paula M. Alves",slug:"paula-m.-alves"}]},{id:"16777",type:"chapter",title:"Surface Modification of Retroviral Vectors for Gene Therapy",slug:"surface-modification-of-retroviral-vectors-for-gene-therapy",totalDownloads:2354,totalCrossrefCites:1,signatures:"Christoph Metzner and John Dangerfield",reviewType:"peer-reviewed",authors:[{id:"39538",title:"Dr.",name:"Christoph",middleName:null,surname:"Metzner",fullName:"Christoph Metzner",slug:"christoph-metzner"},{id:"44916",title:"Dr.",name:"John",middleName:null,surname:"Dangerfield",fullName:"John Dangerfield",slug:"john-dangerfield"}]},{id:"16778",type:"chapter",title:"The Glucocorticoid Receptor in Retroviral Infection",slug:"the-glucocorticoid-receptor-in-retroviral-infection",totalDownloads:2301,totalCrossrefCites:1,signatures:"Brian Fouty and Victor Solodushko",reviewType:"peer-reviewed",authors:[{id:"44470",title:"Dr.",name:"Victor",middleName:null,surname:"Solodushko",fullName:"Victor Solodushko",slug:"victor-solodushko"},{id:"44515",title:"Dr.",name:"Brian",middleName:null,surname:"Fouty",fullName:"Brian Fouty",slug:"brian-fouty"}]},{id:"16779",type:"chapter",title:"Adenoviral Vectors: Potential and Challenges as a Gene Delivery System",slug:"adenoviral-vectors-potential-and-challenges-as-a-gene-delivery-system",totalDownloads:2599,totalCrossrefCites:0,signatures:"Suresh K. Mittal, AnneMarie Swaim and Yadvinder S. Ahi",reviewType:"peer-reviewed",authors:[{id:"46691",title:"Prof.",name:"Suresh",middleName:"K",surname:"Mittal",fullName:"Suresh Mittal",slug:"suresh-mittal"},{id:"46698",title:"Dr.",name:"Yadvinder",middleName:null,surname:"Ahi",fullName:"Yadvinder Ahi",slug:"yadvinder-ahi"},{id:"46700",title:"Mr.",name:"AnneMarie",middleName:null,surname:"Swaim",fullName:"AnneMarie Swaim",slug:"annemarie-swaim"}]},{id:"16780",type:"chapter",title:"Adenovirus-Based Gene Therapy for Cancer",slug:"adenovirus-based-gene-therapy-for-cancer",totalDownloads:2750,totalCrossrefCites:1,signatures:"Changqing Su",reviewType:"peer-reviewed",authors:[{id:"36101",title:"Dr.",name:"Changqing",middleName:null,surname:"Su",fullName:"Changqing Su",slug:"changqing-su"}]},{id:"16781",type:"chapter",title:"Recombinant Adenovirus Vector Infection of Human Dendritic Cells",slug:"recombinant-adenovirus-vector-infection-of-human-dendritic-cells",totalDownloads:2379,totalCrossrefCites:2,signatures:"William Adams and Karin Loré",reviewType:"peer-reviewed",authors:[{id:"38096",title:"Dr.",name:"Karin",middleName:null,surname:"Loré",fullName:"Karin Loré",slug:"karin-lore"},{id:"39307",title:"BSc",name:"William",middleName:"Cecil",surname:"Adams",fullName:"William Adams",slug:"william-adams"}]},{id:"16782",type:"chapter",title:"Harnessing the Potential of Adenovirus Vectored Vaccines",slug:"harnessing-the-potential-of-adenovirus-vectored-vaccines",totalDownloads:2423,totalCrossrefCites:1,signatures:"Peter Johannes Holst and Allan Randrup Thomsen",reviewType:"peer-reviewed",authors:[{id:"49336",title:"Dr",name:"Allan Randrup",middleName:null,surname:"Thomsen",fullName:"Allan Randrup Thomsen",slug:"allan-randrup-thomsen"},{id:"75845",title:"Dr",name:"Peter Johannes",middleName:null,surname:"Holst",fullName:"Peter Johannes Holst",slug:"peter-johannes-holst"},{id:"120290",title:"Dr.",name:"Jan P",middleName:null,surname:"Christensen",fullName:"Jan P Christensen",slug:"jan-p-christensen"}]},{id:"16783",type:"chapter",title:"Adeno Associated Virus Mediated β-Thalassemia Gene Therapy",slug:"adeno-associated-virus-mediated-thalassemia-gene-therapy",totalDownloads:2514,totalCrossrefCites:0,signatures:"Mengqun Tan, Xiaojuan Sun, Zhenqing Liu, Liujiang Song, Jing Tian, Xiaolin Yin and Xinhua Zhang",reviewType:"peer-reviewed",authors:[{id:"39180",title:"Prof.",name:"Mengqun",middleName:null,surname:"Tan",fullName:"Mengqun Tan",slug:"mengqun-tan"},{id:"44756",title:"Dr",name:"Xiaojuan",middleName:null,surname:"Sun",fullName:"Xiaojuan Sun",slug:"xiaojuan-sun"},{id:"100145",title:"Dr.",name:"Zhenqing",middleName:null,surname:"Liu",fullName:"Zhenqing Liu",slug:"zhenqing-liu"},{id:"100146",title:"Dr.",name:"Liujiang",middleName:null,surname:"Song",fullName:"Liujiang Song",slug:"liujiang-song"},{id:"100147",title:"Dr.",name:"Jing",middleName:null,surname:"Tian",fullName:"Jing Tian",slug:"jing-tian"},{id:"100148",title:"Dr.",name:"Xiaolin",middleName:null,surname:"Yin",fullName:"Xiaolin Yin",slug:"xiaolin-yin"},{id:"100149",title:"Dr.",name:"Xinhua",middleName:null,surname:"Zhang",fullName:"Xinhua Zhang",slug:"xinhua-zhang"}]},{id:"16784",type:"chapter",title:"Comparison of AAV Serotypes for Gene Delivery to Dopaminergic Neurons in the Substantia Nigra",slug:"comparison-of-aav-serotypes-for-gene-delivery-to-dopaminergic-neurons-in-the-substantia-nigra",totalDownloads:6139,totalCrossrefCites:5,signatures:"Joanna Korecka, Marijn Schouten, Ruben Eggers, Ayse Ulusoy, Koen Bossers and Joost Verhaagen",reviewType:"peer-reviewed",authors:[{id:"33045",title:"Prof.",name:"Joost",middleName:null,surname:"Verhaagen",fullName:"Joost Verhaagen",slug:"joost-verhaagen"},{id:"33050",title:"MSc",name:"Joanna",middleName:"Aleksandra",surname:"Korecka",fullName:"Joanna Korecka",slug:"joanna-korecka"},{id:"33051",title:"Dr.",name:"Koen",middleName:null,surname:"Bossers",fullName:"Koen Bossers",slug:"koen-bossers"},{id:"43686",title:"Mr",name:"Marijn",middleName:null,surname:"Schouten",fullName:"Marijn Schouten",slug:"marijn-schouten"},{id:"43687",title:"Mr",name:"Ruben",middleName:null,surname:"Eggers",fullName:"Ruben Eggers",slug:"ruben-eggers"},{id:"90274",title:"Dr.",name:"Ayse",middleName:null,surname:"Ulusoy",fullName:"Ayse Ulusoy",slug:"ayse-ulusoy"}]},{id:"16785",type:"chapter",title:"Progress and Challenges in AAV-Mediated Gene Therapy for Duchenne Muscular Dystrophy",slug:"progress-and-challenges-in-aav-mediated-gene-therapy-for-duchenne-muscular-dystrophy",totalDownloads:3078,totalCrossrefCites:0,signatures:"Shin'Ichi Takeda and Takashi Okada",reviewType:"peer-reviewed",authors:[{id:"32038",title:"Dr.",name:"Takashi",middleName:null,surname:"Okada",fullName:"Takashi Okada",slug:"takashi-okada"},{id:"36800",title:"Dr.",name:"Shin",middleName:null,surname:"Takeda",fullName:"Shin Takeda",slug:"shin-takeda"}]},{id:"16786",type:"chapter",title:"Viral Vectors as Tools to Investigate the Role of Dysregulated Proteins in Nervous System Pathologies: the Case of Acquired Motor Neuropathies",slug:"viral-vectors-as-tools-to-investigate-the-role-of-dysregulated-proteins-in-nervous-system-pathologie",totalDownloads:1974,totalCrossrefCites:0,signatures:"Carmen R. Sunico and Bernardo Moreno-Lopez",reviewType:"peer-reviewed",authors:[{id:"44025",title:"Dr.",name:"Bernardo",middleName:null,surname:"Moreno-Lopez",fullName:"Bernardo Moreno-Lopez",slug:"bernardo-moreno-lopez"},{id:"45857",title:"Dr.",name:"Carmen",middleName:null,surname:"R. Sunico",fullName:"Carmen R. Sunico",slug:"carmen-r.-sunico"}]},{id:"16787",type:"chapter",title:"Designing Lentiviral Gene Vectors",slug:"designing-lentiviral-gene-vectors",totalDownloads:14382,totalCrossrefCites:2,signatures:"Oleg Tolmachov, Tanya Tolmachova and Faisal A. Al-Allaf",reviewType:"peer-reviewed",authors:[{id:"28112",title:"Dr.",name:"Oleg",middleName:"E",surname:"Tolmachov",fullName:"Oleg Tolmachov",slug:"oleg-tolmachov"},{id:"71555",title:"Dr.",name:"Faisal A.",middleName:null,surname:"Al-Allaf",fullName:"Faisal A. Al-Allaf",slug:"faisal-a.-al-allaf"},{id:"71556",title:"Dr.",name:"Tanya",middleName:null,surname:"Tolmachova",fullName:"Tanya Tolmachova",slug:"tanya-tolmachova"}]},{id:"16788",type:"chapter",title:"Gene Regulatable Lentiviral Vector System",slug:"gene-regulatable-lentiviral-vector-system",totalDownloads:4412,totalCrossrefCites:2,signatures:"Yasutsugu Suzuki and Youichi Suzuki",reviewType:"peer-reviewed",authors:[{id:"30581",title:"Dr.",name:"Youichi",middleName:null,surname:"Suzuki",fullName:"Youichi Suzuki",slug:"youichi-suzuki"},{id:"43634",title:"Mr",name:"Yasutsugu",middleName:null,surname:"Suzuki",fullName:"Yasutsugu Suzuki",slug:"yasutsugu-suzuki"}]},{id:"16789",type:"chapter",title:"Dendritic Cells and Lentiviral Vectors: Mapping the Way to Successful Immuno Gene Therapy",slug:"dendritic-cells-and-lentiviral-vectors-mapping-the-way-to-successful-immuno-gene-therapy",totalDownloads:2658,totalCrossrefCites:0,signatures:"Cleo Goyvaerts, Grazyna Kochan, David Escors and Karine Breckpot",reviewType:"peer-reviewed",authors:[{id:"28137",title:"Prof.",name:"Karine",middleName:null,surname:"Breckpot",fullName:"Karine Breckpot",slug:"karine-breckpot"},{id:"45265",title:"Prof.",name:"Cleo",middleName:null,surname:"Goyvaerts",fullName:"Cleo Goyvaerts",slug:"cleo-goyvaerts"},{id:"45266",title:"Prof.",name:"David",middleName:null,surname:"Escors",fullName:"David Escors",slug:"david-escors"},{id:"63190",title:"Prof.",name:"Grazyna",middleName:null,surname:"Kochan",fullName:"Grazyna Kochan",slug:"grazyna-kochan"}]},{id:"16790",type:"chapter",title:"Development and Application of HIV Vectors Pseudotyped with HIV Envelopes",slug:"development-and-application-of-hiv-vectors-pseudotyped-with-hiv-envelopes",totalDownloads:2194,totalCrossrefCites:0,signatures:"Koichi Miyake and Takashi Shimada",reviewType:"peer-reviewed",authors:[{id:"28494",title:"Dr.",name:"Koichi",middleName:null,surname:"Miyake",fullName:"Koichi Miyake",slug:"koichi-miyake"},{id:"120353",title:"Dr.",name:"Takashi",middleName:null,surname:"Shimana",fullName:"Takashi Shimana",slug:"takashi-shimana"}]},{id:"16791",type:"chapter",title:"Highly Efficient Retrograde Gene Transfer for Genetic Treatment of Neurological Diseases",slug:"highly-efficient-retrograde-gene-transfer-for-genetic-treatment-of-neurological-diseases",totalDownloads:2184,totalCrossrefCites:0,signatures:"Shigeki Kato, Masahito Kuramochi, Kenta Kobayashi, Ken-Ichi Inoue, Masahiko Takada and Kazuto Kobayashi",reviewType:"peer-reviewed",authors:[{id:"30013",title:"Prof.",name:"Kazuto",middleName:null,surname:"Kobayashi",fullName:"Kazuto Kobayashi",slug:"kazuto-kobayashi"},{id:"45708",title:"Prof.",name:"Shigeki",middleName:null,surname:"Kato",fullName:"Shigeki Kato",slug:"shigeki-kato"},{id:"45709",title:"Prof.",name:"Kenta",middleName:null,surname:"Kobayashi",fullName:"Kenta Kobayashi",slug:"kenta-kobayashi"},{id:"45779",title:"Prof.",name:"Ken-ichi",middleName:null,surname:"Inoue",fullName:"Ken-ichi Inoue",slug:"ken-ichi-inoue"},{id:"45780",title:"Prof.",name:"Masahiko",middleName:null,surname:"Takada",fullName:"Masahiko Takada",slug:"masahiko-takada"},{id:"94638",title:"Dr.",name:"Masahito",middleName:null,surname:"Kuramochi",fullName:"Masahito Kuramochi",slug:"masahito-kuramochi"}]},{id:"16792",type:"chapter",title:"Herpes Simplex Type 1 for Use in Cancer Gene Therapy: Looking Backward to Move Forward",slug:"herpes-simplex-type-1-for-use-in-cancer-gene-therapy-looking-backward-to-move-forward",totalDownloads:2623,totalCrossrefCites:0,signatures:"Breanne Cuddington and Karen Mossman",reviewType:"peer-reviewed",authors:[{id:"33151",title:"Dr.",name:"Karen",middleName:null,surname:"Mossman",fullName:"Karen Mossman",slug:"karen-mossman"},{id:"44238",title:"Prof.",name:"Breanne",middleName:"Palegia",surname:"Cuddington",fullName:"Breanne Cuddington",slug:"breanne-cuddington"}]},{id:"16793",type:"chapter",title:"Gene Therapy of Melanoma Using Inactivated Sendai Virus Envelope Vector (HVJ-E) with Intrinsic Anti-Tumor Activities",slug:"gene-therapy-of-melanoma-using-inactivated-sendai-virus-envelope-vector-hvj-e-with-intrinsic-anti-tu",totalDownloads:2582,totalCrossrefCites:1,signatures:"Yasufumi Kaneda, Eiji Kiyohara, Toshihiro Nakajima and Toshimitsu Itai",reviewType:"peer-reviewed",authors:[{id:"28488",title:"Prof.",name:"Yasufumi",middleName:null,surname:"Kaneda",fullName:"Yasufumi Kaneda",slug:"yasufumi-kaneda"},{id:"32100",title:"Dr.",name:"Eiji",middleName:null,surname:"Kiyohara",fullName:"Eiji Kiyohara",slug:"eiji-kiyohara"},{id:"32101",title:"Dr.",name:"Toshihiro",middleName:null,surname:"Nakajima",fullName:"Toshihiro Nakajima",slug:"toshihiro-nakajima"},{id:"70739",title:"Dr",name:"Toshimitsu",middleName:null,surname:"Itai",fullName:"Toshimitsu Itai",slug:"toshimitsu-itai"}]},{id:"16794",type:"chapter",title:"Pharmacokinetic Study of Viral Vectors for Gene Therapy: Progress and Challenges",slug:"pharmacokinetic-study-of-viral-vectors-for-gene-therapy-progress-and-challenges",totalDownloads:3112,totalCrossrefCites:0,signatures:"Xianxing Xu, Yang Jingwen and Cheng Yuanguo",reviewType:"peer-reviewed",authors:[{id:"42478",title:"Dr.",name:"Xianxing",middleName:null,surname:"Xu",fullName:"Xianxing Xu",slug:"xianxing-xu"},{id:"51927",title:"Prof.",name:"Yuanguo",middleName:null,surname:"Cheng",fullName:"Yuanguo Cheng",slug:"yuanguo-cheng"},{id:"81776",title:"Dr.",name:"Jingwen",middleName:null,surname:"Yang",fullName:"Jingwen Yang",slug:"jingwen-yang"}]}]},relatedBooks:[{type:"book",id:"5267",title:"Tumor Metastasis",subtitle:null,isOpenForSubmission:!1,hash:"ac0d598a394585f0b00dcc15347e1f89",slug:"tumor-metastasis",bookSignature:"Ke Xu",coverURL:"https://cdn.intechopen.com/books/images_new/5267.jpg",editedByType:"Edited by",editors:[{id:"59529",title:"Dr.",name:"Ke",surname:"Xu",slug:"ke-xu",fullName:"Ke Xu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"51889",title:"Hemostatic System in Malignancy: Providing the “Soil” in Metastatic Niche Formation",slug:"hemostatic-system-in-malignancy-providing-the-soil-in-metastatic-niche-formation",signatures:"Elina Beleva, Veselin Popov and Janet Grudeva-Popova",authors:[{id:"185398",title:"Dr.",name:"Elina",middleName:null,surname:"Beleva",fullName:"Elina Beleva",slug:"elina-beleva"},{id:"185444",title:"Prof.",name:"Zhanet",middleName:null,surname:"Grudeva-Popova",fullName:"Zhanet Grudeva-Popova",slug:"zhanet-grudeva-popova"},{id:"185475",title:"Dr.",name:"Veselin",middleName:null,surname:"Popov",fullName:"Veselin Popov",slug:"veselin-popov"}]},{id:"51782",title:"Is Extracellular Matrix a Castle Against to Invasion of Cancer Cells?",slug:"is-extracellular-matrix-a-castle-against-to-invasion-of-cancer-cells-",signatures:"Serdar Altınay",authors:[{id:"185324",title:"Associate Prof.",name:"Serdar",middleName:null,surname:"Altınay",fullName:"Serdar Altınay",slug:"serdar-altinay"}]},{id:"51874",title:"Ovarian Cancer Metastasis: A Unique Mechanism of Dissemination",slug:"ovarian-cancer-metastasis-a-unique-mechanism-of-dissemination",signatures:"Anirban K. Mitra",authors:[{id:"185152",title:"Dr.",name:"Anirban",middleName:"Kumar",surname:"Mitra",fullName:"Anirban Mitra",slug:"anirban-mitra"}]},{id:"51956",title:"Role of Aquaporins in Breast Cancer Progression and Metastasis",slug:"role-of-aquaporins-in-breast-cancer-progression-and-metastasis",signatures:"Maitham A. Khajah and Yunus A. Luqmani",authors:[{id:"40180",title:"Prof.",name:"Yunus",middleName:null,surname:"Luqmani",fullName:"Yunus Luqmani",slug:"yunus-luqmani"},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",fullName:"Maitham Khajah",slug:"maitham-khajah"}]},{id:"51684",title:"Extracellular Vesicles: A Mechanism to Reverse Metastatic Behaviour as a New Approach to Cancer Therapy",slug:"extracellular-vesicles-a-mechanism-to-reverse-metastatic-behaviour-as-a-new-approach-to-cancer-thera",signatures:"Monerah Al Soraj, Salma Bargal and Yunus A. Luqmani",authors:[{id:"185255",title:"Prof.",name:"Yunus",middleName:null,surname:"Luqmani",fullName:"Yunus Luqmani",slug:"yunus-luqmani"},{id:"185459",title:"Dr.",name:"Monerah",middleName:null,surname:"Al Soraj",fullName:"Monerah Al Soraj",slug:"monerah-al-soraj"}]},{id:"51715",title:"Modulation of Gene Expression During Stages of Liver Colonization by Pancreatic Cancer in a Rat Model",slug:"modulation-of-gene-expression-during-stages-of-liver-colonization-by-pancreatic-cancer-in-a-rat-mode",signatures:"Khamael M.K. Al-Taee, Hassan Adwan and Martin R. Berger",authors:[{id:"56407",title:"Prof.",name:"Martin",middleName:null,surname:"Berger",fullName:"Martin Berger",slug:"martin-berger"}]},{id:"51761",title:"Minimal Invasive Surgery of Metastatic Bone Tumor",slug:"minimal-invasive-surgery-of-metastatic-bone-tumor",signatures:"Hyun Guy Kang and San Ha Kang",authors:[{id:"24542",title:"Prof.",name:"Hyun Guy",middleName:null,surname:"Kang",fullName:"Hyun Guy Kang",slug:"hyun-guy-kang"},{id:"190939",title:"Ms.",name:"San Ha",middleName:null,surname:"Kang",fullName:"San Ha Kang",slug:"san-ha-kang"}]},{id:"51880",title:"The Selection Strategy for Circulating Tumor Cells (CTCs) Isolation and Enumeration: Technical Features, Methods, and Clinical Applications",slug:"the-selection-strategy-for-circulating-tumor-cells-ctcs-isolation-and-enumeration-technical-features",signatures:"Jason Chia‐Hsun Hsieh and Tyler Ming‐Hsien Wu",authors:[{id:"182712",title:"Dr.",name:"Chia-Hsun",middleName:null,surname:"Hsieh",fullName:"Chia-Hsun Hsieh",slug:"chia-hsun-hsieh"}]},{id:"51371",title:"Detection of Circulating Tumor Cells and Circulating Tumor Stem Cells in Breast Cancer by Using Flow Cytometry",slug:"detection-of-circulating-tumor-cells-and-circulating-tumor-stem-cells-in-breast-cancer-by-using-flow",signatures:"Yanjie Hu, Jin’e Zheng and Shiang Huang",authors:[{id:"182055",title:"Prof.",name:"Shiang",middleName:null,surname:"Huang",fullName:"Shiang Huang",slug:"shiang-huang"},{id:"185678",title:"Dr.",name:"Yanjie",middleName:null,surname:"Hu",fullName:"Yanjie Hu",slug:"yanjie-hu"},{id:"185679",title:"Dr.",name:"Jin’e",middleName:null,surname:"Zheng",fullName:"Jin’e Zheng",slug:"jin'e-zheng"}]},{id:"51972",title:"Epithelial-Mesenchymal Transition and its Regulation in Tumor Metastasis",slug:"epithelial-mesenchymal-transition-and-its-regulation-in-tumor-metastasis",signatures:"Tao Sun, Yuan Qin and Wei-long Zhong",authors:[{id:"184913",title:"Associate Prof.",name:"Tao",middleName:null,surname:"Sun",fullName:"Tao Sun",slug:"tao-sun"},{id:"184922",title:"Dr.",name:"Yuan",middleName:null,surname:"Qin",fullName:"Yuan Qin",slug:"yuan-qin"},{id:"184923",title:"Dr.",name:"Wei-Long",middleName:null,surname:"Zhong",fullName:"Wei-Long Zhong",slug:"wei-long-zhong"}]},{id:"51771",title:"Importance and Detection of Epithelial-to-Mesenchymal Transition (EMT) Phenotype in CTCs",slug:"importance-and-detection-of-epithelial-to-mesenchymal-transition-emt-phenotype-in-ctcs",signatures:"Joseph W. Po, David Lynch, Paul de Souza and Therese M. Becker\nVI Contents",authors:[{id:"161435",title:"Dr.",name:"Therese",middleName:null,surname:"Becker",fullName:"Therese