\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"5265",leadTitle:null,fullTitle:"Metallic Glasses - Formation and Properties",title:"Metallic Glasses",subtitle:"Formation and Properties",reviewType:"peer-reviewed",abstract:"Metallic glasses and amorphous materials have attracted much more attention in the last two decades. A noncrystalline solid produced by continuous cooling from the liquid state is known as a glass. From the other point of view, a noncrystalline material, obtained by any other process, for example, vapor deposition or solid-state processing methods such as mechanical alloying, but not directly from the liquid state, is referred to as an amorphous material. At this moment, bulk metallic glasses (BMG) are appearing as a new class of metallic materials with unique physical and mechanical properties for structural and functional usage. Extreme values of strength, fracture toughness, magnetic properties, corrosion resistance, and other properties have been registered in BMG materials.",isbn:"978-953-51-2512-9",printIsbn:"978-953-51-2511-2",pdfIsbn:"978-953-51-6667-2",doi:"10.5772/61764",price:119,priceEur:129,priceUsd:155,slug:"metallic-glasses-formation-and-properties",numberOfPages:178,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"53998537d86484c3c753b5af0d11595a",bookSignature:"Behrooz Movahedi",publishedDate:"August 17th 2016",coverURL:"https://cdn.intechopen.com/books/images_new/5265.jpg",numberOfDownloads:11869,numberOfWosCitations:13,numberOfCrossrefCitations:10,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:19,numberOfDimensionsCitationsByBook:1,hasAltmetrics:0,numberOfTotalCitations:42,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 4th 2015",dateEndSecondStepPublish:"November 25th 2015",dateEndThirdStepPublish:"February 29th 2016",dateEndFourthStepPublish:"May 29th 2016",dateEndFifthStepPublish:"June 28th 2016",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"92198",title:"Dr.",name:"Behrooz",middleName:null,surname:"Movahedi",slug:"behrooz-movahedi",fullName:"Behrooz Movahedi",profilePictureURL:"https://mts.intechopen.com/storage/users/92198/images/2100_n.jpg",biography:"Dr. Behrooz Movahedi obtained his PhD degree in Materials Engineering\r\nat Isfahan University of Technology (IUT) in Iran in 2010.\r\nDuring t his period, while on a sabbatical l eave he visited the\r\nSchool of Materials Science and Engineering in Nanyang Technological\r\nUniversity (NTU) in Singapore. After that he joined the Department of Nanotechnology Engineering in the University of Isfahan (UI) as an Associate Professor.\r\nRecently, he is the head of the Nanotechnology Engineering Department in Faculty of Advanced Sciences and Technologies. Dr. Behrooz Movahedi has over 10 years of experience in the nanotechnology, amorphous materials, optical ceramics, and advanced thermal spray coatings for environmental and industrial applications. He was invited as a reviewer in some potential ISI journals such as Materials & Design, Journal of Alloys and Compounds, Surface and Coatings Technology, Applied Surface Science, Journal of Materials Engineering and Performance, Materials Science & Engineering B...",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"University of Isfahan",institutionURL:null,country:{name:"Iran"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"944",title:"Metallurgy",slug:"metals-and-nonmetals-metallurgy"}],chapters:[{id:"50742",title:"Metallic Glasses from the Bottom-up",doi:"10.5772/63514",slug:"metallic-glasses-from-the-bottom-up",totalDownloads:1842,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The main challenge in understanding the relation between the structure and properties of metallic glasses is describing their structure at the atomic level. Currently, their structures are considered simply disordered and indeed our understanding of their structure is as undefined as this term. Following the most advanced structural models of metallic glasses that are based on metal clusters, a bottom-up approach to fabrication of metallic glasses using cluster beam technology is introduced. Using metal clusters to fabricate metallic glasses from the bottom-up, that is, formation of cluster-assembled metallic glasses, provides us with the possibility of varying their structure at the atomic level while keeping their composition unchanged. A unique feature working with cluster-assembled metallic glasses is the independent control of their structure and composition. The advantages of this approach are presented, and its potential toward the resolution of structure–property puzzle in metallic glasses is demonstrated along with the main challenges.",signatures:"Aras Kartouzian and Jerzy Antonowicz",downloadPdfUrl:"/chapter/pdf-download/50742",previewPdfUrl:"/chapter/pdf-preview/50742",authors:[{id:"181509",title:"Dr.",name:"Aras",surname:"Kartouzian",slug:"aras-kartouzian",fullName:"Aras Kartouzian"},{id:"185249",title:"Dr.",name:"Jerzy",surname:"Antonowicz",slug:"jerzy-antonowicz",fullName:"Jerzy Antonowicz"}],corrections:null},{id:"51656",title:"Structural and Dynamical Properties of Metallic Glassy Films",doi:"10.5772/64107",slug:"structural-and-dynamical-properties-of-metallic-glassy-films",totalDownloads:1347,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In this chapter, a series of molecular dynamics simulations have been carried out to explore structural and dynamical features of monatomic liquid metallic films during rapid cooling. Results show a semi‐ordered inhomogeneous morphology containing crystal‐like and disordered regions. The icosahedron contributes to nucleation through the synergy with other short‐range ordered structures and participates in crystal growth via assimilation, but the pinning effect should be overcome. The second‐peak splitting in pair correlation functions is found as the result of a statistical average of crystal‐like and disordered structural regions, not just the amorphous structure. The splitting can be viewed as a prototype of crystal‐like peaks exhibiting distorted and vestigial features. Besides, we use the parameter P(a, τ, ν) for predicting both local structural order and motion propensity. The fraction of crystalline clusters follows a negative power‐law scaling with the cooling rate increasing, which is the inverse of