Chemical contents (mg kg−1) of industrial sewage sludge, urban sewage sludge and Tunisian standard values [12].
\\n\\n
These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\\n\\n\\n\\n\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\n\n\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"10071",leadTitle:null,fullTitle:"Nanowires - Recent Progress",title:"Nanowires",subtitle:"Recent Progress",reviewType:"peer-reviewed",abstract:"Low-dimensional structures have attracted extensive research interest due to their promising applications in nanotechnology. These low-dimensional materials have the potential to make revolutionary changes in science and technology because a reduction in size not only enables a faster speed and greater computing power but also helps reduce device form factors. As such, this book examines the behaviors of oxide nanowires, group III–V compounds, and other nanowires, including basic Si nanowires, metallic wires, and complex geometrical nanowires.",isbn:"978-1-83962-392-9",printIsbn:"978-1-83962-391-2",pdfIsbn:"978-1-83962-393-6",doi:"10.5772/intechopen.87902",price:119,priceEur:129,priceUsd:155,slug:"nanowires-recent-progress",numberOfPages:198,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"3baef9684ce58f9f65a1f1788509220d",bookSignature:"Xihong Peng",publishedDate:"July 14th 2021",coverURL:"https://cdn.intechopen.com/books/images_new/10071.jpg",numberOfDownloads:4474,numberOfWosCitations:0,numberOfCrossrefCitations:3,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:4,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:7,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 9th 2020",dateEndSecondStepPublish:"September 15th 2020",dateEndThirdStepPublish:"November 14th 2020",dateEndFourthStepPublish:"February 2nd 2021",dateEndFifthStepPublish:"April 3rd 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"24647",title:"Prof.",name:"Xihong",middleName:null,surname:"Peng",slug:"xihong-peng",fullName:"Xihong Peng",profilePictureURL:"https://mts.intechopen.com/storage/users/24647/images/system/24647.png",biography:"Dr. Xihong Peng is a professor in the College of Integrative Sciences and Arts, Arizona State University (ASU), Polytechnic Campus. She received a Ph.D. in Physics from Rensselaer Polytechnic Institute, New York, in 2007. She joined ASU as an assistant professor in 2008 and was promoted to professor in 2021. \n\nDr. Peng’s research interests are to explore novel materials and seek their applications in nanoelectronics and alternative energies, as well as to gain a fundamental understanding of the materials’ properties at an atomic level. She has applied physics-based computational methods to investigate a wide range of materials, including group IV, III-V semiconductor nanostructures, and novel materials for applications in fuel cells, photocatalysts, and Li-ion batteries.",institutionString:"Arizona State University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Arizona State University",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"208",title:"Material Science",slug:"nanotechnology-and-nanomaterials-material-science"}],chapters:[{id:"73514",title:"ZnO Nanowire Field-Effect Transistor for Biosensing: A Review",doi:"10.5772/intechopen.93707",slug:"zno-nanowire-field-effect-transistor-for-biosensing-a-review",totalDownloads:489,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The last 19 years have seen intense research made on zinc oxide (ZnO) material, mainly due to the ability of converting the natural n-type material into p-type. For a long time, the p-type state was impossible to attain and maintain. This chapter focuses on ways of improving the doped ZnO material which acts as a channel for nanowire field-effect transistor (NWFET) and biosensor. The biosensor has specific binding which is called functionalization that is achieved by attaching a variety of compounds on the designated sensing area. Reference electrodes and buffers are used as controllers. Top-down fabrication processes are preferred over bottom-up because they pave way for mass production. Different growth techniques are reviewed and discussed. Strengths and weaknesses of the FET and sensor are also reviewed.",signatures:"Nonofo Mathiba Jack Ditshego",downloadPdfUrl:"/chapter/pdf-download/73514",previewPdfUrl:"/chapter/pdf-preview/73514",authors:[{id:"324451",title:"Dr.",name:"Nonofo Mathiba Jack",surname:"Ditshego",slug:"nonofo-mathiba-jack-ditshego",fullName:"Nonofo Mathiba Jack Ditshego"}],corrections:null},{id:"73500",title:"Metal Oxide Nanowires as Building Blocks for Optoelectronic Devices",doi:"10.5772/intechopen.94011",slug:"metal-oxide-nanowires-as-building-blocks-for-optoelectronic-devices",totalDownloads:466,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Metal oxide nanowires have become the new building blocks for the next generation optoelectronic devices due to their specific features such as quantum confinement and high aspect ratio. Thus, they can be integrated as active components in diodes, field effect transistors, photodetectors, sensors, solar cells and so on. ZnO, a n-type semiconductor with a direct wide band gap (3.3 eV) and CuO, a p-type semiconductor with a narrow band gap (1.2–1.5 eV), are two metal oxides which were recently in the spotlight of the researchers for applications in the optoelectronic devices area. Therefore, in this chapter we focused on ZnO and CuO nanowires, the metal oxides nanowire arrays being prepared by straightforward wet and dry methods. Further, in order to emphasize their intrinsic transport properties, lithographic and thin films deposition techniques were used to integrate single ZnO and CuO nanowires into diodes and field effect transistors.",signatures:"Andreea Costas, Nicoleta Preda, Camelia Florica and Ionut