Becker",slug:"therese-becker"},{id:"182626",title:"Mr.",name:"Joseph",middleName:null,surname:"Po",fullName:"Joseph Po",slug:"joseph-po"},{id:"182627",title:"Prof.",name:"Paul",middleName:null,surname:"De Souza",fullName:"Paul De Souza",slug:"paul-de-souza"},{id:"182628",title:"Mr.",name:"David",middleName:null,surname:"Lynch",fullName:"David Lynch",slug:"david-lynch"}]}]}],publishedBooks:[{type:"book",id:"1281",title:"DNA Repair and Human Health",subtitle:null,isOpenForSubmission:!1,hash:"cc31f8578c9beb17ab7967da7f86b7f8",slug:"dna-repair-and-human-health",bookSignature:"Sonya Vengrova",coverURL:"https://cdn.intechopen.com/books/images_new/1281.jpg",editedByType:"Edited by",editors:[{id:"66551",title:"Dr.",name:"Sonya",surname:"Vengrova",slug:"sonya-vengrova",fullName:"Sonya Vengrova"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1701",title:"Osteogenesis",subtitle:null,isOpenForSubmission:!1,hash:"63489682e555540ef423d10335e3bf09",slug:"osteogenesis",bookSignature:"Yunfeng Lin",coverURL:"https://cdn.intechopen.com/books/images_new/1701.jpg",editedByType:"Edited by",editors:[{id:"98348",title:"Prof.",name:"Yunfeng",surname:"Lin",slug:"yunfeng-lin",fullName:"Yunfeng Lin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3299",title:"Novel Gene Therapy Approaches",subtitle:null,isOpenForSubmission:!1,hash:"63b89d6c73b78754a151626a3c29b10b",slug:"novel-gene-therapy-approaches",bookSignature:"Ming Wei and David Good",coverURL:"https://cdn.intechopen.com/books/images_new/3299.jpg",editedByType:"Edited by",editors:[{id:"158796",title:"Prof.",name:"Ming",surname:"Wei",slug:"ming-wei",fullName:"Ming Wei"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3308",title:"Genetic Disorders",subtitle:null,isOpenForSubmission:!1,hash:"c80f7f7d98204c92d8b796db997da35d",slug:"genetic-disorders",bookSignature:"Maria Puiu",coverURL:"https://cdn.intechopen.com/books/images_new/3308.jpg",editedByType:"Edited by",editors:[{id:"31786",title:"Prof.",name:"Maria",surname:"Puiu",slug:"maria-puiu",fullName:"Maria Puiu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4649",title:"Cystic Fibrosis in the Light of New Research",subtitle:null,isOpenForSubmission:!1,hash:"769fa01c7625c98956ac6da8335c78b4",slug:"cystic-fibrosis-in-the-light-of-new-research",bookSignature:"Dennis Wat",coverURL:"https://cdn.intechopen.com/books/images_new/4649.jpg",editedByType:"Edited by",editors:[{id:"92549",title:"Dr.",name:"Dennis",surname:"Wat",slug:"dennis-wat",fullName:"Dennis Wat"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],publishedBooksByAuthor:[{type:"book",id:"500",title:"Viral Gene Therapy",subtitle:null,isOpenForSubmission:!1,hash:"5292fcf7bd6aaceecd23530c35b53600",slug:"viral-gene-therapy",bookSignature:"Ke Xu",coverURL:"https://cdn.intechopen.com/books/images_new/500.jpg",editedByType:"Edited by",editors:[{id:"59529",title:"Dr.",name:"Ke",surname:"Xu",slug:"ke-xu",fullName:"Ke Xu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},onlineFirst:{chapter:{type:"chapter",id:"79802",title:"Bats and Ecosystem Management",doi:"10.5772/intechopen.101600",slug:"bats-and-ecosystem-management",body:'
1. Introduction
Many ecosystems worldwide have become more threatened than ever before through many anthropogenic activities such as urbanization, deforestation and different kinds of pollution. Healthy ecosystems are crucial for human wellbeing improvement, since they provide various ecological services (e.g., insect suppression, pollination, seed dispersal, water and air purification, stabilization of soils, decomposition of wastes, binding of toxic substances, mitigation of diseases, mitigation of floods, and regulation of climate, etc.), many provisions (e.g., food, fuel, fiber, and medicines), and cultural benefits (e.g., esthetic, spiritual, educational, and recreational) [1]. These processes and products are commonly referred to as ecosystem services [2, 3] and have been duly recognized by the United Nations Millennium Ecosystem Assessment [4, 5].
Furthermore, ecosystem services mainly depend on the type of ecosystem as well as the organisms that they constitute. In this chapter, the ecosystem services provided by bats are considered. Bats have been on Earth for over 52 million years [6], with over 1400 species worldwide. They are classified as the second-largest mammalian order with great physiological and ecological diversity [7]. Due to their diverse behavioral, roosting, and feeding habits, many species of bats roost during the daytime in foliage, caves, rock crevices, hollows of trees, beneath exfoliating bark, and different manmade structures [8, 9, 10, 11]. While during the night, bats fill the sky to forage on a variety of food items ranging from insects, nectar, and fruit, to seeds, frogs, fish, small mammals, and even blood.
2. Bat: human interaction
Bat-human interrelationships are probably as old as humanity itself. However, the oldest bat fossils are estimated to date back to the Eocene, exceeding 50 million years ago [6]. These nocturnal, fast-flying, and secretive mammals may have been as enigmatic to human ancestors as they are to most of us today. The ancient coexistence of people and bats has been translated into enormous historical and contemporary cultural representations of bats in local folklore [12, 13, 14]. This ancient connection exquisitely celebrated in abundant reddish-terracotta rock paintings of bats was made by hunter-gatherer colonizers of the northwest Amazon during the Late Pleistocene/Early Holocene transition [15]. Human still considers bats to be loathsome and fearful creatures, despite the countless research investigating the contributions of bats to the ecosystem and the benefits they provide to human wellbeing [16, 17, 18, 19, 20, 21].
2.1 Bat’s negative stigma
Contrary to popular belief, bats do not attack people; they do not get tangled in people’s hair; and even vampire bats are not real vampires (vampire bats lick blood but do not suck blood). Underlying these negative sentiments are relatively pervasive associations between bats and death [22, 23], witchcraft [24, 25, 26], vampires [27, 28, 29], malevolent spirits [30, 31, 32], and evil [33, 34].
Across much of Europe, disdain and fear of bats are largely embroiled in Church doctrine, where bats are often used to symbolize Satan [35]. However, elsewhere (particularly throughout Southeast Asia, China, and Japan), bats are also associated with luck and good fortune [13, 36] and used as spiritual totems [37, 38]. Among several indigenous groups in Mexico, bats have been considered messengers from the underworld and important symbols of fertility [39].
Furthermore, as human numbers increase and people encroach deeper into the remaining natural habitats, human-bat interactions are becoming more frequent, often with undesirable consequences for both humans and bats.
Human-bat conflicts often arise from damage to buildings or as a result of noise/smelly caused by synanthropic species [14, 40] or due to fruit crop invasion by frugivorous species [21, 41]. These are other key areas in which ethnobiological work can substantially contribute to support evidence-based and culturally sensitive strategies aimed at reducing negative feelings toward bats.
2.2 Ecosystem services
An ecosystem is a system consisting of biotic and abiotic components that function together as a unit. The biotic components include all the living things whereas the abiotic components are the non-living things. Thus, an ecosystem science definition entails an ecological community consisting of different populations of organisms that live together in a habitat. Ecology, which is the scientific study of the interactions between populations or between organisms and the environment, can be viewed at the level of an individual, population, community, or ecosystem. Ecology at the level of individuals is mainly concerned with the physiology, reproduction, and development of an organism. At the level of population, ecology deals primarily with the attributes and the various factors affecting the population. At the level of community, ecology investigates the interactions between populations and community patterns. At the ecosystem level, ecology brings them all together to understand how the system functions as a unit [42].
Ecosystem services are the benefits obtained from the environment that increase human well-being. Economic valuation is conducted by measuring the human welfare gains or losses resulting from changes in the provision of ecosystem services. Bats, which live on all continents except Antarctica, are essential members of many types of ecosystems, ranging from rainforests to deserts. By fulfilling their ecosystem roles, bats promote biodiversity and support the health of their ecosystems. Due to the rich diversity of dietary habits of bats, ranging from species that feed on insects and other arthropods to those that feed on fruit, nectar, and flowers, they have long been postulated to play important roles in ecological and economic services. Moreover, other species that feed on seeds, frogs, fish, small mammals, and even blood also play important roles in ecosystems as predators or prey in ecosystems sustainability. Modifying ecosystems to facilitate socioeconomic development is necessary but how can we avoid damaging important ecosystem services? As a prerequisite, we need to understand how ecosystem services contribute to people’s livelihoods and well-being.
2.2.1 Ecological services
Bats have long been known as the main contributor to remarkable ecosystem benefits, are significant suppressors of agricultural pests [43, 44, 45, 46], consume important disease vectors, such as malaria-bearing mosquitos [47], with an important role in seed dispersal, pollination, material and nutrient distribution, and recycle [48].
One of the most troubling problems of the farming industry is insect pests, which affect crop production worldwide. Inhibitors of natural insect pests such as bats, as major predators of arthropods, provide valuable ecosystem benefits for crops cultivation [48, 49]. Indeed, herbivorous arthropods destroy approximately 25–50% of crops worldwide [50, 51], in response to these threats, it is clear that the application of synthetic pesticides has increased which in turn has led to several unintended consequences including human health risks, degradation of ecosystem function, evolved toxicity resistance by pests, and severe alterations in the agribusiness dynamics [50, 52, 53].
Indeed, the elimination of beneficial vertebrate predators that act as biocontrol of insects, such as bats, insect species that are not normally considered pests are often elevated to pest status [53, 54]. Thus, the promotion of biological controls can reduce the widespread and indiscriminate use of chemical pesticides [55]. About 99% of potential crop pests are limited by natural ecosystems [53, 56] of which some fraction can be attributed to predation by bats [57]. For example, a colony of 150 big brown bats (Eptesicus fuscus) in the midwestern United States annually consume approximately 600,000 spotted cucumber beetles (Diabrotica undecimpunctata), 194,000 June beetles (Scarabidae), 158,000 leafhoppers (Cicadellidae), and 335,000 stinkbugs (Pentatomidae), which are severe crop pests [58]. A Brazilian free-tailed bat (Tadarida brasiliensis) can eat up to 20 females of corn earworm moth (Helicoverpa zea), one of the costliest agricultural pest insects in one night [59]. In fact, each moth can potentially produce 10,000 crop-damaging caterpillars each night [60]. Bats are just one of several groups of animals that naturally prey on mosquitoes. A Florida colony of 30,000 southeastern myotis (Myotis austroriparius) eats 50 tons of insects annually, including more than 15 tons of mosquitoes (Figure 1) [61, 62].
Figure 1.
Insectivorous bat species (a) big brown bats (Eptesicus fuscus); (b) Southeastern myotis (Myotis austroriparius); (c) Brazilian free-tailed bat (Tadarida brasiliensis): photos by Merlin Tuttle’s Bat Conservation/MerlinTuttle.org.
Therefore, insectivorous bat species, which largely feed on airborne insects and other arthropods, considerably contribute to the suppression of insects that harm the agricultural industry or transmit specific pathogens to humans, consequently contributing to the maintenance of ecosystem stability.
Another important ecosystem service provided by bats is pollination. Although, bat pollination is relatively uncommon when compared with bird or insect pollination, it involves an impressive number of economically and ecologically important plants [63]. Plant-visiting bats play a remarkable role in facilitating reproductive success and the recruitment of new seedlings [48]. For instance, bat-pollinated columnar cacti (Cactaceae) and agaves (Asparagaceae) are among the most important species as dominant vegetation elements in arid and semiarid habitats (Figure 2) [48].
Figure 2.
A lesser long-nosed bat (Leptonycteris yerbabuenae) feeding on a cross-sectioned saguaro cactus flower: photo by Merlin Tuttle’s Bat Conservation/MerlinTuttle.org.
Furthermore, seed dispersal is a major way in which animals contribute to ecosystem succession by depositing seeds from one area to another [64]. Frugivorous bats play a tremendous role in dispersing the seeds of tropical trees and shrubs to produce fleshy fruits as 50–90% of these trees are adapted to the consumption of vertebrates [65]. Generally, frugivorous bats help maintain the diversity of forests by dispersing seeds across different ecosystems, often introducing novel plant species into previously disturbed landscapes [64].
In contrast to predation, which is an antagonistic population interaction, pollination, and seed dispersal are mutualistic population interactions in which plants provide a nutritional reward (nectar, pollen, and fruit pulp) for a beneficial service [48]. Indeed, frugivorous bats as well as nectarivorous bats provide valuable ecosystem services by pollinating plants, dispersing pollen, and thus helping to maintain the genetic diversity of flowering plants.
Bats offer an important multisensory role in assessing ecosystem health either by directly contributing to regulating services to agricultural production or indirectly by providing forage and nesting habitat for pollinators and seed dispersers. To some extent, bat guano has great ecological potential for soil fertility and nutrient distribution, as bats sprinkle them over the landscape overnight, they facilitate nutrient redistribution within ecosystems [66]. In other words, bat guano supports a great diversity of organisms including arthropods, fungi, bacteria, and lichens representing different trophic levels by supporting their ecosystems [67].
Moreover, bats have enormous potential as bioindicators of both disturbance and the existence of contaminants [68]. They show taxonomic stability, trends in their populations can be monitored, short- and long-term effects on populations can be measured and widely distributed worldwide [68, 69, 70]. Since insectivorous bats occupy high trophic levels, they are sensitive to the accumulations of pesticides and other toxins, and changes in their abundance may reflect changes in populations of arthropod prey species [71]. In particular, changes in bat numbers or activity can be related to climate change, deterioration of water quality, agricultural intensification, loss and fragmentation of habitats, fatalities at wind turbines, disease, pesticide use, and overhunting [68], and hence bat populations are affected by a wide range of stressors that affect many other taxa. Overall, there is an urgent need to implement a global effort for monitoring bat populations, to ensure that their role as bioindicators can be used to their full potential.
2.2.2 Economic services
Estimating the economic importance of bats in agricultural systems is challenging; however, the bats value in pest suppression illustrates an important agricultural service by increasing the monetary gain of farmers, and consequently supporting food security [49]. They consume enormous quantities of insect pests that cost farmers and foresters billions of dollars annually [59]. In USA, due to the fact of insect pests are eliminated by bat predation, the estimated value of bats as a result of reduced costs of pesticide applications is in the range of $3.7–$53 billion per year [66]. These estimates include the reduced costs of unnecessary pesticide applications to suppress insects consumed by bats [72].
Bats provide substantial ecosystem services worldwide, and their benefits to human economies are not limited to agricultural pest control. For example, pioneering research in tropical ecosystems shows the importance of plant-visiting bats in the pollination of valuable fruit crops [73, 74]. There are 289 Old World tropical plant species, which rely on pollination and seed dispersal services by bats for their propagation, providing human with about 448 products in a variety of categories, for instance, wood products (23%); food, drinks and fresh fruit (19%); medicine (15%); dye, fiber, animal fodder, fuel wood, and others (43%) [57]. In addition to some cash crops such as wild bananas (Musa acuminata), mangos (Mangifera indica), breadfruits (Artocarpus altilis), agave (Agave spp.), and durians (Durio spp.) they rely on bats for pollination [57]. Durian, a wildly popular fruit worth more than $230 million per year in Southeast Asia, opens its flower at dusk and relies almost exclusively on fruit bats for pollination [57]. In general, according to the vital role that bats play in the global pollination services, their total economic value is up to $200 billion [75]. Furthermore, bats have a tremendous economic value in maintaining forests through dispersing the seeds of crucial plants for forest reemerging [76]. For instance, the estimated economic value of bat seed dispersal services to giant oak (Quercus virginiana) is $212,000 for acorn seeding and $945,000 for planting saplings [77].
Bats provide some of the world’s finest natural fertilizers known as Guano [78]. Since there are high concentrations of nitrogen and phosphorous in guano [79], it provides some of the world’s finest natural fertilizers [78]. For instance, in Texas the Brazilian free-tailed bat guano has been extracted for fertilizer in thousands of tons from Bracken Cave alone with the current retail sales ranging from $2.86 to $12.10 per kilogram [78].
