\\n\\n
IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\\n\\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\\n\\nLaunching 2021
\\n\\nArtificial Intelligence, ISSN 2633-1403
\\n\\nVeterinary Medicine and Science, ISSN 2632-0517
\\n\\nBiochemistry, ISSN 2632-0983
\\n\\nBiomedical Engineering, ISSN 2631-5343
\\n\\nInfectious Diseases, ISSN 2631-6188
\\n\\nPhysiology (Coming Soon)
\\n\\nDentistry (Coming Soon)
\\n\\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\\n\\nNote: Edited in October 2021
\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/132"}},components:[{type:"htmlEditorComponent",content:'With the desire to make book publishing more relevant for the digital age and offer innovative Open Access publishing options, we are thrilled to announce the launch of our new publishing format: IntechOpen Book Series.
\n\nDesigned to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
\n\nAfter a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
\n\nOur innovative Book Series format brings you:
\n\nIntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\n\nLaunching 2021
\n\nArtificial Intelligence, ISSN 2633-1403
\n\nVeterinary Medicine and Science, ISSN 2632-0517
\n\nBiochemistry, ISSN 2632-0983
\n\nBiomedical Engineering, ISSN 2631-5343
\n\nInfectious Diseases, ISSN 2631-6188
\n\nPhysiology (Coming Soon)
\n\nDentistry (Coming Soon)
\n\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\n\nNote: Edited in October 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"2280",leadTitle:null,fullTitle:"Remote Sensing - Applications",title:"Remote Sensing",subtitle:"Applications",reviewType:"peer-reviewed",abstract:"Nowadays it is hard to find areas of human activity and development that have not profited from or contributed to remote sensing. Natural, physical and social activities find in remote sensing a common ground for interaction and development.\nThis book intends to show the reader how remote sensing impacts other areas of science, technology, and human activity, by displaying a selected number of high quality contributions dealing with different remote sensing applications.",isbn:null,printIsbn:"978-953-51-0651-7",pdfIsbn:"978-953-51-5002-2",doi:"10.5772/2670",price:159,priceEur:175,priceUsd:205,slug:"remote-sensing-applications",numberOfPages:530,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"ceea9c29b9b1f05fc128ae2cf564f110",bookSignature:"Boris Escalante-Ramirez",publishedDate:"June 13th 2012",coverURL:"https://cdn.intechopen.com/books/images_new/2280.jpg",numberOfDownloads:69944,numberOfWosCitations:83,numberOfCrossrefCitations:49,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:113,numberOfDimensionsCitationsByBook:1,hasAltmetrics:0,numberOfTotalCitations:245,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 9th 2011",dateEndSecondStepPublish:"June 6th 2011",dateEndThirdStepPublish:"October 11th 2011",dateEndFourthStepPublish:"November 10th 2011",dateEndFifthStepPublish:"March 9th 2012",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"111500",title:"Dr.",name:"Boris",middleName:null,surname:"Escalante",slug:"boris-escalante",fullName:"Boris Escalante",profilePictureURL:"https://mts.intechopen.com/storage/users/111500/images/system/111500.jpg",biography:"He obtained the title of Electrical Mechanical Engineer at the National Autonomous University of Mexico in 1985, the Master's Degree in Electronic Engineering at the Philips International Institute of Technological Studies in Eindhoven, the Netherlands in 1987, and the Doctorate at the Technische Universiteit Eindhoven in 1992.\nFrom 1986 to 1987 he worked as a Design Engineer at ELCOMA Laboratories in Philips, Eindhoven, The Netherlands, developing speech recognition algorithms for DSPs. From 1987 to 1992 he was an Assistant Researcher at the Institute for Perception Research in the same city, where he began his research activities in the area of Visual Perception.\nSince 1992, he has been a Professor at the Faculty of Engineering of the National Autonomous University of Mexico, and he is currently a full-time Professor 'C'. His areas of interest are the Computational Models of Vision and their Applications to the Restoration, Coding and Analysis of Digital Images and Video.\nHe is a member of the National System of Researchers, level I, level D in the Program of Premiums for Academic Performance of the UNAM, and has received several awards and recognitions throughout his career, among which stands out the National University Distinction in the area of Teaching in Exact Sciences in 1997.\nSince November 2003, he has been the Coordinator of the Postgraduate Program in Computer Science and Engineering at UNAM.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"2",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"653",title:"Remote Sensing",slug:"geology-and-geophysics-remote-sensing"}],chapters:[{id:"37529",title:"Narrowband Vegetation Indices for Estimating Boreal Forest Leaf Area Index",doi:"10.5772/31160",slug:"narrowband-vegetation-indices-for-estimating-boreal-forest-leaf-area-index",totalDownloads:2587,totalCrossrefCites:2,totalDimensionsCites:4,hasAltmetrics:0,abstract:null,signatures:"Ellen Eigemeier, Janne Heiskanen, Miina Rautiainen, Matti Mõttus, Veli-Heikki Vesanto, Titta Majasalmi and Pauline Stenberg",downloadPdfUrl:"/chapter/pdf-download/37529",previewPdfUrl:"/chapter/pdf-preview/37529",authors:[{id:"102410",title:"Dr.",name:"Miina",surname:"Rautiainen",slug:"miina-rautiainen",fullName:"Miina Rautiainen"},{id:"106738",title:"Prof.",name:"Pauline",surname:"Stenberg",slug:"pauline-stenberg",fullName:"Pauline Stenberg"},{id:"126165",title:"Dr.",name:"Ellen",surname:"Eigemeier",slug:"ellen-eigemeier",fullName:"Ellen Eigemeier"},{id:"136979",title:"Dr.",name:"Janne",surname:"Heiskanen",slug:"janne-heiskanen",fullName:"Janne Heiskanen"},{id:"136980",title:"Dr.",name:"Matti",surname:"Mõttus",slug:"matti-mottus",fullName:"Matti Mõttus"},{id:"136983",title:"BSc.",name:"Veli-Heikki",surname:"Vesanto",slug:"veli-heikki-vesanto",fullName:"Veli-Heikki Vesanto"},{id:"136985",title:"MSc.",name:"Titta",surname:"Majasalmi",slug:"titta-majasalmi",fullName:"Titta Majasalmi"}],corrections:null},{id:"37530",title:"Crop Disease and Pest Monitoring by Remote Sensing",doi:"10.5772/35204",slug:"crop-disease-and-pest-monitoring-by-remote-sensing",totalDownloads:9031,totalCrossrefCites:8,totalDimensionsCites:12,hasAltmetrics:0,abstract:null,signatures:"Wenjiang Huang, Juhua Luo, Jingcheng Zhang, Jinling Zhao, Chunjiang Zhao, Jihua Wang, Guijun Yang, Muyi Huang, Linsheng Huang and Shizhou Du",downloadPdfUrl:"/chapter/pdf-download/37530",previewPdfUrl:"/chapter/pdf-preview/37530",authors:[{id:"103431",title:"Dr.",name:"Wenjiang",surname:"Huang",slug:"wenjiang-huang",fullName:"Wenjiang Huang"},{id:"151635",title:"Dr.",name:"Juhua",surname:"Luo",slug:"juhua-luo",fullName:"Juhua Luo"},{id:"151636",title:"Dr.",name:"Jingcheng",surname:"Zhang",slug:"jingcheng-zhang",fullName:"Jingcheng Zhang"},{id:"151637",title:"Prof.",name:"Chunjiang",surname:"Zhao",slug:"chunjiang-zhao",fullName:"Chunjiang Zhao"},{id:"151638",title:"Prof.",name:"Jihua",surname:"Wang",slug:"jihua-wang",fullName:"Jihua Wang"}],corrections:null},{id:"37531",title:"Seasonal Variability of Vegetation and Its Relationship to Rainfall and Fire in the Brazilian Tropical Savanna",doi:"10.5772/35287",slug:"seasonal-variability-of-vegetation-and-its-relationship-to-rainfall-and-fire-in-the-brazilian-tr",totalDownloads:2288,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:null,signatures:"Jorge Alberto Bustamante, Regina Alvalá and Celso von Randow",downloadPdfUrl:"/chapter/pdf-download/37531",previewPdfUrl:"/chapter/pdf-preview/37531",authors:[{id:"113882",title:"Dr.",name:"Celso",surname:"Von Randow",slug:"celso-von-randow",fullName:"Celso Von Randow"},{id:"113883",title:"Dr.",name:"Regina",surname:"Alvalá",slug:"regina-alvala",fullName:"Regina Alvalá"},{id:"144075",title:"Dr.",name:"Jorge",surname:"Bustamante",slug:"jorge-bustamante",fullName:"Jorge Bustamante"}],corrections:null},{id:"37532",title:"Land Cover Change Detection in Southern Brazil Through Orbital Imagery Classification Methods",doi:"10.5772/36940",slug:"strategies-of-change-detection-in-southern-brazil-by-orbital-imagery-classification-methods",totalDownloads:1980,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:null,signatures:"José Maria Filippini Alba, Victor Faria Schroder and Mauro Ricardo R. 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Unrestricted access to calorie-dense food, along with a reduction in physical activity, has resulted in a rapid rise in metabolic disorders. One such condition, type 2 diabetes (T2D), has increased dramatically in recent times, with the International Diabetes Foundation estimating that 371 million people worldwide have T2D, with this number expected to increase to greater than 550 million by 2030 (http://www.idf.org/diabetesatlas/5e/Update2012). T2D is characterized by fasting blood glucose levels higher than 7.0 mM or two-hour blood glucose levels higher than 11.1 mM after a glucose tolerance test. T2D rarely occurs in isolation and is frequently associated with a number of comorbidities, including obesity, dyslipidemia, cardiovascular disease, and inflammation, collectively referred to as the metabolic syndrome.
A central aspect of the disorders comprising the metabolic syndrome is insulin resistance; defined as an impaired ability for insulin to regulate fuel metabolism in target tissues. With respect to glucose homeostasis the main insulin-responsive tissues involved are skeletal muscle, liver and adipose tissue. Under normal physiological conditions, insulin is released into the circulation from the beta cells in the islets of Langerhans in the pancreas in response to the ingestion of a meal. Upon binding to its receptor, insulin stimulates a well-described signaling cascade [1] involving the phosphorylation, docking and translocation of a series of signaling molecules, ultimately leading to alterations in specific endpoints of glucose and lipid metabolism (Figure 1):
In skeletal muscle, insulin promotes the translocation of the glucose transporter GLUT4 to the plasma membrane to increase glucose uptake and also stimulates glycogen synthesis.
The major hepatic actions of insulin are the promotion of glycogen and lipid synthesis and the suppression of gluconeogenesis.
In adipose tissue, insulin stimulates GLUT4-mediated glucose uptake and lipid synthesis, and additionally represses lipolysis, leading to net lipid accumulation.
Insulin signaling pathway. Binding of insulin to the insulin receptor initiates a signaling cascade that involves multiple phosphorylation events (green circles) and leads to alterations in glucose and lipid metabolism.
In the insulin resistant state, the effect of insulin on the above pathways is compromised, leading to insufficient uptake of glucose into tissues and an impaired suppression of hepatic glucose output. To overcome the diminished effectiveness of insulin, the pancreatic beta cells secrete more insulin. The ensuing hyperinsulinemia can adequately compensate for the insulin resistance in most of the population, however in genetically susceptible individuals, the beta cells ultimately fail in the face of the increased workload and this leads to elevated blood glucose levels and T2D. Thus insulin resistance can be considered a very early and important player in the pathogenesis of T2D.
At the molecular level, the precise mechanisms responsible for insulin resistance are not fully elucidated. Studies have reported overactivation of stress-related and inflammatory pathways in tissues of insulin resistant humans and rodents. For example, ER stress was shown by the Hotamisligil lab to be present in the liver of obese mice and subsequent studies using chaperones that reduce ER stress revealed improvements in metabolic homeostatsis [2,3]. Oxidative stress has also been implicated in the development of insulin resistance, with studies showing elevated reactive oxygen species generation in insulin resistant cell models, rodents and humans [4-6]. Finally, inflammation in adipose tissue and liver (and to some extent muscle) has been reported in obese, insulin-resistant humans and rodents [7,8]. While the above factors are often described as causative players in the development of insulin resistance, it still remains unresolved whether they are the primary factors leading to diminished insulin action, or if they arise as a consequence of insulin resistance.
One factor that is one of the earliest defects associated with insulin resistance and T2D is lipid accumulation in non-adipose tissues [9-13]. Under conditions of excess nutrient supply, fatty acids and their metabolites inappropriately spillover into tissues such as skeletal muscle, liver and the heart, precipitating defects in insulin action. More specifically, while elevated triglycerides are frequently reported in tissues of insulin resistant humans and rodents, the accumulation of metabolically active long chain acyl-CoAs (LCACoAs) and other cytosolic lipid metabolites, such as ceramides and diacylglycerol (DAG), are considered to be more directly linked with insulin resistance [9,10]. In support of this, the above lipid metabolites can activate many pathways and factors (e.g. protein kinase C, c-jun N-terminal kinase (JNK), reactive oxygen species, the nuclear factor κB (NFκB) pathway, protein phosphatase A2 (PPA2) and cytokines) that directly antagonize insulin signal transduction and glucose metabolism pathways [9,10].
The extent of lipid accumulation within any given tissue is determined by several factors. Under conditions of elevated lipid availability, enhanced uptake of fat into tissues contributes to greater lipid deposition [14,15]. This increased uptake is associated with greater expression and/or translocation of fatty acid transport proteins (e.g. CD36). Any impairment in the utilization (oxidation) of lipids would also be predicted to increase partitioning of lipids into storage pools. Indeed, over the last decade a popular theory has emerged suggesting that defects in mitochondrial oxidative metabolism, particularly in skeletal muscle, lead to obesity and lipid accumulation and thus may play an important role in the pathogenesis of insulin resistance and T2D [16].