Enculescu",downloadPdfUrl:"/chapter/pdf-download/73500",previewPdfUrl:"/chapter/pdf-preview/73500",authors:[{id:"184343",title:"Dr.",name:"Nicoleta",surname:"Preda",slug:"nicoleta-preda",fullName:"Nicoleta Preda"},{id:"325256",title:"Dr.",name:"Andreea",surname:"Costas",slug:"andreea-costas",fullName:"Andreea Costas"},{id:"329570",title:"Dr.",name:"Camelia",surname:"Florica",slug:"camelia-florica",fullName:"Camelia Florica"},{id:"329572",title:"Dr.",name:"Ionut",surname:"Enculescu",slug:"ionut-enculescu",fullName:"Ionut Enculescu"}],corrections:null},{id:"73499",title:"Synthesis of Nanowire Using Glancing Angle Deposition and Their Applications",doi:"10.5772/intechopen.94012",slug:"synthesis-of-nanowire-using-glancing-angle-deposition-and-their-applications",totalDownloads:335,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Nanowires are highly attractive for advanced nanoelectronics and nanoscience applications, due to its novel properties such as increased surface area, large aspect ratio, and increased surface scattering of electrons and phonons. The design and fabrication of nanowires array provide a great platform to overcome the challenges/limitation of its counter partner. This chapter focuses on the synthesis of metal oxide nanowire and axial heterostructure nanowire array using the Glancing angle deposition (GLAD) technique. The structural, optical and electrical properties are studied. This GLAD technique offers control over one-dimensional (1D) nanostructure growth with self-alignment capability. It is also reviewed in an effort to cover the various application in this area of optoelectronic devices and wettability applications that had been synthesized using GLAD.",signatures:"Chinnamuthu Paulsamy, Pheiroijam Pooja and Heigrujam Manas Singh",downloadPdfUrl:"/chapter/pdf-download/73499",previewPdfUrl:"/chapter/pdf-preview/73499",authors:[{id:"324443",title:"Assistant Prof.",name:"Chinnamuthu",surname:"Paulsamy",slug:"chinnamuthu-paulsamy",fullName:"Chinnamuthu Paulsamy"},{id:"324444",title:"Ms.",name:"Pheiroijam",surname:"Pooja",slug:"pheiroijam-pooja",fullName:"Pheiroijam Pooja"},{id:"327097",title:"Mr.",name:"Heigrujam Manas",surname:"Singh",slug:"heigrujam-manas-singh",fullName:"Heigrujam Manas Singh"}],corrections:null},{id:"72523",title:"Recent Progress in Gallium Nitride for Photoelectrochemical Water Splitting",doi:"10.5772/intechopen.92848",slug:"recent-progress-in-gallium-nitride-for-photoelectrochemical-water-splitting",totalDownloads:874,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"With the constant consumption of traditional energy sources, it is urgent to explore and develop new energy sources. Photoelectrochemical (PEC) water splitting is a method of preparing energy that can continuously generate hydrogen fuel without pollution to the environment. As an important part of the PEC water splitting system, the choice of semiconductor photoelectrode is crucial. Among these materials, gallium nitride (GaN) has attracted considerable attention due to its tunable band gap, favorable band edge positions, wide band gap, and good stability. In the past years, many reports have been obtained in GaN for PEC water splitting. This review summarizes the GaN as photoelectrodes for PEC water splitting, and methods to improve the efficiency of GaN for PEC water splitting also will be summarized from change morphology, doping, surface modification, and composition of solid solution or multiple-metal incorporation. Eventually, the future research directions and challenges of GaN for PEC water splitting are also discussed.",signatures:"Fangliang Gao, Qing Liu, Jiang Shi and Shuti Li",downloadPdfUrl:"/chapter/pdf-download/72523",previewPdfUrl:"/chapter/pdf-preview/72523",authors:[{id:"318528",title:"Dr.",name:"Fangliang",surname:"Gao",slug:"fangliang-gao",fullName:"Fangliang Gao"},{id:"318548",title:"Dr.",name:"Qing",surname:"Liu",slug:"qing-liu",fullName:"Qing Liu"},{id:"318549",title:"Dr.",name:"Jiang",surname:"Shi",slug:"jiang-shi",fullName:"Jiang Shi"},{id:"320603",title:"Prof.",name:"Shuti",surname:"Li",slug:"shuti-li",fullName:"Shuti Li"}],corrections:null},{id:"74335",title:"III-Nitride Nanowires: Future Prospective for Photovoltaic Applications",doi:"10.5772/intechopen.95011",slug:"iii-nitride-nanowires-future-prospective-for-photovoltaic-applications",totalDownloads:354,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Photovoltaic (PV) technology could be a promising candidate for clean and green source of energy. The nanowire technology provides extra mileage over planar solar cells in every step from photon absorption to current generation. Indium Gallium Nitride (InxGa1-xN) is a recently revised material with such a bandgap to absorb nearly whole solar spectrum to increase the conversion efficiency copiously. One of the major technological challenge is in-built polarization charges. This chapter highlights the basic advantageous properties of InxGa 1−xN materials, its growth technology and state-of-the-art application towards PV devices. The most important challenges that remain in realizing a high-efficiency InxGa 1−xN PV device are also discussed. III-Nitride nanowires are also explored in detail to overcome the challenges. Finally, conclusions are drawn about the potential and future aspect of InxGa 1−xN material based nanowires towards terrestrial as well as space photovoltaic applications.",signatures:"Soumyaranjan Routray and Trupti Lenka",downloadPdfUrl:"/chapter/pdf-download/74335",previewPdfUrl:"/chapter/pdf-preview/74335",authors:[{id:"323752",title:"Dr.",name:"Soumyaranjan",surname:"Routray",slug:"soumyaranjan-routray",fullName:"Soumyaranjan Routray"},{id:"339714",title:"Prof.",name:"Trupti",surname:"Lenka",slug:"trupti-lenka",fullName:"Trupti Lenka"}],corrections:null},{id:"74814",title:"In