P(a, τ, ν).",signatures:"Hui Li, Weikang Wu and Kun Zhang",downloadPdfUrl:"/chapter/pdf-download/51656",previewPdfUrl:"/chapter/pdf-preview/51656",authors:[{id:"6986",title:"Prof.",name:"Hui",surname:"Li",slug:"hui-li",fullName:"Hui Li"},{id:"185755",title:"Dr.",name:"Weikang",surname:"Wu",slug:"weikang-wu",fullName:"Weikang Wu"},{id:"185756",title:"Dr.",name:"Kun",surname:"Zhang",slug:"kun-zhang",fullName:"Kun Zhang"}],corrections:null},{id:"51226",title:"Structure of the Metallic Glass and Evolution of Electronical Properties during Glass Transition in Atomic Level",doi:"10.5772/63676",slug:"structure-of-the-metallic-glass-and-evolution-of-electronical-properties-during-glass-transition-in-",totalDownloads:1266,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Metallic glass (MGs) has many unique properties such as low density, low Young's modulus, and so on. These unique physical and mechanical properties attract much attention on their application in manufacturing production. While, structural properties such as complete absence of the long‐range order and most MGs are consist of equal or more than ternary constituent which complex factors make that the atomic level structure of metallic glass still have not well known by researchers. The limited methods and data sets obtained by experiment make the acknowledge in uncovering atomic structure of melt states of alloy, and the supercooled liquid about the alloy is absent as well. These messages are important to improve and increase the understanding of MGs, as we know that glasses are essentially frozen liquid made by quenching of their high‐temperature melts. Computer simulation method is an useful tool to obtain structure messages of melt and the supercooled liquid. The static, dynamical properties as a function of temperature can also be investigated by ab initio MD simulation. The atomic level rearrangement consists of both local topological structure change and chemical reordering and evolution of electronic properties of the Al87Ni7Nd6 and Ca50Mg20Cu30 alloy during the glass transition process is investigated, and the discussion of the results is given in this chapter.",signatures:"HaiJun Chang",downloadPdfUrl:"/chapter/pdf-download/51226",previewPdfUrl:"/chapter/pdf-preview/51226",authors:[{id:"183096",title:"Dr.",name:"Chang",surname:"Haijun",slug:"chang-haijun",fullName:"Chang Haijun"}],corrections:null},{id:"51475",title:"Corrosion Resistance and Electrocatalytic Properties of Metallic Glasses",doi:"10.5772/63677",slug:"corrosion-resistance-and-electrocatalytic-properties-of-metallic-glasses",totalDownloads:2782,totalCrossrefCites:4,totalDimensionsCites:10,hasAltmetrics:0,abstract:"Metallic glasses exhibit excellent corrosion resistance and electrocatalytic properties, and present extensive potential applications as anticorrosion, antiwearing, and catalysis materials in many industries. The effects of minor alloying element, microstructure, and service environment on the corrosion resistance, pitting corrosion, and electrocatalytic efficiency of metallic glasses are reviewed. Some scarcities in corrosion behaviors, pitting mechanism, and eletrocatalytic reactive activity for hydrogen are discussed. It is hoped that the overview is beneficial for some researcher paying attention to metallic glasses.",signatures:"Shanlin Wang",downloadPdfUrl:"/chapter/pdf-download/51475",previewPdfUrl:"/chapter/pdf-preview/51475",authors:[{id:"182701",title:"Prof.",name:"Shanlin",surname:"Wang",slug:"shanlin-wang",fullName:"Shanlin Wang"}],corrections:null},{id:"51279",title:"Structure and Mechanical Behaviour of Cu‐Zr‐Ni‐Al Amorphous Alloys Produced by Rapid Solidification",doi:"10.5772/63513",slug:"structure-and-mechanical-behaviour-of-cu-zr-ni-al-amorphous-alloys-produced-by-rapid-solidification",totalDownloads:1374,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The amorphous ribbons of Cu50Zr40Ni5Al5 alloy were manufactured by rapid solidification. The ribbons were investigated by X‐ray diffraction (XRD), scanning electron microscopy coupled with energy dispersive spectroscopy (SEM‐EDX) and differential scanning calorimetry (DSC). The activation energy of the crystallisation in amorphous alloys was determined by Kissenger technique. The mechanical properties of the ribbons were characterized using Vickers microhardness (HV) tester. According to the XRD and SEM results, the Cu50Zr40Ni5Al5 alloys have a fully amorphous structure. The EDX analysis of the ribbons showed that compositional homogeneity of the Cu50Zr40Ni5Al5 alloy was fairly high. From the DSC curves of the amorphous ribbons, it was determined that glass transition temperature (Tg) is around 440–442°C and super‐cooled liquid region (ΔTx = Tx - Tx) before crystallisation is around 61–64°C. The microhardness of the as‐quenched ribbons was measured about 550 HV. However, this microhardness value decreased with increasing annealing temperature and it was calculated about 465 HV after annealing temperature of 800°C.",signatures:"Celal Kursun and Musa Gogebakan",downloadPdfUrl:"/chapter/pdf-download/51279",previewPdfUrl:"/chapter/pdf-preview/51279",authors:[{id:"181811",title:"Ph.D.",name:"Celal",surname:"Kurşun",slug:"celal-kursun",fullName:"Celal Kurşun"},{id:"182484",title:"Prof.",name:"Musa",surname:"Gogebakan",slug:"musa-gogebakan",fullName:"Musa Gogebakan"}],corrections:null},{id:"51549",title:"Mechanical Behavior of Zr-Based Metallic Glasses and Their Nanocomposites",doi:"10.5772/64221",slug:"mechanical-behavior-of-zr-based-metallic-glasses-and-their-nanocomposites",totalDownloads:1911,totalCrossrefCites:4,totalDimensionsCites:5,hasAltmetrics:0,abstract:"In the present chapter, results of our recent investigations on the role of gallium (Ga) on the aluminum (Al) site in Zr69.5Al7.5-xGaxCu12Ni11 metallic glass (MG) composition have been discussed. The material tailoring and cooling rate effects on the mechanical behavior of Zr-based metallic glasses and their nanocomposites have been studied. The substitution of Ga on the Al site in Zr–Al–Cu–Ni alloy affects the nucleation and growth characteristics of quasicrystals (QCs) and consequently changes the morphology of nanoquasicrystals. The Zr69.5Al7.5-xGaxCu12Ni11 system displayed metallic glass formation in the range of x = 0–7.5. In this process, we have