The mitochondrion is the key site for energy production in cells, providing a platform for the oxidation of fuel substrates to produce ATP. During the oxidative metabolism of nutrients (primarily glucose and fatty acids under normal circumstances), reducing equivalents (NADH or FADH2) are generated from glycolysis, the TCA cycle and β-oxidation. When NADH and FADH2 are oxidized to NAD+ or FAD, electrons pass along the mitochondrial electron transport chain coupled to the pumping of protons into the intermembrane space through complex I, III and IV. The electrons are transferred to oxygen at complex IV to produce H2O. The pumped protons generate an electrochemical gradient across the inner mitochondrial membrane, which is used as the driving force for the ATP synthase (complex V) to produce ATP. The electrochemical gradient may also dissipate through uncoupling proteins (UCP), producing heat in a process referred to as thermogenesis.
During the oxidative metabolism of glucose and fatty acids, reducing equivalents (NADH or FADH2) are generated from glycolysis, the TCA cycle and β-oxidation. When NADH and FADH2 are oxidized to NAD+ or FAD, electrons pass along the mitochondrial respiratory chain while protons are pumped into the intermembrane space through complex I, III and IV. The electrons are transferred to oxygen at complex IV to produce H2O. The pumped protons generate an electrochemical gradient across the inner mitochondrial membrane, which is used as the driving force for ATP synthase (complex V) to produce ATP. Protons can also enter the matrix through uncoupling proteins. Deficiencies in mitochondrial fatty acid oxidation can lead to the buildup of bioactive lipid intermediates (red circle) that can cause insulin resistance.
Mitochondrial function within a given tissues is regulated at a number of different levels, including the number or density of mitochondria. The biogenesis of new mitochondria involves a coordinated interaction between the nuclear and mitochondrial genomes [17]. The mitochondrial genome encodes for 13 protein subunits of the mitochondrial respiratory complexes, as well tRNAs and rRNAs necessary for the translation of the mitochondrial-encoded proteins. The nuclear genome therefore encodes the vast majority of mitochondrial proteins and also encodes the transcription factor responsible for controlling mitochondrial transcription, namely TFAM. Proteins encoded by the nucleus are translated in the cytosol and imported into the appropriate mitochondrial compartments via a suite of import complexes [18]. Thus it is obvious that mitochondrial biogenesis is an extremely complex process, reliant upon the exquisite orchestration of separate genomes and multiple cellular processes.
The master regulators of the mitochondrial biogenic program are the peroxisome proliferator-activated receptor gamma (PPARγ) coactivator (PGC-1) family of transcriptional coactivators. The PGC-1 proteins are promiscuous coactivators that interact with and promote transcriptional activity in the key transcription factors (described below) that regulate the expression of genes involved in mitochondrial substrate oxidation, fibre-type determination, mitochondrial biogenesis and mitochondrial function [17,19]. The PGC-1 proteins do not bind directly to DNA, but instead recruit a wide array of chromatin-remodelling cofactors to transcriptional complexes. PGC-1α was the first described member of this family, initially identified in a screen for activators of PPARγ in brown adipocytes [20]. The other members of the family, PGC-1β and PRC were identified based on sequence homology to PGC-1α [21,22]. Overexpression and knockout studies for PGC-1 proteins have provided clear evidence that these coactivator proteins induce increases in mitochondrial oxidative capacity and promote a switch to a more oxidative fibre type in muscle [23-27].
PGC-1α appears to be the most responsive member of this family, with PGC-1β proposed to be important in the regulation of basal mitochondrial content [28]. Environmental stimuli such as exercise, fasting and cold exposure can induce a rapid increase in PGC-1α expression and activity [19]. PGC-1α also promotes its own expression through a feed-forward mechanism [29]. The activity of PGC-1α is regulated by a number of post-translational mechanisms including acetylation and phosphorylation. The relative level of PGC-1α acetylation is determined by the balance between the activity of the acetyltransferase GCN5 and the NAD+ dependent deacetylase SIRT1 [30,31]. With respect to phosphorylation, the energy sensing kinase AMPK has been shown to directly phosphorylate PGC-1α and alter its transcriptional activity [32]. Thus in responsive to specific stimuli, changes in the concentrations of key molecules within the intracellular milieu (e.g. NAD+, adenine nucleotides) results in stimulation of upstream regulators of PGC-1α activity and initiaition of the mitochondrial biogenic cascade. While the role of PGC-1α in regulating mitochondrial biogenesis is well established, recent work from the Spiegelman lab has described a novel splice isoform of PGC-1α that also regulates skeletal muscle hypertrophy [33], indicating there is still much to learn about the biology of the PGC-1 transcriptional coactivator proteins.
PGC-1 proteins orchestrate the mitochondrial biogenic program by promoting transcriptional activity through a variety of transcription factors. Nuclear transcription factors bind to specific sequences in gene promoter regions to regulate transcription of a subset of specific genes. The key transcription factors that regulate many of the genes involved in the respiratory chain and other mitochondrial pathways are described below.
NRF-1 plays a crucial role in coordinating nuclear and mitochondrial gene expression. It induces the expression of TFAM, as well as other components of the mitochondrial transcriptional machinery (e.g. TFB1M and TFB2M) [34,35]. NRF-1 also promotes the expression of mitochondrial import proteins that are involved in transporting nuclear-encoded proteins into mitochondria. Forced overexpression of NRF-1 in skeletal muscle in mice, results in increased expression of a subset of mitochondrial proteins, but no net increase in mitochondrial oxidative capacity [36]. Deletion of NRF-1 in mice on the other hand has been shown to be embryonic lethal, due to disruption of mitochondrial function [37].
Nuclear respiratory factor-2 (NRF-2 humans/GABP mice) is a second critical transcription factor that regulates the expression of proteins involved in mitochondrial function and biogenesis. The target genes of NRF-2 include all respiratory complex IV subunits, TFAM and a range of other proteins involved in mitochondrial transcription and replication [38]. Consistent with the findings in NRF-1 knockout animals, NRF-2 deletion also causes a lethal phenotype, underlying the crucial importance of this transcription factor [39].
The estrogen related receptor family contains 3 members, ERRα, ERRβ, ERRγ. ERRs regulate the expression of a wide array of genes involved in substrate uptake, the TCA cycle, fatty acid oxidation (FAO), oxidative phosphorylation and mitochondrial fusion [40,41]. ERRα knockout mice only display a mild phenotype [42], however deletion of the other two isoforms results in a lethal phenotype [43,44].
Similar to the ERR family, PPARs nuclear receptors that exist as 3 separate isoforms PPARα, PPARδ, PPARγ. The expression of PPARs varies markedly across different tissues, with PPARα being highly expressed in liver, PPARδ in skeletal muscle and PPARγ in adipose tissue [45]. PPARs are activated by long-chain polyunsaturated fatty acids and a range of lipid derivatives, and several mitochondrial genes, particularly those involved in fatty acid oxidation, are amongst their gene targets [46,47]. Several lipid lowering (e.g. fibrates) and anti-diabetic drugs (e.g. thiazolidinediones) target the PPAR proteins.
A range of mitochondrial genes are also regulated by the transcription factor YY1. Puigserver’s group have shown that the regulation of mitochondrial oxidative function by mTOR is regulated through YY1 [48] and recently it has been shown that mitochondrial function and morphology are abnormal in mice with muscle-specific YY1 knockout, highlighting an important role for this transcription factor in regulating mitochondrial function [49].
In addition to the biogenesis of new organelles, mitochondrial content is also partly determined by the rate of degradation. Indeed, mitochondrial autophagy (or mitophagy) is now recognized as a key quality control process regulating mitochondrial homeostasis [50]. Autophagy is a conserved cellular event in which damaged organelles and proteins are degraded in a two-step process, that first involves the formation of a double membrane structure called the ‘autophagosome’, followed by the fusion of the autophagosome with lysosomes and the subsequent degradation of the enveloped contents. Mitophagy can be inititiated by a number of events that signal stress within mitochondria, such as opening of the permeability transition pore or fragmentation of mitochondria [51,52]. The list of proteins that are thought to be involved in the mitophagy process (e.g. PINK1, Parkin, Nix) is increasing rapidly [50]. From a physiological perspective, mitophagy plays important roles in several developmental processes, such as red blood cell maturation and the removal of paternal mitochondria following fertilization of the oocyte [53-55]. However, recent evidence also suggests that abnormal mitophagic activity may contribute to the aging process, as well as a number of different diseases, such as neurodegenerative disorders [56].
While the number of mitochondria is obviously an important determinant of the oxidative capacity of different tissues, variations in the intrinsic properties of mitochondria are also critical. Mitochondria from different sites in the body can have different capacities for the same process. For example, mitochondria from red slow-twitch and white fast-twitch muscle display very different rates of fatty acid oxidation [57]. This difference is in line with the functional requirements of these muscles, and is likely related to the differences in protein expression of key enzymes in this pathway [58]. In addition to differential expression of proteins within specific pathways, another emerging factor that may influence mitochondrial oxidative capacity is post-translational modifications of mitochondrial enzymes. Following translation, many different facets of protein function (activity, subcellular localization, protein-protein interactions) can be altered by the addition of functional groups to specific residues in the protein. The most well-described PTM is likely phosphorylation, and proteomics screens have revealed widespread phosphorylation of mitochondrial proteins [59]. The activity of specific mitochondrial proteins, such as uncoupling protein 3, has been shown to be directly regulated by phosphorylation [60]. Other recent work has shown that perhaps the most abundant PTM in mitochondria is lysine acetylation. Acetylation involves the transfer of an acetyl group from acetyl-CoA to a lysine residue in specific proteins. More than 30% of mitochondrial proteins have been shown to be acetylated, and reversible lysine acetylation/deacetylation has been shown to impact on the activity of a large range of mitochondrial enzymes involved in virtually all metabolic pathways within this organelle [61]. In addition to phosphorylation and acetylation, numerous other PTMs (e.g. glutathionylation, nitrosylation, succinylation) have been described as being present in mitochondria [62-64], and their functional importance remains to be determined.
Mitochondria are not static organelles, but exist largely as a reticular network. Mitochondria are constantly engaged in the process of fusion and fission, providing morphological plasticity to allow adjustments in response to the prevailing cellular stresses and metabolic requirements [65]. Mitochondrial fusion is mediated by the mammalian GTPases mitofusin 1 and mitofusin 2, as well as optic atrophy protein 1 (Opa1). Fusion occurs in a two-step process, which initially involves fusion of the outer membrane (mediated by mitofusins), followed by subsequent fusion of the inner membrane (driven by Opa1) [66,67]. Fission is regulated by another GTPase, dynamin-related protein 1 (Drp1), which resides in the cytosol and is recruited to the mitochondrial surface to engage other key components of the fission machinery (e.g. Fis 1) [68,69]. The fusion process is thought to allow two mitochondria to functionally complement each other through the exchange and repartitioning of their respective components (e.g. copies of the genome, metabolic enzymes and metabolites). Fission on the other hand is important both in the separation of the organelle into daughter cells during cell division and also in isolating and targeting damaged mitochondria for degradation. Collectively the balance of fusion and fission allows mitochondria to form a spectrum of shapes from small individual units to elongated interconnected networks.
In muscle cells, the mitochondrial network is arranged into two discrete, but interconnected pools – the subsarcolemmal (SS) pool near the cell surface, and the intermyofibrillar (IMF) pool in the interior of the cell between myofibres [70-72]. These two pools of mitochondria have been reported to display some differences in their metabolic characteristics, with SS mitochondria appearing to be more responsive to increase their oxidative capacity following an exercise stimuli than IMF mitochondria [57,73]. Despite the differences between mitochondrial pools, it has been proposed that the arrangement of mitochondria may important for efficient mitochondrial function; SS mitochondria have greater access to oxygen and metabolic substrates, and the proton gradient generated through substrate oxidation in the SS pool may potentially contribute fuel ATP synthesis in the IMF pool, where energy demands are highest during contraction [71].
As detailed above, mitochondria represent complex organelles and perturbations in any aspect of mitochondrial regulation and function, could impact on metabolic homeostasis. The mitochondrial theory of insulin resistance has developed over the last 10-15 years and is based on the notion that defective mitochondrial metabolism will result in inadequate substrate oxidation, leading to a buildup of lipid metabolites and the subsequent development of insulin resistance. Support for this theory comes from many studies in humans and rodents, which have largely examined skeletal muscle and are reviewed below.
In the late 1990’s and early part of last decade, several groups published studies showing that muscle from obese and insulin resistant subjects displayed reduced oxidative enzyme activity [74-76]. Some of these studies also examined lipid oxidation either in muscle homogenates, or by making RQ measurements across the leg, and it was shown that fatty acid oxidation was also decreased in obese, insulin resistant subjects compared to age-matched controls, potentially suggesting that defects in mitochondrial metabolism may be involved in the development of obesity and insulin resistance [74,75]. In 2002, Kelley’s group showed that there was lower NADH:O2 oxidoreductase activity and reduced mitochondrial size, as determined by electron microscopy, in muscle of obese subjects with insulin resistance and/or T2D compared to controls [77]. A year later, two influential microarray studies were published, reporting a coordinated downregulation of genes involved in mitochondrial biogenesis and oxidative phosphorylation in subjects with T2D and non-diabetic individuals with a family history (FH+) of T2D [78,79]. These microarray studies were considered particularly important, as they documented a reduction in the master regulator of mitochondrial biogenesis, PGC-1α, and thus they provided a mechanism for the reduced oxidative gene expression. They were also important, as they showed that abnormal mitochondrial gene expression could be observed in insulin resistant relatives of patients with T2D and thus may be a pathogenic factor in the ‘pre-diabetic’ state. Overall the conclusion from these studies was that depressed PGC-1α levels, due to genetic predisposition, physical inactivity, or excessive caloric intake, could lead to a reduction in mitochondrial content, predisposing individuals to develop insulin resistance and T2D.