Situ TEM Studies of III-V Nanowire Growth Mechanism",doi:"10.5772/intechopen.95690",slug:"in-situ-tem-studies-of-iii-v-nanowire-growth-mechanism",totalDownloads:287,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Growing nanowires inside a transmission electron microscope (TEM) and observing the process in situ has contributed immensely to understanding nanowire growth mechanisms. Majority of such studies were on elemental semiconductors – either Si or Ge – both of which are indirect bandgap semiconductors. Several compound semiconductors on the other hand have a direct bandgap making them more efficient in several applications involving light absorption or emission. During compound nanowire growth using a metal catalyst, the difference in miscibility of the nanowire species inside the metal catalyst are different, making its growth dynamics different from elemental nanowires. Thus, studies specifically focusing on compound nanowires are necessary for understanding its growth dynamics. This chapter reviews the recent progresses in the understanding of compound semiconductor nanowire growth obtained using in situ TEM. The concentrations of the nanowire species in the catalyst was studied in situ. This concentration difference has been shown to enable independent control of layer nucleation and layer growth in nanowires. In situ TEM has also enabled better understanding of the formation of metastable crystal structures in nanowires.",signatures:"Carina B. Maliakkal",downloadPdfUrl:"/chapter/pdf-download/74814",previewPdfUrl:"/chapter/pdf-preview/74814",authors:[{id:"330342",title:"Dr.",name:"Carina B.",surname:"Maliakkal",slug:"carina-b.-maliakkal",fullName:"Carina B. Maliakkal"}],corrections:null},{id:"76740",title:"Indium (In)-Catalyzed Silicon Nanowires (Si NWs) Grown by the Vapor–Liquid–Solid (VLS) Mode for Nanoscale Device Applications",doi:"10.5772/intechopen.97723",slug:"indium-in-catalyzed-silicon-nanowires-si-nws-grown-by-the-vapor-liquid-solid-vls-mode-for-nanoscale-",totalDownloads:261,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Stacking fault free and planar defects (twin plane) free catalyzed Si nanowires (Si NWs) is essential for the carrier transport in the nanoscale devices applications. In this chapter, In-catalyzed, vertically aligned and cone-shaped Si NWs arrays were grown by using vapor–liquid–solid (VLS) mode on Si (111) substrates. We have successfully controlled the verticality and (111)-orientation of Si NWs as well as scaled down the diameter to 18 nm. The density of Si NWs was also enhanced from 2.5 μm−2 to 70 μm−2. Such vertically aligned, (111)-oriented p-type Si NWs are very important for the nanoscale device applications including Si NWs/c-Si tandem solar cells and p-Si NWs/n-InGaZnO Heterojunction LEDs. Next, the influence of substrate growth temperature (TS), cooling rate (∆TS/∆????) on the formation of planar defects, twining along [112] direction and stacking fault in Si NWs perpendicular to (111)-orientation were deeply investigated. Finally, one simple model was proposed to explain the formation of stacking fault, twining of planar defects in perpendicular direction to the axial growth direction of Si NWs. When the TS was decreased from 600°C with the cooling rate of 100°C/240 sec to room temperature (RT) after Si NWs growth then the twin planar defects perpendicular to the substrate and along different segments of (111)-oriented Si NWs were observed.",signatures:"M. Ajmal Khan and Yasuaki Ishikawa",downloadPdfUrl:"/chapter/pdf-download/76740",previewPdfUrl:"/chapter/pdf-preview/76740",authors:[{id:"252365",title:"Dr.",name:"M.Ajmal",surname:"Khan",slug:"m.ajmal-khan",fullName:"M.Ajmal Khan"},{id:"356591",title:"Dr.",name:"Yasuaki",surname:"Ishikawa",slug:"yasuaki-ishikawa",fullName:"Yasuaki Ishikawa"}],corrections:null},{id:"74847",title:"Nanowires Integrated to Optical Waveguides",doi:"10.5772/intechopen.95689",slug:"nanowires-integrated-to-optical-waveguides",totalDownloads:295,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Chip-scale integrated optical devices are one of the most developed research subjects in last years. These devices serve as a bridge to overcome size mismatch between diffraction-limited bulk optics and nanoscale photonic devices. They have been employed to develop many on-chip applications, such as integrated light sources, polarizers, optical filters, and even biosensing devices. Among these integrated systems can be found the so-called hybrid photonic-plasmonic devices, structures that integrate plasmonic metamaterials on top of optical waveguides, leading to outstanding physical phenomena. In this contribution, we present a comprehensive study of the design of hybrid photonic-plasmonic systems consisting of periodic arrays of metallic nanowires integrated on top of dielectric waveguides. Based on numerical simulations, we explain the physics of these structures and analyze light coupling between plasmonic resonances in the nanowires and the photonic modes of the waveguides below them. With this chapter we pretend to attract the interest of research community in the development of integrated hybrid photonic-plasmonic devices, especially light interaction between guided photonic modes and plasmonic resonances in metallic nanowires.",signatures:"Ricardo Téllez-Limón and Rafael Salas-Montiel",downloadPdfUrl:"/chapter/pdf-download/74847",previewPdfUrl:"/chapter/pdf-preview/74847",authors:[{id:"325011",title:"Dr.",name:"Ricardo",surname:"Tellez-Limon",slug:"ricardo-tellez-limon",fullName:"Ricardo Tellez-Limon"},{id:"325455",title:"Dr.",name:"Rafael",surname:"Salas-Montiel",slug:"rafael-salas-montiel",fullName:"Rafael Salas-Montiel"}],corrections:null},{id:"73506",title:"Gate-All-Around FETs: Nanowire and Nanosheet