Finally, it is important to recognize the extraordinary value of bats to ancient and contemporary traditions and science. Recently, bats provide esthetic contributions through cave visits, nocturnal tours in national parks, and educational nature programs. Like other wildlife recreational activities, bat watching is considerably growing [80]. Besides providing adventure and life memories to the public, it generates income for the communities and companies involved [80]. For instance, Congress Avenue Bridge, one of the largest urban bat colonies in the USA, is visited by 200–1500 visitors every evening with a value of $3 million per year [80, 81]. Bats also commonly appear as symbols or logos in popular movies (e.g., Batman), products (e.g., Bacardi rum), and holidays (e.g., Halloween), and all major revenue-generating endeavors [82]. Moreover, many novel technological advances have been inspired by bat echolocation and locomotion, such as sonar systems, biomedical ultrasound, sensors for autonomous systems, wireless communication, and BATMAVs (bat-like motorized aerial vehicles) [83]. Also, in the medical sector, the saliva of vampire bats with its anticlotting chemicals has been investigated as a potential anticoagulant for people who are at high risk of blood clots and strokes [84].
Although, some of these services provide direct benefits to humans (e.g., food, fuel, fiber, and fertilizer), most ecosystem services offer indirect benefits (e.g., pest suppression, seed dispersal, and pollination). Often, little attention is paid to “free” services provided by ecosystems either because the benefits of the services are not fully understood by decision makers or because the benefits accrue to non-owners of the ecosystem providing the service [48]. Information on nonmarket values of ecosystem services can be used to inform decisions regarding whether to protect existing ecosystem services, improve the current provision of ecosystem services, or restore previously lost ecosystem services [4, 85].
Finally, although much of the public and some policy makers may view the precipitous decline of bats worldwide as only of academic interest, the economic and ecological consequences of losing so many bats could be substantial. Thus, a deeper understanding of bat-human inter-relationships, the importance of bat diversity, and ecosystem management is crucial for healthy ecosystems and human well-being (Figure 3).
Figure 3.
Ecosystem services provided by bats by Ramírez-Fráncel [86].
3. Ecosystem management
The management and protection of ecosystems are essential to the functioning of ecosphere processes and for the well-being of the biotic and abiotic components of the Earth. Different sectors of society view ecosystem management in terms of their own economic, cultural and societal needs. Management should involve all stakeholders and balance local interests with the broader public interest. Effective ecosystem management depends on both cultural and biological diversity, the dynamic relationship within a species, among species and between species and their abiotic environment, as well as the physical and chemical interactions within the environment [87].
There are different perspectives of environmental management, one of which deals with human needs as central such as protecting a young forest because it may be able to be logged in the future which is known as anthropocentric perspective. While the egocentric perspective deals with the needs of environments as central, for example allowing farmers to extract less water from the river to permit more water to flow downstream [88]. Thus, we must appropriately value and manage ecosystems because of their multiple values to humanity and/or because of their value to other ecosystems and both scenarios lead to a healthier environment and more human well-being.
As human numbers increase and people encroach deeper into the remaining natural habitats, human-bat interactions are becoming more frequent, with often undesirable consequences for both humans and bats [14]. However, bats are often considered keystone species, as they play an important role in many ecosystem services [89], bat populations are declining worldwide mainly because of habitat destruction [90] and increased population control [91, 92]. Additionally, the lack of knowledge about bats makes them an easy target for disease-related fears [93, 94, 95] and a potential target for persecution [28, 96].
Indeed, bat management requires a comprehensive approach that must consider the development of culturally appropriate strategies that minimize zoonotic health risks and support bat diversity and its associated ecosystem services [97]. However, even with some communities expressing positive attitudes toward bats, bat control efforts and roost destruction are significant threats to the taxon. Thus, healthy comprehensive management depends on a robust understanding of the importance of bat diversity and emphasizes the non-lethal actions by the general public, health officials, and pest/wildlife managers [98]. It is essential to document people’s relationship with bats and to incorporate these perceptions into educational efforts and management decisions, consequently increasing the potential for successful conservation efforts. While comprehensive management can be more costly in the short term (compared to typical pest control efforts), the long-term results should provide the best sustainable outcomes that are satisfactory to people, bats, and the environment [99].
The key to sustainable development is to strike a balance between the exploitation of natural resources for socio-economic development and the preservation of ecosystem services. In other words, healthy ecosystems are a prerequisite for sustainable development and all ecosystem services provided by different vertebrate animals, such as bats, compromise options for present and future generations. Hence, it is important to demonstrate that undervaluing one ecosystem service is likely to lead to the loss of many.
4. Conclusion
In conclusion, for the benefit of present and future generations, bat management by governmental agencies and NGOs needs to be evaluated. Additionally, more understanding is needed of how ecosystem services provided by bats contribute to livelihoods and how far the benefits provided by bats elevate their detrimental impact. Furthermore, in the context of accelerating environmental change, there is an urgent need to identify ecosystem conservation, restoration, and management strategies that are likely to support biodiverse and adaptive ecosystems in the future. We hope that increased awareness about these nocturnal, fast-flying, and secretive mammals can help build synergies between international scientific knowledge, conservation priorities, and local cultural values, which together can promote the benefits of the ecosystem services provided by bats (Video 1, https://www.merlintuttle.org/video/the-importance-of-bats/).
Acknowledgments
We would like to express our special thanks of gratitude to Dr. Merlin D. Tuttle “Founder & Executive Director, Merlin Tuttle’s Bat Conservation” and Dr. Ramírez-Fráncel for their worthwhile support to our work.
\n',keywords:"agricultural pests, ecosystem services, bioindicators, environmental stressors",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/79802.pdf",chapterXML:"https://mts.intechopen.com/source/xml/79802.xml",downloadPdfUrl:"/chapter/pdf-download/79802",previewPdfUrl:"/chapter/pdf-preview/79802",totalDownloads:117,totalViews:0,totalCrossrefCites:0,dateSubmitted:"September 7th 2021",dateReviewed:"November 12th 2021",datePrePublished:"January 22nd 2022",datePublished:"April 20th 2022",dateFinished:"December 25th 2021",readingETA:"0",abstract:"Bats are among the most misperceived and undervalued animals on the planet. For wildlife ecologists, they are wonderful and incredibly fascinating creatures, but people’s feelings about bats are often negative, perhaps because bats are so mysterious. Unfortunately, these fears and myths about bats threaten conservation, biodiversity, and the entire ecosystem. Bats are among the most diverse and geographically dispersed group of living mammals. They contribute to several ecosystem services and act as biological pest crop control agents. Their abundance may reflect changes in populations of arthropod prey species. Also, bats have significant potentials as bioindicators that demonstrate measurable responses to climate change and habitat loss and that induce large-scale impacts on the biota. Indeed, bat conservation is fundamental not only for biodiversity, but also because these flying mammals provide essential ecological and economic services to humans.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/79802",risUrl:"/chapter/ris/79802",signatures:"Kareem M. Soliman and Wiame W. Emam",book:{id:"11032",type:"book",title:"Bats",subtitle:"Disease-Prone but Beneficial",fullTitle:"Bats - Disease-Prone but Beneficial",slug:"bats-disease-prone-but-beneficial",publishedDate:"April 20th 2022",bookSignature:"Heimo Mikkola",coverURL:"https://cdn.intechopen.com/books/images_new/11032.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-80355-013-8",printIsbn:"978-1-80355-012-1",pdfIsbn:"978-1-80355-014-5",isAvailableForWebshopOrdering:!0,editors:[{id:"144330",title:"Dr.",name:"Heimo",middleName:"Juhani",surname:"Mikkola",slug:"heimo-mikkola",fullName:"Heimo Mikkola"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"424622",title:"Dr.",name:"Kareem M.",middleName:null,surname:"Soliman",fullName:"Kareem M. Soliman",slug:"kareem-m.-soliman",email:"dr_kariemsoliman@yahoo.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"425404",title:"Dr.",name:"Wiame W.",middleName:null,surname:"Emam",fullName:"Wiame W. Emam",slug:"wiame-w.-emam",email:"dr_wiameemam@yahoo.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Ain Shams University",institutionURL:null,country:{name:"Egypt"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Bat: human interaction",level:"1"},{id:"sec_2_2",title:"2.1 Bat’s negative stigma",level:"2"},{id:"sec_3_2",title:"2.2 Ecosystem services",level:"2"},{id:"sec_3_3",title:"2.2.1 Ecological services",level:"3"},{id:"sec_4_3",title:"2.2.2 Economic services",level:"3"},{id:"sec_7",title:"3. Ecosystem management",level:"1"},{id:"sec_8",title:"4. Conclusion",level:"1"},{id:"sec_9",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Chivian E, Bernstein A, editors. Sustaining life. In: How Human Health Depends on Biodiversity. New York: Oxford University Press; 2008'},{id:"B2",body:'Daily GC, editor. Nature’s Services. Societal Dependence on Natural Ecosystems. Washington, DC: Island Press; 1997'},{id:"B3",body:'Daily GC, Söderqvist T, Aniyar S, Arrow K, Dasgupta P, Ehrlich PR, et al. The value of nature and the nature of value. Science. 2000;289(5478):395-396. DOI: 10.1126/science.289.5478.395'},{id:"B4",body:'Joseph A, Neville JA, Colin DB, Doris C, Stephen RC, Juan CC, et al. Millennium ecosystem assessment. In: Ecosystems and Human Well-Being: A Framework for Assessment. Washington, DC: Island Press; 2003'},{id:"B5",body:'Walter VR, Harold A M, Angela C, Doris C, Stephen RC, Kanchan C, et al. Millennium ecosystem assessment. In: Ecosystems and Human Well-Being: Synthesis. Washington, DC: Island Press; 2005'},{id:"B6",body:'Simmons NB, Seymour KL, Habersetzer J, Gunnell GF. Primitive early eocene bat from Wyoming and the evolution of flight and echolocation. Nature. 2008;451:U818-U816. DOI: 10.1038/nature06549'},{id:"B7",body:'Simmons NB, Cirranello AL. Bat Species of the World: A Taxonomic and Geographic Database [web page]. 2021. Available from: https://batnames.org/'},{id:"B8",body:'Patterson BD, Willig MR, Stevens RD. Trophic strategies, niche partitioning, and patterns of ecological organization. In: Kunz TH, Fenton MB, editors. Bat Ecology. Chicago: University of Chicago Press; 2003. pp. 536-579'},{id:"B9",body:'Simmons NB, Conway M. Evolution and ecological diversity of bats. In: Kunz TH, Fenton MB, editors. Bat Ecology. Chicago: University of Chicago Press; 2003. pp. 493-535'},{id:"B10",body:'Kunz TH. Ecology of Bats. 1st ed. Vol. XVIII. Boston, MA: Springer; 1982. p. 450. DOI: 10.1007/978-1-4613-3421-7'},{id:"B11",body:'Chaverri G, Kunz TH. Ecological determinants of social systems: Perspectives on the role of roosting ecology in the social behavior of tent-roosting bats. In: Macedo R, editor. Behavioral Ecology of Tropical Animals, Advances in the Study of Behavior. Vol. 42. New York: Academic Press; 2010. pp. 275-318. DOI: 10.1016/S0065-3454(10)42009-4'},{id:"B12",body:'Lawrence EA. The sacred bee, the filthy pig, and the bat out of hell: Animal symbolism as cognitive biophilia. In: Kellert SR, editor. The Biophilia Hypothesis. Washington, D.C: Island Press; 1993. pp. 301-341'},{id:"B13",body:'Low M, Hoong WZ, Shen Z, Murugavel B, Mariner N, Paguntalan LM, et al. Bane or blessing? Reviewing cultural values of bats across the Asia-Pacific region. Journal of Ethnobiology. 2021;41(1):18-34. DOI: 10.2993/0278-0771-41.1.18'},{id:"B14",body:'Rocha R, Fernández-Llamazares A, López-Baucells A, Andrimatandrina SFM, Andriatafika ZE, Burgas D, et al. Human-bat interactions in rural southwestern Madagascar through a biocultural lens. Journal of Ethnobiology. 2021;41(1):53-69. DOI: 10.2993/0278-0771-41.1.53'},{id:"B15",body:'Morcote-Ríos G, Aceituno FJ, Iriarte J, Robinson M, Chaparro-Cárdenas JL. colonisation and early peopling of the colombian amazon during the late pleistocene and the early holocene: New evidence from La Serranía La Lindosa. Quaternary International. 2021;578:5-19. DOI: 10.1016/j.quaint.2020.04.026'},{id:"B16",body:'Polák J, Rádlová S, Janovcová M, Flegr J, Landová E, Frynta D. Scary and nasty beasts: Self-reported fear and disgust of common phobic animals. British Journal of Psychology. 2020;111(2):297-321. DOI: 10.1111/bjop.12409'},{id:"B17",body:'Todd J. Dreaming the bat out of the shadow. Psychological Perspectives. 2016;59(2):219-241. DOI: 10.1080/00332925.2016.1170566'},{id:"B18",body:'Deshpande K, Kelkar N. How do fruit bat seed shadows benefit agroforestry? Insights from local perceptions in Kerala, India. Biotropica. 2015;47(6):654-659. DOI: 10.1111/btp.12275'},{id:"B19",body:'Fagan KE, Willcox EV, Willcox AS. Public attitudes toward the presence and management of bats roosting in buildings in Great Smoky Mountains National Park, Southeastern United State. Biological Conservation. 2018;220(1):132-139. DOI: 10.1016/j.biocon.2018.02.004'},{id:"B20",body:'Lim VC, Wilson JJ. Public perceptions and knowledge of, and responses to, bats in urban areas in Peninsular Malaysia. Anthrozoös. 2019;32(6):825-834. DOI: 10.1080/08927936.2019.1673063'},{id:"B21",body:'Shapiro HG, Willcox AS, Ader DR, Willcox EV. Attitudes towards and relationships with cave-roosting bats in northwest Cambodia. Journal of Ethnobiology. 2021;41(1):87-104. DOI: 10.2993/0278-0771-41.1.87'},{id:"B22",body:'Fernández-Llamazares Á, Cabeza M. Rediscovering the potential applications of indigenous storytelling for conservation practice. Conservation Letters. 2018;11(3):e12398. DOI: 10.1111/conl.12398'},{id:"B23",body:'Kingston T. Cute, creepy, or crispy—How values, attitudes and norms shape behavior toward bats. In: Voigt CC, Kingston T, editors. Bats in the Anthropocene: Conservation of Bats in a Changing World. Springer International Publishing; 2015. pp. 571-595. DOI: 10.1007/978-3-319-25220-9_18'},{id:"B24",body:'Lunney D, Moon C. Blind to bats. In: Law B, Eby P, Lunney D, Lumsden L, editors. The Biology and Conservation of Australasian Bats. Mosman, NSW, Australia: Royal Zoological Society of NSW; 2011. pp. 44-63. DOI: 10.7882/FS.2011.008'},{id:"B25",body:'Musila S, Prokop P, Gichuki N. Knowledge and perceptions of, and attitudes to, bats by people living around Arabuko-Sokoke Forest, Malindi-Kenya. Anthrozoös. 2018;31:247-262. DOI: 10.1080/08927936.2018.1434065'},{id:"B26",body:'Tuttle MD. Fear of bats and its consequences. Journal of Bat Research and Conservation. 2017;10(1):66-69. DOI: 10.14709/BarbJ.10.1.2017.09'},{id:"B27",body:'Prokop R, Tunnicliffe SD. “Disgusting” animals: Primary school children’s attitudes and myths of bats and spiders. Eurasia Journal of Mathematics, Science & Technology Education. 2008;4(2):87-97. DOI: 10.12973/ejmste/75309'},{id:"B28",body:'Prokop P, Fančovičová J, Kubiatko M. Vampires are still alive: Slovakian students’ attitudes toward bats. Anthrozoös. 2009;22:19-30. DOI: 10.2752/175303708X390446'},{id:"B29",body:'Rydell J, Eklöf J, Riccucci M, du Père-Lachaise C. Bats and vampires in French romanticism. Journal of Bat Research & Conservation. 2018;11:83-91. DOI: 10.14709/BarbJ.11.1.2018.10'},{id:"B30",body:'Tanalgo KC. Wildlife hunting by indigenous people in a Philippine protected area: A perspective from Mt. Apo National Park, Mindanao Island. Journal of Threatened Taxa. 2017;9:10307-10313. DOI: 10.11609/jott.2967.9.6.10307-10313'},{id:"B31",body:'Tanalgo KC, Teves RD, Salvaña FRP, Baleva RE, Tabora JAG. Human-bat interactions in caves of south-central Mindanao, Philippines. Wildlife Biology in Practice. 2016;12:1-14'},{id:"B32",body:'Tatai E. An iconographical approach to representations of the devil in medieval Hungary. Christian Demonology and Popular Mythology. 2006;2:54'},{id:"B33",body:'Charro M. Murciélagos: Príncipes de las Tinieblas. Revista Folklore. 1999;19:111-118'},{id:"B34",body:'Frembgen JW. Embodying evil and bad luck: Stray notes on the folklore of bats in southwest Asia. Asian Folklore Studies. 2006;65(2):241-247. Available from: https://www.jstor.org/stable/30030400'},{id:"B35",body:'Eklöf J, Rydell J. Attitudes towards bats in swedish history. Journal of Ethnobiology. 2021;41:35-52. DOI: 10.2993/0278-0771-41.1.35'},{id:"B36",body:'Pham HMA, Yonn-Soon L. A study on the classifications and symbolic meanings of Vietnamese traditional patterns. International Journal of Human Ecology. 2008;9(1):29-40'},{id:"B37",body:'Hall LS, Richards G. Flying Foxes: Fruit and Blossom Bats of Australia. Sydney: UNSW Press; 2000'},{id:"B38",body:'Hadnes M, Schumacher H. The Gods are watching: An experimental study of religion and traditional belief in Burkina Faso. Journal for the Scientific Study of Religion. 2012;51(4):689-704. DOI: 10.1111/j.1468-5906.2012.01676.x'},{id:"B39",body:'Retana-Guiascón OG, Navarijo-Ornelas ML. Los valores culturales de los murciélagos. Revista Mexicana de Mastozoología. 2012;2(1):18-26. DOI: 10.22201/ie.20074484e.2012.2.1.19'},{id:"B40",body:'Voigt CC, Phelps KL, Aguirre LF, Corrie Schoeman M, Vanitharani J, Zubaid A. Bats and buildings: The conservation of synanthropic bats. In: Voigt CC, Kingston T, editors. Bats in the Anthropocene: Conservation of Bats in a Changing World. Cham, Switzerland: Springer; 2016. pp. 427-462. DOI: 10.1007/978-3-319-25220-9_14'},{id:"B41",body:'Aziz SA, Clements GR, Giam X, Forget PM, Campos-Arceiz A. Coexistence and conflict between the island flying fox (Pteropus hypomelanus) and humans on Tioman Island, Peninsular Malaysia. Human Ecology. 