In the ensuing decade since these landmark studies were published, there has been intense research into this field and one issue that has arisen is how to best measure mitochondrial function/dysfunction. Numerous approaches have been employed, including measurements of parameters in frozen muscle samples (e.g. mRNA, protein content, oxidative enzyme activity and mtDNA), functional assessment of substrate oxidation in fresh samples (e.g. radiolabelled fatty acid oxidation, mitochondrial respiration measurements) and non-invasive magnetic resonance spectroscopy (MRS) with 31P or 13C to determine
In line with the microarray studies noted above, mRNA levels for a variety of mitochondrial genes have been shown to be reduced in muscle biopsies obtained from various insulin resistant populations, including lean insulin-resistant offspring of patients with T2D [80], obese subjects [81], patients with polycystic ovarian syndrome [82] and subjects with established T2DM [83,84]. The level of mtDNA was also shown to be lower in both obese, insulin resistant subjects and obese subjects with T2D [85,86]. Heilbronn et al. [81] demonstrated reduced protein expression of respiratory chain subunits in obese insulin-resistant subjects and consistent with these findings, a recent proteomics study comparing lean, obese and T2D subjects, showed patterns of reduced mitochondrial proteins in the insulin-resistant subjects [87]. The activity of specific enzymes involved in oxidative pathways have been reported to be lower in various insulin-resistant populations [81,86,88,89] and additionally electron microscopy studies have reported reduced mitochondrial size and density in insulin-resistant muscle [77,80,86]. Interestingly, in the studies reporting mitochondrial deficiencies, there has been disparate results regarding which population of mitochondria may underlie the functional defects. Ritov et al. [86] reported that the number and functional activity of subsarcolemmal mitochondria was reduced in obesity and T2D, while a more recent study found similar subsarcolemmel mitochondrial content in lean controls, lean insulin-resistant non-diabetic subjects and insulin-resistant T2D subjects, however intermyofibrillar mitochondrial content was reduced in the latter two groups [90]. Differences in mitochondrial function may not only be present within different intramuscular populations, but also between different muscles across the body. Rabol and colleagues used high resolution respirometry to measure mitochondrial function in saponin-permeabilised fibres from m. deltoideus and m. vastus lateralis and observed reduced respiratory capacity only in the leg muscles of type 2 diabetic subjects compared to lean controls [91].
In addition to the above studies, several investigators have also measured
A number of investigations have sought to determine if there is an intrinsic difference in the functional capacity per mitochondrion that may underlie the reductions in mitochondrial function reported with MRS. Some studies examining respiration or fatty acid oxidation in isolated mitochondria or permeabilised muscle fibres, have reported that the functional capacity per mitochondrion in insulin resistant and/or type 2 diabetic subjects is similar or only very mildly reduced [85,88,91,101-103] in insulin-resistant individuals, but when normalized to muscle mass, a substantial reduction is seen in insulin-resistant subjects [85,88,101]. These studies therefore only see marked differences when mitochondrial capacity is expressed per unit mass of skeletal muscle and thus indicate that
One limitation of the aforementioned studies is that they only provide static measurements of different populations at a given time and are unable to delineate whether the observed defects in mitochondrial metabolism are primary drivers of insulin resistance or arise as a consequence of decreases in insulin action. In this regard, intervention studies in rodents and humans have provided some experimental evidence that manipulations which result in declines in insulin action, are also associated with mitochondrial dysfunction. For example, infusion of fatty acids into humans for 6–48h to mimic the effects of chronic lipid overload resulted in a robust induction of whole-body insulin resistance and reduced insulin-stimulated ATP synthesis rates and expression of mRNA encoding PGC1α and other mitochondrial genes in muscle [104-106]. In healthy male subjects, high-fat feeding for 3 days was sufficient to reduce mRNA levels of PGC1α, PGC-1β and several other mitochondrial genes in skeletal muscle [107]. Similarly, genetic, or high-fat diet-induced obesity and insulin resistance in rodents has been reported by several groups to reduce mitochondrial gene expression, protein expression and mitochondrial respiration in skeletal muscle [107-111]. Providing additional evidence of a link between mitochondrial dysfunction and insulin resistance is the fact that antiretroviral therapy used to suppress human immunodeficiency virus infection causes insulin resistance in association with mtDNA copy number [112]. Collectively, the above studies illustrate that there are many instances where defects in mitochondrial metabolism and impairments in insulin action occur in conjunction with each other in skeletal muscle.
The liver plays a major role in regulating glucose homeostasis, producing glucose during the fasting state and storing glucose after the ingestion of a meal. Hepatic insulin resistance causes impaired glycogen synthesis and reduced suppression of endogenous glucose and is closely correlated with excess accumulation of lipid in liver. Chronic elevation of liver lipid content is referred to as non-alcoholic liver disease (NAFLD) and this condition progresses to non-alcoholic steatohepatitis (NASH) when inflammatory and fibrotic processes become involved.
A range of different parameters have been studied in rodents and humans with respect to liver mitochondrial metabolism. The collective findings indicate that the liver appears to be able to adapt to an excess of lipid by upregulating fatty acid oxidative capacity and TCA cycle activity, but this is not always coupled to a concomitant increase in electron transport chain activity, and as a consequence reactive oxygen species are produced (see [113] for an excellent review on the topic). There are also some
White adipose tissue (WAT) serves a principal role as the most important energy store in the body. However it has become increasingly clear over the last decade that WAT is also an active endocrine organ, releasing adipokines that influence whole-body energy homeostasis and insulin action. Mitochondrial content in WAT is low compared to other tissues, however the diversity of mitochondrial proteins in WAT has been shown to be greater than in muscle and heart [117]. Intact mitochondrial metabolism is critical for maintaining normal WAT functions, such as the appropriate synthesis and secretion of adipokines and cycling reactions involved in lipid synthesis [118].
WAT mitochondrial content has been reported to be reduced in insulin-resistant humans and rodents. In women with T2D, electron transport chain genes were shown to be downregulated in visceral WAT independently of obesity and perhaps as a consequence of TNFalpha-induced inflammation [119]. In obese humans, mtDNA copy number was reported to be lower than in control subjects and was directly correlated with basal and insulin-stimulated lipogenesis [120]. In rodent models of genetic or dietary-induced obesity and insulin resistance, there are reductions in mtDNA copy number, mitochondrial density and mitochondrial OXPHOS activity [121-123]. Administration of thiazolidinediones promotes mitochondrial biogenesis in WAT in animals and humans, in conjunction with improved whole-body insulin sensitivity [46,123], suggesting that specific changes in WAT mitochondrial metabolism in obesity and T2D, may be imparting whole-body metabolic consequences. Indeed, recent work has shown adipose-restricted alterations in mitochondrial activity can have profound effects on global glucose and lipid homeostasis [124,125].
Unlike WAT, the principal function of brown adipose tissue (BAT) is energy dissipation, rather than energy storage. BAT has a high mitochondrial density per gram of tissue, and the unique presence of uncoupling protein 1 (UCP1) allows brown adipocytes to couple the oxidation of lipids, not to ATP synthesis, but to heat generation via proton leak across the mitochondrial inner membrane. Interest in brown adipose tissue has recently soared on the back of 3 important papers published in 2009 that unequivocally demonstrated the presence of functional BAT in humans [126-128]. There is an inverse correlation between BAT activity (as assessed by fluorodeoxyglucose PET) and obesity, suggesting that individuals with low BAT mitochondrial activity, may be prone to obesity and other metabolic diseases [126,127,129-131].
Like skeletal muscle, translocation of GLUT4 in response to insulin occurs in myocardium. This process is blunted in insulin-resistant humans and animals in association with other abnormalities in fuel metabolism ([132-134]. With respect to mitochondrial metabolism, genetic and diet-induced obesity and type 2 diabetes in rodents is associated impaired mitochondrial function [135-137]. MRS studies in individuals with T1DM, T2DM, obesity and/or NAFLD have also reported that that there is a decreased ratio of phosphocreatine:ATP in myocardium, potentially indicating derangements in mitochondrial substrate metabolism in these populations [138-142].
As noted in the previous section, mitochondrial dysfunction is frequently documented in insulin resistant states and there are many possible factors that may underlie this relationship.
Insulin is a potent anabolic hormone and it has been proposed that mitochondrial dysfunction may emerge secondary to insulin resistance. Insulin infusion in humans leads to increases in mitochondrial gene expression, higher oxidative enzyme activity and elevated ATP synthesis in muscle [143,144]. This response is attenuated in insulin-resistant T2D individuals, supporting a direct role for insulin resistance leading to mitochondrial dysfunction [143]. Further evidence for this notion comes from a study by Karakelides et al, who showed that acute insulin removal from subjects with type 1 diabetes, caused reductions in mitochondrial ATP production and in mitochondrial gene expression in skeletal muscle [145]. Additionally a recent study in patients with congenital defects in insulin signal transduction, reported that mitochondrial function (assessed by phosphocreatine recovery rates) in muscle was reduced in this population [146]. Finally a recent study that induced insulin resistance by prolonged fasting, also reported defects in mitochondrial function [147]. Overall these studies indicate that insulin can directly regulate mitochondrial biogenesis and metabolism, and therefore it is plausible that some of the mitochondrial defects observed in insulin-resistant subjects, could be a consequence of the insulin resistance itself.
Any perturbation in the dynamics of the mitochondrial network could potentially contribute to the pathogenesis of insulin resistance in skeletal muscle. The complex process of mitochondrial fission and fusion has been described above and alterations in key proteins mediating these dynamic events have been reported in insulin resistant and obese states. The expression of mitofusin 2 (MFN2), which appears to have additional pleitropic effects in cells beyond the maintenance of the mitochondrial network [148-152], is reduced in the skeletal muscle of obese insulin-resistant humans, type 2 diabetic humans and diabetic Zucker rats [149,153] and correlates with the capacity for glucose oxidation [154]. Repression of MFN2 in L6E9 muscle cells and 10T/2 fibroblasts results in decreased glucose oxidation, cellular respiration, mitochondrial membrane potential, and causes fragmentation of the mitochondrial network [149] and liver-specific deletion of MFN2 results in glucose intolerance and impairments in insulin signaling [155]. Recent work has also shown that mice deficient in the mitochondrial protease OMA1, display obesity and altered metabolic homeostasis, due to altered processing of the inner membrane fusion protein OPA1 and disruptions in mitochondrial morphology and fuel metabolism [156]. It has also been reported that abnormalitieis in mitochondrial fission events may play a role lipid-induced insulin resistance. In C2C12 muscle cells, palmitic acid (but not other long-chain fatty acids) was shown to induce mitochondrial fragmentation in conjunction with insulin resistance and this effect could be blocked by genetic or pharmacological inhibition of Drp1 [157]. Analysis of tissues from
Physical inactivity has recently been reported to be as big a risk factor for non-communicable diseases as smoking, stressing the importance of exercise in metabolic health [158]. Exercise is one of the major stimuli for mitochondrial biogenesis and chronic inactivity results in decreases in mitochondrial number in muscle [159]. A number of studies have shown that obesity and other metabolic disorders are characterised by decreased physical activity levels and elevations in sedentary behaviour [160-162]. Interestingly the sedentary behaviours (e.g. sitting time) do not seem to be influenced by changes in weight and have been suggested to be biologically determined [161]. Given these differences, it is likely that some of the mitochondrial defects reported in overweight or obese insulin-resistant subjects may be explained, in part, by low levels of physical activity.
There is evidence in the literature that the metabolic phenotype of skeletal muscle may be strongly influenced by genetic programming. For example, despite being cultured under similar conditions for several weeks, studies have shown that primary human skeletal muscle cells in culture display a similar metabolic phenotype (e.g. gene expression and lipid partitioning) to that of the donor subject from which they originated [163,164]. Mutations in nuclear-encoded genes involved in mitochondrial function (e.g. PGC-1α, NDUFB6) have been linked with insulin action and T2D, as have mtDNA deletions [165,166]. An emerging area of research is also the regulation of mitochondrial function by epigenetic factors. Barres et al showed that the promoter of PGC-1a is methylated at non-CpG sites and exposure of primary human myotubes to hyperlipidemia or inflammatory stimuli, promoted PGC-1α hypermethylation. Intriguingly PGC-1α hypermethylation was observed in muscle of T2D patients in conjunction with reduced mitochondrial density [167]. PGC-1α hypermethylation has also been linked with insulin resistance in non-alcoholic fatty liver disease [168]. A number of other studies have also reported that methylation of other mitochondrial genes (e.g. NDUFB6 and ATP50) as well as TFAM, can be regulated by methylation and associated with insulin resistance. [166,168-170]. One recent study has also shown that methylation of mitochondrial DNA is also correlated with severity of NAFLD [171]. In addition to methylation, acetylation can also influence gene transcription and the potential importance of this epigenetic factor is highlighted by a recent study showing that pharmacological inhibition of HDAC1 in cells and obese animals could promote mitochondrial biogenesis and improve metabolic phenotype [172]. Overall the above studies indicate that specific chromatin modifications may influence mitochondrial function in insulin resistance and T2D.