Structure",doi:"10.5772/intechopen.94060",slug:"gate-all-around-fets-nanowire-and-nanosheet-structure",totalDownloads:744,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"DC/AC performances of 3-nm-node gate-all-around (GAA) FETs having different widths and the number of channels (Nch) from 1 to 5 were investigated thoroughly using fully-calibrated TCAD. There are two types of GAAFETs: nanowire (NW) FETs having the same width (WNW) and thickness of the channels, and nanosheet (NS) FETs having wide width (WNS) but the fixed thickness of the channels as 5 nm. Compared to FinFETs, GAAFETs can maintain good short channel characteristics as the WNW is smaller than 9 nm but irrespective of the WNS. DC performances of the GAAFETs improve as the Nch increases but at decreasing rate because of the parasitic resistances at the source/drain epi. On the other hand, gate capacitances of the GAAFETs increase constantly as the Nch increases. Therefore, the GAAFETs have minimum RC delay at the Nch near 3. For low power applications, NWFETs outperform FinFETs and NSFETs due to their excellent short channel characteristics by 2-D structural confinement. For standard and high performance applications, NSFETs outperform FinFETs and NWFETs by showing superior DC performances arising from larger effective widths per footprint. Overall, GAAFETs are great candidates to substitute FinFETs in the 3-nm technology node for all the applications.",signatures:"Jun-Sik Yoon, Jinsu Jeong, Seunghwan Lee, Junjong Lee and Rock-Hyun Baek",downloadPdfUrl:"/chapter/pdf-download/73506",previewPdfUrl:"/chapter/pdf-preview/73506",authors:[{id:"231361",title:"Dr.",name:"Jun-Sik",surname:"Yoon",slug:"jun-sik-yoon",fullName:"Jun-Sik Yoon"},{id:"329367",title:"Mr.",name:"Jinsu",surname:"Jeong",slug:"jinsu-jeong",fullName:"Jinsu Jeong"},{id:"329368",title:"Mr.",name:"Seunghwan",surname:"Lee",slug:"seunghwan-lee",fullName:"Seunghwan Lee"},{id:"329369",title:"Mr.",name:"Junjong",surname:"Lee",slug:"junjong-lee",fullName:"Junjong Lee"},{id:"329370",title:"Prof.",name:"Rock-Hyun",surname:"Baek",slug:"rock-hyun-baek",fullName:"Rock-Hyun Baek"}],corrections:null},{id:"73701",title:"Engineering the Color and the Donor-Acceptor Behavior in Nanowires: Blend Versus Coaxial Geometry",doi:"10.5772/intechopen.94214",slug:"engineering-the-color-and-the-donor-acceptor-behavior-in-nanowires-blend-versus-coaxial-geometry",totalDownloads:373,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The blending or the bilayering of two complementary species are the dominant methods for in-solution-processed thin film devices to get a strong donor-acceptor behavior. They propose opposite strategies for the respective arrangement of the two species, a central point for energy and/or charge transfer. In this work, we propose to engineer at the scale of the exciton diffusion length the organization of a donor (poly(vinyl-carbazole), PVK) and an acceptor (poly(para-phenylene-vinylene), PPV) in a nanowire geometry. A two-step template strategy was used to fabricate coaxial nanowires with PPV and PVK, alternatively as the core or the shell material. Their stationary and time-resolved photoluminescence properties were investigated and compared to the case of PVK-PPV blend. Their respective characteristics are direct evidences of the dominant mechanisms responsible for the emission properties.",signatures:"Mohamed Mbarek and Kamel Alimi",downloadPdfUrl:"/chapter/pdf-download/73701",previewPdfUrl:"/chapter/pdf-preview/73701",authors:[{id:"145723",title:"Prof.",name:"Alimi",surname:"Kamel",slug:"alimi-kamel",fullName:"Alimi Kamel"},{id:"325937",title:"Associate Prof.",name:"mohamed",surname:"mbarek",slug:"mohamed-mbarek",fullName:"mohamed mbarek"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"3066",title:"Nanowires",subtitle:"Recent Advances",isOpenForSubmission:!1,hash:"5c6a1098e69cd1ff0fd11e0d8b702b06",slug:"nanowires-recent-advances",bookSignature:"Xihong Peng",coverURL:"https://cdn.intechopen.com/books/images_new/3066.jpg",editedByType:"Edited by",editors:[{id:"24647",title:"Prof.",name:"Xihong",surname:"Peng",slug:"xihong-peng",fullName:"Xihong Peng"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7640",title:"Perspective of Carbon Nanotubes",subtitle:null,isOpenForSubmission:!1,hash:"8b85a9957fad5206369eadf0c1ffa27d",slug:"perspective-of-carbon-nanotubes",bookSignature:"Hosam El-Din Saleh and Said Moawad Mohamed El-Sheikh",coverURL:"https://cdn.intechopen.com/books/images_new/7640.jpg",editedByType:"Edited by",editors:[{id:"144691",title:"Prof.",name:"Hosam M.",surname:"Saleh",slug:"hosam-m.-saleh",fullName:"Hosam M. 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Alzheimer’s disease (AD) is one of the major progressive and irreversible neurodegenerative diseases associated with aging [1]. The first case was identified by Dr. Alois Alzheimer in 1901 who presented the clinical and neuropathological characteristics of this disease on November 3, 1906 at the 37th meeting of the Society of Southwest German Psychiatrists in Tübingen, Germany [2]. AD is a progressively degenerative disease that destroys the patient\'s functional capacity and is the primary cause for loss of functional capacity among the elderly in developed countries [3]. AD accounts for 60–80% of all dementia cases, as described in the Organisation for Economic Cooperation and Development (OECD) report. The number of people worldwide living with AD was estimated at between 27 million and 36 million in 2016 [4, 5]. AD symptoms worsen over time at a variable rate; on average; AD patients live between 4 and 8 years after diagnosis, but they could live until 20 years, depending on various factors. Once installed, three main stages of pathological progression of AD have been defined, namely early, middle and late.