2017;45:377-389. DOI: 10.1007/s10745-017-9905-6'},{id:"B42",body:'The Concept of the Ecosystem. Umich. Edu. 2017. Available from: https://globalchange.umich.edu/globalchange1/current/lectures/kling/ecosystem/ecosystem.html'},{id:"B43",body:'Maas B, Karp DS, Bumrungsri S, Darras K, Gonthier D, Huang JC, et al. Bird and bat predation services in tropical forests and agroforestry landscapes. Biological Reviews. 2016;91:1081-1101. DOI: 10.1111/brv.12211'},{id:"B44",body:'Puig-Montserrat X, Torre I, López-Baucells A, Guerrieri E, Monti MM, Ràfols-García R, et al. Pest control service provided by bats in mediterranean rice paddies: Linking agroecosystems structure to ecological functions. Mammalian Biology. 2015;80:237-245. DOI: 10.1016/j.mambio.2015.03.008'},{id:"B45",body:'Puig-Montserrat X, Flaquer C, Gómez-Aguilera N, Burgas A, Mas M, Tuneu C, et al. Bats actively prey on mosquitoes and other deleterious insects in rice paddies: Potential impact on human health and agriculture. Pest Management Science. 2020;76:3759-3769. DOI: 10.1002/ps.5925'},{id:"B46",body:'Wanger TC, Darras K, Bumrungsri S, Tscharntke T, Klein AM. Bat pest control contributes to food security in Thailand. Biological Conservation. 2014;171:220-223. DOI: 10.1016/j.biocon.2014.01.030'},{id:"B47",body:'Kemp J, López-Baucells A, Rocha R, Wangensteen OS, Andriatafika Z, Nair A, et al. bats as potential suppressors of multiple agricultural pests: A case study from Madagascar. Agriculture, Ecosystems & Environment. 2019;269:88-96. DOI: 10.1016/j.agee.2018.09.027'},{id:"B48",body:'Kunz TH, de Torrez EB, Bauer D, Lobova T, Fleming TH. Ecosystem services provided by bats. Annals of the New York Academy of Sciences. 2011;1223:1-38. DOI: 10.1111/j.1749-6632.2011.06004.x'},{id:"B49",body:'de Groot R, Brander L, van der Ploeg S, Costanza R, Bernard F, Braat L, et al. Global estimates of the value of ecosystems and their services in monetary units. Ecosystem Services. 2012;1:50-61. DOI: 10.1016/j.ecoser.2012.07.005'},{id:"B50",body:'Pimentel D, Krummel J, Gallahan D, Hough J, Merrill A, Schreiner I, et al. Benefits and costs of pesticide use in the US food production. Bioscience. 1978;28:778-784. DOI: 10.2307/1307251'},{id:"B51",body:'Pimentel D, McLaughlin L, Zepp A, Lakitan B, Kraus T, Kleinman P, et al. Environmental and economic effects of reducing pesticide use. Agriculture, Ecosystems & Environment. 1993;46:1-4. DOI: 10.1016/0167-8809(93)90030-S'},{id:"B52",body:'Benbrook CM. Pest management at the crossroads. New York: Consumers Union (1996). The Journal of Agricultural Science. 1998;130:119-123. DOI: 10.1017/S0021859697245120'},{id:"B53",body:'Naylor RL, Ehrlich PR. Natural pest control services and agriculture. In: Daily GC, editor. Nature’s Services. Societal Dependence on Natural Ecosystems. Washington, DC: Island Press; 1997. pp. 151-176'},{id:"B54",body:'National Research Council. Alternative Agriculture. Washington, DC: National Academies Press; 1989'},{id:"B55",body:'United States Environmental Protection Agency. Integrated Pest Management (IPM) Principles. 2009. Available from: http://www.epa.gov/opp00001/factsheets/ipm.htm'},{id:"B56",body:'Debach P, Rosen D. Biological Control by Natural Enemies. 2nd ed. London: Cambridge University Press; 1991. SB975.D39 1991'},{id:"B57",body:'Fujita MS, Tuttle MD. Flying foxes (Chiroptera: Pteropodidae): Threatened animals of key ecological and economic importance. Conservation Biology. 1991;5:455-463. DOI: 10.1111/j.1523-1739.1991.tb00352.x'},{id:"B58",body:'Whitaker JO. Food of the big brown bat Eptesicus fuscus from maternity colonies in Indiana and Illinois. American Midland Naturalist. 1995;134:346-360. DOI: 10.2307/2426304'},{id:"B59",body:'Keeley BW, Tuttle MD. Bats in American Bridges. Resource Publication #4. Austin, Tex.: Bat Conservation International, Inc.; 1999'},{id:"B60",body:'McCracken GF. Bats aloft: A study of high-altitude feeding. Bats. 1996;14:7-101'},{id:"B61",body:'Anthony ELP, Kunz TH. Feeding strategies of the little brown bat (Myotis lucifugus) in southern New Hampshire. Ecology. 1977;58:775-786. DOI: 10.2307/1936213'},{id:"B62",body:'Reiskind MH, Wund MA. Experimental assessment of the impacts of northern long-eared bats on ovipositing Culex (Diptera: Culicidae) mosquitoes. Journal of Medical Entomology. 2009;46:1037-1044. DOI: 10.1603/033.046.0510'},{id:"B63",body:'Fleming TH, Muchhala N. Nectar-feeding bird and bat niches in two worlds: Pantropical comparisons of vertebrate pollination systems. Journal of Biogeography. 2008;35:764-780. DOI: 10.1111/j.1365-2699.2007.01833.x'},{id:"B64",body:'Duncan RS, Chapman CA. Seed dispersal and potential forest succession in abandoned agriculture in tropical Africa. Ecological Applications. 1999;9:998-1008. DOI: 10.1890/1051-0761'},{id:"B65",body:'Howe HF, Smallwood J. Ecology of seed dispersal. Annual Review of Ecology and Systematics. 1982;13:201-228. DOI: 10.1146/annurev.es.13.110182.001221'},{id:"B66",body:'Boyles JG, Cryan PM, McCracken GF, Kunz TH. Economic importance of bats in agriculture. Science. 2011;332:41-42. DOI: 10.1126/science.1201366'},{id:"B67",body:'Polis GA, Anderson WB, Holt RD. Toward an integration of landscape and food web ecology: The dynamics of spatially subsidized food webs. Annual Review of Ecology and Systematics. 1997;28:289-316. DOI: 10.1146/annurev.ecolsys.28.1.289'},{id:"B68",body:'Jones G, Jacobs D, Kunz TH, Wilig MR, Racey PA. CarpeNoctem: The importance of bats as bioindicators. Endangered Species Research. 2009;8:93-115. DOI: 10.3354/esr00182'},{id:"B69",body:'Fenton MB. Science and the conservation of bats: Where to next? Wildlife Society Bulletin. 2003;31:6-15. DOI: 10.2307/3784355'},{id:"B70",body:'Fenton MB, Acharya L, Audet D, Hickey MBC, Merriman C, Obrist MK, et al. Phyllostomid bats (Chiroptera: Phyllostomidae) as indicators of habitat disruption in the neotropics. Biotropica. 1992;24:440-446. DOI: 10.2307/2388615'},{id:"B71",body:'Hutson AM, Mickleburgh SP, Racey PA. Microchiropteran Bats: Global Status Survey and Conservation Action Plan. Gland, Switzerland: IUCN/SSC chiroptera specialist group, IUCN; 2001. DOI: 10.2305/IUCN.CH.2001.SSC-AP.1.en'},{id:"B72",body:'Cleveland CJ, Betke M, Federico P, Frank JD, Hallam TG, Horn J, et al. Economic value of the pest control service provided by Brazilian free-tailed bats in south-central Texas. Frontiers in Ecology and the Environment. 2006;4:238-243. DOI: 10.1890/1540-9295'},{id:"B73",body:'Bumrungsri S, Sripaoraya E, Chongsiri T, Sridith K, Racey PA. The pollination ecology of durian (Durio zibethinus, Bombacaceae) in southern Thailand. Journal of Tropical Ecology. 2009;25:85-92. DOI: 10.1017/S0266467408005531'},{id:"B74",body:'Bumrungsri S, Harbit A, Benzie C, Carmouche K, Sridith K, Racey PA. The pollination ecology of two species of Parkia (Mimosaceae) in southern Thailand. Journal of Tropical Ecology. 2008;24:467-475. DOI: 10.1017/S0266467408005191'},{id:"B75",body:'Gallai N, Salles JM, Settele J, Vaissi’ere BE. Economic valuation of the vulnerability of world agriculture confronted with pollinator decline. Ecological Economics. 2009;68:810-821. DOI: 10.1016/j.ecolecon.2008.06.014'},{id:"B76",body:'Buddenhagen IW. Bats and disappearing wild bananas: Can bats keep commercial bananas on supermarket shelves? Bats. 2008;26:1-6'},{id:"B77",body:'Hougner C, Colding J, Söderqvist T. Economic valuation of a seed dispersal service in the Stockholm National Urban Park, Sweden. Ecological Economics. 2006;59:364-374. DOI: 10.1016/j.ecolecon.2005.11.007'},{id:"B78",body:'Tuttle MD, Moreno A. Cave-Dwelling Bats of Northern Mexico: Their Value and Conservation Needs. Austin, Texas, USA: Bat Conservation International, Inc.; 2005'},{id:"B79",body:'Hutchinson GE. Survey of existing knowledge of biogeochemistry: The biogeochemistry of vertebrate excretion. Bulletin of the American Museum of Natural History. 1950;96:1-554. Available from: http://hdl.handle.net/2246/918'},{id:"B80",body:'Tapper R. Wildlife Watching and Tourism: A Study on the Benefits and Risks of a Fast Growing Tourism Activity and Its Impacts on Species. Bonn, Germany: UNEP/CMS Secretariat; 2006'},{id:"B81",body:'Pennisi LA, Holland SM, Stein TV. Achieving bat conservation through tourism. Journal of Ecotourism. 2004;3:195-207. DOI: 10.1080/14664200508668432'},{id:"B82",body:'Brown DE. Vampiro: The Vampire Bat in Fact and Fantasy. 1st ed. Silver City, NM: High-Lonesome Books; 1994'},{id:"B83",body:'Bunget G, Seelecke S. BATMAV: A 2-DOF bio-inspired flapping flight platform. The International Society for Optics and Photonics. 2010;7643B:1-11. DOI: 10.1117/12.853398'},{id:"B84",body:'Schleuning WD. Vampire bat plasminogen activator DSPAalpha-1 (desmoteplase): A thrombolytic drug optimized by natural selection. Pathophysiology of Haemostasis and Thrombosis. 2000;31:118-122. DOI: 10.1159/000048054'},{id:"B85",body:'National Research Council. Valuing Ecosystem Services: Towards Better Environmental Decision-Making. Washington, DC: National Academies Press; 2005'},{id:"B86",body:'Ramírez-Fráncel LA, García-Herrera LV, Losada-Prado S, Reinoso-Flórez G, Sánchez-Hernández A, Estrada-Villegas S, et al. Bats and their vital ecosystem services: A global review. Integrative Zoology. 2021;0:1-22. DOI: 10.1111/1749-4877.12552'},{id:"B87",body:'Bellera EE, McClenachan L, Zavaleta ES, Larsen LG. Past forward: Recommendations from historical ecology for ecosystem management. Global Ecology and Conservation. 2020;21:e00836. DOI: 10.1016/j.gecco.2019.e00836'},{id:"B88",body:'Rülke J, Rieckmann M, Nzau JM, Teucher M. How ecocentrism and anthropocentrism influence human–environment relationships in a Kenyan biodiversity hotspot. Sustainability. 2020;12:8213. DOI: 10.3390/su12198213'},{id:"B89",body:'Ghanem SJ, Voigt CC. Increasing awareness of ecosystem services provided by bats. Advances in the Study of Behavior. 2012;44:279-302. DOI: 10.1016/b978-0-12-394288-3.00007-1'},{id:"B90",body:'Elliot WR. Protecting caves and cave life. In: Culver DC, White WB, editors. Encyclopedia of Caves. Amsterdam: Elsevier; 2014. pp. 458-467'},{id:"B91",body:'Reid JL. Knowledge and experience predict indiscriminate bat-killing intentions among Costa Rican men. Biotropica. 2016;48:394-404. DOI: 10.1111/btp.12279'},{id:"B92",body:'Frick WF, Kingston T, Flanders J. A review of the major threats and challenges to global bat conservation. Annals of the New York Academy of Sciences. 2020;1469:5-25. DOI: 10.1111/nyas.14045'},{id:"B93",body:'Olival KJ, Hosseini PR, Zambrana-Torrelio C, Ross N, Bogich TL, Daszak P. Host and viral traits predict zoonotic spillover from mammals. Nature. 2017;546:646-650. DOI: 10.1038/nature22975'},{id:"B94",body:'López-Baucells A, Rocha JR, Fernández-Llamazares Á. When bats go viral: Negative framings in virological research imperil bat conservation. Mammal Review. 2018;48:62-66. DOI: 10.17863/CAM.21045'},{id:"B95",body:'Centers for Disease Control and Prevention (CDC). Coronavirus disease 2019 (COVID-19). Atlanta, Georgia, USA: Centers for Disease Control and Prevention; 2020. Available from: https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/summary.html#emergence'},{id:"B96",body:'Dickman AJ, Hazzah L. Money, myths and man-eaters: Complexities of human– wildlife conflict. In: Angelici FM, editor. Problematic wildlife. Springer; 2016. pp. 339-356. DOI: 10.1007/978-3-319-22246-2_16'},{id:"B97",body:'MacFarlane D, Rocha R. Guidelines for communicating about bats to prevent persecution in the time of COVID-19. Biological Conservation. 2020;248:108650. DOI: 10.1016/j.biocon.2020.108650'},{id:"B98",body:'Fagan KE, Willcox EV, Willcox AS. Public attitudes toward the presence and management of bats roosting in buildings in Great Smoky Mountains National Park, Southeastern United States. Biological Conservation. 2018;220:132-139. DOI: 10.1016/j.biocon.2018.02.004'},{id:"B99",body:'Frantz SC, Laniewicz BR. Comprehensive management of commensal bats. In: Brittingham MC, Kays J, McPeake R, editors. The Ninth Wildlife Damage Management Conference Proceedings. PA, USA: State College; 2000. Available from: http://wildlifedamage.unl.edu'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Kareem M. Soliman",address:"dr_kariemsoliman@yahoo.com",affiliation:'
Faculty of Science, Ain Shams University, Cairo, Egypt
'},{corresp:null,contributorFullName:"Wiame W. Emam",address:null,affiliation:'
Faculty of Science, Ain Shams University, Cairo, Egypt
'}],corrections:null},book:{id:"11032",type:"book",title:"Bats",subtitle:"Disease-Prone but Beneficial",fullTitle:"Bats - Disease-Prone but Beneficial",slug:"bats-disease-prone-but-beneficial",publishedDate:"April 20th 2022",bookSignature:"Heimo Mikkola",coverURL:"https://cdn.intechopen.com/books/images_new/11032.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-80355-013-8",printIsbn:"978-1-80355-012-1",pdfIsbn:"978-1-80355-014-5",isAvailableForWebshopOrdering:!0,editors:[{id:"144330",title:"Dr.",name:"Heimo",middleName:"Juhani",surname:"Mikkola",slug:"heimo-mikkola",fullName:"Heimo Mikkola"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"341173",title:"Ph.D.",name:"Gadi",middleName:null,surname:"Borkow",email:"gadib@medcu.com",fullName:"Gadi Borkow",slug:"gadi-borkow",position:null,biography:null,institutionString:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"1",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:null},booksEdited:[],chaptersAuthored:[{id:"75798",title:"Copper, an Abandoned Player Returning to the Wound Healing Battle",slug:"copper-an-abandoned-player-returning-to-the-wound-healing-battle",abstract:"Copper has two key properties that endow it as an excellent active ingredient to be used in the “wound healing battle”. First, copper plays a key role in angiogenesis, dermal fibroblasts proliferation, upregulation of collagen and elastin fibers production by dermal fibroblasts, and it serves as a cofactor of Lysyl oxidase needed for efficient dermal extracellular matrix (ECM) protein cross-linking. Secondly, copper has potent wide-spectrum biocidal properties. Both gram-positive and gram-negative bacteria, including antibiotic resistant bacteria and hard to kill bacterial spores, fungi and viruses, when exposed to high copper concentrations, are killed. Copper has been used as a biocide for centuries by many different civilizations. Impregnation of copper oxide microparticles in wound dressings allows continuous release of copper ions. This results not only in the protection of the wounds and wound dressings from pathogens, but more importantly, enhances wound healing. The article discusses the molecular mechanisms of enhanced wound healing by the copper oxide impregnated dressings, which include in situ upregulation of pro-angiogenic factors and increased blood vessel formation. It also includes clinical cases showing clearance of infection, induction of granulation and epithelialization of necrotic wounds, reduction of post-operative swelling inflammation and reduction of scar formation, in wounds when they were treated with copper oxide impregnated dressings. We show the positive outcome at all wound healing stages of using the copper impregnated wound dressings, indicating the neglected critical role copper plays in wound healing.",signatures:"Gadi Borkow and Eyal Melamed",authors:[{id:"341173",title:"Ph.D.",name:"Gadi",surname:"Borkow",fullName:"Gadi Borkow",slug:"gadi-borkow",email:"gadib@medcu.com"}],book:{id:"9076",title:"Recent Advances in Wound Healing",slug:"recent-advances-in-wound-healing",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"182585",title:"Dr.",name:"Jeffrey W.",surname:"Shupp",slug:"jeffrey-w.-shupp",fullName:"Jeffrey W. Shupp",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"MedStar Washington Hospital Center",institutionURL:null,country:{name:"United States of America"}}},{id:"184084",title:"Prof.",name:"Mohammad",surname:"Bayat",slug:"mohammad-bayat",fullName:"Mohammad Bayat",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Shahid Beheshti University of Medical Sciences",institutionURL:null,country:{name:"Iran"}}},{id:"256112",title:"Prof.",name:"Sufan",surname:"Chien",slug:"sufan-chien",fullName:"Sufan Chien",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"297718",title:"BSc.",name:"Bonnie C.",surname:"Carney",slug:"bonnie-c.-carney",fullName:"Bonnie C. Carney",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Georgetown University",institutionURL:null,country:{name:"United States of America"}}},{id:"320705",title:"Dr.",name:"Priyanka",surname:"Chhabra",slug:"priyanka-chhabra",fullName:"Priyanka Chhabra",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"329488",title:"MSc.",name:"Kajol",surname:"Bhati",slug:"kajol-bhati",fullName:"Kajol Bhati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"332100",title:"Dr.",name:"Santhini",surname:"Elango",slug:"santhini-elango",fullName:"Santhini Elango",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"332102",title:"Dr.",name:"Amalorpava Mary",surname:"Loordhuswamy",slug:"amalorpava-mary-loordhuswamy",fullName:"Amalorpava Mary Loordhuswamy",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"332297",title:"Dr.",name:"Taryn E.",surname:"Travis",slug:"taryn-e.-travis",fullName:"Taryn E. Travis",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332297/images/14559_n.jpg",biography:null,institutionString:null,institution:{name:"MedStar Washington Hospital Center",institutionURL:null,country:{name:"United States of America"}}},{id:"345625",title:"Assistant Prof.",name:"Danijela",surname:"Semenič",slug:"danijela-semenic",fullName:"Danijela Semenič",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null}]},generic:{page:{slug:"open-access-funding-funders-list",title:"List of Funders by Country",intro:"
If your research is financed through any of the below-mentioned funders, please consult their Open Access policies or grant ‘terms and conditions’ to explore ways to cover your publication costs (also accessible by clicking on the link in their title).
\n\n
IMPORTANT: You must be a member or grantee of the listed funders in order to apply for their Open Access publication funds. Do not attempt to contact the funders if this is not the case.
",metaTitle:"List of Funders by Country",metaDescription:"If your research is financed through any of the below-mentioned funders, please consult their Open Access policies or grant ‘terms and conditions’ to explore ways to cover your publication costs (also accessible by clicking on the link in their title).",metaKeywords:null,canonicalURL:"/page/open-access-funding-funders-list",contentRaw:'[{"type":"htmlEditorComponent","content":"
UK Research and Innovation (former Research Councils UK (RCUK) - including AHRC, BBSRC, ESRC, EPSRC, MRC, NERC, STFC.) Processing charges for books/book chapters can be covered through RCUK block grants which are allocated to most universities in the UK, which then handle the OA publication funding requests. It is at the discretion of the university whether it will approve the request.)