Oxidative stress can be defined as a chronic imbalance between the production of reactive species and the protection against these species by antioxidant defenses, ultimately leading to macromolecular damage. Reactive oxygen species (ROS) are an unavoidable byproduct of metabolic reactions within cells and a major site for ROS production is the mitochondrion [173]. Studies from a number of different groups have shown that in genetic or diet-induced obese rodents, there is increase ROS production [4,5,174,175]. Importantly, most [4,5,175,176], but not all studies [177] show that insulin action is improved by genetic or pharmacological attenuatation of mitochondrial ROS production, indicating an especially important role for generation of reactive species in this organelle. Since mitochondria are particularly susceptible to oxidative attack [178,179], it is possible that overactive ROS generation in response to obesity or high dietary lipid supply, may lead to defects in mitochondrial function. Indeed, Bonnard et al. fed mice a long-term diet rich in fat and sugar and concluded that under their specific experimental conditions, oxidative stress was involved in the induction of mitochondrial dysfunction [108].
As noted above, there is an emerging appreciation for the fact that specific mitochondrial enzymes and pathways may be regulated by post-translational modifications. Several groups have shown that mitochondrial acetylation is increased in tissues of diet-induced obese mice [180,181]. SIRT3 is a key regulator of mitochondrial acetylation and the expression of this deacetylase enzyme is markedly reduced in a number of different experimental models of insulin resistance and diabetes [181-183]. SIRT3 KO mice display insulin resistance in muscle [182] and these mice also exhibit an accelerated development of the metabolic syndrome when challenged with long-term high fat diet, in association with pronounced hyperacetylation of liver mitochondria [181]. Interestingly, in addition to showing that SIRT3 KO mice have a compromised phenotype, Hirschey et al have also shown that a point mutation in SIRT3 that results in reduced activity of this protein, is associated with the development of metabolic syndrome in humans [181]. The above studies suggest that altered acetylation of mitochondrial proteins may associate with insulin resistance and impaired mitochondrial function, and while further study in this field is required, there is some evidence that other mitochondrial PTMs may also be altered in insulin resistance and T2D [184,185].
Despite the frequent association of mitochondrial dysfunction and insulin resistance, evidence of a cause-and-effect relationship between the two is still lacking. In fact, a substantial literature now exists in both humans and rodents directly challenging the notion that deficiencies in mitochondrial oxidative capacity are an obligate part of the link between lipid accumulation (obesity) and insulin resistance.
Trenell and colleagues used MRS to determine basal and maximal ATP turnover in muscle of well-controlled T2D patients compared with physical activity-, age- and weight-matched control subjects and observed no difference between the two groups [186]. A similar finding was reported in a separate population where post-exercise phosphocreatine recovery indicated similar mitochondrial function between obese patients in either the early or advanced stages of T2D and normoglycemic controls matched for age, body composition and habitual physical activity levels [187]. A further study from the same group also recently reported similar
The studies above provide evidence that at least in those populations, mitochondrial dysfunction does not seem to be present in a number of insulin resistant groups. In line with these examples of a discordant relationship between these two variables, several human intervention studies have also shown that changes in insulin sensitivity can occur without concurrent improvements in mitochondrial function. For instance, dietary restriction in overweight and obese subjects enhanced insulin sensitivity, without altering mtDNA, cardiolipin content or NADH-oxidase activity [192]. Improved insulin sensitivity was reported in insulin-resistant subjects with a family history of T2D following 7 days of treatment with the anti-lipolytic agent acipimox, yet mitochondrial gene expression in muscle actually declined in these subjects [193]. Treatment of diabetic patients with rosiglitazone improved insulin sensitivity, without altering
To complement the studies in humans, a number of investigators have used gene-manipulated mice to more directly test whether specifically targeting mitochondrial metabolism, can induce changes in insulin sensitivity. Mitochondrial oxidative capacity was shown to be compromised in muscle-specific TFAM knockout mice, however these animals exhibited improved glucose clearance during a glucose tolerance test and maintained insulin-stimulated glucose uptake in muscle [197]. TFAM knockout in adipose tissue was recently shown to protect against diet-induced obesity and insulin resistance, despite causing abnormalities in mitochondrial function [125]. Similar findings were reported in mice with liver or muscle-specific deletion of apoptosis-inducing factor. These animals exhibited a gene expression pattern of mitochondrial oxidative phosphorylation deficiency similar to that observed in human insulin resistance [78,79], however they were lean and insulin-sensitive and did not manifest the usual deleterious effects of a high-fat diet [198]. A number of groups have also targeted other regulators of mitochondrial function in mice. Due to their key role in mitochondrial biogenesis, muscle-specific knockout of PGC-1α or loss-of-function mutation of PGC-1β produced the expected decline in markers of mitochondrial function yet insulin sensitivity in muscle was preserved or in fact slightly enhanced in these animals compared to wild-type counterparts [26,199]. Two separately generated lines of muscle-specific PGC-1α transgenic mice have shown predictable increases in many mitochondrial parameters, but these animals are insulin resistant, potentially due to excessive fatty acid delivery into muscle [200] or decreased GLUT4 expression [201]. In other examples of a dissociation between insulin resistance and mitochondrial dysfunction, it has been shown that Zucker diabetic fatty (ZDF) rats display normal
Dietary studies are another robust approach to test whether mitochondrial defects can be causally linked with changes in insulin action. Feeding rats an iron-deficient diet causes a deficiency in mitochondrial electron transport chain enzymes, however this is not associated with the development of insulin resistance [205]. In 2007, our group showed that high-fat feeding in mice induced insulin resistance and was associated with increased expression of a PGC-1α and a number of mitochondrial proteins, elevated oxidative enzyme activity and higher fatty acid oxidation rates [206]. Furthermore we also demonstrated that similar changes in markers of mitochondrial metabolism were present in muscle from high-fat fed rats,
One interesting observation to come out of the dietary studies in rodents is that from Muoio’s group. They reported that the increased mitochondrial fatty acid oxidation that occurs in response to high-fat feeding, results in the generation of acylcarnitines as incomplete oxidation products [214]. This acylcarnitine signature, which is thought to disturb the mitochondrial CoA equilibrium and indicate a state of mitochondrial stress, has also been observed in humans with obesity and T2D [215,216]. Whether the acylcarnitines can directly contribute to the development of insulin resistance is currently unclear, but recent work suggests that these metabolites serve as a marker for the inability of mitochondria to efficiently transition between fuel substrates [217].
In summary, while there are a large number of studies that document an association between mitochondrial dysfunction and insulin resistance in lean and obese subjects, there is now a significant literature showing that alterations in mitochondrial function in muscle and insulin action are not always correlated. There are a myriad of differences between studies that may explain these discrepancies, including the particular population of individuals studied and their ethnic background and physical fitness level, the muscle group examined, the dietary regime employed in rodent and human studies (e.g. duration of feeding, fat content and composition) and the particular assay/technique used to assess mitochondrial function.
While the precise role of mitochondria as pathogenic drivers of insulin resistance and T2D remains controversial, it should be recognized that even if mitochondrial defects arise secondary to the development of insulin resistance or as a consequence of obesity, reductions in oxidative fuel metabolism are likely to accelerate ectopic lipid deposition in non-adipose tissues and thereby exacerbate the insulin-resistant state. Therefore it would appear that stimulating mitochondrial biogenesis and fuel metabolism, could have beneficial effects for treating metabolic diseases. Evidence in this regard is summarised below
Exercise robustly stimulates mitochondrial biogenesis in muscle and has a multitude of health benefits, including improving insulin action. An 8 week cycling regime in sedentary elderly subjects increased muscle fatty acid oxidative capacity and in parallel improved insulin-mediated glucose disposal [218]. A ten week exercise training program produced similar improvements in insulin sensitivity and muscle oxidative enzyme activity in both first degree relatives of T2D patients compared with age-, sex- and BMI-matched controls [219]. Toledo reported that 4 months of exercise training in T2D patients increased skeletal muscle mitochondrial density, cardiolipin content and mitochondrial oxidation enzymes, in conjunction with a 60% improvement in insulin sensitivity [220]. Aerobic cycling training for 10 weeks in obese, T2D male subjects induced an ~20% increase in insulin sensitivity and a 40% increase in mitochondrial content, with these changes of a similar magnitude to that observed in matched control subjects [221]. Twelve weeks of combined progressive training was also sufficient to overcome the
Caloric restriction has been shown to improve insulin sensitivity in humans [222,223] and to improve markers of mitochondrial function in muscle of humans and rodents [224,225]. Many of the beneficial effects of calorie restriction have been proposed to be through stimulation of the SIRT1 pathway. Indeed studies have shown that activators of SIRT1 (e.g. resveratrol and more potent specific activators) can enhance mitochondrial metabolism and improve insulin action in rodent models of insulin resistance and T2D [226-229]. Recently it was also shown that 30 days of resveratrol supplementation improved some markers of mitochondrial function in muscle of obese subjects, in parallel with improved HOMA-IR and reduced hepatic lipid levels [230]. These effects seem to be limited to metabolically compromised subjects, as resveratrol did not improve markers of glycaemic control in non-obese women with normal glucose tolerance [231]. An alternative approach to using direct SIRT1 activators to mimic calorie restriction, is to increase the intracellular levels of NAD+, the obligate co-factor for the sirtuin reaction. Indeed two recent studies using different NAD+ precursors, nicotinamide mononucleotide or nicotinamide riboside, have both reported beneficial metabolic effects on metabolic homeostasis in animals models of insulin resistance and T2D [232,233].
As noted above, energy dissipation or wasting can occur in a process known as mitochondrial uncoupling. While this occurs naturally through uncoupling proteins, there are also a pharmacological agents that can induce mitochondrial uncoupling, such as DNP (2,4-dintirophenol). These uncoupling agents are generally lipophilic weak acids, that cause mitochondrial uncoupling by transporting protons across the mitochondrial inner membrane into the matrix, deprotonating and then exiting as anions before repeating the catalytic cycle. Uncoupling agents have been successfully used in the past as obesity treatments. In the 1930’s DNP was shown to be an effective weight-loss drug in humans, providing an important proof-of-concept that the stimulation of energy expenditure by uncoupling is not necessarily compensated for by an increase in caloric intake [234]. Despite its success as an anti-obesity therapy, DNP was withdrawn from the market in 1938 as it (like most uncouplers) has a narrow therapeutic window, with overdoses causing serious complications (even death) by compromising cellular energy homeostasis. Due to the current obesity epidemic, and illicit sales via the internet, it is alarming to see that DNP has made a comeback as a weight loss agent, with predictable lethal results [235,236]. Thus, while mitochondrial uncoupling with DNP does not appears to be a safe weight-loss therapy, other more recently described uncoupling agents may potentially have a safer profile for use in humans [237-239]. An additional approach may to be to upregulate physiological uncoupling in brown adipose tissue, via sympathomimetic agents or agonists for thyroid hormone or bile acid receptors.
Natural compounds are another rich source of potential therapeutics for obesity and type diabetes, as there is often a long history of use of these compounds in the treatment of metabolic diseases states. One such compound is berberine, a natural plant alkaloid that has been used as a traditional medicine in many Asian countries. Berberine was shown to improve insulin sensitivity in a range of animal models [240] and there is also evidence of beneficial effects in humans [241]. Although enhancing mitochondrial function appears to be an effective treatment for insulin resistance, we showed that berberine acted through inhibition of Complex 1 of the electron transport chain [242]. This mild mitochondrial inhibition led to the activation of AMPK and subsequent metabolic benefits. Interestingly this pattern of mild inhibition of mitochondrial metabolism has been reported in other insulin-sensitising medicinal plants [243] and is also a characteristic of metformin and thiazolidinediones, which are frontline anti-diabetic therapies [242,244,245].
The mitochondrial dysfunction theory of insulin resistance, proposes that defects in mitochondrial metabolism are key events involved in the pathogenesis of insulin resistance. At present, the available literature does not provide strong evidence for this relationship, and there is mounting evidence that mitochondrial defects observed in insulin-resistant individuals are likely acquired (e.g. due to low physical activity or caloric excess), or develop secondary to the insulin resistance itself. Furthermore, with respect to muscle, another important issue that needs to be considered is whether the ~30% reduction in mitochondrial function that has been observed in some insulin-resistant humans would limit the oxidation of fatty acids, leading to lipid accumulation as proposed [16]. At rest the rate of oxygen utilization in muscle is low; and the fact that muscle has enormous capacity to increase substrate oxidation over normal levels, means that there is substantial ‘spare’ capacity in this system to maintain fatty acid utilization under normal free-living conditions when energy requirements are low. Despite the unanswered questions about the precise role that mitochondria play in insulin resistance and T2D, therapies targeting this important organelle, should be explored for the the treatment of insulin resistance and its associated metabolic disorders.
In April 2014 [1] Maltese educational psychologist Mr Juan Camilleri and I tabled a petition with the Parliament of Malta. We recommended the use of alternative access to and production of literacy for national academic examinations and throughout education. At the time, the Rector of the University of Malta (UM) refused to accept the petition, which is why we then tabled it with the Parliament of Malta. Since then, significant changes at the UM and the Ministry for Education and Employment indicate that Malta has started to embrace the rationale of this petition [2]. Notwithstanding, I think that there is still long way to go both locally and globally, particularly with reference to attitudes within the academic world. In spite of literature affirming that the ability to read and intelligence are not correlated [3, 4], people with dyslexia still experience being looked down upon by educators and fellow students due to their challenges with literacy (e.g., [5, 6, 7]). This chapter will discuss experiences of university students with dyslexia and suggest possible strategies that can be considered, also in the context of the present health situation. This chapter embraces Kannangara’s [8] model From Languishing to Thriving Dyslexia.