\nIn the early stage, a person may have memory lapses, such as forgetting familiar words or names, losing or misplacing a valuable object, or being unable to plan or organize. The middle stage is the longest and can last many years. The person with middle stage AD may confuse words, become easily frustrated or angry, and has increased difficulty expressing thoughts and performing routine tasks. In late stage or severe dementia, the person loses the ability to respond to the environment, to carry on a conversation and, eventually, to control movement; memory and cognitive skills continue to worsen, personality changes may occur and individuals need extensive help with daily activities [5]. According to the age of onset, AD can be classified as: early‐onset or familial AD accounting for only 5–10 % of AD cases, or late‐onset or sporadic AD accounting for the rest of the AD cases. Familial AD is associated with mutations in the genes for presenilin (PS) 1 and 2 and/or amyloid precursor protein (APP); its symptoms appear at 30–50 years of age, whereas the majority of sporadic cases develop after age 65 [6].
\nAD is a multifactorial disease that is a pathologically and etiologically complex. There are a few causative genes which have been linked to the relatively small proportion of patients with early‐onset familial AD [7]. The molecular analysis of families with early‐onset AD has made it possible to identify mutations in genes associated with the disease: APP, PS 1 and PS 2, and the mean onset age is 45. Mutations in Apolipoprotein E ε4 (Apo E ε4) genes are present in 15–20% of AD cases appearing after 65 years of age. Three additional genes.
\nThere are numerous hypotheses to explain the appearance of sporadic AD, such as head trauma, neuroinflammation, poor dietary habits and the lack of exercise, but the cause is still unknown [8, 9]. A possible explanation is that the abundant knowledge of AD biochemistry has not yet been well integrated into the cellular context of brain [10].
\nIn order to elucidate the AD etiology, animal models that have genetic mutations linked to familial AD and show the same disease progression pattern have been developed. These models are either based on: (1) the overexpression of APP and secretases [11, 12]; (2) mutated APP [13, 14]; or (3) the overexpression of human APP (hAPP) together with mutated forms of PS [15]. Notwithstanding these mutations, such mouse models rarely develop neurofibrillary tangles (NFTs). To simulate tau pathology, a microtubule‐associated protein tau (MAPT) mutation associated with frontotemporal dementia is included in the 3xTg‐AD mouse, in which the expression of hAPP and mutated forms of PS and tau are combined [16, 17]. Currently, at least 11 rodent models that exhibit AD characteristics, such as Aβ accumulation, tau pathology, neuronal loss and pathophysiology of glial cells, are being studied [6, 18].
\nFor the AD definition, relevant representative book chapters, journal articles and a web page were selected aiming to first summarize the basics of well‐established knowledge on Alzheimer\'s disease that included its biochemical, neuropathological and physiological features. Then, a literature search with the computerized PubMed data base was conducted in February, 2016 with no limit of date. We used the following search terms: (Malnutrition AND Senescence), (Malnutrition AND Alzheimer), and (Senescence). Then, relevant references cited in papers found via this search were reviewed. Studies were selected if they either provided updated information on the AD basics or regarding the biological mechanisms underlying Alzheimer’s disease. Case studies were excluded. A total of 170 journal articles, four book chapters and a web page were selected.
\nAutopsy studies examining the incidence of neuropathological lesions and clinical symptoms reveal that AD often occurs in conjunction with other pathologies, specifically, vascular and Lewy body dementias. The overlap of pathologies suggests the existence of common pathophysiological mechanisms [19].
\nIn AD brains, many cellular and molecular changes coincide with changes in the proteins and genes implicated. The two primary lesions associated with AD are NFTs and the senile plaques first described by Alois Alzheimer. Graeber and co‐workers explained in 1998 that the tissue sections of cerebral cortex from Auguste D had numerous NFTs and many amyloid plaques, especially in the upper cortical layer of the brain [20]. In this tissue, NFTs can be seen as accumulations of abnormally phosphorylated tau protein within the perikaryal cytoplasm of cortical neurons, and senile plaques consist of a central core of amyloid‐β (Aβ), a 4‐kD peptide, surrounded by abnormally configured neuronal processes or neurites; the neurites are localized similarly in animal models such as the PDAPP first model, which develops plaques and cognitive deficits similar to those in humans [13].