UK Research and Innovation (former Research Councils UK (RCUK) - including AHRC, BBSRC, ESRC, EPSRC, MRC, NERC, STFC.) Processing charges for books/book chapters can be covered through RCUK block grants which are allocated to most universities in the UK, which then handle the OA publication funding requests. It is at the discretion of the university whether it will approve the request.)
Wellcome Trust (Funding available only to Wellcome-funded researchers/grantees)
\n
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[],filtersByRegion:[],offset:0,limit:12,total:null},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{hasNoEditors:"1",sort:"dateEndThirdStepPublish",src:"EDCMP",topicId:"5"},books:[{type:"book",id:"11605",title:"Bamboo",subtitle:null,isOpenForSubmission:!0,hash:"378d957561b27c86b750a9c7841a5d18",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11605.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11616",title:"Foraging",subtitle:null,isOpenForSubmission:!0,hash:"955b60bb658c8d1a09dd4efc9bf6674b",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11616.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11649",title:"Carnivora",subtitle:null,isOpenForSubmission:!0,hash:"cfe96fa2ecf64b22057163f9896dc476",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11649.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11792",title:"Insects as Food",subtitle:null,isOpenForSubmission:!0,hash:"4f553a9813d17305dcd47eb334670001",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11792.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11794",title:"Coconut Cultivation",subtitle:null,isOpenForSubmission:!0,hash:"48e1cb42a4162f64cae3a2e777472f21",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11794.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11809",title:"Lagomorpha",subtitle:null,isOpenForSubmission:!0,hash:"1e8fd5779205c16e5797b05455dc5be0",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/11809.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"12151",title:"Poultry Farming",subtitle:null,isOpenForSubmission:!0,hash:"acd89c676ce6c3da7af23d64e30828f6",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/12151.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"12152",title:"Goat Science",subtitle:null,isOpenForSubmission:!0,hash:"1f9e21fea921239af0661bac6ce744d9",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/12152.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"12154",title:"Organic Fertilizers",subtitle:null,isOpenForSubmission:!0,hash:"8634d6ecdb6fc207336d8b95a169e400",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/12154.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"12155",title:"Wheat",subtitle:null,isOpenForSubmission:!0,hash:"cfce6d123dc0c02739966c81c53c7567",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/12155.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"12156",title:"Legumes",subtitle:null,isOpenForSubmission:!0,hash:"a97becd6aa14a480ce28c05a3116f639",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/12156.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"12158",title:"Insecticides",subtitle:null,isOpenForSubmission:!0,hash:"247c6afbbb411e49d33864c1911b3242",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/12158.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:39},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:11},{group:"topic",caption:"Business, Management and Economics",value:7,count:7},{group:"topic",caption:"Chemistry",value:8,count:17},{group:"topic",caption:"Computer and Information Science",value:9,count:16},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:15},{group:"topic",caption:"Engineering",value:11,count:32},{group:"topic",caption:"Environmental Sciences",value:12,count:7},{group:"topic",caption:"Immunology and Microbiology",value:13,count:11},{group:"topic",caption:"Materials Science",value:14,count:11},{group:"topic",caption:"Mathematics",value:15,count:6},{group:"topic",caption:"Medicine",value:16,count:100},{group:"topic",caption:"Nanotechnology and Nanomaterials",value:17,count:2},{group:"topic",caption:"Neuroscience",value:18,count:7},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:11},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:7},{group:"topic",caption:"Robotics",value:22,count:2},{group:"topic",caption:"Social Sciences",value:23,count:32},{group:"topic",caption:"Technology",value:24,count:1}],offset:12,limit:12,total:39},popularBooks:{featuredBooks:[{type:"book",id:"9974",title:"E-Learning and Digital Education in the Twenty-First Century",subtitle:null,isOpenForSubmission:!1,hash:"88b58d66e975df20425fc1dfd22d53aa",slug:"e-learning-and-digital-education-in-the-twenty-first-century",bookSignature:"M. Mahruf C. Shohel",coverURL:"https://cdn.intechopen.com/books/images_new/9974.jpg",editors:[{id:"94099",title:"Dr.",name:"M. Mahruf C.",middleName:null,surname:"Shohel",slug:"m.-mahruf-c.-shohel",fullName:"M. Mahruf C. Shohel"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"11001",title:"Density Functional Theory",subtitle:"Recent Advances, New Perspectives and Applications",isOpenForSubmission:!1,hash:"82d53383af78ab41eb982086c02fb2bb",slug:"density-functional-theory-recent-advances-new-perspectives-and-applications",bookSignature:"Daniel Glossman-Mitnik",coverURL:"https://cdn.intechopen.com/books/images_new/11001.jpg",editors:[{id:"198499",title:"Dr.",name:"Daniel",middleName:null,surname:"Glossman-Mitnik",slug:"daniel-glossman-mitnik",fullName:"Daniel Glossman-Mitnik"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10356",title:"Natural Medicinal Plants",subtitle:null,isOpenForSubmission:!1,hash:"943e56ccaaf19ff696d25aa638ae37d6",slug:"natural-medicinal-plants",bookSignature:"Hany A. El-Shemy",coverURL:"https://cdn.intechopen.com/books/images_new/10356.jpg",editors:[{id:"54719",title:"Prof.",name:"Hany",middleName:null,surname:"El-Shemy",slug:"hany-el-shemy",fullName:"Hany El-Shemy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"11752",title:"Natural Drugs from Plants",subtitle:null,isOpenForSubmission:!1,hash:"a0a83c0822608ef7592bf16a5ed0ada4",slug:"natural-drugs-from-plants",bookSignature:"Hany A. El-Shemy",coverURL:"https://cdn.intechopen.com/books/images_new/11752.jpg",editors:[{id:"54719",title:"Prof.",name:"Hany",middleName:null,surname:"El-Shemy",slug:"hany-el-shemy",fullName:"Hany El-Shemy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10251",title:"Plankton Communities",subtitle:null,isOpenForSubmission:!1,hash:"e11e441ca2d2d5f631b1b4704505cfb6",slug:"plankton-communities",bookSignature:"Leonel Pereira and Ana Marta Gonçalves",coverURL:"https://cdn.intechopen.com/books/images_new/10251.jpg",editors:[{id:"279788",title:"Dr.",name:"Leonel",middleName:null,surname:"Pereira",slug:"leonel-pereira",fullName:"Leonel Pereira"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10830",title:"Animal Feed Science and Nutrition",subtitle:"Production, Health and Environment",isOpenForSubmission:!1,hash:"79944fc8fbbaa329aed6fde388154832",slug:"animal-feed-science-and-nutrition-production-health-and-environment",bookSignature:"Amlan Kumar Patra",coverURL:"https://cdn.intechopen.com/books/images_new/10830.jpg",editors:[{id:"310962",title:"Dr.",name:"Amlan",middleName:"Kumar",surname:"Patra",slug:"amlan-patra",fullName:"Amlan Patra"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10584",title:"Engineered Wood Products for Construction",subtitle:null,isOpenForSubmission:!1,hash:"421757c56a3735986055250821275a51",slug:"engineered-wood-products-for-construction",bookSignature:"Meng Gong",coverURL:"https://cdn.intechopen.com/books/images_new/10584.jpg",editors:[{id:"274242",title:"Dr.",name:"Meng",middleName:null,surname:"Gong",slug:"meng-gong",fullName:"Meng Gong"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9670",title:"Current Trends in Wheat Research",subtitle:null,isOpenForSubmission:!1,hash:"89d795987f1747a76eee532700d2093d",slug:"current-trends-in-wheat-research",bookSignature:"Mahmood-ur-Rahman Ansari",coverURL:"https://cdn.intechopen.com/books/images_new/9670.jpg",editors:[{id:"185476",title:"Dr.",name:"Mahmood-ur-Rahman",middleName:null,surname:"Ansari",slug:"mahmood-ur-rahman-ansari",fullName:"Mahmood-ur-Rahman Ansari"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9032",title:"Corporate Social Responsibility",subtitle:null,isOpenForSubmission:!1,hash:"f609bf3251d7cc7bae0099a4374adfc3",slug:"corporate-social-responsibility",bookSignature:"Beatrice Orlando",coverURL:"https://cdn.intechopen.com/books/images_new/9032.jpg",editors:[{id:"232969",title:"Prof.",name:"Beatrice",middleName:null,surname:"Orlando",slug:"beatrice-orlando",fullName:"Beatrice Orlando"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10681",title:"Biodegradation Technology of Organic and Inorganic Pollutants",subtitle:null,isOpenForSubmission:!1,hash:"9a6e10e02788092872fd249436898e97",slug:"biodegradation-technology-of-organic-and-inorganic-pollutants",bookSignature:"Kassio Ferreira Mendes, Rodrigo Nogueira de Sousa and Kamila Cabral Mielke",coverURL:"https://cdn.intechopen.com/books/images_new/10681.jpg",editors:[{id:"197720",title:"Ph.D.",name:"Kassio",middleName:null,surname:"Ferreira Mendes",slug:"kassio-ferreira-mendes",fullName:"Kassio Ferreira Mendes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9808",title:"Contemporary Topics in Patient Safety",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"fb6371607c2c6c02c6a2af8892765aba",slug:"contemporary-topics-in-patient-safety-volume-1",bookSignature:"Stanislaw P. Stawicki and Michael S. Firstenberg",coverURL:"https://cdn.intechopen.com/books/images_new/9808.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9544",title:"Global Trade in the Emerging Business Environment",subtitle:null,isOpenForSubmission:!1,hash:"fb8cb09b9599246add78d508a98273d5",slug:"global-trade-in-the-emerging-business-environment",bookSignature:"Muhammad Mohiuddin, Jingbin Wang , Md. Samim Al Azad and Selim Ahmed",coverURL:"https://cdn.intechopen.com/books/images_new/9544.jpg",editors:[{id:"418514",title:"Dr.",name:"Muhammad",middleName:null,surname:"Mohiuddin",slug:"muhammad-mohiuddin",fullName:"Muhammad Mohiuddin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:4380},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9974",title:"E-Learning and Digital Education in the Twenty-First Century",subtitle:null,isOpenForSubmission:!1,hash:"88b58d66e975df20425fc1dfd22d53aa",slug:"e-learning-and-digital-education-in-the-twenty-first-century",bookSignature:"M. Mahruf C. Shohel",coverURL:"https://cdn.intechopen.com/books/images_new/9974.jpg",publishedDate:"May 18th 2022",numberOfDownloads:3385,editors:[{id:"94099",title:"Dr.",name:"M. Mahruf C.",middleName:null,surname:"Shohel",slug:"m.-mahruf-c.-shohel",fullName:"M. Mahruf C. Shohel"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"11001",title:"Density Functional Theory",subtitle:"Recent Advances, New Perspectives and Applications",isOpenForSubmission:!1,hash:"82d53383af78ab41eb982086c02fb2bb",slug:"density-functional-theory-recent-advances-new-perspectives-and-applications",bookSignature:"Daniel Glossman-Mitnik",coverURL:"https://cdn.intechopen.com/books/images_new/11001.jpg",publishedDate:"May 18th 2022",numberOfDownloads:1875,editors:[{id:"198499",title:"Dr.",name:"Daniel",middleName:null,surname:"Glossman-Mitnik",slug:"daniel-glossman-mitnik",fullName:"Daniel Glossman-Mitnik"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10356",title:"Natural Medicinal Plants",subtitle:null,isOpenForSubmission:!1,hash:"943e56ccaaf19ff696d25aa638ae37d6",slug:"natural-medicinal-plants",bookSignature:"Hany A. El-Shemy",coverURL:"https://cdn.intechopen.com/books/images_new/10356.jpg",publishedDate:"May 11th 2022",numberOfDownloads:3842,editors:[{id:"54719",title:"Prof.",name:"Hany",middleName:null,surname:"El-Shemy",slug:"hany-el-shemy",fullName:"Hany El-Shemy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"11752",title:"Natural Drugs from Plants",subtitle:null,isOpenForSubmission:!1,hash:"a0a83c0822608ef7592bf16a5ed0ada4",slug:"natural-drugs-from-plants",bookSignature:"Hany A. El-Shemy",coverURL:"https://cdn.intechopen.com/books/images_new/11752.jpg",publishedDate:"May 11th 2022",numberOfDownloads:3008,editors:[{id:"54719",title:"Prof.",name:"Hany",middleName:null,surname:"El-Shemy",slug:"hany-el-shemy",fullName:"Hany El-Shemy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10251",title:"Plankton Communities",subtitle:null,isOpenForSubmission:!1,hash:"e11e441ca2d2d5f631b1b4704505cfb6",slug:"plankton-communities",bookSignature:"Leonel Pereira and Ana Marta Gonçalves",coverURL:"https://cdn.intechopen.com/books/images_new/10251.jpg",publishedDate:"May 18th 2022",numberOfDownloads:1109,editors:[{id:"279788",title:"Dr.",name:"Leonel",middleName:null,surname:"Pereira",slug:"leonel-pereira",fullName:"Leonel Pereira"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10830",title:"Animal Feed Science and Nutrition",subtitle:"Production, Health and Environment",isOpenForSubmission:!1,hash:"79944fc8fbbaa329aed6fde388154832",slug:"animal-feed-science-and-nutrition-production-health-and-environment",bookSignature:"Amlan Kumar Patra",coverURL:"https://cdn.intechopen.com/books/images_new/10830.jpg",publishedDate:"May 18th 2022",numberOfDownloads:1010,editors:[{id:"310962",title:"Dr.",name:"Amlan",middleName:"Kumar",surname:"Patra",slug:"amlan-patra",fullName:"Amlan Patra"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10584",title:"Engineered Wood Products for Construction",subtitle:null,isOpenForSubmission:!1,hash:"421757c56a3735986055250821275a51",slug:"engineered-wood-products-for-construction",bookSignature:"Meng Gong",coverURL:"https://cdn.intechopen.com/books/images_new/10584.jpg",publishedDate:"April 28th 2022",numberOfDownloads:3918,editors:[{id:"274242",title:"Dr.",name:"Meng",middleName:null,surname:"Gong",slug:"meng-gong",fullName:"Meng Gong"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9670",title:"Current Trends in Wheat Research",subtitle:null,isOpenForSubmission:!1,hash:"89d795987f1747a76eee532700d2093d",slug:"current-trends-in-wheat-research",bookSignature:"Mahmood-ur-Rahman Ansari",coverURL:"https://cdn.intechopen.com/books/images_new/9670.jpg",publishedDate:"May 11th 2022",numberOfDownloads:1654,editors:[{id:"185476",title:"Dr.",name:"Mahmood-ur-Rahman",middleName:null,surname:"Ansari",slug:"mahmood-ur-rahman-ansari",fullName:"Mahmood-ur-Rahman Ansari"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9032",title:"Corporate Social Responsibility",subtitle:null,isOpenForSubmission:!1,hash:"f609bf3251d7cc7bae0099a4374adfc3",slug:"corporate-social-responsibility",bookSignature:"Beatrice Orlando",coverURL:"https://cdn.intechopen.com/books/images_new/9032.jpg",publishedDate:"March 16th 2022",numberOfDownloads:7686,editors:[{id:"232969",title:"Prof.",name:"Beatrice",middleName:null,surname:"Orlando",slug:"beatrice-orlando",fullName:"Beatrice Orlando"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10681",title:"Biodegradation Technology of Organic and Inorganic Pollutants",subtitle:null,isOpenForSubmission:!1,hash:"9a6e10e02788092872fd249436898e97",slug:"biodegradation-technology-of-organic-and-inorganic-pollutants",bookSignature:"Kassio Ferreira Mendes, Rodrigo Nogueira de Sousa and Kamila Cabral Mielke",coverURL:"https://cdn.intechopen.com/books/images_new/10681.jpg",publishedDate:"April 20th 2022",numberOfDownloads:3444,editors:[{id:"197720",title:"Ph.D.",name:"Kassio",middleName:null,surname:"Ferreira Mendes",slug:"kassio-ferreira-mendes",fullName:"Kassio Ferreira Mendes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"10251",title:"Plankton Communities",subtitle:null,isOpenForSubmission:!1,hash:"e11e441ca2d2d5f631b1b4704505cfb6",slug:"plankton-communities",bookSignature:"Leonel Pereira and Ana Marta Gonçalves",coverURL:"https://cdn.intechopen.com/books/images_new/10251.jpg",editedByType:"Edited by",publishedDate:"May 18th 2022",editors:[{id:"279788",title:"Dr.",name:"Leonel",middleName:null,surname:"Pereira",slug:"leonel-pereira",fullName:"Leonel Pereira"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10830",title:"Animal Feed Science and Nutrition",subtitle:"Production, Health and Environment",isOpenForSubmission:!1,hash:"79944fc8fbbaa329aed6fde388154832",slug:"animal-feed-science-and-nutrition-production-health-and-environment",bookSignature:"Amlan Kumar Patra",coverURL:"https://cdn.intechopen.com/books/images_new/10830.jpg",editedByType:"Edited by",publishedDate:"May 18th 2022",editors:[{id:"310962",title:"Dr.",name:"Amlan",middleName:"Kumar",surname:"Patra",slug:"amlan-patra",fullName:"Amlan Patra"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10853",title:"Recent Advances in Polynomials",subtitle:null,isOpenForSubmission:!1,hash:"9e8671bae09ccaa8b8e276c639a737fc",slug:"recent-advances-in-polynomials",bookSignature:"Kamal Shah",coverURL:"https://cdn.intechopen.com/books/images_new/10853.jpg",editedByType:"Edited by",publishedDate:"May 18th 2022",editors:[{id:"231748",title:"Dr.",name:"Kamal",middleName:null,surname:"Shah",slug:"kamal-shah",fullName:"Kamal Shah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10871",title:"Computed-Tomography (CT) Scan",subtitle:null,isOpenForSubmission:!1,hash:"966d8cf74fa27eea1b9cbc9a6ee94993",slug:"computed-tomography-ct-scan",bookSignature:"Reda R. Gharieb",coverURL:"https://cdn.intechopen.com/books/images_new/10871.jpg",editedByType:"Edited by",publishedDate:"May 18th 2022",editors:[{id:"225387",title:"Prof.",name:"Reda R.",middleName:"R.",surname:"Gharieb",slug:"reda-r.-gharieb",fullName:"Reda R. Gharieb"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10903",title:"Genetically Modified Plants and Beyond",subtitle:null,isOpenForSubmission:!1,hash:"4d7ed4faab99c92cd4d676dc86501df9",slug:"genetically-modified-plants-and-beyond",bookSignature:"Idah Sithole Niang",coverURL:"https://cdn.intechopen.com/books/images_new/10903.jpg",editedByType:"Edited by",publishedDate:"May 18th 2022",editors:[{id:"90172",title:"Prof.",name:"Idah",middleName:null,surname:"Sithole-Niang",slug:"idah-sithole-niang",fullName:"Idah Sithole-Niang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10904",title:"Fusarium",subtitle:"An Overview of the Genus",isOpenForSubmission:!1,hash:"49d9063e43f94bd1517d65fbc58b93c3",slug:"fusarium-an-overview-of-the-genus",bookSignature:"Seyed Mahyar Mirmajlessi",coverURL:"https://cdn.intechopen.com/books/images_new/10904.jpg",editedByType:"Edited by",publishedDate:"May 18th 2022",editors:[{id:"100573",title:"Dr.",name:"Seyed Mahyar",middleName:null,surname:"Mirmajlessi",slug:"seyed-mahyar-mirmajlessi",fullName:"Seyed Mahyar Mirmajlessi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10654",title:"Brain-Computer Interface",subtitle:null,isOpenForSubmission:!1,hash:"a5308884068cc53ed31c6baba756857f",slug:"brain-computer-interface",bookSignature:"Vahid Asadpour",coverURL:"https://cdn.intechopen.com/books/images_new/10654.jpg",editedByType:"Edited by",publishedDate:"May 18th 2022",editors:[{id:"165328",title:"Dr.",name:"Vahid",middleName:null,surname:"Asadpour",slug:"vahid-asadpour",fullName:"Vahid Asadpour"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10676",title:"Recent Applications in Graph Theory",subtitle:null,isOpenForSubmission:!1,hash:"900c60742d224080732bd16bd25ccba8",slug:"recent-applications-in-graph-theory",bookSignature:"Harun Pirim",coverURL:"https://cdn.intechopen.com/books/images_new/10676.jpg",editedByType:"Edited by",publishedDate:"May 18th 2022",editors:[{id:"146092",title:"Dr.",name:"Harun",middleName:null,surname:"Pirim",slug:"harun-pirim",fullName:"Harun Pirim"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11196",title:"New Updates in E-Learning",subtitle:null,isOpenForSubmission:!1,hash:"6afaadf68e2a0a4b370ac5ceb5ca89c6",slug:"new-updates-in-e-learning",bookSignature:"Eduard Babulak",coverURL:"https://cdn.intechopen.com/books/images_new/11196.jpg",editedByType:"Edited by",publishedDate:"May 18th 2022",editors:[{id:"10086",title:"Prof.",name:"Eduard",middleName:null,surname:"Babulak",slug:"eduard-babulak",fullName:"Eduard Babulak"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9974",title:"E-Learning and Digital Education in the Twenty-First Century",subtitle:null,isOpenForSubmission:!1,hash:"88b58d66e975df20425fc1dfd22d53aa",slug:"e-learning-and-digital-education-in-the-twenty-first-century",bookSignature:"M. Mahruf C. Shohel",coverURL:"https://cdn.intechopen.com/books/images_new/9974.jpg",editedByType:"Edited by",publishedDate:"May 18th 2022",editors:[{id:"94099",title:"Dr.",name:"M. Mahruf C.",middleName:null,surname:"Shohel",slug:"m.-mahruf-c.