come out with a new glass composition; Zr-Ga-Cu-Ni with glass transition temperature (Tg)—614 K. The effect of cooling rate on the glass forming ability (GFA) and mechanical properties for this new metallic glass composition has been discussed and compared with some other Zr-based metallic glasses. The various indentation parameters such as microhardness, yield strength, strain hardening constant, nature of shear band formation, and so on for the alloys have been analyzed. The study is focused on investigations of these materials to understand the structure (microstructure) property correlations.",signatures:"Devinder Singh, R.K. Mandal, R.S. Tiwari and O.N. Srivastava",downloadPdfUrl:"/chapter/pdf-download/51549",previewPdfUrl:"/chapter/pdf-preview/51549",authors:[{id:"106764",title:"Prof.",name:"Rajiv Kumar",surname:"Mandal",slug:"rajiv-kumar-mandal",fullName:"Rajiv Kumar Mandal"},{id:"184180",title:"Dr.",name:"Devinder",surname:"Singh",slug:"devinder-singh",fullName:"Devinder Singh"},{id:"184181",title:"Prof.",name:"R.S.",surname:"Tiwari",slug:"r.s.-tiwari",fullName:"R.S. Tiwari"},{id:"184182",title:"Prof.",name:"O.N.",surname:"Srivastava",slug:"o.n.-srivastava",fullName:"O.N. Srivastava"}],corrections:null},{id:"51366",title:"On the Prospects of Using Metallic Glasses for In-vessel Mirrors for Plasma Diagnostics in ITER",doi:"10.5772/63885",slug:"on-the-prospects-of-using-metallic-glasses-for-in-vessel-mirrors-for-plasma-diagnostics-in-iter",totalDownloads:1347,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"This chapter reviews main results obtained on mirror-like samples made of several grades of bulk metallic glasses (BMG). Experiments were carried out under simulated conditions typical for the operation of plasma facing in-vessel mirrors of optical plasma diagnostics in fusion reactor ITER. Bombardment with D0 and T0 atoms radiated from burning plasma was predicted to be the main reason for the degradation of optical properties of such mirrors. Therefore, to simulate the behavior of mirrors in ITER, mirror-like samples were subjected to bombardment by ions of deuterium plasma with fixed or wide energy distribution. The effects of ion bombardment on optical properties, development of roughness, uptake of deuterium, appearance of blisters, and manifestation of some chemical processes are presented and discussed.",signatures:"Vladimir S. Voitsenya, Alexandra F. Bardamid, Martin Balden, Flaviu Gostin, Sergey V. Khovrich, Vladimir G. Konovalov, Konstantin V. Kovtun, Petro M. Lytvyn, Sergey V. Ketov, Dmitri V. Luzguine-Luzgin, Sergei I. Solodovchenko, Anatoly N. Shapoval, Anatoly F. Shtan’, Vladislav N. Bondarenko, Ivan V. Ruzhkov, Ol’ga O. Skoryk and Andrei A. Vasil’ev",downloadPdfUrl:"/chapter/pdf-download/51366",previewPdfUrl:"/chapter/pdf-preview/51366",authors:[{id:"183133",title:"Dr.",name:"Vladimir",surname:"Voitsenya",slug:"vladimir-voitsenya",fullName:"Vladimir Voitsenya"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"3817",title:"Developments in Corrosion Protection",subtitle:null,isOpenForSubmission:!1,hash:"8ff86fac7ac8bce142fdc3c0e5a79f30",slug:"developments-in-corrosion-protection",bookSignature:"M. 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Rissanen, Markku Kankaanpää,\nMika P. Tarvainen and Pasi A. 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Andrade, Alcimar B. Soares, Slawomir J. Nasuto and Peter J. 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Jain, S. Datta and S. Majumder",authors:[{id:"62746",title:"Dr.",name:"Ravi Kant",middleName:null,surname:"Jain",fullName:"Ravi Kant Jain",slug:"ravi-kant-jain"}]},{id:"40122",title:"Application of Surface Electromyography in the Dynamics of Human Movement",slug:"application-of-surface-electromyography-in-the-dynamics-of-human-movement",signatures:"César Ferreira Amorim and Runer Augusto Marson",authors:[{id:"150135",title:"Ph.D.",name:"Runer",middleName:"Augusto",surname:"Marson",fullName:"Runer Marson",slug:"runer-marson"},{id:"151438",title:"PhD.",name:"César Ferreira",middleName:null,surname:"Amorim",fullName:"César Ferreira Amorim",slug:"cesar-ferreira-amorim"}]},{id:"40121",title:"Virtual and Augmented Reality: A New Approach to Aid Users of Myoelectric Prostheses",slug:"virtual-and-augmented-reality-a-new-approach-to-aid-users-of-myoelectric-prostheses",signatures:"Alcimar Barbosa Soares, Edgard Afonso Lamounier Júnior, Adriano de Oliveira Andrade and Alexandre Cardoso",authors:[{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",slug:"adriano-andrade"},{id:"151483",title:"Dr.",name:"Alcimar",middleName:"Barbosa",surname:"Soares",fullName:"Alcimar Soares",slug:"alcimar-soares"},{id:"158350",title:"Dr.",name:"Edgard",middleName:null,surname:"Lamounier",fullName:"Edgard Lamounier",slug:"edgard-lamounier"},{id:"158351",title:"Dr.",name:"Alexandre",middleName:null,surname:"Cardoso",fullName:"Alexandre Cardoso",slug:"alexandre-cardoso"}]},{id:"40131",title:"Signal Acquisition Using Surface EMG and Circuit Design Considerations for Robotic Prosthesis",slug:"signal-acquisition-using-surface-emg-and-circuit-design-considerations-for-robotic-prosthesis",signatures:"Muhammad Zahak Jamal",authors:[{id:"151261",title:"B.Sc.",name:"Zahak",middleName:null,surname:"Jamal",fullName:"Zahak Jamal",slug:"zahak-jamal"}]}]}],publishedBooks:[{type:"book",id:"5148",title:"Proof and Concepts in Rapid Diagnostic Tests and Technologies",subtitle:null,isOpenForSubmission:!1,hash:"5be88795cc424e500a8fddcadf383fc9",slug:"proof-and-concepts-in-rapid-diagnostic-tests-and-technologies",bookSignature:"Shailendra K. 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In common neuropsychiatric conditions such as schizophrenia and depression, evidence indicates that neuroinflammation plays a role in the disease pathogenesis [2]. Long-lasting effects of neuroinflammation in such neuropsychiatric conditions are implicated with altered innate immune responses in the absence of specific pathogens [2]. However, until recently, it is not well understood how innate immunity, which was thought to have no lasting memory unlike adaptive immunity, can exert prolonged actions on the CNS. The recent discovery of innate immune memory (trained immunity vs. tolerance) shed a light in a long postulated role of innate immunity in neuropsychiatric diseases [3, 4].