To start, I will share the experience of an academic I heard speak during an international conference I attended in 2015. She used to work in a University in Europe. She had been working at this university for over 25 years and had always received positive feedback and evaluation reports about her lecturing, research, administration, co-ordination and research. She had never felt the need to disclose her profile of dyslexia. However, one day she mentioned her profile en passant during a meeting with University academic and administration. From that day on, the university started asking her to recheck her work, her work started to be supervised; and she was given the message that the university had concerns about her profile. The situation was so stressful for her that it became untenable and she actually had to leave her place of work. It seems that, after 25 years of sterling service to her university, the main focus became her profile rather than her actual sterling output and track record.
At the outset, I would like to declare that one cannot diminish the extreme importance of reading and spelling skills and techniques. Globalisation is placing new demands on the kinds of literacies we need both in our work and in the daily demands of everyday life. A good quality basic education equips one with literacy skills for life and further learning. In most developed and developing countries, literacy skills are fundamental to daily living and affect the social, political, civic, economic and personal lives of citizens, directly affecting wellbeing [8]. Where literacy still does not have a fundamental function, oppression and poverty prevail [9, 10, 11]. Johnson and Kress [12] noted that “globalization is frequently thought about in economic terms alone, but there is equally a cultural globalization which is no less, maybe even more, potent in its shaping to the ways in which we communicate and represent meaning” (p. 5).
Literacy is regarded as a means to address poverty and oppression (e.g., [9, 13, 14, 15]). The post-war era has seen literacy on nations’ educational, economic and political agendas (e.g., [15, 16, 17]). The United Nations’ Educational, Scientific and Cultural Organisation (UNESCO) perceives literacy as a human right, a tool of personal empowerment, a means for social and human development, and at the heart of basic education for all [15]. The UNESCO Education for All (EFA) committee noted that eradicating poverty, reducing child mortality, addressing population growth, achieving gender equality and ensuring sustainable development, peace, democracy and empowerment are some of the good reasons why literacy is at EFA’s core [15]. Indeed, since its foundation in 1946, UNESCO has been at the forefront of global literacy efforts and is dedicated to keeping literacy high on national, regional and international agendas [18].
Hirsch [19] proposed that failing to teach children what they must learn in order to be able to cope with further learning in school is the greatest form of injustice in education which can be prevented. What I challenge is what is regarded as a must to learn and how one defines literacy.
The literature is clear. Access to the printed text paves the way for learning and economic growth and justifies ensuring that young learners learn to read as early and as expediently as possible (e.g., [9, 20, 21]). The speed and effectiveness of this early literacy learning process affects success in learning and has a Matthew Effect (e.g., [22, 23, 24]). However, education needs to include those for whom learning to read is not so easy. Pedagogies need to embrace this and must use teaching strategies which include media other than the printed text to access learning, particularly in a context where technology is the reality of the day.
There is consensus that the ultimate purpose of reading printed text is to understand its meaning [25]. Research indicates that slow and effortful word-decoding/word-recognition abilities limit reading comprehension abilities (e.g., [4, 26, 27]) and affect academic success [28], with success depending on the ability to read and write [29]. I simply want my dream to become a reality for all: “for whom reading and writing is not such an easy task or choice, alternatives for access to medium and expression of knowledge should be available so long as the aims and objectives of examinations are not compromised” ([1], p. 1).
Children and young people with dyslexia and other challenges are failing their national examinations due to access to medium and choice of medium of expression [30]. This is not only disheartening for the individual, but also a brain drain on communities, impacting the economy and wellbeing of families, communities and countries [31]. Education still needs to understand the need to teach all our children how to read and write, whilst at the same time addressing the need of access to learning without the use of the verbal visual [32, 33].
Literature clearly evidences the negative effects challenges with literacy have on the wellbeing of persons with dyslexia (e.g. [34, 35, 36, 37]). Educational systems and educators must avoid unnecessary suffering by challenging their definition of learning and performance in examinations [30, 38]. Inasmuch as literacy must be given priority in education, for those with neurological challenges to access it, technology needs to be used as a compensatory strategy and a tool [39].
Reading comprehension is the ability to actively understand ideas and integrate them with prior knowledge to create efficient memory structures [28]. Since it is one of the most complex human activities, any reading theory must address underlying cognitive and linguistic processes involved in comprehension [40]. According to the Single View of Reading (SVR) model, linguistic comprehension contributes to reading comprehension [40] as does accurate and efficient word decoding/recognition [26]. Florit and Cain’s [41] meta-analysis concluded that linguistic comprehension is a strong predictor of reading comprehension in transparent orthographies [e.g., Finnish) whilst word decoding skills were more influential in deep orthographies [e.g., English). Other researchers oppose this model, referring to more complexities.
For example, the Direct and Indirect Effects of Text Comprehension Model refers to relational pathway between lower- and higher-level skills involved in reading comprehension [42]. Lower-level skills include working memory, attention, vocabulary and grammatical knowledge, oral language [42] which are necessary to address higher-level skills such as inferences, perspective taking, comprehension monitoring, verbal working memory, and knowledge on text structures (e.g., [43, 44, 45]). Motivation, interest and purpose are then additional contributing factors [46].
My reflection on these two models’ sets of skills needed for reading comprehension is that for all the skills required, effective and fluent word recognition are skills which can be replaced by technology, whilst the other skills can still be developed and addressed so that readers interact and involve themselves with written language to extract and construct new meaning.
The theory of this chapter is that, wherever possible and so long as the academic learning and assessment objectives are retained, one should be allowed to choose whether, in light of their profile of abilities, skills and challenges, they would prefer to learn, study, access knowledge, develop skills and sit for their examinations orally, using the voice to produce printed material for examiners to read, in handwritten format or using the word processor/tablet. This should be regarded as a choice for all, rather than an examination access arrangement; in the same way that one chooses to sit for examinations using their prescriptive glasses or writing with blue or black pens.
Let us take the subject of History as an example. The aims and objectives of the History curricula and syllabi, as well as its content, never indicate that reading and writing per se are required. Why is it then such an issue and such a waste of human and financial resources for our system and for families to conclude whether candidates should sit for History orally, in typewritten format or handwritten format? One may query: but what about language examination? In my opinion, the same rationale can apply as the knowledge of knowing a language and being able to produce material for others to read is different from the ability to read and spell. Therefore, unless the examination objective is specifically the skills of decoding or encoding or the skill of producing written material through handwriting, the same rationale applies.
In dictionaries, an essay is usually defined as a “short literary composition on a particular theme or subject, usually in prose and generally analytic, speculative, or interpretative” ([47], para.1). No definition on the word essay includes that this task must have been written, typed, swiped or dictated. As such, it is perhaps about time that the ability to spin a yarn or present a thesis for others to read in another space and time is differentiated from the ability to spell, particularly in the context of modern technology. Essays can be produced using two (swiping), three (handwriting), ten (typing) fingers or no (voice-activated technology) fingers. This is not to diminish the importance of spelling, but simply to do justice to competencies required to produce essays. One would need a good speller to proofread documents. This is different from the ability to transform thoughts, creativity, theories, arguments and ideas into readable linguistic communication for others to access in another time and space. Does one ever question or reflect upon the spelling ability of great authors? Is the spelling of authors ever criticised or addressed when books/articles/ scientific journals are published?
Research findings consistently conclude that early literacy learning affects success in learning (e.g. [22, 23, 48]). It is therefore of utmost importance that early education also includes the use of technology to access and present print for those struggling with literacy (e.g., [49, 50, 51]) as pupils are learning to break the code to literacy. Standard computers themselves already incorporate adaptations to address all aspects of literacy [52]. Free downloadable material (e.g., [53, 54, 55]) allows one to add applications. The market also has commercial affordable apparata which not only provide text-to-speech and speech-to-text but also present organisation features for general (e.g., [56, 57, 58]) or examination use [59, 60].
Any research in this area is complicated by difficulties defining dyslexia. Most agree that dyslexia involves reading ability below age- and IQ-matched peers, which is not attributable to poor visual or auditory acuity or inadequate instruction; and where intellect is not affected by specific challenges attributed to this profile (e.g., [4, 61, 62]). Research findings, mostly quantitative, seem to indicate that dyslexia can be categorised into five challenged areas of brain function: phonological, visual, memory, semantic and kinaesthetic (e.g. [4, 61, 63]), where effects continue throughout lifetimes (e.g., [62, 64, 65]). However, there is still considerable debate in education and neuroscience literature regarding underlying causes, age distribution, diagnosis, identification, appropriate assessment methods and intervention (e.g., [66, 67, 68]).
The Guardian [69] lately presented a long article on whether dyslexia actually exists. Citing challenging literature that states that distinguishing between dyslexia and other reading difficulties results in children not being eligible for intervention [70]. Kale [69] referred to Yule’s (1976) conclusion that:
Whilst I agree that (1) terminology and diagnostic conclusions should not deter access to intervention; (2) one should focus on behaviour, skills and abilities rather than labelling; (3) Intervention techniques designed for the dyslexia population are inclusive strategies and beneficial for all, I disagree with Yale. Ample research findings evidence this established neurological profile which, more often than not, co-occurs with other neurological profiles [71]. Apart from educational and psychological research on dyslexia, neuroscience research is leading to a deeper understanding of the identification, diagnosis and management of dyslexia. Such hard evidence provides for strong and persuasive lobbying for change [3, 4].
Snowling et al. [4] acknowledged challenges with co-occurrence and cut-offs and concluded that “Optimal outcomes for these children require us to embrace the dimensional nature of dyslexia and its associated complexities; to fail to do so is negligent and arguably morally indefensible” (p. 508). Lastly, knowledge about dyslexia may benefit all those who present challenges learning to read, whether they have a profile of dyslexia or not (e.g., [9, 20, 71]).
My views regarding learning and examination access arrangement as a choice-for-all rather than a concession for some, clearly presents that my framework and worldview is framed within principles of inclusion [72], diversity [73, 74] and otherness [75, 76]. This echoes Furedi’s [77] resistance to the use of a diagnosis disability and pathologisation to justify allowances and additional support. Further, I frame dyslexia within Kannangara’s [8] (2015) From Languishing to Thriving Dyslexia model, which lobbies for support, understanding and resilience.
Zeleke’s [78] and Burden’s [35] meta-analyses concluded that academic self-esteem and self-concept (ASC) are founded early and tend to be very stable and rather unaffected by later, more successful experiences. This then affects choices for further education, as is represented by data available regarding university students and research findings. Burden [35] reflected that values regarding, “how competent we think we are, …how much in control of the outcomes we consider ourselves to be…[how] we react to disappointment and failure, the strategies that we have…effort we are prepared to invest in order to succeed,”(p. 20) affect ASC.
Therefore, it can be assumed that studies available on dyslexic university students would involve a particular dyslexic population which would have enough required abilities and skills to have enabled them to build ASC allowing them to remain resilient and motivated to learn and who, perhaps, were in supportive home environments and school systems [8, 30]. The question that lingers is: what brain drain are our communities experiencing because school environments lead students to low ASC?
Research findings consistently suggest that teachers and lecturers fail to understand the complexities related to dyslexia and other learning challenges (e.g., [79, 80, 81]). They tend to perceive dyslexia as similar to other learning difficulties [82] and are less likely to account for students’ abilities [81]. Lack of understanding and adequate appropriate support may lead to students not completing their studies or graduating with inferior degree classifications than deserved. Caskey’s [83] Australian research identified that adult dyslexics tend to live in a “dual world, one that is related to the Medical versus Social Model of Disability. Despite the research on ‘ableism’ …adult students diagnosed with dyslexia were navigating through the system barriers searching for support, between the inclusion and exclusion zones” (p. 264). However, when “advocate, support and services were provided…in the form of advocacy, success can occur” ([83], p. 266).
Kannangara [8] concluded that experiences can present a model where one can either languish or thrive with a profile of dyslexia. She reported that, a thriving dyslexic presents positive acceptance towards challenges, embraces difficulties, uses signature strengths to address obstacles, learns from criticisms, perseveres, withstands, and finds alternative approaches to address failures. Unfortunately, a 2019 report [84] by the British Dyslexia Association (BDA) evidenced that parents reported the following effects of a profile of dyslexia on their children: 82% try to hide their struggles; 88% experience poor self-esteem, 84% suffer from anxiety; 52% try to avoid school; 78% feel embarrassed; 48% had been bullied, 95% experience frustration, 58% avoid discussing their dyslexia, and 82% try to hide their difficulties relating to dyslexia.
BDA [84] concluded that “children and young people are uncomfortable, and experience negative emotions linked to their dyslexia …our data may demonstrate an association between dyslexia and mental health difficulties” (p. 19).
Studies exploring school experiences through interviews offer an overall experience of strong, negative emotions (e.g., [34, 85, 86]). Studies exploring how dyslexic people make sense of their positive and negative emotions in relation to school experiences have also presented positive experience (e.g., [8, 87, 88]). One needs to, however, take into consideration that some of the participants of such studies were students attending specialised schools (e.g. [35, 88, 89]). Hellendoorn and Ruijssenaars [90] interviewed 27 dyslexic adults, 8 of whom had negative, 11 mixed and 8 positive experiences. Hughes and Dawson [86] interviewed 54 dyslexic adults. Just over half said they mostly disliked school. Riddick et al. [91] interviewed 16 dyslexic students in higher education, of whom only three reported overall positive experiences. Though none of these studies claim to be representative of the whole population of dyslexic people, they suggest that from one third to one half of dyslexic adults may remember school in primarily negative terms.