-shohel",fullName:"M. Mahruf C. Shohel"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"8",title:"Chemistry",slug:"chemistry",parent:{id:"1",title:"Physical Sciences, Engineering and Technology",slug:"physical-sciences-engineering-and-technology"},numberOfBooks:188,numberOfSeries:0,numberOfAuthorsAndEditors:4202,numberOfWosCitations:8457,numberOfCrossrefCitations:4329,numberOfDimensionsCitations:10902,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicId:"8",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"10861",title:"Furan Derivatives",subtitle:"Recent Advances and Applications",isOpenForSubmission:!1,hash:"fdfc39cecd82f91b0effac994f75c877",slug:"furan-derivatives-recent-advances-and-applications",bookSignature:"Anish Khan, Mohammed Muzibur Rahman, M. Ramesh, Salman Ahmad Khan and Abdullah Mohammed Ahmed Asiri",coverURL:"https://cdn.intechopen.com/books/images_new/10861.jpg",editedByType:"Edited by",editors:[{id:"293058",title:"Dr.",name:"Anish",middleName:null,surname:"Khan",slug:"anish-khan",fullName:"Anish Khan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9937",title:"Recent Advances in Gas Chromatography",subtitle:null,isOpenForSubmission:!1,hash:"2d37a39be8412d39e729669c9c73ebb8",slug:"recent-advances-in-gas-chromatography",bookSignature:"Fabrice Mutelet",coverURL:"https://cdn.intechopen.com/books/images_new/9937.jpg",editedByType:"Edited by",editors:[{id:"186677",title:"Dr.",name:"Fabrice",middleName:null,surname:"Mutelet",slug:"fabrice-mutelet",fullName:"Fabrice Mutelet"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10999",title:"Carbene",subtitle:null,isOpenForSubmission:!1,hash:"605a68d742896b92a81b245cdacc150a",slug:"carbene",bookSignature:"Satyen Saha and Arunava Manna",coverURL:"https://cdn.intechopen.com/books/images_new/10999.jpg",editedByType:"Edited by",editors:[{id:"226917",title:"Dr.",name:"Satyen",middleName:null,surname:"Saha",slug:"satyen-saha",fullName:"Satyen Saha"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10884",title:"Bisphenols",subtitle:null,isOpenForSubmission:!1,hash:"d73ec720cb7577731662ac9d02879729",slug:"bisphenols",bookSignature:"Pınar Erkekoğlu",coverURL:"https://cdn.intechopen.com/books/images_new/10884.jpg",editedByType:"Edited by",editors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoğlu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoğlu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10581",title:"Alkaline Chemistry and Applications",subtitle:null,isOpenForSubmission:!1,hash:"4ed90bdab4a7211c13cd432aa079cd20",slug:"alkaline-chemistry-and-applications",bookSignature:"Riadh Marzouki",coverURL:"https://cdn.intechopen.com/books/images_new/10581.jpg",editedByType:"Edited by",editors:[{id:"300527",title:"Dr.",name:"Riadh",middleName:null,surname:"Marzouki",slug:"riadh-marzouki",fullName:"Riadh Marzouki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10799",title:"Phenolic Compounds",subtitle:"Chemistry, Synthesis, Diversity, Non-Conventional Industrial, Pharmaceutical and Therapeutic Applications",isOpenForSubmission:!1,hash:"339199f254d2987ef3167eef74fb8a38",slug:"phenolic-compounds-chemistry-synthesis-diversity-non-conventional-industrial-pharmaceutical-and-therapeutic-applications",bookSignature:"Farid A. Badria",coverURL:"https://cdn.intechopen.com/books/images_new/10799.jpg",editedByType:"Edited by",editors:[{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11072",title:"Sample Preparation Techniques for Chemical Analysis",subtitle:null,isOpenForSubmission:!1,hash:"38fecf7570774c29c22a0cbca58ba570",slug:"sample-preparation-techniques-for-chemical-analysis",bookSignature:"Massoud Kaykhaii",coverURL:"https://cdn.intechopen.com/books/images_new/11072.jpg",editedByType:"Edited by",editors:[{id:"349151",title:"Prof.",name:"Massoud",middleName:null,surname:"Kaykhaii",slug:"massoud-kaykhaii",fullName:"Massoud Kaykhaii"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10443",title:"Accenting Lipid Peroxidation",subtitle:null,isOpenForSubmission:!1,hash:"783b476008fbd1917ab059fb9f07b93c",slug:"accenting-lipid-peroxidation",bookSignature:"Pınar Atukeren",coverURL:"https://cdn.intechopen.com/books/images_new/10443.jpg",editedByType:"Edited by",editors:[{id:"54960",title:"Dr.",name:"Pınar",middleName:null,surname:"Atukeren",slug:"pinar-atukeren",fullName:"Pınar Atukeren"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10776",title:"Cellulose Science and Derivatives",subtitle:null,isOpenForSubmission:!1,hash:"947660259ce1915c3cac58bf7d990424",slug:"cellulose-science-and-derivatives",bookSignature:"Arpit Sand and Sangita Banga",coverURL:"https://cdn.intechopen.com/books/images_new/10776.jpg",editedByType:"Edited by",editors:[{id:"287032",title:"Associate Prof.",name:"Arpit",middleName:null,surname:"Sand",slug:"arpit-sand",fullName:"Arpit Sand"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10701",title:"Alkenes",subtitle:"Recent Advances, New Perspectives and Applications",isOpenForSubmission:!1,hash:"f6dd394ef1ca2d6472220de6a79a0d9a",slug:"alkenes-recent-advances-new-perspectives-and-applications",bookSignature:"Reza Davarnejad",coverURL:"https://cdn.intechopen.com/books/images_new/10701.jpg",editedByType:"Edited by",editors:[{id:"88069",title:"Associate Prof.",name:"Reza",middleName:null,surname:"Davarnejad",slug:"reza-davarnejad",fullName:"Reza Davarnejad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9932",title:"Analytical Chemistry",subtitle:"Advancement, Perspectives and Applications",isOpenForSubmission:!1,hash:"18f54a89cdbbafde70f56e55e122171a",slug:"analytical-chemistry-advancement-perspectives-and-applications",bookSignature:"Abhay Nanda Srivastva",coverURL:"https://cdn.intechopen.com/books/images_new/9932.jpg",editedByType:"Edited by",editors:[{id:"293623",title:"Dr.",name:"Abhay Nanda",middleName:null,surname:"Srivastva",slug:"abhay-nanda-srivastva",fullName:"Abhay Nanda Srivastva"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10507",title:"Current Topics in Chirality",subtitle:"From Chemistry to Biology",isOpenForSubmission:!1,hash:"692993cd6e2996714124df690df7c2e9",slug:"current-topics-in-chirality-from-chemistry-to-biology",bookSignature:"Takashiro Akitsu",coverURL:"https://cdn.intechopen.com/books/images_new/10507.jpg",editedByType:"Edited by",editors:[{id:"147861",title:"Dr.",name:"Takashiro",middleName:null,surname:"Akitsu",slug:"takashiro-akitsu",fullName:"Takashiro Akitsu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:188,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"36171",doi:"10.5772/36942",title:"Research of Calcium Phosphates Using Fourier Transform Infrared Spectroscopy",slug:"research-of-calcium-phosphates-using-fourier-transformation-infrared-spectroscopy",totalDownloads:9190,totalCrossrefCites:128,totalDimensionsCites:369,abstract:null,book:{id:"1591",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",title:"Infrared Spectroscopy",fullTitle:"Infrared Spectroscopy - Materials Science, Engineering and Technology"},signatures:"Liga Berzina-Cimdina and Natalija Borodajenko",authors:[{id:"110522",title:"Prof.",name:"Liga",middleName:null,surname:"Berzina-Cimdina",slug:"liga-berzina-cimdina",fullName:"Liga Berzina-Cimdina"},{id:"112181",title:"MSc.",name:"Natalija",middleName:null,surname:"Borodajenko",slug:"natalija-borodajenko",fullName:"Natalija Borodajenko"}]},{id:"36178",doi:"10.5772/36323",title:"Applications of FTIR on Epoxy Resins - Identification, Monitoring the Curing Process, Phase Separation and Water Uptake",slug:"applications-of-ftir-on-epoxy-resins-identification-monitoring-the-curing-process-phase-separatio",totalDownloads:20770,totalCrossrefCites:81,totalDimensionsCites:248,abstract:null,book:{id:"1591",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",title:"Infrared Spectroscopy",fullTitle:"Infrared Spectroscopy - Materials Science, Engineering and Technology"},signatures:"María González González, Juan Carlos Cabanelas and Juan Baselga",authors:[{id:"107857",title:"Prof.",name:"Juan",middleName:null,surname:"Baselga",slug:"juan-baselga",fullName:"Juan Baselga"},{id:"138113",title:"Dr.",name:"María",middleName:null,surname:"González",slug:"maria-gonzalez",fullName:"María González"},{id:"138114",title:"Dr.",name:"Juan C.",middleName:null,surname:"Cabanelas",slug:"juan-c.-cabanelas",fullName:"Juan C. Cabanelas"}]},{id:"53973",doi:"10.5772/66927",title:"Phenolic Compounds in Water: Sources, Reactivity, Toxicity and Treatment Methods",slug:"phenolic-compounds-in-water-sources-reactivity-toxicity-and-treatment-methods",totalDownloads:7209,totalCrossrefCites:70,totalDimensionsCites:152,abstract:"Phenolic compounds exist in water bodies due to the discharge of polluted wastewater from industrial, agricultural and domestic activities into water bodies. They also occur as a result of natural phenomena. These compounds are known to be toxic and inflict both severe and long‐lasting effects on both humans and animals. They act as carcinogens and cause damage to the red blood cells and the liver, even at low concentrations. Interaction of these compounds with microorganisms, inorganic and other organic compounds in water can produce substituted compounds or other moieties, which may be as toxic as the original phenolic compounds. This chapter dwells on the sources and reactivity of phenolic compounds in water, their toxic effects on humans, and methods of their removal from water. Specific emphasis is placed on the techniques of their removal from water with attention on both conventional and advanced methods. Among these methods are ozonation, adsorption, extraction, photocatalytic degradation, biological, electro‐Fenton, adsorption and ion exchange and membrane‐based separation.",book:{id:"6029",slug:"phenolic-compounds-natural-sources-importance-and-applications",title:"Phenolic Compounds",fullTitle:"Phenolic Compounds - Natural Sources, Importance and Applications"},signatures:"William W. Anku, Messai A. Mamo and Penny P. Govender",authors:[{id:"195237",title:"Dr.",name:"Messai",middleName:"A.",surname:"Mamo",slug:"messai-mamo",fullName:"Messai Mamo"},{id:"196465",title:"Dr.",name:"William Wilson",middleName:null,surname:"Anku",slug:"william-wilson-anku",fullName:"William Wilson Anku"},{id:"196466",title:"Dr.",name:"Penny",middleName:null,surname:"Govender",slug:"penny-govender",fullName:"Penny Govender"}]},{id:"36184",doi:"10.5772/36186",title:"Infrared Spectroscopy in the Analysis of Building and Construction Materials",slug:"infrared-spectroscopy-of-cementitious-materials",totalDownloads:7767,totalCrossrefCites:74,totalDimensionsCites:149,abstract:null,book:{id:"1591",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",title:"Infrared Spectroscopy",fullTitle:"Infrared Spectroscopy - Materials Science, Engineering and Technology"},signatures:"Lucia Fernández-Carrasco, D. Torrens-Martín, L.M. Morales and Sagrario Martínez-Ramírez",authors:[{id:"107401",title:"Dr.",name:"Lucia J",middleName:null,surname:"Fernández",slug:"lucia-j-fernandez",fullName:"Lucia J Fernández"}]},{id:"53128",doi:"10.5772/66368",title:"Phenolic Compounds: Functional Properties, Impact of Processing and Bioavailability",slug:"phenolic-compounds-functional-properties-impact-of-processing-and-bioavailability",totalDownloads:9257,totalCrossrefCites:73,totalDimensionsCites:137,abstract:"In this chapter, we discuss the influence of the processing methods on the content of phenolic compounds in fruits and vegetables. The intake of fruits and vegetables based‐foods are associated with delayed aging and a decreased risk of chronic disease development. Fruits and vegetables can be consumed in natura, but the highest amounts are ingested after some processing methods, such as cooking procedures or sanitizing methods. These methods are directly methods are directly related to alteration on the phenolic content. In addition, the postharvest conditions may modify several phytochemical substances. Phenolic compounds are referred to as phytochemicals found in a large number of foods and beverages. The relative high diversity of these molecules produced by plants must be taken into account when methods of preparation are employed to obtain industrial or homemade products. Phenolic compounds comprise one (phenolic acids) or more (polyphenols) aromatic rings with attached hydroxyl groups in their structures. Their antioxidant capacities are related to these hydroxyl groups and phenolic rings. Despite the antioxidant activity, they have many other beneficial effects on human health. However, before attributing health benefits to these compounds, absorption, distribution, and metabolism of each phenolic compound in the body are important points that should be considered.",book:{id:"5609",slug:"phenolic-compounds-biological-activity",title:"Phenolic Compounds",fullTitle:"Phenolic Compounds - Biological Activity"},signatures:"Igor Otavio Minatel, Cristine Vanz Borges, Maria Izabela Ferreira,\nHector Alonzo Gomez Gomez, Chung-Yen Oliver Chen and\nGiuseppina Pace Pereira Lima",authors:[{id:"146379",title:"Dr.",name:"Giuseppina",middleName:null,surname:"Lima",slug:"giuseppina-lima",fullName:"Giuseppina Lima"},{id:"194002",title:"MSc.",name:"Cristine",middleName:null,surname:"Vanz Borges",slug:"cristine-vanz-borges",fullName:"Cristine Vanz Borges"},{id:"194003",title:"Prof.",name:"Igor Otavio",middleName:null,surname:"Minatel",slug:"igor-otavio-minatel",fullName:"Igor Otavio Minatel"},{id:"194004",title:"Dr.",name:"Maria Izabela",middleName:null,surname:"Ferreira",slug:"maria-izabela-ferreira",fullName:"Maria Izabela Ferreira"},{id:"194005",title:"Prof.",name:"Hector",middleName:null,surname:"Gomez-Gomez",slug:"hector-gomez-gomez",fullName:"Hector Gomez-Gomez"},{id:"194006",title:"Prof.",name:"Chung-Yen Oliver",middleName:null,surname:"Chen",slug:"chung-yen-oliver-chen",fullName:"Chung-Yen Oliver Chen"}]}],mostDownloadedChaptersLast30Days:[{id:"55500",title:"Interpretation of Mass Spectra",slug:"interpretation-of-mass-spectra",totalDownloads:12288,totalCrossrefCites:10,totalDimensionsCites:23,abstract:"The chapter includes an introduction to the main ionisation techniques in mass spectrometry and the way the resulting fragments can be analysed. First, the fundamental notions of mass spectrometry are explained, so that the reader can easily cover this chapter (graphs, main pick, molecular ion, illogical pick, nitrogen rule, etc.). Isotopic percentage and nominal mass calculation are also explained along with fragmentation mechanism. A paragraph emphasises the ionisation energy issues, the basics of ionisation voltage, the developing potential and the energy balance. A frame time of the main theoretical milestones in both theory and experimental mass spectrometry is highlighted here. In the second part of the chapter, the molecular fragmentation for alkanes, iso-alkanes, cycloalkanes, halogen, alcohols, phenols, ethers, carbonyl compounds, carboxylic acids and functional derivatives, nitrogen compounds (amines, nitro compounds), sulphur compounds, heterocycles and biomolecules (amino acids, steroids, triglycerides) is explained. Fragmentation schemes are followed by the simplified spectra, which help the understanding of such complex phenomena. At the end of the chapter, acquisition of mass spectrum is discussed. The chapter presented here is an introduction to mass spectrometry, which, we think, helps the understanding of the mechanism of fragmentation corroborating spectral data and molecular structures.",book:{id:"5735",slug:"mass-spectrometry",title:"Mass Spectrometry",fullTitle:"Mass Spectrometry"},signatures:"Teodor Octavian Nicolescu",authors:[{id:"196775",title:"Dr.",name:"Teodor Octavian",middleName:"Octavian",surname:"Nicolescu",slug:"teodor-octavian-nicolescu",fullName:"Teodor Octavian Nicolescu"}]},{id:"57909",title:"Validation of Analytical Methods",slug:"validation-of-analytical-methods",totalDownloads:6777,totalCrossrefCites:12,totalDimensionsCites:19,abstract:"Method validation is a key element in the establishment of reference methods and within the assessment of a laboratory’s competence in generating dependable analytical records. Validation has been placed within the context of the procedure, generating chemical data. Analytical method validation, thinking about the maximum relevant processes for checking the best parameters of analytical methods, using numerous relevant overall performance indicators inclusive of selectivity, specificity, accuracy, precision, linearity, range, limit of detection (LOD), limit of quantification (LOQ), ruggedness, and robustness are severely discussed in an effort to prevent their misguided utilization and ensure scientific correctness and consistency among publications.",book:{id:"6379",slug:"calibration-and-validation-of-analytical-methods-a-sampling-of-current-approaches",title:"Calibration and Validation of Analytical Methods",fullTitle:"Calibration and Validation of Analytical Methods - A Sampling of Current Approaches"},signatures:"Tentu Nageswara Rao",authors:[{id:"220824",title:"Dr.",name:"Tentu",middleName:null,surname:"Nageswara Rao",slug:"tentu-nageswara-rao",fullName:"Tentu Nageswara Rao"}]},{id:"55440",title:"Solubility Products and Solubility Concepts",slug:"solubility-products-and-solubility-concepts",totalDownloads:2888,totalCrossrefCites:6,totalDimensionsCites:7,abstract:"The chapter refers to a general concept of solubility product Ksp of sparingly soluble hydroxides and different salts and calculation of solubility of some hydroxides, oxides, and different salts in aqueous media. A (criticized) conventional approach, based on stoichiometry of a reaction notation and the solubility product of a precipitate, is compared with the unconventional/correct approach based on charge and concentration balances and a detailed physicochemical knowledge on the system considered, and calculations realized according to generalized approach to electrolytic systems (GATES) principles. An indisputable advantage of the latter approach is proved in simulation of static or dynamic, two-phase nonredox or redox systems.",book:{id:"5891",slug:"descriptive-inorganic-chemistry-researches-of-metal-compounds",title:"Descriptive Inorganic Chemistry Researches of Metal Compounds",fullTitle:"Descriptive Inorganic Chemistry Researches of Metal Compounds"},signatures:"Anna Maria Michałowska-Kaczmarczyk, Aneta Spórna-Kucab and\nTadeusz Michałowski",authors:[{id:"35273",title:"Prof.",name:"Tadeusz",middleName:null,surname:"Michalowski",slug:"tadeusz-michalowski",fullName:"Tadeusz Michalowski"},{id:"203867",title:"Dr.",name:"Anna Maria",middleName:null,surname:"Michałowska-Kaczmarczyk",slug:"anna-maria-michalowska-kaczmarczyk",fullName:"Anna Maria Michałowska-Kaczmarczyk"},{id:"203868",title:"Dr.",name:"Aneta",middleName:null,surname:"Spórna-Kucab",slug:"aneta-sporna-kucab",fullName:"Aneta Spórna-Kucab"}]},{id:"62736",title:"Radioisotope: Applications, Effects, and Occupational Protection",slug:"radioisotope-applications-effects-and-occupational-protection",totalDownloads:4454,totalCrossrefCites:7,totalDimensionsCites:14,abstract:"This chapter presents a brief introduction to radioisotopes, sources and types of radiation, applications, effects, and occupational protection. The natural and artificial sources of radiations are discussed with special reference to natural radioactive decay series and artificial radioisotopes. Applications have played significant role in improving the quality of human life. The application of radioisotopes in tracing, radiography, food preservation and sterilization, eradication of insects and pests, medical diagnosis and therapy, and new variety of crops in agricultural field is briefly described. Radiation interacts with matter to produce excitation and ionization of an atom or molecule; as a result physical and biological effects are produced. These effects and mechanisms are discussed. The dosimetric quantities used in radiological protection are described. Radiological protections and the control of occupational and medical exposures are briefly described.",book:{id:"5903",slug:"principles-and-applications-in-nuclear-engineering-radiation-effects-thermal-hydraulics-radionuclide-migration-in-the-environment",title:"Principles and Applications in Nuclear Engineering",fullTitle:"Principles and Applications in Nuclear Engineering - Radiation Effects, Thermal Hydraulics, Radionuclide Migration in the Environment"},signatures:"Sannappa Jadiyappa",authors:[{id:"239626",title:"Dr.",name:null,middleName:null,surname:"Sannappa J.",slug:"sannappa-j.",fullName:"Sannappa J."