Since the existence of the immune system was recognized more than 50 years ago, the immune system has been thought to be comprised of two components, innate immunity and adaptive immunity. Innate immunity is the arm that mounts nonspecific, acute immune responses, by sensing microbial by-products called pathogen-associated molecular patterns (PAMPs) or by-products derived from tissue injuries called damage-associated molecular patterns (DAMPs) [5]. Signaling through PAMPs and DAMPs are thought to play a major role in plant immunity [6]. In animals, adaptive immunity is the arm that develops antigen (Ag)-specific responses. The development of Ag-specific responses requires lengthy processes including antigen (Ag) processing by Ag-presenting cells (APCs), Ag presentation to T and B cells, and TCR or immunoglobulin gene arrangements of T and B lymphocytes, respectively, which lead to the development of Ag-specific T and B cells and finally antibodies (Abs) [7]. Adaptive immunity effectively eliminates hazards from the body through Ag-specific cellular and humoral immune responses [7]. Adaptive immunity results in the development of long-lasting Ag-specific memory T/B cells [8]. In this way, the body retains immune memory against specific pathogens for a prolonged time. It is well known that individuals who have survived measles will retain measles-specific immune defense for life.
In contrast, immunology textbooks have long taught us that innate immunity does not have any lasting effects or memory, and it is mainly effective in containing infection until adaptive immunity takes over. Innate immunity has also been known to shape adaptive immunity through multiple mechanisms such as affecting actions of APCs, thereby indirectly modifying adaptive immune responses [7]. However, recent exciting research revealed that innate immunity can have its own memory, following an immune stimulus, and this depends on time, amount, and the kinds of stimuli through metabolic and epigenetic changes [3, 9]. More importantly, the stimuli that evoke innate immune memory are not restricted to microbes; nonpathogenic challenges such as stress and obesity are also found to cause innate immune memory [3, 10].
As described previously, despite the accumulating evidence, it was difficult to understand how innate immunity exerts lasting effects, in the absence of specific pathogens or other persistent environmental stimuli, in neuropsychiatric conditions. The recognition of innate immune memory (trained immunity vs. tolerance) has provided us new insights with regard to the role of innate immunity in physiological as well as pathogenic consequences in the brain. In this chapter, research efforts shaping a concept of innate immune memory (trained immunity vs. innate immune tolerance) will be discussed first. In the latter part of the chapter, a potential role of innate immune memory in neuropsychiatric conditions, especially in ASD, will be discussed.
The presence of innate immune memory was first suspected because of unexpected, nonspecific effects of vaccinations. This is best known for a Bacillus Calmette-Guérin (BCG) vaccine. Epidemiological studies and subsequent randomized trials showed that the BCG vaccination not only provided protection for tuberculosis but also protection against other pathogens, especially those causing respiratory infection, which resulted in a reduction in infant mortality greater than expected for reducing tuberculosis-associated mortality [11, 12]. Likewise, the measles vaccination resulted in a striking reduction in children’s mortality, which was again not to be explained by the reduction in mortality caused by measles [11]. These epidemiological observations were further explored by researchers in the Netherlands. They first demonstrated that innate immune memory does exist in animal models [13]. Namely, these researchers showed that BCG provided enhanced protection against
Adaptive changes observed in “in vitro” models of trained immunity with β-glucan, a representative PAMP from
This metabolic shift described above results in the replenishment of the Krebs cycle by metabolization of glutamine into glutamate and α-keto-glutamate, leading to an accumulation of fumarate [23, 24]. Higher concentration of fumarate inhibits the KDM5 family of H3K4 demethylase that eventually leads to epigenetic reprogramming [23]. It has been reported that in the initial phase of trained immunity, lysine 27 of histone 3 (H3K27) is acetylated and lysine 4 of histone 3 (H3K4) is methylated rapidly [25]. Although H3K27Ac gradually returns to the baseline over time, H3K4me3 was found to remain elevated in the trained immunity [25]. Such epigenetic histone modification (accumulation of H3K4me3) is known to lead to the remodeling of the local chromatin into an open and accessible state, resulting in the facilitation of the loading of transcriptional machinery. The remaining accumulation of H3K4me3 on chromatin has been implicated in the establishment of the epigenetic memory in the trained immunity [25, 26]. It was hypothesized that H3K4me3 increases the local hydrophobicity of the chromatin, allowing for liquid-liquid phase separated transcription factors to engage with the DNA in the aqueous environment of the nucleus, subsequently rendering loading of transcriptional machinery onto promoters [27, 28, 29]. This will allow cells to start rapid transcription of the genes necessary for immune responses, thereby causing a much stronger Ag nonspecific pro-inflammatory response.
Long noncoding RNAs (lncRNAs) can function as a molecular scaffold where multiple protein complexes can assemble, and they also guide these complexes to specific gene loci [30]. Recent research disclosed a new class of lncRNAs named immune gene-priming lncRNAs (IPLs), and IPLs were found to have a crucial role in the accumulation of H3K4me3 on chromatin [31]. A candidate IPL, termed upstream master lncRNA of the inflammatory chemokine locus (UMLILO), was found to be crucial for trained immunity; ablation of the UMLILO transcript abolished β-glucan-induced trained immunity in both human and murine monocytes [30].
As shown in epidemiological studies of vaccinations, trained immunity, caused by metabolic and epigenetic changes, will be beneficial in providing broader immune defense and promoting tissue repair [32]. On the other hand, maladapted trained immunity can be detrimental to human health. Chronic inflammatory conditions including neuropsychiatric conditions have been implicated with maladapted changes in trained immunity [2, 9]. It should also be noted that induction of trained immunity appears to be associated with doses of PAMP, perhaps DAMP in humans; depending on the dose and the kinds of PAMP/DAMP, tolerance can be induced, instead of trained immunity [2]. It has been shown that low to moderate doses of β-glucan, tri-DAP, and muramyl dipeptides are reported to induce trained immunity [33]. It also needs to be cautioned that the effects of trained immunity are likely associated with individual’s genetic and epigenetic background. For example, nonspecific effects of infant BCG vaccination are reported to be heterogeneous, affected by multiple genetic and environmental factors including age, gender, interactions with other vaccines, and exposure to infectious pathogens at the time of BCG vaccination [34].