Currently, the highest level of global academic examination is Doctorate of Philosophy (PhD), for which most university use oral examination (viva voce) (e.g. [92, 93, 94]). Doctorate examination boards do not question, query, consider or ask for verification whether the verbal-visual 80,000–120,000 word PhD document has been handwritten, typewritten, dictated to a secretary, or produced through assisted technology. The Board of Examiners simply accepts the PhD Document, as this would still the candidate’s work irrespective of the process of the medium of expression. On the other hand, examiners may choose to read the work in the traditional format or use assisted technology to listen to the document. The conundrum is: why it is then not so easy for students in compulsory or university education to be given such choices? Rather an oxymoron!
Examinations at critical stages in students’ education are becoming increasingly more high stakes [38, 95]. They provide students with necessary qualifications for further education or employment [96]. They therefore have a significant impact on students’ life chances and opportunities [97], thus dominating students’ lives and school experiences, further influencing future plans affecting life styles (e.g., no time for extracurricular activities) due to the constant pressure to do well [96, 97]. This of course applies to all students but may be more stressful for those with a profile of dyslexia (e.g., [8, 34, 89]).
Research findings clearly indicate that examinations have an impact on all students’ lives (e.g., [98, 99, 100]). However, “the effects of examinations may be magnified for those who enter the process already labouring under a disadvantage” ([101] p. 8). Research findings consistently conclude that dyslexic students experience greater challenges than non-dyslexic students when sitting for examinations. These challenges include reading fluency and accuracy, auditory sequential short-term memory, sequencing, and organisation of ideas that all impact on the performance of students in examinations (e.g., [102, 103, 104]).
The lack of scientific consensus about what dyslexia really is leads examination boards to query this profile [4]. Crisp et al. [102] lamented that assessment communities have continued to persist that difficulties and challenges students with dyslexia face are similar to students with weak reading abilities or lower cognitive skills. Chetcuti et al. [38] presented the voices of young people with dyslexia and concluded that the participants shared their “frustrations, anxieties and hopes for a fairer examinations system” (p. 445). To address equity, fair play and wellbeing, dyslexic youth in the Chetcuti et al. [39] research perceived a need for radical transformations of examination systems and implored for participatory justice [105, 106], where they should “participate meaningfully throughout the decision-making processes” ([107], p. 346). Hence, my argument to switch to choice rather than examination concessions.
Whilst it is generally accepted that dyslexia affects 10–15% of the general population (e.g., [3, 108, 109]), research evidences underrepresentation at universities. For example, Richardson and Wydell [110] reported 0.48% British-based; and Stampoltzis and Polychronopoulou [111] 0.16% Greek University Students noting reading difficulties. Further, during academic year 2019–2020, out of 11,117 students attending the UM, only 201 (1.18%) students registered with its Access Disability Support Unit (ADSU). Of these, seven (0.06%) described themselves as Specific Learning Difficulties/Learning Difficulties, six as dyscalculic (o.o5%) and 36 (o.33%) as dyslexic.1
Richardson and Wydell [110] reported that their analysis of databases of students in British higher education evidenced 0.46% in 1995–1996 and 1.51% by 2000-to 2001. Mortimore and Crozier’ [112] reported that between 1999 and 2010, British University students with dyslexia or Specific Learning Difficulties almost quadrupled: from 8370 to 32,655. Richardson [113] reported that the situation continued to improve, as in 2013–2014, 37,710 students with dyslexia or other specific learning difficulties (4.97% of all freshers) were admitted to their first year of study. Likewise, UM reported an increase of students requesting examination access arrangements for national examinations: from 1.6% in 2004 to 10.9% in 2019 [114]. This may mean that most Maltese University Students do not inform UM of their profile and do not utilise any possible learning and examination arrangements. This needs further research.
Richardson [113] reflected that “the increase in the prevalence of dyslexia amongst students in UK higher education may reflect changes in diagnostic procedures, public awareness and admissions policies” (p. 325) and the need for more flexible admission policies by institutions of higher education. Likewise, Olofsson et al. [115] reported that “there are now more students with dyslexia in [Swedish] university courses, in both actual and proportional numbers, from 3634 (1.2%) in 2009 to 5457 (about 1.9%) in 2013” (p. 338). They attributed this increase to four factors: (1) earlier identification and provision; (2) financial and other support in higher education; (3) wider access for older students, thus including those who had performed poorly at school because of undetected dyslexia; and (4) the adoption of more flexible university admissions policies.
Although the literature is limited, studies seem to indicate that success in higher education is “not impossible for students with dyslexia but may be more difficult” ([116], p. 3). Olofsson et al. [115] reported that around 20% Swedish university students with dyslexia required additional time to complete their degrees, whilst others were able to progress at a normal pace. Richardson and Wydell [110] reported that approximately 40% UK dyslexic graduates obtained first-class or upper second-class honours. This was, however, lower than the 50% rate for graduates with no reported disabilities. Mortimore and Crozier’s [112] study across 17 higher education institutions also concluded challenges with academic skills, higher risk of either discontinuing or acquiring inferior degrees due to a lack of appropriate support. Byrne [117] further noted that, whilst the proportion of British university dyslexic students has lately increased to around 5%, a significant attainment gap remains, as only “around 40% of dyslexic students achieve a 2.1 or above, compared to 52% of non-dyslexic students” (para. 2). Richardson and Wydell [110] used a 1995–1996 British higher education database and discovered that it was more common among students with dyslexia than among other students to either abandon their studies in the first year of study or not finish their study programmes.
This is happening in spite of enshrined university legislations stressing that educational access is moral and humanitarian imperative (e.g., [2, 118, 119]). One also needs to take into considerations that such statistics include students who declare and know that they have such a profile. One then wonders how many more may be university students without awareness of, or fear of disclosing, their profile of dyslexia. Notwithstanding, we still need to take heed of these data as it is “important to identify factors that could contribute to poor representation and experiences of dyslexic students in higher education and seek appropriate solutions” ([116], p. 3).
Despite vast knowledge and conclusive findings, this population continues to struggle to achieve and maintain success. While enrolment in post-secondary institutions has increased [120], the dropout rate, unemployment rate, more placement in lower prestige jobs, lower income and poverty remain high [121].
Research on dyslexia and university students also presents challenging experiences. For example, Denhart [5] reported that her participants’ “three [main] findings [were] inextricably bound with the reluctance to ask for accommodations: (a) an overwhelming workload that is (b) unrecognized and (c) yields products incommensurate with the effort (p. 493)”. Additionally, Lock and Layton’s [6] participants and Rodis et al.’s [7] autobiographical accounts presented experiences where lecturers perceived dyslexic university students as lazy or lacking effort, also because lecturers were not aware of students’ profiles [122]. Rodis et al. [7] and Greenbaum et al. [123] reported that their participants’ fear of stigma was worse than others’ perceptions of laziness or lack of motivation, even if this led to exhaustion and illness. Further, these participants also regarded the use of accommodations as a failure. This highlights that “the finest accommodations based on the most sophisticated science will have no value if intolerance denies their use” [5], p. 495.
Most research on dyslexia and higher education addresses diagnosis, cognitive abilities, compensation strategies and study techniques (e.g., [124, 125, 126]). Less research has been directed towards students’ own experiences of inclusion in higher education [38, 127]. Olofsson et al. [115] reported that in 2011, Swedish researcher Eriksson Gustavsson carried out a study with 186 students with dyslexia attending six Swedish higher education six institutions. Gustavsson reported that the rate of study of most students was lower than expected, but only few had an extremely slow rate of study. Further, limited achievements had occurred early on in their studies.
Olofsson et al. [115] carried out a study with 50 Swedish students with dyslexia using semi-structured interviews and a self-report scale. Their participants reported that reading course books in English (not their mother tongue) and taking notes during lessons were the two most challenging tasks. They felt less challenges when textbooks were in Swedish, and with spelling and written assignments. Half rated themselves as good and slightly more than 10% as particularly good with regard to reading and understanding textbooks in Swedish, whilst their confidence in spelling was less good. On the other hand, 90% rated their ability to find information on Google or other sites on the Internet as good (46%) or very good (44%), whilst 88%, rated their ability to find what they look for on the Internet as good (52%) or very good (36%). Regarding the continuation and completing of a university degree, Olofsson et al. [115] reported that this depended on the students’ rate of study. They concluded that about half:
British and Maltese bachelor’s degrees are classified as first, second-upper, second-lower or third class. A first-class or second-upper class is often described as a good degree. Richardson and Wydell [110] found that 53.6% of students with no disability and 43.9% of students with dyslexia were awarded good degrees. The difference in these proportions was rated highly significant, even when possible effects of demographic and programme-related variables were considered. However, data on detailed accounts of students with dyslexia’s higher education academic attainment are difficult because national statistics are not collected about other academic outcomes, since many do not disclose their profile, because of description of profile, and due to co-occurrence.
Pino and Mortari’s [127] systematic review of published studies on inclusion of students with dyslexia in higher education identified 15, mostly qualitative, studies. They concluded that, whilst valuable information for support services was presented, there was no evidence on attainment. Richardson and Wydell [110] reported that whilst they were aware that the British Open University is known for attracting students with dyslexia, perhaps due to its option for distance learning, they unfortunately had to exclude Open University students from a more detailed analysis because many had been omitted from the database. Richardson and Wydell [110] had concluded that students with dyslexia who had taken undergraduate modules in 2003 with the British Open University were as likely as were nondisabled students to complete their modules. However, they were more likely to obtain poorer grades. A problem with the study was that they were concerned only with students with dyslexia and no other disabilities. They in fact omitted students with dyslexia and additional disabilities from their sample. This is problematic, especially with the conclusion that co-occurrence with other profiles is now considered the norm, exception [71].
Further to the context of co-occurrence [71], one needs to consider that a profile of dyslexia does not merely involve challenges to access literacy. Such a profile may also include difficulties organising essays, timekeeping, expressing ideas verbally, concentrating and using short-term memory, listening and organisation (e.g., [4, 112, 115]). For example, Simmons and Singleton [128] concluded that dyslexic university students experience challenges drawing inferences from complex texts. They, however, did not specify if alternative access to verbal visual print would have affected such results. This is supported by conclusions that reading characteristics vary widely between students [129].
Studies on writing skills conclude that dyslexic university students present particular challenges with spelling (e.g., [124, 130, 131]), overall written text quality [130, 131], number of words written [132], organisation [112], and vocabulary chosen [132]. On the other hand, comparative differences between university students with or without dyslexia indicate no significant differences in sentence structure, length of sentences [132], expression of ideas or other higher order skills [130]. These findings indicate that such students can cope with university learning, if given the chance, the appropriate support, and with training for university academic [83, 117]. As one youth shared: “I wonder how many great minds were lost simply because the type of intelligence [, access,] and ideas they had were not the the examiners wanted” ([38], p. 439).
Often, these studies refer to challenges experienced using traditional access and presentation of verbal visual print. Therefore, there is a dearth in the literature for one to conclude whether one would experience such challenges if technology were to be used. This is similar to literature available regarding foreign language learning. For example, the British Dyslexia Association (BDA) promotes [133] that “dyslexic children should be given the opportunity to learn a foreign language. Many …will enjoy the multi-sensory methods of language teaching …Learning a foreign language broadens pupils’ horizons as their awareness of other cultures develops” ([133], para. 1). However, BDA also seems to be chained by traditional access to literacy and pedagogy for foreign language teaching, as it suggests that, “Some languages may be more problematic for dyslexic learners. Languages such as French and English are less transparent than other languages” ([133], para. 2). In a context where (a) the literature clearly concludes that foreign language learning and bilingualism has a positive effect on general cognitive development (e.g., [134, 135, 136]); and (b) the EU requires all its citizens to be tri-lingual [137], there seems to be the practice to discourage persons with dyslexia to learn a foreign language. Contrastingly, I have to date not found any literature (written in Maltese, English or Italian) to support this myth.
Literature addressing day-to-day experiences of university students with dyslexia is dearth. Whilst there is a considerable body of literature exploring overall university experiences of students with a broad range of disabilities, including students with dyslexia (e.g., [138, 139, 140]), such studies tend to focus on physical access, social stigma, reasonable adjustments (e.g., [138, 141, 142]). Further, findings regarding dyslexic students are difficult to differentiate from other findings of these studies.
Research available addressing experiences (e.g. [115, 116, 127]) evidences challenges, difficulties and frustration. Participants reported difficulties with notetaking, reading journal articles and course books, technology, accessibility and adjustments. These studies seem to indicate that some students, “will overcome these difficulties, [but] the additional effort may lead to greater frustration and lower completion rates than might otherwise be expected” ([116], p. 16). Further, MacCullagh et al. [116] rightly acknowledged that disadvantages may include, “insufficient time to research topics broadly, difficulty balancing paid work and other responsibilities, mental health risks of overwork and less time to participate in social, sporting, artistic and other extra-curricular activities” (p. 16).
Pino and Mortari [127] conducted a systematic review of published research on the university experiences of students with dyslexia and reported finding 15 relevant studies. They synthesised the findings in five key themes: (1) Coping strategies (Study skills and Compensatory Strategies); (2) Profile identification; (3) Interaction with academic staff; (4) Accessibility and adjustments to learning and assessment; and (5) Use of technologies.
Helpful study skills included making notes from books, accessing materials in multiple formats, colour coding, concept mapping and discussing ideas verbally. Compensatory strategies included downloading slides prior to lectures, obtaining copies of lecture notes, lecture recordings help from family and friends, meta-cognitive skills included time planning, graphic organisation of information and meta-affective skills.