}]},{id:"58596",title:"Linearity of Calibration Curves for Analytical Methods: A Review of Criteria for Assessment of Method Reliability",slug:"linearity-of-calibration-curves-for-analytical-methods-a-review-of-criteria-for-assessment-of-method",totalDownloads:7865,totalCrossrefCites:17,totalDimensionsCites:41,abstract:"Calibration curve is a regression model used to predict the unknown concentrations of analytes of interest based on the response of the instrument to the known standards. Some statistical analyses are required to choose the best model fitting to the experimental data and also evaluate the linearity and homoscedasticity of the calibration curve. Using an internal standard corrects for the loss of analyte during sample preparation and analysis provided that it is selected appropriately. After the best regression model is selected, the analytical method needs to be validated using quality control (QC) samples prepared and stored in the same temperature as intended for the study samples. Most of the international guidelines require that the parameters, including linearity, specificity, selectivity, accuracy, precision, lower limit of quantification (LLOQ), matrix effect and stability, be assessed during validation. Despite the highly regulated area, some challenges still exist regarding the validation of some analytical methods including methods when no analyte-free matrix is available.",book:{id:"6379",slug:"calibration-and-validation-of-analytical-methods-a-sampling-of-current-approaches",title:"Calibration and Validation of Analytical Methods",fullTitle:"Calibration and Validation of Analytical Methods - A Sampling of Current Approaches"},signatures:"Seyed Mojtaba Moosavi and Sussan Ghassabian",authors:[{id:"216099",title:"Dr.",name:"Sussan",middleName:null,surname:"Ghassabian",slug:"sussan-ghassabian",fullName:"Sussan Ghassabian"},{id:"216101",title:"Mr.",name:"Seyed Mojtaba",middleName:null,surname:"Moosavi",slug:"seyed-mojtaba-moosavi",fullName:"Seyed Mojtaba Moosavi"}]}],onlineFirstChaptersFilter:{topicId:"8",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81908",title:"Behaviors of Multi-Droplets Impacting on a Flat Wall",slug:"behaviors-of-multi-droplets-impacting-on-a-flat-wall",totalDownloads:3,totalDimensionsCites:0,doi:"10.5772/intechopen.105007",abstract:"Microscopic characteristics of fuel spray are very important for atomization and mixture formation. The droplet size, number density, velocity distribution as well as minimum distance reveal the quality of spray and atomization, which affects the subsequent combustion and emissions for different engines such as vehicle, marine and aircraft. Moreover, in the internal combustion engine, the spray-wall impingement is difficult to avoid, which is the main source for soot emissions. Nowadays, regulations for emissions become straight by governments. Therefore, it is urgent for us to alleviate the energy and emissions crisis. In this study, the droplets behaviors will be characterized under the related engine working state. Firstly, the experimental setup and measurement were explained in detail. Then, images process method was induced to calculate the droplet size, velocity and distance among them. Finally, results of the impinging spray were presented. One thing should be noted, as the dense region is not available to detect the droplets by the observation. Therefore, a spray “slicer” was designed and applied to cut the spray slim. Finally, multi-droplets were generated, and the results can be concluded as well. All the results could provide insights into the impacting behaviors for better understanding the droplet dynamics.",book:{id:"11205",title:"Droplet Dynamics",coverURL:"https://cdn.intechopen.com/books/images_new/11205.jpg"},signatures:"Hongliang Luo and Feixiang Chang"},{id:"81902",title:"Green Methods of Chemical Analysis and Pollutant Removal",slug:"green-methods-of-chemical-analysis-and-pollutant-removal",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.104829",abstract:"This chapter deals with chemical analysis and pollutant removal methods that follow some of the 12 principles of Green Chemistry. In this chapter, the 12 principles of the Green Chemistry along with the short description are highlighted. Several chemical analysis methods are presented, that are both used for chemical identification and concentration determination, whether conventionally or instrumentally. The conventional chemical analysis methods evaluated in this chapter include volumetric and gravimetric, while the instrumental ones presented are limited to atomic absorption spectrometry (AAS) and X-ray fluorescence (XRF) for determination of the analyte concentration, and Infrared spectrometry (IR) and X-ray diffraction (XRD) for chemical identification. Additionally, the pollutant removal methods involving conventional and advanced processes, are reviewed. The conventional chemical removal methods such as precipitation, coagulation, and adsorption are illustrated. The advanced methods in removing chemical pollutants discussed in this chapter are photocatalytic degradation, photo-oxidation/reduction, Fenton and Photo-Fenton, and ozonation. In the description of the chemical analysis and the chemical pollutant removal methods, the evaluation of the unsuitableness or suitableness toward some of the Green Chemistry principles are also accompanied. In addition, the ways to make the less green methods to be greener are also proposed.",book:{id:"11211",title:"Green Chemistry - New Perspectives",coverURL:"https://cdn.intechopen.com/books/images_new/11211.jpg"},signatures:"Endang Tri Wahyuni and Eko Sri Kunarti"},{id:"81907",title:"Fundamental Principles to Address Green Chemistry & Green Engineering for Sustainable Future",slug:"fundamental-principles-to-address-green-chemistry-green-engineering-for-sustainable-future",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.104717",abstract:"The background of green chemistry represents the dramatic module of a new millennium, the substantiable chemical process steam for evaluation in designing phase to incorporate the principles of GC (Green Chemistry) in 1990s. there has been a tremendous success in developing a new product and process which are more compatible with biological, zoological and botanical perspective to illuminate the sustainability goal, this chapter represents the simplified way to lookout different approach adopted in GC-research, the methodology enhance the chemical process economics, concomitant which deduct the environmental burden. This review merely focusing on eco-friendly protocol which replace the traditional method of synthesis followed in chemistry to synthesize lifesaving drugs, with prevention outgoing waste from industries. GC and chemical engineering or green engineering (GE) should produce eco-friendly chemical process for drug design which likely to be spread rapidly in next few decades. This chapter explains in-depth and compact with detailed glimpse of environment friendly-protocol and principle bridging continent and scientific discipline to create new solution.",book:{id:"11211",title:"Green Chemistry - New Perspectives",coverURL:"https://cdn.intechopen.com/books/images_new/11211.jpg"},signatures:"Nikhat Farhana, Mohammed Gulzar Ahmed, Mohammed Asif Iqbal, Natasha Naval Aggarwal, Prajitha Biju, Ashwini Somayaji, Abdul Rahamanulla, Nishmitha Gretta D’Souza, Sudhina Makuttan, Tahreen Taj, Abdullah Khan and Roshan Sayeed"},{id:"80825",title:"Contribution to the Calculation of Physical Properties of BeSe Semiconductor",slug:"contribution-to-the-calculation-of-physical-properties-of-bese-semiconductor",totalDownloads:3,totalDimensionsCites:0,doi:"10.5772/intechopen.102888",abstract:"We expose various physical parameters of binary compound BeSe in the stable zinc blend and NiAs structures using the functional HSE hybrid, GGA-PBE, and LDA. We deduce elastic constants, mechanical parameters, and wave velocities according to different orientations. BeSe semiconductor has Γ-X (2.852 eV) and Γ-K (0.536 eV) bandgap in zinc blend and NiAs structures. Electrons transit from Se-p site to the Be-s state and show covalent bonding. Optical absorption peaks result from electronic transitions under ultraviolet light irradiation.",book:{id:"11210",title:"Chalcogens",coverURL:"https://cdn.intechopen.com/books/images_new/11210.jpg"},signatures:"Mohamed Amine Ghebouli and Brahim Ghebouli"},{id:"80910",title:"Calorimetry to Quantify Protein-Ligand Binding",slug:"calorimetry-to-quantify-protein-ligand-binding",totalDownloads:3,totalDimensionsCites:0,doi:"10.5772/intechopen.102959",abstract:"Isothermal titration calorimetry (ITC) is the preferred method used to study biochemical reactions like protein-ligand binding due to its sensitivity, accuracy, and precision. ITC measures directly the heat absorbed or released (∆H) associated with a given binding process. A typical ITC experiment allows the dissection of the binding energy of a reaction into ligand-enzyme association constant (Ka), change in enthalpy (∆H), change in entropy (∆S), change in Gibbs-free energy (∆G), and the stoichiometry of association (N). The change in heat capacity (∆Cp) is obtained from the measurements of binding enthalpy over a range of temperatures. The magnitude and signs of the thermodynamic parameters that were obtained provide insight into the nature of interactions involved in the binding process. The strength of interaction is thermodynamically favorable is determined by the Gibbs free energy. ∆G is an important thermodynamic descriptor of a binding reaction since it dictates the binding affinity and is in turn defined by the enthalpy and entropy changes expressed in the following equation: ∆G = ∆H–T∆S. Up-close, this reflects the contradistinctions of two thermodynamic effects at a molecular level—the propensity to drop to lower energy (bond formation, negative ∆H), counterbalanced by the innate thermal Brownian motion’s destructive characteristic (bond breakage, positive ∆S).",book:{id:"10696",title:"Applications of Calorimetry",coverURL:"https://cdn.intechopen.com/books/images_new/10696.jpg"},signatures:"Salerwe Mosebi"},{id:"81713",title:"Transition Metals-Based Metal-Organic Frameworks, Synthesis, and Environmental Applications",slug:"transition-metals-based-metal-organic-frameworks-synthesis-and-environmental-applications",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.104294",abstract:"This work illustrates examples of metal-organic frameworks (MOFs) derived from transition metals and their environmental applications in areas of catalysis, sorption, and hydrogen evolution. Explanation of some of the techniques employed for their synthesis has been discussed. On the other hand, the advantages of the use of hybrid materials such as the metal-organic frameworks are exposed in this book as well a detailed description of the different linkers and metals used for the synthesis of this kind of porous materials going through the methodologies and techniques utilized by different authors to obtain good-quality crystalline applicable materials. Adjustments of linker geometry, length, ratio, and the functional group can tune the size, shape, and internal surface property of an MOF for a targeted application. The uses of MOFs are exploring new different areas of chemistry such as catalysis, adsorption, carrier systems, hydrogen evolution, photocatalysis, and more. Different examples of MOFs from Scandium to Zinc are well described in this book, and finally, a brief description of some common environmental applications such as metals and azo dyes sorption, hydrogen evolution, and catalyst in the transesterification process of vegetable oils to produce biodiesel is explored and commented.",book:{id:"11216",title:"Sorption - From Fundamentals to Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11216.jpg"},signatures:"Lidia E. Chiñas-Rojas, Guadalupe Vivar-Vera, Yafeth F. Cruz-Martínez, Seth Limón Colohua, José María Rivera and Eric Houbron"}],onlineFirstChaptersTotal:86},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:288,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,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:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:1,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. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"May 24th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:27,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"10",title:"Animal Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/10.jpg",isOpenForSubmission:!0,editor:{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null},{id:"11",title:"Cell Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/11.jpg",isOpenForSubmission:!0,editor:{id:"133493",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",profilePictureURL:"https://mts.intechopen.com/storage/users/133493/images/3091_n.jpg",biography:"Prof. Dr. Angel Catalá \r\nShort Biography Angel Catalá was born in Rodeo (San Juan, Argentina). He studied \r\nchemistry at the Universidad Nacional de La Plata, Argentina, where received aPh.D. degree in chemistry (Biological Branch) in 1965. From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). W inner of the Bimbo PanAmerican Nutrition, Food Science and Technology Award 2006 and 2012, South AmericaHuman Nutrition, Professional Category. 2006 award in pharmacology, Bernardo\r\nHoussay, in recognition of his meritorious works of research. Angel Catalá belongto the Editorial Board of Journal of lipids, International Review of Biophysical ChemistryFrontiers in Membrane Physiology and Biophysics, World Journal oExperimental Medicine and Biochemistry Research International, W orld Journal oBiological Chemistry, Oxidative Medicine and Cellular Longevity, Diabetes and thePancreas, International Journal of Chronic Diseases & Therapy, International Journal oNutrition, Co-Editor of The Open Biology Journal.",institutionString:null,institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},editorTwo:null,editorThree:null},{id:"12",title:"Human Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",isOpenForSubmission:!0,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. His interest later turned to the molecular mechanism and attenuating strategy of sarcopenia (age-related muscle atrophy). His opinion is to attenuate sarcopenia by improving autophagic defects using nutrient- and pharmaceutical-based treatments.",institutionString:null,institution:{name:"Tokyo Institute of Technology",institutionURL:null,country:{name:"Japan"}}},editorTwo:null,editorThree:{id:"331519",title:"Dr.",name:"Kotomi",middleName:null,surname:"Sakai",slug:"kotomi-sakai",fullName:"Kotomi Sakai",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000031QtFXQA0/Profile_Picture_1637053227318",biography:"Senior researcher Kotomi Sakai, Ph.D., MPH, works at the Research Organization of Science and Technology in Ritsumeikan University. She is a researcher in the geriatric rehabilitation and public health field. She received Ph.D. from Nihon University and MPH from St.Luke’s International University. Her main research interest is sarcopenia in older adults, especially its association with nutritional status. Additionally, to understand how to maintain and improve physical function in older adults, to conduct studies about the mechanism of sarcopenia and determine when possible interventions are needed.",institutionString:null,institution:{name:"Ritsumeikan University",institutionURL:null,country:{name:"Japan"}}}},{id:"13",title:"Plant Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/13.jpg",isOpenForSubmission:!0,editor:{id:"332229",title:"Prof.",name:"Jen-Tsung",middleName:null,surname:"Chen",slug:"jen-tsung-chen",fullName:"Jen-Tsung Chen",profilePictureURL:"https://mts.intechopen.com/storage/users/332229/images/system/332229.png",biography:"Dr. Jen-Tsung Chen is currently a professor at the National University of Kaohsiung, Taiwan. He teaches cell biology, genomics, proteomics, medicinal plant biotechnology, and plant tissue culture. Dr. Chen\\'s research interests include bioactive compounds, chromatography techniques, in vitro culture, medicinal plants, phytochemicals, and plant biotechnology. He has published more than ninety scientific papers and serves as an editorial board member for Plant Methods, Biomolecules, and International Journal of Molecular Sciences.",institutionString:"National University of Kaohsiung",institution:{name:"National University of Kaohsiung",institutionURL:null,country:{name:"Taiwan"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:43,paginationItems:[{id:"81796",title:"Apoptosis-Related Diseases and Peroxisomes",doi:"10.5772/intechopen.105052",signatures:"Meimei Wang, Yakun Liu, Ni Chen, Juan Wang and Ye Zhao",slug:"apoptosis-related-diseases-and-peroxisomes",totalDownloads:3,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"The Metabolic Role of Peroxisome in Health and Disease",coverURL:"https://cdn.intechopen.com/books/images_new/10837.jpg",subseries:{id:"11",title:"Cell Physiology"}}},{id:"81723",title:"Peroxisomal Modulation as Therapeutic Alternative for Tackling Multiple Cancers",doi:"10.5772/intechopen.104873",signatures:"Shazia Usmani, Shadma Wahab, Abdul Hafeez, Shabana Khatoon and Syed Misbahul Hasan",slug:"peroxisomal-modulation-as-therapeutic-alternative-for-tackling-multiple-cancers",totalDownloads:3,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"The Metabolic Role of Peroxisome in Health and Disease",coverURL:"https://cdn.intechopen.com/books/images_new/10837.jpg",subseries:{id:"11",title:"Cell Physiology"}}},{id:"81638",title:"Aging and Neuropsychiatric Disease: A General Overview of Prevalence and Trends",doi:"10.5772/intechopen.103102",signatures:"Jelena Milić",slug:"aging-and-neuropsychiatric-disease-a-general-overview-of-prevalence-and-trends",totalDownloads:14,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Senescence",coverURL:"https://cdn.intechopen.com/books/images_new/10935.jpg",subseries:{id:"11",title:"Cell Physiology"}}},{id:"81566",title:"New and Emerging Technologies for Integrative Ambulatory Autonomic Assessment and Intervention as a Catalyst in the Synergy of Remote Geocoded Biosensing, Algorithmic Networked Cloud Computing, Deep Learning, and Regenerative/Biomic Medicine: Further Real",doi:"10.5772/intechopen.104092",signatures:"Robert L. Drury",slug:"new-and-emerging-technologies-for-integrative-ambulatory-autonomic-assessment-and-intervention-as-a-",totalDownloads:9,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Autonomic Nervous System - Special Interest Topics",coverURL:"https://cdn.intechopen.com/books/images_new/10835.jpg",subseries:{id:"12",title:"Human Physiology"}}}]},overviewPagePublishedBooks:{paginationCount:11,paginationItems:[{type:"book",id:"7264",title:"Calcium and Signal Transduction",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7264.jpg",slug:"calcium-and-signal-transduction",publishedDate:"October 24th 2018",editedByType:"Edited by",bookSignature:"John N. Buchholz and Erik J. Behringer",hash:"e373a3d1123dbd45fddf75d90e3e7c38",volumeInSeries:1,fullTitle:"Calcium and Signal Transduction",editors:[{id:"89438",title:"Dr.",name:"John N.",middleName:null,surname:"Buchholz",slug:"john-n.-buchholz",fullName:"John N. Buchholz",profilePictureURL:"https://mts.intechopen.com/storage/users/89438/images/6463_n.jpg",biography:"Full Professor and Vice Chair, Division of Pharmacology, Loma Linda University, School of Medicine. He received his B.S. Degree in Biology at La Sierra University, Riverside California (1980) and a PhD in Pharmacology from Loma Linda University School of Medicine (1988). Post-Doctoral Fellow at University of California, Irvine, College of Medicine 1989-1992 with a focus on autonomic nerve function in blood vessels and the impact of aging on the function of these nerves and overall blood vessel function. Twenty years of research funding and served on NIH R01 review panels, Editor-In-Chief of Edorium Journal of Aging Research. Serves as a peer reviewer for biomedical journals. Military Reserve Officer serving with the 100 Support Command, 100 Troop Command, 40 Infantry Division, CA National Guard.",institutionString:null,institution:{name:"Loma Linda University",institutionURL:null,country:{name:"United States of America"}}}]},{type:"book",id:"6925",title:"Endoplasmic Reticulum",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6925.jpg",slug:"endoplasmic-reticulum",publishedDate:"April 17th 2019",editedByType:"Edited by",bookSignature:"Angel Català",hash:"a9e90d2dbdbc46128dfe7dac9f87c6b4",volumeInSeries:2,fullTitle:"Endoplasmic Reticulum",editors:[{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}}]},{type:"book",id:"6924",title:"Adenosine Triphosphate in Health and Disease",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6924.jpg",slug:"adenosine-triphosphate-in-health-and-disease",publishedDate:"April 24th 2019",editedByType:"Edited by",bookSignature:"Gyula Mozsik",hash:"04106c232a3c68fec07ba7cf00d2522d",volumeInSeries:3,fullTitle:"Adenosine Triphosphate in Health and Disease",editors:[{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",institutionURL:null,country:{name:"Hungary"}}}]},{type:"book",id:"8008",title:"Antioxidants",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/8008.jpg",slug:"antioxidants",publishedDate:"November 6th 2019",editedByType:"Edited by",bookSignature:"Emad Shalaby",hash:"76361b4061e830906267933c1c670027",volumeInSeries:5,fullTitle:"Antioxidants",editors:[{id:"63600",title:"Prof.",name:"Emad",middleName:null,surname:"Shalaby",slug:"emad-shalaby",fullName:"Emad Shalaby",profilePictureURL:"https://mts.intechopen.com/storage/users/63600/images/system/63600.png",biography:"Dr. Emad Shalaby is a professor of biochemistry on the Biochemistry Department Faculty of Agriculture, Cairo University. He\nreceived a short-term scholarship to carry out his post-doctoral\nstudies abroad, from Japan International Cooperation Agency\n(JICA), in coordination with the Egyptian government. Dr.