\nThese histopathological features start in the temporal lobe and extend to the Meynert nucleus that projects to the hippocampus and to the frontal, parietal and occipital cortices, all of which have important roles in the control of cognitive functions; gradually, these lesions destroy a person\'s memory and ability to learn, to reason, to communicate and to carry out daily activities [21, 22]. The first histopathological lesion is the intracellular NFT, which consists largely of twisted, hyperphosphorylated filaments of the microtubule‐associated protein tau. The second lesion type is the extracellular plaque of differently sized, small amyloid peptides called Aβ that are derived via sequential proteolytic cleavages of APP [23]. The two types of lesions seem to form independently, with tangles appearing first [24]. Affected regions typically exhibit synaptic and neuronal loss, with cholinergic and glutamatergic neurons being the most affected [25], as well as inflammation, gliosis, oxidative stress and neuronal dystrophy [8].
\nNew technologies based on structural and functional neuroimaging and on the biochemical analysis of cerebrospinal fluid have established interesting correlates of intracerebral amyloidosis in individuals with mild, pre‐dementia symptoms.
\nWhole brain volume changes are used as surrogate markers for AD neuropathology in clinical studies; the extent to which these changes can be attributed to pathological features of AD in the aging brain may be established using other signs of brain atrophy in patients showing cognitive impairment [26]. The relationship between pathology and brain atrophy is not simple and linear; neither is the distinction between normal aging and the disease, which is a complicated issue. Aging, dementia diagnosis and AD pathologies closely correlate with enlargement of the brain ventricles but not with reduced total brain volume. Ventricle enlargement may be a response to various conditions and reflect changes in both white and gray matter of the brain, and may be related to cerebrovascular disease and AD. Clinically, brain atrophy in AD patients precedes symptoms. Researchers have proposed using brain atrophy as a surrogate marker for pathology in clinical trials and longitudinal studies. For example, decreased hippocampal volume is considered an acceptable marker in people with mild cognitive impairment (MCI) and at early stages of AD.
\nIt is well established that AD leads to nerve cell death and tissue loss throughout the brain. As more neurons die, more brain regions are affected and over time, the brain shrinks dramatically leading to functional impairment. The atrophy pattern involves white matter and largely spares the isocortex and hippocampus, which is different from that reported in AD patients [27]. The atrophy of the medial temporal lobe, including the entorhinal cortex, amygdala and hippocampus, is closely related to impairment for forming new memories. The hippocampus in AD patients may lose 3–4% of its volume in a year, whereas average loss in a normal brain is less than 1%. Thus, these hippocampal alterations are one of the best‐established signs of AD. Furthermore, the hippocampus is more susceptible to reduced blood flow, which occurs in cortical amyloid angiopathy.
\nSome studies evaluating brain atrophy in the transgenic PDAPP mouse model found a reduction in hippocampal volume and severe atrophy or agenesis of fiber tracts, fornix and corpus callosum [28–30]. ApoE ε4 is associated with increased risk of sporadic AD and of conversion from mild cognitive impairment to AD. ApoE ε4 also plays an important role in brain atrophy and memory impairment by modulating amyloid production and deposition [31].
\nMicroglia is the innate immune cell in the brain that, as a result of brain injury like infection or traumatic injury, produces cytokines and may remain primed in a state where a second stimulus produces an exaggerated activation (hyper‐reactivity). This response may be triggered by traumatic brain injury, infection or aging [32, 33], which are risk factors for developing AD. Hyper‐activated microglia is importantly involved in this process [33–35].
\nExtracellular accumulation of Aβ protein and intracellular accumulation of tau in brain tissues have been described in animal models of AD, as well as in some mechanical stress‐based diseases with different mechanisms, such as traumatic brain injury, arterial hypertension and normal pressure hydrocephalus.
\nNumerous studies dealing with AD have shown evidence for synaptic dysfunction, which correlates with cognitive decline along with an abundance of plaques or tangles [36]. Synapse abnormalities in AD brain tissue were first described by Gonatas and colleagues [37]. Quantitative ultrastructural and immunohistochemical
Dysfunction of synaptic communication in cortical and hippocampal networks has been suggested as one of the neuropathological hallmarks of the early stages of AD and has been increasingly referred to as a “synaptopathy”, in which the soluble oligomeric Aβ peptide plays a pivotal role in disrupting synaptic function and, thus, in neuronal network activity [42, 43]. In addition, high levels of soluble Aβ oligomers show a strong correlation with synaptic dysfunction, which contributes to neurodegeneration. This reflects the loss or damage to synapses that occurs as the disease progresses, which in turn produces functional degeneration of specific neuronal circuits and consequent aberrant activity in neural networks; however, the exact mechanisms are still unknown. One possibility is the immediate‐early gene Arc/Arg3.1 (early‐expression activity‐regulated cytoskeletal gene, here referred to as Arc), one of the genes known to be vital for memory consolidation and synaptic plasticity. Also, the mapping of Arc expression patterns in brain networks has been extensively used as a marker of memory‐relevant neuronal activity history. A recent study by Morin et al. proposes that in 3xTg‐AD mice, intraneuronal Aβ expression in the hippocampus could increase unspecific neuronal activation and subsequent Arc protein expression, which might impair further memory‐stabilizing processes [44]. Understanding the link between intracellular Aβ and Arc/Arg3.1 protein function should help disentangle the molecular and cellular mechanisms underlying episodic memory deficits during the early phases of AD and could clarify the role of disrupted hippocampal excitability in memory retrieval deficits occurring in early‐stage AD‐like pathology.