It has been reported that pre-administration of pro-inflammatory innate cytokines [interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), and IL-6] provided protection against a variety of microbes [35]. Among the cytokines administered, IL-1 showed superior effects over TNF-α or IL-6 [35]. In BCG-vaccinated individuals, increase in production of these innate cytokines by monocytes in response to other microbes, other than BCG, was also found; this effect was again the most dependent on IL-1β [32]. IL-1β has also been reported to be crucial in the induction of trained immunity in NK cells [36]. On the other hand, in individuals with chronic mucocutaneous candidiasis, STAT-1-mediated type II interferon (IFN) induction was found to be crucial for induction of trained immunity [37]. The role of type II IFN (IFN-γ) in animal models was also reported by Kaufmann et al. [16]. However, in humans, innate immunity-associated protection (trained immunity) has been mainly implicated with IL-1β and other IL-1 families [38].
As detailed in the previous section, a metabolic shift from oxidative phosphorylation to aerobic glycolysis through the Hypoxia inducible factor-1α (HIF-1α) pathway downstream to mTOR is crucial for the development of trained immunity, since inhibition of this pathway is abolished induction of trained immunity [21]. Namely, in HIF-1α knockout mice, trained immunity was not induced [21]. IL-1β is known to be a direct target of HIF-1α [39], having a HIF-1α binding site in the promoter region of IL-1β gene [40]. It is now thus proposed that HIF-1α-induced IL-1β also plays a role in epigenetic changes, through histone modifications [35]. Alternatively, IL-1β has been shown to upregulate HIF-1α [41].
Given the role of IL-1β in trained immunity, excessive, dysregulated production of IL-1β is likely to cause maladapted trained immunity and resultant pathogenic consequences. This may be observed in patients with autoinflammatory syndromes associated with gene mutation that lead to overproduction of IL-1β, including cryopyrin associated periodic syndrome (CAPS) [38, 42]. On the other hand, impaired induction of trained immunity can also cause detrimental effects. It was reported that patients with chronic mucocutaneous candidiasis exhibit impaired induction of STAT-1-dependent, trained immunity in response to β-glucan [37].
The above-described metabolic shift is not limited to glucose metabolism. Changes in glutamine and cholesterol metabolism have also shown to be crucial in trained immunity [24]. Consequently, it is thought that increased cholesterol content also plays a role in the development of trained immunity. Interestingly, increased levels of oxidized low-density lipoprotein (OxLDL) caused by dysregulated cholesterol metabolism are found to induce trained immunity in human monocytes [10]. Such a finding indicates a pathogenic role for maladapted trained immunity in atherosclerosis, since monocyte and macrophage cells are known to play a major role in plaque formation in vascular endothelium, a major histologic change in atherosclerosis [10].
As detailed in the previous section, trained immunity causes a metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis, rendering macrophage and monocyte lineage cells to classically activated cells or M1 phenotype; these cells exhibit impaired OXPHOS and anabolic repurposing of the tricarboxylic acid (TCA) cycle [43, 44]. In contrast, alternatively activated or the M2 phenotype of macrophages and monocytes has balanced processes of OXPHOS and TCA cycle activation; enhanced glycolytic generation of pyruvate fuels the TCA cycle, paralleling the induction of OXPHOS [44]. Trained macrophages via ß-glucan exposure are shown to reveal M1 phenotype [21]. Generation of M1 vs. M2 phenotypes of macrophages indicates the importance of regulating innate immune responses for prevention of excessive, potentially harmful inflammatory responses. In addition to generation of M2 phenotype, hypo-responsiveness of innate immunity has been described as endotoxin tolerance and compensatory anti-inflammatory response syndrome (CARS) [45]. Such regulatory mechanisms also have lasting effects, as observed in trained immunity.
Endotoxin tolerance in innate immunity was first shown in rodent models of sepsis. Namely, survival from sepsis is associated with diminished or absence of responses to LPS, an endotoxin [46]. Subsequently, it was shown that previous exposure to a sublethal dose of LPS led to resistance to a lethal dose of LPS in rodents [46]. Endotoxin tolerance is thought to be a result of innate immune memory with lasting immune hypo-responsiveness, even to non-LPS stimulants [47]. Phenotypic changes of tolerant innate immune cells are characterized with less production of inflammatory cytokines (TNF-α, IL-12, IL-6) and increase in production of counter-regulatory cytokines (IL-10 and TGF-β) upon stimulation [48, 49]. CARS was recognized as a clinical syndrome which is thought to represent a phase of immune “exhaustion,” following initial potent immune activation, known as systemic inflammatory response syndrome (SIRS) [50]. Peripheral blood monocytes and neutrophils from CARS patients are reported to reveal similar phenotype to endotoxin-tolerant cells observed in rodent models [45, 49]. Recent research revealed that persistent effects of endotoxin tolerance and CARS are mediated by lncRNAs as well as microRNAs (miRNAs).
LPS activates TLR4 which leads to the activation of the myeloid differentiation factor 88 (MyD88)-mediated pathway and the TIR-domain-containing adaptor-inducing interferon-β (TRIF) pathway [45]. The molecular signature of endotoxin tolerance involves downregulation of TLR4, decreased recruitment of MyD88 or TRIF to TLR4, decreased activation of IL-1 receptor-associated kinase (IRAK)1 and IRAK4, diminished nuclear factor κ chain of B-cell (NF-κB) signaling, as well as upregulation of negative regulatory molecules including SH2 domain-containing inositol phosphatase 1 (SHIP1) [51].
Recent research revealed a role of miRNAs in the regulation of endotoxin tolerance. Specifically, miR-155 and miR-146α have been shown to regulate endotoxin tolerance [52]. MiR-146α reduces TLR signaling, by targeting IRAK1 and TRAF6, key components of TLR signaling pathway [53]. In contrast, miR-155 is reported to inhibit expression of SHIP1 and SOCS1, negative regulators of TLR signaling, prohibiting or attenuating tolerance induction by endotoxin [54, 55]. Several other miRNAs are also implicated with regulation of endotoxin intolerance [45]. It was shown recently that miR-221/miR-222 regulates functional reprogramming of macrophages during LPS-induced tolerization [47]. miR-221/miR-222 targets brahma-regulated gene 1 (Brg1), rendering transcriptional silencing of a subset of inflammatory genes that depend on SWI/SNF and STAT-mediated chromatin remodeling [47].