\nShalaby speaks fluent English and his native Arabic. He has 77\ninternationally published research papers, has attended 15 international conferences, and has contributed to 18 international books and chapters.\nDr. Shalaby works as a reviewer on over one hundred international journals and is\non the editorial board of more than twenty-five international journals. He is a member of seven international specialized scientific societies, besides his local one, and\nhe has won seven prizes.",institutionString:"Cairo University",institution:{name:"Cairo University",institutionURL:null,country:{name:"Egypt"}}}]}]},openForSubmissionBooks:{},onlineFirstChapters:{},subseriesFiltersForOFChapters:[],publishedBooks:{},subseriesFiltersForPublishedBooks:[],publicationYearFilters:[],authors:{paginationCount:617,paginationItems:[{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNVJQA4/Profile_Picture_2022-03-07T13:23:04.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Associate Prof.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/15648_n.jpg",biography:"Dr. Mohd Aftab Siddiqui is currently working as Assistant Professor in the Faculty of Pharmacy, Integral University, Lucknow for the last 6 years. He has completed his Doctor in Philosophy (Pharmacology) in 2020 from Integral University, Lucknow. He completed his Bachelor in Pharmacy in 2013 and Master in Pharmacy (Pharmacology) in 2015 from Integral University, Lucknow. He is the gold medalist in Bachelor and Master degree. He qualified GPAT -2013, GPAT -2014, and GPAT 2015. His area of research is Pharmacological screening of herbal drugs/ natural products in liver and cardiac diseases. He has guided many M. Pharm. research projects. He has many national and international publications.",institutionString:"Integral University",institution:null},{id:"255360",title:"Dr.",name:"Usama",middleName:null,surname:"Ahmad",slug:"usama-ahmad",fullName:"Usama Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255360/images/system/255360.png",biography:"Dr. Usama Ahmad holds a specialization in Pharmaceutics from Amity University, Lucknow, India. He received his Ph.D. degree from Integral University. Currently, he’s working as an Assistant Professor of Pharmaceutics in the Faculty of Pharmacy, Integral University. From 2013 to 2014 he worked on a research project funded by SERB-DST, Government of India. He has a rich publication record with more than 32 original articles published in reputed journals, 3 edited books, 5 book chapters, and a number of scientific articles published in ‘Ingredients South Asia Magazine’ and ‘QualPharma Magazine’. He is a member of the American Association for Cancer Research, International Association for the Study of Lung Cancer, and the British Society for Nanomedicine. Dr. Ahmad’s research focus is on the development of nanoformulations to facilitate the delivery of drugs that aim to provide practical solutions to current healthcare problems.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. Dr. Khullar has a keen research interest in genetics of hypertension, and is currently studying pharmacogenetics of hypertension.",institutionString:"Post Graduate Institute of Medical Education and Research",institution:{name:"Post Graduate Institute of Medical Education and Research",country:{name:"India"}}},{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",biography:"Xianquan Zhan received his MD and Ph.D. in Preventive Medicine at West China University of Medical Sciences. He received his post-doctoral training in oncology and cancer proteomics at the Central South University, China, and the University of Tennessee Health Science Center (UTHSC), USA. He worked at UTHSC and the Cleveland Clinic in 2001–2012 and achieved the rank of associate professor at UTHSC. Currently, he is a full professor at Central South University and Shandong First Medical University, and an advisor to MS/PhD students and postdoctoral fellows. He is also a fellow of the Royal Society of Medicine and European Association for Predictive Preventive Personalized Medicine (EPMA), a national representative of EPMA, and a member of the American Society of Clinical Oncology (ASCO) and the American Association for the Advancement of Sciences (AAAS). He is also the editor in chief of International Journal of Chronic Diseases & Therapy, an associate editor of EPMA Journal, Frontiers in Endocrinology, and BMC Medical Genomics, and a guest editor of Mass Spectrometry Reviews, Frontiers in Endocrinology, EPMA Journal, and Oxidative Medicine and Cellular Longevity. He has published more than 148 articles, 28 book chapters, 6 books, and 2 US patents in the field of clinical proteomics and biomarkers.",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",country:{name:"China"}}},{id:"297507",title:"Dr.",name:"Charles",middleName:"Elias",surname:"Assmann",slug:"charles-assmann",fullName:"Charles Assmann",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/297507/images/system/297507.jpg",biography:"Charles Elias Assmann is a biologist from Federal University of Santa Maria (UFSM, Brazil), who spent some time abroad at the Ludwig-Maximilians-Universität München (LMU, Germany). He has Masters Degree in Biochemistry (UFSM), and is currently a PhD student at Biochemistry at the Department of Biochemistry and Molecular Biology of the UFSM. His areas of expertise include: Biochemistry, Molecular Biology, Enzymology, Genetics and Toxicology. He is currently working on the following subjects: Aluminium toxicity, Neuroinflammation, Oxidative stress and Purinergic system. Since 2011 he has presented more than 80 abstracts in scientific proceedings of national and international meetings. Since 2014, he has published more than 20 peer reviewed papers (including 4 reviews, 3 in Portuguese) and 2 book chapters. He has also been a reviewer of international journals and ad hoc reviewer of scientific committees from Brazilian Universities.",institutionString:"Universidade Federal de Santa Maria",institution:{name:"Universidade Federal de Santa Maria",country:{name:"Brazil"}}},{id:"217850",title:"Dr.",name:"Margarete Dulce",middleName:null,surname:"Bagatini",slug:"margarete-dulce-bagatini",fullName:"Margarete Dulce Bagatini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217850/images/system/217850.jpeg",biography:"Dr. Margarete Dulce Bagatini is an associate professor at the Federal University of Fronteira Sul/Brazil. She has a degree in Pharmacy and a PhD in Biological Sciences: Toxicological Biochemistry. She is a member of the UFFS Research Advisory Committee\nand a member of the Biovitta Research Institute. She is currently:\nthe leader of the research group: Biological and Clinical Studies\nin Human Pathologies, professor of postgraduate program in\nBiochemistry at UFSC and postgraduate program in Science and Food Technology at\nUFFS. She has experience in the area of pharmacy and clinical analysis, acting mainly\non the following topics: oxidative stress, the purinergic system and human pathologies, being a reviewer of several international journals and books.",institutionString:"Universidade Federal da Fronteira Sul",institution:{name:"Universidade Federal da Fronteira Sul",country:{name:"Brazil"}}},{id:"226275",title:"Ph.D.",name:"Metin",middleName:null,surname:"Budak",slug:"metin-budak",fullName:"Metin Budak",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226275/images/system/226275.jfif",biography:"Metin Budak, MSc, PhD is an Assistant Professor at Trakya University, Faculty of Medicine. He has been Head of the Molecular Research Lab at Prof. Mirko Tos Ear and Hearing Research Center since 2018. His specializations are biophysics, epigenetics, genetics, and methylation mechanisms. He has published around 25 peer-reviewed papers, 2 book chapters, and 28 abstracts. He is a member of the Clinical Research Ethics Committee and Quantification and Consideration Committee of Medicine Faculty. His research area is the role of methylation during gene transcription, chromatin packages DNA within the cell and DNA repair, replication, recombination, and gene transcription. His research focuses on how the cell overcomes chromatin structure and methylation to allow access to the underlying DNA and enable normal cellular function.",institutionString:"Trakya University",institution:{name:"Trakya University",country:{name:"Turkey"}}},{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",slug:"anca-pantea-stoian",fullName:"Anca Pantea Stoian",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",biography:"Anca Pantea Stoian is a specialist in diabetes, nutrition, and metabolic diseases as well as health food hygiene. She also has competency in general ultrasonography.\n\nShe is an associate professor in the Diabetes, Nutrition and Metabolic Diseases Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. She has been chief of the Hygiene Department, Faculty of Dentistry, at the same university since 2019. Her interests include micro and macrovascular complications in diabetes and new therapies. Her research activities focus on nutritional intervention in chronic pathology, as well as cardio-renal-metabolic risk assessment, and diabetes in cancer. She is currently engaged in developing new therapies and technological tools for screening, prevention, and patient education in diabetes. \n\nShe is a member of the European Association for the Study of Diabetes, Cardiometabolic Academy, CEDA, Romanian Society of Diabetes, Nutrition and Metabolic Diseases, Romanian Diabetes Federation, and Association for Renal Metabolic and Nutrition studies. She has authored or co-authored 160 papers in national and international peer-reviewed journals.",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",country:{name:"Romania"}}},{id:"279792",title:"Dr.",name:"João",middleName:null,surname:"Cotas",slug:"joao-cotas",fullName:"João Cotas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/279792/images/system/279792.jpg",biography:"Graduate and master in Biology from the University of Coimbra.\n\nI am a research fellow at the Macroalgae Laboratory Unit, in the MARE-UC – Marine and Environmental Sciences Centre of the University of Coimbra. My principal function is the collection, extraction and purification of macroalgae compounds, chemical and bioactive characterization of the compounds and algae extracts and development of new methodologies in marine biotechnology area. \nI am associated in two projects: one consists on discovery of natural compounds for oncobiology. The other project is the about the natural compounds/products for agricultural area.\n\nPublications:\nCotas, J.; Figueirinha, A.; Pereira, L.; Batista, T. 2018. An analysis of the effects of salinity on Fucus ceranoides (Ochrophyta, Phaeophyceae), in the Mondego River (Portugal). Journal of Oceanology and Limnology. in press. DOI: 10.1007/s00343-019-8111-3",institutionString:"Faculty of Sciences and Technology of University of Coimbra",institution:null},{id:"279788",title:"Dr.",name:"Leonel",middleName:null,surname:"Pereira",slug:"leonel-pereira",fullName:"Leonel Pereira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/279788/images/system/279788.jpg",biography:"Leonel Pereira has an undergraduate degree in Biology, a Ph.D. in Biology (specialty in Cell Biology), and a Habilitation degree in Biosciences (specialization in Biotechnology) from the Faculty of Science and Technology, University of Coimbra, Portugal, where he is currently a professor. In addition to teaching at this university, he is an integrated researcher at the Marine and Environmental Sciences Center (MARE), Portugal. His interests include marine biodiversity (algae), marine biotechnology (algae bioactive compounds), and marine ecology (environmental assessment). Since 2008, he has been the author and editor of the electronic publication MACOI – Portuguese Seaweeds Website (www.seaweeds.uc.pt). He is also a member of the editorial boards of several scientific journals. Dr. Pereira has edited or authored more than 20 books, 100 journal articles, and 45 book chapters. He has given more than 100 lectures and oral communications at various national and international scientific events. He is the coordinator of several national and international research projects. In 1998, he received the Francisco de Holanda Award (Honorable Mention) and, more recently, the Mar Rei D. Carlos award (18th edition). He is also a winner of the 2016 CHOICE Award for an outstanding academic title for his book Edible Seaweeds of the World. In 2020, Dr. Pereira received an Honorable Mention for the Impact of International Publications from the Web of Science",institutionString:"University of Coimbra",institution:{name:"University of Coimbra",country:{name:"Portugal"}}},{id:"61946",title:"Dr.",name:"Carol",middleName:null,surname:"Bernstein",slug:"carol-bernstein",fullName:"Carol Bernstein",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61946/images/system/61946.jpg",biography:"Carol Bernstein received her PhD in Genetics from the University of California (Davis). She was a faculty member at the University of Arizona College of Medicine for 43 years, retiring in 2011. Her research interests focus on DNA damage and its underlying role in sex, aging and in the early steps of initiation and progression to cancer. In her research, she had used organisms including bacteriophage T4, Neurospora crassa, Schizosaccharomyces pombe and mice, as well as human cells and tissues. She authored or co-authored more than 140 scientific publications, including articles in major peer reviewed journals, book chapters, invited reviews and one book.",institutionString:"University of Arizona",institution:{name:"University of Arizona",country:{name:"United States of America"}}},{id:"182258",title:"Dr.",name:"Ademar",middleName:"Pereira",surname:"Serra",slug:"ademar-serra",fullName:"Ademar Serra",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/182258/images/system/182258.jpeg",biography:"Dr. Serra studied Agronomy on Universidade Federal de Mato Grosso do Sul (UFMS) (2005). He received master degree in Agronomy, Crop Science (Soil fertility and plant nutrition) (2007) by Universidade Federal da Grande Dourados (UFGD), and PhD in agronomy (Soil fertility and plant nutrition) (2011) from Universidade Federal da Grande Dourados / Escola Superior de Agricultura Luiz de Queiroz (UFGD/ESALQ-USP). Dr. Serra is currently working at Brazilian Agricultural Research Corporation (EMBRAPA). His research focus is on mineral nutrition of plants, crop science and soil science. Dr. Serra\\'s current projects are soil organic matter, soil phosphorus fractions, compositional nutrient diagnosis (CND) and isometric log ratio (ilr) transformation in compositional data analysis.",institutionString:"Brazilian Agricultural Research Corporation",institution:{name:"Brazilian Agricultural Research Corporation",country:{name:"Brazil"}}}]}},subseries:{item:{id:"12",type:"subseries",title:"Human Physiology",keywords:"Anatomy, Cells, Organs, Systems, Homeostasis, Functions",scope:"Human physiology is the scientific exploration of the various functions (physical, biochemical, and mechanical properties) of humans, their organs, and their constituent cells. The endocrine and nervous systems play important roles in maintaining homeostasis in the human body. Integration, which is the biological basis of physiology, is achieved through communication between the many overlapping functions of the human body's systems, which takes place through electrical and chemical means. Much of the basis of our knowledge of human physiology has been provided by animal experiments. Because of the close relationship between structure and function, studies in human physiology and anatomy seek to understand the mechanisms that help the human body function. The series on human physiology deals with the various mechanisms of interaction between the various organs, nerves, and cells in the human body.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11408,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. His interest later turned to the molecular mechanism and attenuating strategy of sarcopenia (age-related muscle atrophy). His opinion is to attenuate sarcopenia by improving autophagic defects using nutrient- and pharmaceutical-based treatments.",institutionString:null,institution:{name:"Tokyo Institute of Technology",institutionURL:null,country:{name:"Japan"}}},editorTwo:null,editorThree:{id:"331519",title:"Dr.",name:"Kotomi",middleName:null,surname:"Sakai",slug:"kotomi-sakai",fullName:"Kotomi Sakai",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000031QtFXQA0/Profile_Picture_1637053227318",biography:"Senior researcher Kotomi Sakai, Ph.D., MPH, works at the Research Organization of Science and Technology in Ritsumeikan University. She is a researcher in the geriatric rehabilitation and public health field. She received Ph.D. from Nihon University and MPH from St.Luke’s International University. Her main research interest is sarcopenia in older adults, especially its association with nutritional status. Additionally, to understand how to maintain and improve physical function in older adults, to conduct studies about the mechanism of sarcopenia and determine when possible interventions are needed.",institutionString:null,institution:{name:"Ritsumeikan University",institutionURL:null,country:{name:"Japan"}}},series:{id:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261"},editorialBoard:[{id:"213786",title:"Dr.",name:"Henrique P.",middleName:null,surname:"Neiva",slug:"henrique-p.-neiva",fullName:"Henrique P. Neiva",profilePictureURL:"https://mts.intechopen.com/storage/users/213786/images/system/213786.png",institutionString:null,institution:{name:"University of Beira Interior",institutionURL:null,country:{name:"Portugal"}}},{id:"39275",title:"Prof.",name:"Herbert Ryan",middleName:null,surname:"Marini",slug:"herbert-ryan-marini",fullName:"Herbert Ryan Marini",profilePictureURL:"https://mts.intechopen.com/storage/users/39275/images/9459_n.jpg",institutionString:null,institution:{name:"University of Messina",institutionURL:null,country:{name:"Italy"}}},{id:"196218",title:"Dr.",name:"Pasquale",middleName:null,surname:"Cianci",slug:"pasquale-cianci",fullName:"Pasquale Cianci",profilePictureURL:"https://mts.intechopen.com/storage/users/196218/images/system/196218.png",institutionString:null,institution:{name:"University of Foggia",institutionURL:null,country:{name:"Italy"}}}]},onlineFirstChapters:{},publishedBooks:{},testimonialsList:[{id:"18",text:"It was great publishing with IntechOpen, the process was straightforward and I had support all along.",author:{id:"71579",name:"Berend",surname:"Olivier",institutionString:"Utrecht University",profilePictureURL:"https://mts.intechopen.com/storage/users/71579/images/system/71579.png",slug:"berend-olivier",institution:{id:"253",name:"Utrecht University",country:{id:null,name:"Netherlands"}}}},{id:"27",text:"The opportunity to work with a prestigious publisher allows for the possibility to collaborate with more research groups interested in animal nutrition, leading to the development of new feeding strategies and food valuation while being more sustainable with the environment, allowing more readers to learn about the subject.",author:{id:"175967",name:"Manuel",surname:"Gonzalez Ronquillo",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",slug:"manuel-gonzalez-ronquillo",institution:{id:"6221",name:"Universidad Autónoma del Estado de México",country:{id:null,name:"Mexico"}}}},{id:"8",text:"I work with IntechOpen for a number of reasons: their professionalism, their mission in support of Open Access publishing, and the quality of their peer-reviewed publications, but also because they believe in equality.",author:{id:"202192",name:"Catrin",surname:"Rutland",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",slug:"catrin-rutland",institution:{id:"134",name:"University of Nottingham",country:{id:null,name:"United Kingdom"}}}}]},submityourwork:{pteSeriesList:[],lsSeriesList:[],hsSeriesList:[],sshSeriesList:[],subseriesList:[],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:null},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/341173",hash:"",query:{},params:{id:"341173"},fullPath:"/profiles/341173",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()