\nActivated Arc/Arg3.1 is targeted to the post‐synaptic density of synaptically active dendritic spines where it associates with polysomes. Arc interacts with endophilin 2/3 and dynamin, contributing to α‐amino‐3‐hydroxyl‐5‐methyl‐4‐isoxazole‐propionate (AMPA) type glutamate receptor (AMPAR) modulation by enhancing receptor endocytosis. The Arc‐endosome also traffics APP and physically associates with PS 1, thereby increasing the amount of activity‐dependent Aβ [45]. This may be a positive feedback mechanism in which removal of the AMPAR from the synapse will produce a significant loss of dendritic spines and synaptic activity, resulting in synaptic failure similar to that observed in AD. Activity of the
The APP is a type 1 transmembrane glycoprotein of 110–130 kDa, one of the most abundant proteins in the central nervous system (CNS), and is cut by α‐secretase within the sequence of amino acids that comprise the Aβ peptide, precluding formation of amyloid peptides [49]. In the amyloidogenic pathway, APP is cleaved instead by β‐secretase, releasing a smaller N‐terminal fragment (sAPPβ) and a longer C‐terminal fragment (C99) that contains the full amyloidogenic sequence of amino acids. A further cleavage of APP by γ‐secretase yields the Aβ peptide. In brain, there is an equilibrium between Aβ peptide production and its clearance [50]. How Aβ is removed from the brain is not entirely clear, but is mediated by two proteins: apolipoprotein E (APOE) and the insulin‐degrading enzyme (IDE) that may inhibit its aggregation [51]. Disadvantageous genetic polymorphisms (such as the ε4 allele of APOE) and pathological conditions related to abnormal IDE homeostasis (e.g., diabetes mellitus) that may favor the amyloidogenic cleavage of APP and/or decrease Aβ clearance from the brain will therefore facilitate Aβ accumulation in neural tissues and the downstream effects of the amyloid cascade [52].
\nAβ is produced by endoproteolysis, post‐translational processing of the amyloid precursor protein (APP), which is achieved by the sequential cleavage of APP by groups of enzymes or enzyme complexes termed α‐, β‐ and γ‐secretases [53]. The first transgenic mouse (PDAPP) model that developed amyloid plaque pathology was generated by Games and colleagues to express human APP containing mutations associated with early‐onset AD; results obtained in these mice support a primary role for APP/Aβ in the genesis of AD and show they could provide a preclinical model for testing therapeutic drugs [13]. Since then, other mouse models have been created that recapitulate all aspects of AD including processing of the APP. However, not all APP transgenic mice have cognitive impairment, cellular loss and other AD characteristics, and they fail to replicate the full human disease. Some models actually confirm that the reduction of Aβ is insufficient to rescue memory function once downstream processes are underway. Conversely, other studies in mice predict that immunization against Abfix might prevent cognitive decline if administered early enough [54]. Also, Schenk et al. [55] studied transgenic mouse models and reported that their active immunization alleviated the burden of amyloid plaque, suggesting a potential therapeutic strategy [56].
\nBrain injury is reported to accelerate Aβ deposition and exacerbate Alzheimer’s disease associated with impairment of cognition prior to the emergence of Aβ plaques. However, the relationships between Aβ levels (Aβ 40, A β42, or the ratio of Aβ 42 to Aβ 40), gender, age and cognitive function were measured in five mouse models (Tg2576, APP, PS 1, APP(OSK)‐Tg, 3xTg‐AD), see reference [57]. They used behavior tests such as escape latency times in the Morris water maze or exploratory preference percentage in the novel object recognition test. Tg2576 mice, overexpressing human APP695 concentration six times greater than that of normal mouse APP levels, show higher levels of Aβ40 and Aβ42 and Aβ deposits that begin at 9 months of age [58]. The APP models express hAPPSw and APP751 isoforms under the control of the murine Thy1 promoter. As a result, this mouse exhibits levels of human APP seven times greater than that of wild‐type mice, and its Aβ plaques begin at 6 months of age. The APP(OSK)‐Tg mouse expresses APP harboring the Osaka (E693) mutation, and it exhibits intraneuronal Aβ oligomers and memory impairment from 8 months of age. The PS 1 model expresses human PS with the mutation M146L or M146V via the PDGF‐β promoter and higher levels of endogenous mouse Aβ1‐42/43 [59]. The 3xTg‐AD, triple‐transgenic model exhibits both Aβ and tau pathologies and mimics human AD [60]. Thus, the possible role of Aβ in AD cognitive decline needs to be further investigated, fueled by other possible hypotheses and explanations [57].