Recent research also revealed a role of lncRNAs in endotoxin tolerance; lncRNAs exert transcriptional, posttranscriptional, and translational regulation of gene expression [56, 57, 58]. Multiple lncRNAs are reported to regulate target molecules of TLR4 signaling pathways. LPS-responsive lncRNAs Mirt2, THRIl, MALTAT1, NKILA, lincRNA-21, and SeT have been reported to suppress expression of pro-inflammatory mediators including TNF-α [45]. For example, Mirt2 is reported to inhibit TRAF6 ubiquitination, leading to a decrease in TNF-α production [59]. However, at this time, relationships between actions of miRNAs and lncRNA in innate immune tolerance are not well understood. Other soluble mediators such as cytokines (IL-1β, IL-10, TGF-β, and TNF-α) are also reported to induce cross-tolerance or cytokine-mediated tolerance, causing a signaling cascade similar to that observed in TLR signaling [60]. In contrast, interferons (IFN-γ, α2-IFN, etc.) are known to abrogate endotoxin tolerance [61, 62]. Again these soluble mediators exert their actions on endotoxin tolerance via modulation of intracellular lncRNAs [45].
This type of innate immune memory (tolerance) is thought to be important in maintaining brain homeostasis, and impaired tolerance of innate immunity has been suspected in chronic neurodegenerative conditions such as Alzheimer’s disease [9]. Aging is associated with an increased load of gram-negative bacteria in the GI tract and mouth mucosa, resulting in an increase in endotoxin levels in the blood and the brain [62]. However, aging individuals tolerate higher LPS levels in the brain through developing endotoxin tolerance [63].
It is known that innate immunity does exist in the brain, playing a crucial role in brain morphogenesis and homeostasis. The major innate immune cells in the central nervous system (CNS) are microglial cells which are endogenously generated in the brain, but they can also be developed from bone marrow-derived monocytes, which are called BM-derived microglial cells (BMDM) [64, 65]. BMDM-induced inflammation has been implicated in neuropsychiatric conditions [64, 65]. It has also been reported that peripherally derived macrophages modulate microglial function after CNS injury; in this case, they are reported to exert anti-inflammatory effects [66]. Other innate immune cells in the CNS such as astrocytes are also known to exert important physiological roles [9, 67].
Inflammation in the periphery can prompt immune responses in the brain [1, 4]. Given the effects of trained immunity (activation vs. tolerance) in rodent models and humans, the development of maladapted innate immune memory in the CNS is expected to result in undesired, hazardous effects to the brain. However, reports concerning the effects of trained immunity and/or innate immune tolerance in the brain have been limited. Nevertheless, it was shown that microglial cells isolated from adult rats that were exposed to
Independent of the studies concerning trained immunity in the brain, persistent effects of maternal immune activation (MIA) on fetuses have been extensively studied, as one of the best studied rodent models of ASD [70]. In this model, sterile inflammation in pregnant rodents was induced with the use of PAMPs such as LPS, poly I:C, resulting in impaired neuropsychiatric symptoms in offspring in their adult years [70]. That is, offspring of MIA mothers have been shown to suffer from persistent behavioral symptoms and cognitive deficits frequently seen in ASD subjects later in life [70]. In addition, MIA also causes persistent alteration of adaptive immunity [71]. However, in this model, it is not yet well understood how innate immune memory (most likely trained immunity in this model) plays a role in a MIA model, causing persistent behavioral changes and impaired cognitive development. Children exposed to stressful events during the fetal and newborn period have also been reported to have higher levels of pro-inflammatory cytokines and neurodevelopmental impairment than control children [2]. Given the research findings in molecular mechanisms of trained immunity described in the previous section, there is a possibility that maladapted trained immunity contributes to the onset and progress of some neuropsychiatric disorders.
Tolerized innate immunity in the brain is thought to be crucial for limiting excessive inflammatory responses during brain tissue repair that involves phagocytosis of apoptotic cells and damaged tissue debris by tolerant phagocytes [72]. In rodent models, disruption of this pathway leads to neuroinflammation and subsequent neuronal damage [73]. An important regulator of this pathway is the triggering receptor expressed on myeloid cells 2 (TREM-2), which is expressed on microglial cells [74]. Blockade of TREM-2 was shown to exacerbate experimental autoimmune encephalitis (EAE), a rodent model of multiple sclerosis (MS) [75]. Apolipoprotein E (ApoE) which is a TREM-2 ligand was shown to have a role in maintaining tolerized phenotype of phagocytic cells [74]. This interaction was found to be impaired in patients with Alzheimer’s disease [9]. In animal models of Alzheimer’s disease treated with trained immunity vs. tolerance inducing stimuli, it was reported that long-term modulation of brain immune responses were observed, and the authors attributed this prolonged effects on innate immune memory to reprogramming of microglial cells [4].
In the previous section describing molecular pathways associated with trained immunity, the importance of mTOR signaling has been repeatedly shown. One thing we learned from the research on trained immunity is that multiple lineage cells reveal metabolic and epigenetic reprogramming in the process of innate immune memory, which, in animal models, can also be applied to microglial cells [4]. Interestingly, brain dysfunction caused by dysregulated mTOR signaling has been implicated in several neuropsychiatric disorders. In the next paragraph, we summarize mTOR-related brain dysfunctions and proposed mechanisms.
One of the expected consequences of excessive mTOR signaling caused by trained immunity is the impairment of lysosomal degradation of intracellular components, since mTOR activation inhibits autophagy via inhibition of the early steps of autophagosome biogenesis [76, 77]. Autophagy is a key physiological cellular function that clears intracellular molecules and thought to be developed to adjust the state of nutrient depletion [76, 77]. However, this is also an important mechanism to remove misfolded proteins that naturally occur in living cells [22]. In addition to degradation of misfolded proteins, autophagy also degrades altered subcellular organelles, such as the mitochondria [22]. Prolonged dysfunction in autophagy can lead to detrimental effects and is implicated in the pathogenesis of multiple neuropsychiatric conditions including dementia, movement disorders, seizures, brain ischemia, ASD, affective disorder, and schizophrenia [78, 79, 80, 81, 82]. In rodent models of depression, tuberous sclerosis, and ASD, rapamycin (sirolimus), a representative mTOR inhibitor, has been shown to attenuate social interactions and reverse behavioral effects on their neuropsychiatric symptoms [83, 84, 85, 86]. Thus metabolic and epigenetic changes caused by trained immunity may have profound effects through altered levels of autophagy, as a result of metabolic and epigenetic reprograming, as detailed in the previous section.