Notwithstanding, Pino and Mortari [127] concluded gaps in the literature, particularly regarding strategies for improvement. The available research findings also report difficulties identifying main ideas in text, preparing for tests [126], reading course books and taking notes [143]. Again, one needs further exploration regarding the use of technology as such studies sometimes do not differentiate between traditional reading and reading using technology. For example, Olofsson et al. [143] reported additional information from the internet as a key compensatory strategy; whilst Kirby et al. [126] reported study aids, time management strategies and deep learning approaches as key compensatory strategies. More research exploring study practices and opportunities for support is needed.
MacCullagh et al.’s [116] semi-structured interviews based on best practice methodologies yielded similar data to literature (e.g., [115, 126, 127]). Findings concluded positive themes such as appreciation for engaging speaking style, flexible lecture formats, deep engagement with learning tasks and self-directed learning. Further, students with dyslexia “reported spending a great deal of effort on learning tasks. Participants with dyslexia described engaging with learning tasks intensively and frequently, using multiple strategies. Possible advantages of this effort could include deeper learning and development of creative problem-solving skills” ([116], p. 16). It is interesting that such behaviours [144] are highly sought after in workplaces (e.g. [145, 146, 147]). Further, such characteristics are also helpful for all students (e.g. [148, 149, 150]).
Disadvantages also include insufficient time to research topics broadly, difficulty balancing paid work and other responsibilities, mental health risks of overwork, and less time to participate in extra-curricular and social activities. These findings add to moral and legal justifications for understanding rather than judging profile of university students with dyslexia. Future research in this area could focus on number of hours per week spent on learning tasks. MacCullagh et al. [116] also discussed that the very coping learning strategy these individuals use are strategies which actually lead to deeper learning and memory. One also needs to consider that such individuals would probably be more highly motivated to be university students, given that they keep striving despite challenges. Additionally, they would most probably have the necessary support system which led them to thrive in, rather than languish for, higher education [8].
Also noteworthy was the strong appreciation among students with dyslexia for face-to-face lectures and for recorded lectures that included a video of the lecturer’s face. This is particularly important considering recent trends in the higher education sector towards partially and wholly online courses. Such changes must be critically appraised to prevent compounding disadvantages for students with dyslexia. It may be important to continue offering some face-to-face lectures, and to ensure that recorded lectures include a video of the lecturer talking. This is extremely relevant and important in the current health challenges humans are experiencing. The question would be: how can we find a technological alternative to address the participants’ recommended face-to-face intervention?
Studies addressing use of services indicate a strong uptake for resources such as additional time in examinations, dyslexia-support tutors and information technology assistance [112, 143]. Other services include appropriately skilled note-takers, lecture slides in advance, support with organisation and support with academic writing (e.g., [38, 112, 143]).
However, international data consistently reports poor uptake of support services by students with dyslexia. Reasons include poor awareness of services, poor suitability of services and non-disclosure. Most services seem to be designed for people with low vision, illiteracy, general learning disabilities or physical disabilities, rather than students with dyslexia per se. New services may therefore need to be designed specifically for students with dyslexia or existing services tailored to specific needs as identified by students themselves. For example, students suggest dyslexia-specific tutoring and tailored note-taking services (e.g., [112, 143, 151]).
Research findings on appropriate, satisfying and effective support and strategies are consistent with current best practices on inclusive design and accessibility standards [152]. For example, findings of appreciation for videos, images and face-to-face teaching support the efficacy of multi-modal or multi-sensory teaching for dyslexic learners. This reflects current research and best practice where all learners generally benefit from having information presented in auditory, tactile and visual modalities [151]. Further, all students learn better from lectures presented in shorter 5–20 minute segments rather than longer 60–120 minute sessions [153]. This is in keeping with recent educational trends towards the flipped classroom model, in which lectures are broken into smaller chunks and interspersed with other activities [154].
Research also indicates that dyslexic students mostly manage their own difficulties on an individual level with minimal access to or assistance from each other. Participants reported developing a unique set of compensatory strategies in isolation from others and without any sharing or supporting each other, support groups or dyslexia associations and agencies (e.g. [115, 116, 127]). In the context of the broader disability and social inclusion literature [155, 156] moving towards a more collectivist community approach is optimal, as students would benefit from collaborating and sharing their ideas, strategies, experiences and insights. For example, MacCullagh et al.’s [116] participants noted that university students with dyslexia not only face considerable learning and assessment challenges but also exhibit strengths. They reported helpful and effective strategies at individual and institutional levels, study techniques, adjustments to course materials, variety of teaching and assessment formats, and specific staff and student training. These were considered as effective measures towards university success for students with dyslexia.
MacCullagh et al. [116] linked appropriate and effective learning experiences to university legislation on equity and opportunity, and notes that research findings, “add to moral and legal justifications for provision of accommodations for university students with dyslexia” (p. 16). Likewise, when focusing on post-secondary assessment, Chetcuti et al. [38] implore for more fair play and feedback from young people with dyslexia themselves as the main stakeholders.
Studies addressing issues of shame and humiliation cannot just address the university experience, but need to also understand the whole school experience. Many share stories of humiliation, mostly due to being made to read aloud in class or taking longer and/or being punished for taking longer to complete work (e.g. [90, 157, 158]). Participants in such studies narrate that the humiliation was not only due to public exposure of their reading and writing difficulties, but also ridicule from teachers. Such negative experiences affect so deeply, they linger throughout one’s lifetime as a traumatic and permanent experience (e.g. [38, 85, 157]) or what Khan [159] termed as cumulative trauma.
Persons with covert challenges tend to report more negative experiences that those with overt challenges [160]. Barga [161] explored the experiences of nine university students with dyslexia and evidenced experiences of labelling and stigma as barriers to learning. Six participants deliberately did not disclose for fear of rejection, ridicule and stigmatisation. Likewise, Rao [162] reported non-disclosure to avoid negative social repercussion, even though participants were aware that this may have hinder their academic progress and success. Further, the literature continues to evidence stigma towards such a population as being intellectually inferior (e.g., [5, 30, 157]). Dyslexic university students’ preference to manage their own difficulties with minimal access to assistance (e.g. [112, 151, 153]) supports research findings indicating shame, embarrassment (e.g. [84, 163, 164]) and complex decision-making processes regarding disclosure [164]. One needs to dream of better inclusive societal approaches and attitudes (e.g., [34, 155, 156]).
Mortimer and Crozier [112, 165] reported that students in their studies expressed frustration at “the lack of communication between the [support] unit and the academic departments. Academic tutors frequently had little knowledge about dyslexia” [112, p, 248]. One of their participants shared how she was publicly Chastised: “In my exam, the lecturer didn’t realise I had extra time. In the hall, in public, he said, ‘Put your bloody pen down’. I had to say ‘I’m sorry I’m dyslexic’. It made me feel like a total leper. There is a lack of communication between departments, some know, some don’t (p. 248).” Mortimer and Crozier [112] reported that:
Regarding labelling and teachers’ perceptions, strategies and actions, research presents various scenarios. These include difficulties to teach, less intelligence, and feeling sorry for the students (e.g., [166, 167, 168]). Frymier and Wanzer [169] also noted that such perceptions often stem from the issue of hidden challenges and negotiations regarding fair accommodations, also in respect to other students. This strengthens my thesis that such accommodation should be a choice-for-all rather than an accommodation. Lock and Layton [6] concluded that lecturers in their study believed that such a label was to get out of doing work, out of laziness, or not trying hard enough. This belief was reaffirmed even when these lecturers were presented with studies that such a population tends to work itself to illness and exhaustion to achieve levels expected from their peers (e.g., [5, 38, 170]).
The literature indicates several reasons for such stigma. These include lack of knowledge [171], invisibility of profile [172], accommodation perceived as cheating by teachers and peers [173], self-fulfilling prophecies leading to underperformance and even criminality [174, 175], confirmation of bias with beliefs, ignoring individual characteristics (e.g., [176, 177, 178]) and generation of negative expectations [179].
Labelling, however, also has positive effects as willing teachers may be able to interpret behaviours better to then provide appropriate teaching strategies (e.g., [34, 180, 181]). Further, the label also helps one’s understanding of one’s own behaviour (e.g., [158, 166, 182]).
One cannot underestimate that dyslexia presents challenges to university lecturers (e.g., [122, 183, 184]). This population has not been visible, although it has always existed (e.g., [112, 165, 185]). Since the challenges are invisible, teaching adaptations for such a population have perhaps been neglected. Widened access to university studies for students with functional disorders, such as dyslexia, have led to this neglect being made visible [143].
Teachers are undoubtedly important people in the lives of dyslexic schoolchildren and teachers who help or hinder play a part in dyslexic people’s lives. Teachers remembered most negatively were those who humiliated dyslexic pupils in front of their peers. Many report negative teachers’ attitudes towards dyslexic-type difficulties, and lack of knowledge about dyslexia and intervention for dyslexic difficulties. However, pupils who had attended specialist schools were more likely to report positive experiences [88].
Riddick et al. [91] reported that three dyslexic student-participants in higher education experienced positive school experiences and stated that their lecturers had acknowledged their profile, were sensitive to their needs and had provided helpful intervention. A participant from Hellendoorn and Ruijssenaars’ [90] study reported that “I will never forget Mr X. When he came in my life, something changed, because he really understood. He at least gave me credit for the hard work I did, even though I still could not read” (p. 233). In contrast, others speak of teachers who treated them as if they were unintelligent and/or lazy, refused to accept that students were dyslexic and/or provide any accommodation and/or taught them inappropriately (e.g., [90, 91, 167]).
Students with dyslexia judged support received from specialists, teachers from special schools, licenced remedial teachers, speech therapists and psychomotor therapists favourably (e.g. [90, 91, 186]). Burden [88] reported that out of 50 dyslexic boys, 62% explained that mainstream teachers had not understood their feelings, whereas at their specialist school only 4% felt the teachers did not understand their profiles. These findings suggest a need for additional training [9].
Technology has improved so much [187], that schools [188, 189]must consider its use to access and create print (e.g., [189, 190, 191]). Technology is regarded as the “fourth revolution in the means of production of knowledge following language, writing and print” ([190], p. 39). Warschauer and Matuchniak [192] reported a broad consensus among educators, communciation scholars, sociologists and economists that, “information and communication technolgoies (ICT)…bridge the interactive features of speech and archival characterists of writing” (p. 179). Gutenberg’s printing press (c. 1440) started the third revolution - printing. However, it took centuries for printing to truly infiltrate and affect society with the advent of industrial Revolution (c. 1760). The transition between the third (Print) and fourth (Technology) revolution was faster. We have transitioned from an industrial to an informative economy in mere decades [193, 194].
Given the present global health situation, such research is now even more important. Current social distancing has necessitated more independent learning and further use of technology [195]. This may prove more beneficial if the necessary skills are addressed. An Economist’s [196] weekly editorial dedicated to the absent university student reported that:
One also needs to be cautious and not conclude that millennials and younger generations are automatically technology experts or comfortable with all computer usage. For example, Prensky [197] reported that, with regard to reading materials, approximately half of the students in their study (average age 23.7 years), both dyslexic (7 of 13) and non-dyslexic (11 of 20), expressed difficulty reading text online and using learning technologies. This contradicts assertions that the ‘net generation’ is all ‘digital natives’ and can be expected to use educational technology with ease and proficiency. Rather, the data from this study support Kennedy, et al.’s [198] conclusion that students in the ‘net generation’ are not necessarily technology experts and may require explicit technology training. This may also be due to their school experiences regarding Access to literacy and learning.
UNESCO [199] reports that “at least 750 million youth and adults still cannot read and write and 250 million children are failing to acquire basic literacy skills” [para. 3], thus excluding excludes them from “full participation in their communities and societies” [para.3]. Clinton’s [200] International Literacy Day message implored that:
In this chapter, I endeavoured to reflect on what should be considered as literacy in the 21st century and how our communities need to ensure that all who want to pursue further academic education may do so easily and with dignity. The aim was to help highlight what literacy means in the 21st century and what competencies relate to intelligence and academic success, or otherwise. In human’s fourth revolution of knowledge, transmission and sharing [190], whilst we need to appropriately train educators to ensure that all become proficient in all literacies as early as possible (e.g. [9, 20, 21]), we must also consider that traditional skills of reading and writing cannot continue to remain obstacles [201] for whom such skills are not so easy to learn and become proficient in. As Leonardi da Vinci noted: “I would rather have a scientific mind without literary skills, than a literary person without a scientific mind”2.
I would like to thank my colleagues, Dr Anne Marie Callus and Marchita Mangiafico for providing me with the data regarding University of Malta students. I would also like to thank all those children and young people with dyslexia whose experiences and wisdom have enriched my life, including my son.
The author declares no conflict of interest.
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\n\nHOW COPYRIGHT WORKS WITH OPEN ACCESS LICENSES?
\n\nAgreement samples are listed here for the convenience of prospective Authors:
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\n\nThe following definitions apply in this Copyright Policy:
\n\nAuthor - in order to be identified as an Author, three criteria must be met: (i) Substantial contribution to the conception or design of the Work, or the acquisition, analysis, or interpretation of data for the Work; (ii) Participation in drafting or revising the Work; (iii) Approval of the final version of the Work to be published.