In this section, we discuss a possible role for trained immunity in the onset and progress of ASD. As a clinician, the author observed that an apparent strong immune stimulus altered the responses to subsequent immune stimuli in some, but not all ASD children and these ASD children also exhibit fluctuating neuropsychiatric symptoms, following microbial infection [87, 88]. As discussed in the previous section, in the MIA model of ASD, prolonged effects of MIA on the offspring brain can be explained through a concept of trained immunity occurring to the fetus at the time of sterile immune activation in the mother. This may have also happened in ASD subjects as described above. However, it should be noted that ASD is a behaviorally defined syndrome, diagnosed on the basis of behavioral symptoms, except for a minority of ASD cases that have well-defined gene mutations [89]. Therefore, based on the author’s clinical experience, it is likely that trained immunity plays a role in a subset of ASD subjects for whom neuroinflammation is associated in their ASD pathogenesis.
In ASD patients, just like in other neuropsychiatric conditions, a role of inflammation has been long suspected, and more and more evidence has been accumulating [90, 91, 92]. In the research of innate immune abnormalities in ASD children, we have also found evidence of dysregulated innate immune responses, shifting to pro-inflammatory responses in a subset of ASD subjects [88, 93, 94]. We also experienced that these ASD subjects suffer from various comorbid medical conditions involving the gastrointestinal (GI) tract and other organs [87]. Retrospectively, our findings may be reflecting maladapted innate immunity as a form of trained immunity in such ASD subjects; these ASD subjects may fall into an ASD subset which we have called inflammatory autism, mimicking the rodent ASD model of MIA [93]. Our previous findings that may indicate altered innate immune memory in such ASD patients are as follows:
In some but not all the ASD subjects, we found significant changes in innate immune abnormalities which are best reflected in changes in IL-1β/IL-10 ratios produced by purified peripheral blood monocytes (PBMo) [88, 93]. Namely, some patients reveal high ratios of IL-1β/IL-10, while others showed low ratios, and these rations can change from time to time, depending on their exposure to immune insults [93].
ASD subjects who revealed high and/or low IL-1β/IL-10 ratios also revealed fluctuating behavioral symptoms following immune insults [94]. Parents of these subjects often describe more severe, prolonged illnesses and frequent respiratory infection following microbial infection [87]. They also seem to reveal significant changes in their behavioral symptoms and cognitive activity with immune stimuli not associated with microbial infection; these ASD children may exhibit worsening neuropsychiatric symptoms, following flare-ups of aeroallergen allergy, delayed-type food allergy, and adverse reactions to medications including vaccinations [87, 94].
ASD subjects who revealed high and/or low IL-1β/IL-10 ratios also revealed changes in production of inflammatory monocyte cytokines including TNF-α and IL-6 [93, 95].
PBMo from ASD subjects who revealed altered IL-1β/IL-10 ratios also revealed changes in miRNA expression by PBMo, as compared to cells obtained from neurotypical, non-ASD controls [93].
We also studied changes in mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) obtained from ASD subjects and non-ASD controls. Our results revealed evidence of altered mitochondrial respiration in association with changes in IL-1β/IL-10 ratios by PBMo in ASD subjects [95].
In recent studies, we also found changes in miRNA in sera of ASD subjects, when tested by high-throughput deep sequencing. Again, changes in serum miRNA levels are closely associated with changes in IL-1β/IL-10 ratios by PBMo, production of monocyte cytokines (TNF-β, IL-6, IL-10, CCL2 mostly), along with parameters of mitochondrial respiration (manuscript submitted for publication). Interestingly, in ASD subjects, miRNA levels are mostly decreased, as compared to non-ASD controls (submitted for publication). Targeted genes by miRNAs that are altered in serum levels in ASD subjects with high or low IL-1β/IL-10 ratios are associated with pathways involved in innate immune responses, including the mTOR signaling pathway (unpublished observation).
The above-described findings may be best explained by altered innate immune responses associated with innate immune memory (trained immunity vs. tolerance). So, if this is the case, for these ASD subjects, can clinical features that indicate an alternation of innate immune memory be detected? The author is a pediatric immunologist and, as indicated before, as stated previously, observes exacerbation of neuropsychiatric symptoms, following immune insults. Herein, a representative ASD case, in which trained immunity may be associated with the onset and progression of ASD, is presented.
A 10-year-old female child presented to the pediatric allergy/immunology clinic at our institution secondary to fluctuating behavioral symptoms. Fluctuation of behavioral symptoms often occurred, following microbial infection.
The patient was born at 41 weeks of gestation via cesarean section due to breech presentation, following an uneventful pregnancy. The patient was developing typically until 24 months of age and then suffered from significant developmental regression. Prior to the onset of the developmental regression, parents took the patient to South Asia to visit other family members and friends. During this visit, the patient suffered an insect bite which was complicated by a secondary bacterial skin infection. When treated with oral antibiotics abroad, the patient developed generalized hives and severe GI symptoms (nausea, vomiting, diarrhea, and bloating): the patient then became intolerant to multiple foods. After returning to the United States, the patient was given multiple vaccinations including live vaccines to catch up the vaccination schedule. All these vaccines were given while the patient was still suffering from GI symptoms and an active skin infection. Within several days after vaccinations (multiple vaccines given all together), noticeable loss of cognitive and motor skills became apparent in the patient. The patient was eventually diagnosed with ASD around 2.5 years of age.