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The CC BY 3.0 and CC BY 4.0 license permits Works to be freely shared in any medium or format, as well as the reuse and adaptation of the original contents of Works (e.g. figures and tables created by the Authors), as long as the source Work is cited and its Authors are acknowledged in the following manner:
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It focuses on the success of these resources in the process of finding and discovering new and effective drug compounds that can be useful for human resources. From many years, natural products have been acting as a source of therapeutic agents and have shown beneficial uses. Only natural product drug discovery plays an important role to develop the scientific evidence of these natural resources. Research in drug discovery needs to develop robust and viable lead molecules, which step forward from a screening hit to a drug candidate through structural elucidation and structure identification through GC–MS, NMR, IR, HPLC, and HPTLC. The development of new technologies has revolutionized the screening of natural products in discovering new drugs. Utilizing these technologies gives us an opportunity to perform research in screening new molecules using a software and database to establish natural products as a major source for drug discovery. It finally leads to lead structure discovery. 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Previously, seaweeds were only used as gelling and thickening agents in the food or pharmaceutical industries, recent researches have revealed their potential as complementary medicine. The red, brown and green seaweeds have been shown to have therapeutic properties for health and disease management, such as anticancer, antiobesity, antidiabetic, antihypertensive, antihyperlipidemic, antioxidant, anticoagulant, anti-inflammatory, immunomodulatory, antiestrogenic, thyroid stimulating, neuroprotective, antiviral, antifungal, antibacterial and tissue healing properties. In proposed chapter, we discussed various active compounds include sulphated polysaccharides, phlorotannins, carotenoids (e.g. fucoxanthin), minerals, peptides and sulfolipids, with proven benefits against degenerative metabolic diseases. 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As our early ancestors learned to recognize and consume selected plants, civilization and personal and group health could advance. Traditional medicine would become part of every civilization with medicinal and aromatic plants widely used and applied to maintain life. Undoubtedly, the variety of available plant materials would be tasted and tested to determine whether a plant was valuable as a food or medicine. Today, a variety of available herbs and spices are used and enjoyed throughout the world and continue to promote good health. As the benefits from medicinal and aromatic plants are recognized, these plants will have a special role for humans in the future.",book:{id:"8290",slug:"pharmacognosy-medicinal-plants",title:"Pharmacognosy",fullTitle:"Pharmacognosy - Medicinal Plants"},signatures:"Maiko Inoue, Shinichiro Hayashi and Lyle E. 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Essential oils are used in almost every field of life and because of these characteristics, the market of essential oils is growing rapidly. Essential oils are used in the aromatherapy and act as antioxidant, antimicrobial, antifungal, pain relievers, anxiety, depression. In the field of cosmetics and industries, the essential oils are used rapidly and mostly used in the perfume industries which are growing increasingly. Essential oils are used in the food preservations and many food items. Essential oils are used as the folk herbal medicines and their fragrance is used for the improvement of the mood and as the depression release.",book:{id:"7855",slug:"essential-oils-oils-of-nature",title:"Essential Oils",fullTitle:"Essential Oils - Oils of Nature"},signatures:"Muhammad Irshad, Muhammad Ali Subhani, Saqib Ali and Amjad Hussain",authors:[{id:"286484",title:"Dr.",name:"Muhammad",middleName:null,surname:"Irshad",slug:"muhammad-irshad",fullName:"Muhammad Irshad"},{id:"304731",title:"Mr.",name:"Muhammad",middleName:null,surname:"Ali Subhani",slug:"muhammad-ali-subhani",fullName:"Muhammad Ali Subhani"},{id:"316772",title:"Dr.",name:"Amjad",middleName:null,surname:"Hussain",slug:"amjad-hussain",fullName:"Amjad Hussain"},{id:"316773",title:"Dr.",name:"Saqib",middleName:null,surname:"Ali",slug:"saqib-ali",fullName:"Saqib Ali"}]}],mostDownloadedChaptersLast30Days:[{id:"66742",title:"Introductory Chapter: Alkaloids - Their Importance in Nature and for Human Life",slug:"introductory-chapter-alkaloids-their-importance-in-nature-and-for-human-life",totalDownloads:3950,totalCrossrefCites:14,totalDimensionsCites:29,abstract:null,book:{id:"6828",slug:"alkaloids-their-importance-in-nature-and-human-life",title:"Alkaloids",fullTitle:"Alkaloids - Their Importance in Nature and Human Life"},signatures:"Joanna Kurek",authors:[{id:"214632",title:"Dr.",name:"Joanna",middleName:null,surname:"Kurek",slug:"joanna-kurek",fullName:"Joanna Kurek"}]},{id:"65128",title:"Natural Products in Drug Discovery",slug:"natural-products-in-drug-discovery",totalDownloads:6532,totalCrossrefCites:16,totalDimensionsCites:39,abstract:"Drug discovery using natural products is a challenging task for designing new leads. It describe the bioactive compounds derived from natural resources, its phytochemical analysis, characterization and pharmacological investigation. It focuses on the success of these resources in the process of finding and discovering new and effective drug compounds that can be useful for human resources. From many years, natural products have been acting as a source of therapeutic agents and have shown beneficial uses. Only natural product drug discovery plays an important role to develop the scientific evidence of these natural resources. Research in drug discovery needs to develop robust and viable lead molecules, which step forward from a screening hit to a drug candidate through structural elucidation and structure identification through GC–MS, NMR, IR, HPLC, and HPTLC. The development of new technologies has revolutionized the screening of natural products in discovering new drugs. Utilizing these technologies gives us an opportunity to perform research in screening new molecules using a software and database to establish natural products as a major source for drug discovery. It finally leads to lead structure discovery. Powerful new technologies are revolutionizing natural herbal drug discovery.",book:{id:"8290",slug:"pharmacognosy-medicinal-plants",title:"Pharmacognosy",fullTitle:"Pharmacognosy - Medicinal Plants"},signatures:"Akshada Amit Koparde, Rajendra Chandrashekar Doijad and Chandrakant Shripal Magdum",authors:[{id:"268668",title:"Dr.",name:"Akshada",middleName:"Amit",surname:"Koparde",slug:"akshada-koparde",fullName:"Akshada Koparde"}]},{id:"64420",title:"Medicinal Plants for Treatment of Prevalent Diseases",slug:"medicinal-plants-for-treatment-of-prevalent-diseases",totalDownloads:4709,totalCrossrefCites:5,totalDimensionsCites:16,abstract:"This chapter focuses on reviewing publications on medicinal plants used in the treatment of common diseases such as malaria, cholera, pneumonia, tuberculosis and asthma. Traditional medicine is still recognized as the preferred primary health care system in many rural communities, due to a number of reasons including affordability and effectiveness. The review concentrated on current literature on medicinal plants, highlighting on information about ethnobotany, phytochemistry and pharmacology. The search for publications on medicinal plants with scientifically proven efficacy was carried out using electronic databases such as Science Direct, Google Scholar, SciFinder and PubMed. In all, about 46 species of different families with potent biological and pharmacological activities were reviewed. All the plants reviewed exhibited potent activity confirming their various traditional uses and their ability to treat prevalent diseases.",book:{id:"8290",slug:"pharmacognosy-medicinal-plants",title:"Pharmacognosy",fullTitle:"Pharmacognosy - Medicinal Plants"},signatures:"Susana Oteng Mintah, Tonny Asafo-Agyei, Mary-Ann Archer, Peter Atta-Adjei Junior, Daniel Boamah, Doris Kumadoh, Alfred Appiah, Augustine Ocloo, Yaw Duah Boakye and Christian Agyare",authors:[{id:"182058",title:"Dr.",name:"Christian",middleName:null,surname:"Agyare",slug:"christian-agyare",fullName:"Christian Agyare"},{id:"186987",title:"Dr.",name:"Yaw Duah",middleName:null,surname:"Boakye",slug:"yaw-duah-boakye",fullName:"Yaw Duah Boakye"},{id:"268666",title:"Ms.",name:"Susana",middleName:null,surname:"Oteng Mintah",slug:"susana-oteng-mintah",fullName:"Susana Oteng Mintah"},{id:"282286",title:"Ms.",name:"Mary-Ann",middleName:null,surname:"Archer",slug:"mary-ann-archer",fullName:"Mary-Ann Archer"},{id:"282288",title:"Mr.",name:"Tonny",middleName:null,surname:"Asafo-Agyei",slug:"tonny-asafo-agyei",fullName:"Tonny Asafo-Agyei"},{id:"282290",title:"Mr.",name:"Peter",middleName:null,surname:"Atta-Adjei Junior",slug:"peter-atta-adjei-junior",fullName:"Peter Atta-Adjei Junior"},{id:"282291",title:"Dr.",name:"Daniel",middleName:null,surname:"Boamah",slug:"daniel-boamah",fullName:"Daniel Boamah"},{id:"282293",title:"MSc.",name:"Newman",middleName:null,surname:"Osafo",slug:"newman-osafo",fullName:"Newman Osafo"},{id:"282294",title:"Dr.",name:"Alfred",middleName:null,surname:"Appiah",slug:"alfred-appiah",fullName:"Alfred Appiah"},{id:"282297",title:"Prof.",name:"Augustine",middleName:null,surname:"Ocloo",slug:"augustine-ocloo",fullName:"Augustine Ocloo"}]},{id:"68027",title:"Biological Importance of Essential Oils",slug:"biological-importance-of-essential-oils",totalDownloads:1951,totalCrossrefCites:17,totalDimensionsCites:24,abstract:"Essential oils are the volatile compounds having the oily fragrance. Essential oils are obtained from the different plant parts, and they are extracted from the different techniques and the most preferable method of extraction is the hydrodistillation which is cheap and easy to use. Plant parts including the flowers, leaves, stem, bark and roots are used for the isolation of essential oils. Essential oils are used in almost every field of life and because of these characteristics, the market of essential oils is growing rapidly. Essential oils are used in the aromatherapy and act as antioxidant, antimicrobial, antifungal, pain relievers, anxiety, depression. In the field of cosmetics and industries, the essential oils are used rapidly and mostly used in the perfume industries which are growing increasingly. Essential oils are used in the food preservations and many food items. 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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. 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He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. 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She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}},{id:"441116",title:"Dr.",name:"Jovanka M.",middleName:null,surname:"Voyich",slug:"jovanka-m.-voyich",fullName:"Jovanka M. Voyich",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Montana State University",country:{name:"United States of America"}}},{id:"330412",title:"Dr.",name:"Muhammad",middleName:null,surname:"Farhab",slug:"muhammad-farhab",fullName:"Muhammad Farhab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"349495",title:"Dr.",name:"Muhammad",middleName:null,surname:"Ijaz",slug:"muhammad-ijaz",fullName:"Muhammad Ijaz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}}]}},subseries:{item:{id:"5",type:"subseries",title:"Parasitic Infectious Diseases",keywords:"Blood Borne Parasites, Intestinal Parasites, Protozoa, Helminths, Arthropods, Water Born Parasites, Epidemiology, Molecular Biology, Systematics, Genomics, Proteomics, Ecology",scope:"Parasitic diseases have evolved alongside their human hosts. In many cases, these diseases have adapted so well that they have developed efficient resilience methods in the human host and can live in the host for years. Others, particularly some blood parasites, can cause very acute diseases and are responsible for millions of deaths yearly. Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. In the current atmosphere of the Coronavirus pandemic, communities around the world, particularly those in different underdeveloped areas, are faced with the growing challenges of the high burden of parasitic diseases. At the same time, they are faced with the Covid-19 pandemic leading to what some authors have called potential syndemics that might worsen the outcome of such infections. Therefore, it is important to conduct studies that examine parasitic infections in the context of the coronavirus pandemic for the benefit of all communities to help foster more informed decisions for the betterment of human and animal health.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11401,editor:{id:"67907",title:"Dr.",name:"Amidou",middleName:null,surname:"Samie",slug:"amidou-samie",fullName:"Amidou Samie",profilePictureURL:"https://mts.intechopen.com/storage/users/67907/images/system/67907.jpg",biography:"Dr. Amidou Samie is an Associate Professor of Microbiology at the University of Venda, in South Africa, where he graduated for his PhD in May 2008. He joined the Department of Microbiology the same year and has been giving lectures on topics covering parasitology, immunology, molecular biology and industrial microbiology. He is currently a rated researcher by the National Research Foundation of South Africa at category C2. He has published widely in the field of infectious diseases and has overseen several MSc’s and PhDs. His research activities mostly cover topics on infectious diseases from epidemiology to control. His particular interest lies in the study of intestinal protozoan parasites and opportunistic infections among HIV patients as well as the potential impact of childhood diarrhoea on growth and child development. He also conducts research on water-borne diseases and water quality and is involved in the evaluation of point-of-use water treatment technologies using silver and copper nanoparticles in collaboration with the University of Virginia, USA. He also studies the use of medicinal plants for the control of infectious diseases as well as antimicrobial drug resistance.",institutionString:null,institution:{name:"University of Venda",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null,series:{id:"6",title:"Infectious Diseases",doi:"10.5772/intechopen.71852",issn:"2631-6188"},editorialBoard:[{id:"188881",title:"Dr.",name:"Fernando José",middleName:null,surname:"Andrade-Narváez",slug:"fernando-jose-andrade-narvaez",fullName:"Fernando José Andrade-Narváez",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRIV7QAO/Profile_Picture_1628834308121",institutionString:null,institution:{name:"Autonomous University of Yucatán",institutionURL:null,country:{name:"Mexico"}}},{id:"269120",title:"Dr.",name:"Rajeev",middleName:"K.",surname:"Tyagi",slug:"rajeev-tyagi",fullName:"Rajeev Tyagi",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRaBqQAK/Profile_Picture_1644331884726",institutionString:"CSIR - Institute of Microbial Technology, India",institution:null},{id:"336849",title:"Prof.",name:"Ricardo",middleName:null,surname:"Izurieta",slug:"ricardo-izurieta",fullName:"Ricardo Izurieta",profilePictureURL:"https://mts.intechopen.com/storage/users/293169/images/system/293169.png",institutionString:null,institution:{name:"University of South Florida",institutionURL:null,country:{name:"United States of America"}}}]},onlineFirstChapters:{paginationCount:13,paginationItems:[{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. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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