Eventually, the patient’s GI symptoms subsided, but this subject never regained the cognitive skills that this patient had once acquired prior to the onset of developmental regression. Prior to advancing to pre-kindergarten, the patient was given booster doses of vaccines which were well tolerated. However, after starting pre-kindergarten, the patient started getting sick frequently with upper respiratory infections, which often evolved into ear infection. The patient missed many days of school, since the patient suffered a prolonged course of illness and more severe symptoms, as compared to peers. While the patient presented with symptoms of upper respiratory infection, this patient’s behavioral symptoms continue to fluctuate, most evident in worsening of obsessive compulsive behaviors and frequency of “rage” episodes. Worsening behavioral symptoms would always follow immune insults, worse in a convalescence stage. Avoidance of sick contacts by placing the patient in home schooling attenuated the fluctuating behavioral symptoms. At 7–8 years of age, the fluctuating behavioral symptoms seen were mainly associated with teething. After the completion of teething, behavioral symptoms became more stable. However, the patient stopped growing, falling under the first percentile of the growth curve in height and weight. An exhausting workup for primary mitochondrial diseases, endocrine diseases, primary immunodeficiency with known gene mutations, and congenital metabolic and genetic diseases was unrevealing. However, video electric encephalogram revealed a focal epileptic activity. Family history is negative for neuropsychiatric, genetic, autoimmune, immune, and metabolic diseases.
In the case presented above, did neuroinflammation caused by maladapted trained immunity have a role in her clinical features? It is hard to prove, but it may be speculated that the initial stressful events that occurred abroad shaped trained immunity in this patient, and the subsequent multiple unrelated immune stimuli may have caused prolonged maladapted trained immunity, leading to persistent neuroinflammation and impairment of cognitive activity, as observed in the MIA models of ASD. Interestingly, changes in GI conditions, such as changes in microbiome, have been implicated with neuropsychiatric diseases, triggering maladapted trained immunity [96]. It is also reported that trained innate immunity can be induced in human monocytes by cow’s milk [97]. Thus her severe GI symptoms and subsequent intolerance to multiple foods may be associated with excessive trained immunity in the gut of this patient.
As summarized in the previous section, we have found that IL-1β/IL-10 ratios produced by PBMo are altered in some ASD subjects in association with fluctuating behavioral symptoms [94]. Thus if innate immune memory (trained immunity) is associated with her above-described remarkable clinical symptoms, we may also find altered IL-1β/IL-10 ratios, as an indicator of altered innate immune responses.
Thus we assessed IL-1β/IL-10 ratios produced by PBMo in response to a panel of innate immune stimuli, including β-glucan, as reported previously [95]. As shown in Figure 1, the presented case revealed increase in IL-1β/IL-10 ratios in response to zymosan, CL097, and β-glucan. High IL-1β/IL-10 ratio in response to CL097, an agonist of TLR7/TLR8, was especially striking. We also observed increase in production of TNF-α and IL-6 and decrease in the production of IL-10, as well. Given these findings, it is possible that maladapted trained immunity may have caused excessive inflammatory responses to various innate immune stimuli, which then led to developmental regression and fluctuating behavioral symptoms in this presented case.
IL-1β/IL-10 ratios produced by purified peripheral blood monocytes in response to medium only (no stimulus), LPS (TLR4 agonist), zymosan (TLR2/TLR6 agonist), CL097 (TLR7/TLR8 agonist), and β-glucan in the presented case (patient) and control cells from a non-ASD neurotypical subject. IL-1β/IL-10 ratios are shown in a log scale.
Our deepening knowledge of innate immune memory (trained immunity vs. tolerance) has shed light on the understanding of nonspecific effects of microbial infection and other immune stimuli, which have been implicated in the onset and progress of various neuropsychiatric diseases. Recent research indicates a possibility for a role of maladapted innate immune memory in various neuropsychiatric conditions. The finding of innate immune memory is especially exciting in the field of neuroimmunology, since we now likely have better tools for addressing the long-suspected role of immune-mediated inflammation that is not associated with specific pathogens or environmental factors, in various neuropsychiatric conditions. The concept of innate immune memory will be especially important in addressing insults to the brain during the early years of CNS development, and the resultant lasting intellectual disabilities, as seen in MIA models [70]. More importantly, an improved understanding of the role of innate immune memory (trained immunity vs. tolerance) in pathogenic neuroinflammation can lead to novel therapeutic measures that are desperately needed for the treatment of neuropsychiatric diseases.
The part of the study presented in this manuscript was funded from the Jonty Foundation, St. Paul, MN. The author is thankful for the critical review of this manuscript by Dr. L. Huguenin.
The author has nothing to declare.
Ab | antibody |
Ag | antigen |
APC | Ag-presenting cells |
ApoE | apolipoprotein E |
ASD | autism spectrum disorders |
BCG | Bacillus Calmette-Guérin |
Brg1 | brahma-regulated gene 1 |
BMDM | cell, bone marrow-derived microglial cell |
CAPS | cryopyrin-associated periodic syndrome |
CARS | compensatory anti-inflammatory response syndrome |
CNS | central nervous system |
DAMPs | damage-associated molecular patterns |
EAE | experimental autoimmune encephalitis |
GI | gastrointestinal |
HIF-1α | hypoxia inducible factor-1α |
IFN | interferon |
IL | interleukin |
IPLs | immune gene-priming lncRNAs |
lncRNAs | long noncoding RNAs |
IRAK | interleukin-1 receptor-associated kinase |
LPS | lipopolysaccharide |
MIA | maternal immune activation |
MS | multiple sclerosis |
MyD88 | myeloid differentiation factor 88 |
mTOR | mammalian target of rapamycin |
NF-κB | nuclear factor of κ chain of B cells |
NK | natural killer |
OxLDL | oxidized low-density lipoprotein |
OXPHOS | oxidative phosphorylation |
PAMPs | pathogen-associated molecular patterns |
PBMCs | peripheral blood mononuclear cells |
PBMo | peripheral blood monocytes |
SHIP1 | SH2 domain-containing inositol phosphatase 1 |
SPUH | Saint Peter’s University Hospital |
TCA | tricarboxylic acid |
TLR | Toll-like receptor |
TNF | tumor necrosis factor |
TREM-2 | triggering receptor expressed on myeloid cells 2 |
TRIF | TIR-domain-containing adaptor-inducing interferon-ß |
TSC | tuberous sclerosis complex |
UMLILO | upstream master lncRNAs of the inflammatory chemokine locus |
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. 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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{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:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{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. 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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. 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