\nGenetic association studies reveal that several genes such as ApoE are associated with multiple age‐related disorders, indicating that these genes could play a crucial role in their causation. The e4 allele of the apolipoprotein E (ApoE) gene is the best‐known genetic risk factor for AD, because it has been suggested to affect both Aβ and NFT pathology in AD. ApoE is a 34‐kDa lipid‐binding protein that functions in the transport of triglycerides and cholesterol in multiple tissues by interacting with lipoprotein receptors on target cells; these functions are particularly critical for the central nervous system where ApoE transport of cholesterol is important for the maintenance of myelin and neuronal membranes [60]. Polymorphism of the ApoE gene has been implicated in many chronic cardiovascular (myocardial infarction, hypertension, coronary heart) and neuronal diseases. The ApoE ε4 genotype not only is a risk factor for cardiovascular disease but also it combines synergistically with age, atherosclerosis, peripheral vascular disease or type‐2 diabetes to increase the risk of AD [62–66].
\nThe ApoE gene is expressed most highly in the liver and brain; genome‐wide association studies have confirmed the ε4 allele of ApoE as the strongest genetic risk factor for AD [67, 68], because over 60% of persons with AD harbor at least one ApoE‐ε4 allele, and recent data indicate complex interactions between age, ApoE genotype and gender [61]. In reference [69], Dowell et al. used NMR to study two age groups: a young group (average age, 21 years) and a mid‐age group (average age, 50 years); they reported that there are regional white matter brain volume and cortical thickness differences between genotype groups at each age. They raised the possibility that an over‐engagement with these regions by e4+ individuals in youth may have a neurogenic effect that is observable later in life. According to a genome‐wide association study of cerebrospinal fluid (CSF) from AD subjects, several single nucleotide polymorphisms (SNPs) in the ApoE gene region of the brain were also associated with phosphorylated tau (p tau) elevated levels in the CSF. When cerebrospinal fluid levels of Aβ 1–42 were analyzed together with tau/p tau, a significant correlation was found with SNPs of the ApoE gene. ApoE is also a crucial regulator of the innate immune system, which promotes pro‐inflammatory responses that could exacerbate AD pathogenesis [70].
\nIn 2002, Colton et al. demonstrated that ApoE regulates the production of nitric oxide (NO), a critical cytoactive factor released by active macrophages. Thus, due to greater NO production, ApoE4 carriers characteristically have high levels of oxidative/nitrosative stress and a higher incidence of AD, a mechanism that explains the genetic association between ApoE4 and human diseases [71].
\nBesides the accumulation of soluble and toxic Aβ‐aggregates, tau accumulation causes oxidative stress and mitochondrial dysfunction, and it is linked to the initiation of the tau cascade. The tauopathies are a group of degenerative diseases with histopathology characterized by filamentary inclusions composed of tau protein in neurons (NFT pathology). These are abundant in many neurodegenerative diseases, including AD, Pick\'s disease, argyrophilic grain disease and frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP‐17) [72]. In AD, the presence of neurofibrillary tangles (NFT) composed of tau is prominent, and their density correlates with neuronal loss and clinical severity [72, 74]. Dystrophic neurites are all sites of accumulation of pathological paired helical filaments (PHFs) that appear to be central to neurofibrillary degeneration of neuropathology and that contain (the microtubule‐associated protein) tau as an integral structural component [75–78]. Also, tau processing in AD, leading to the formation of paired helical filaments, is driven by aggregation and polymerization, and appears to be associated with abnormal phosphorylation and truncation processes [79]. Mouse models expressing the P301L mutation causing neurofibrillary degeneration have been generated to study neurofibrillary pathologies [80]; and this mutation facilitates the development in transgenic mice of tauopathies [81–83] that recapitulate human tauopathies [83]; these mice provided the opportunity to test experimentally whether the distribution or timing of neurofibrillary pathology is influenced by the pathogenic mutations that cause AD. However, the physiology of tau protein is different in adult mice and humans; because mouse brain contains only isoforms like 4R, while in normal adult human there is a balance between 3R and 4R isoforms [85].
\nThere is a clear link between type 2 diabetes mellitus and AD, and the use of antidiabetic drugs such as metformin has been proposed as a potential therapy for AD. There is also experimental evidence that metformin may have beneficial effects on cognition [86]. However, it remains unknown whether, in the absence of insulin resistance or diabetes, chronic treatment with metformin ameliorates tau pathology and behavioral performance in a transgenic model of neurodegenerative tauopathy
In order to elucidate the molecular mechanisms underlying the post‐translational modifications of Aβ and tau, several transgenic mouse models have been developed. One of these models is the 3xTg‐AD transgenic mouse, carrying three transgenes encoding the APPSWE, S1M146V and TauP301L proteins. Ontiveros‐Torres et al. reported the hippocampal accumulation of fibrillar Aβ as a function of age and hyperphosphorylation patterns of TauP301L at both its N‐ and C‐termini: the expression of activated protein kinases and mediators of inflammation was monitored from 3 to 28 months as well. These authors reported that the accumulation of Aβ oligomers results in an inflammatory environment that upregulates kinases involved in hyperphosphorylation of the TauP301L polypeptide. The 3xTg‐AD mouse is an excellent model for further studying pathological modifications of key factors in AD [88].
\nToday, an increasing number of epidemiological, clinical and experimental studies suggest an association between toxicant and drug exposure during the perinatal period and the development of metabolic‐related diseases and neurotoxicity later in life. A study called ‘The developmental origins of health and adult disease’ (DOHaD) addressed fundamental issues in the emerging areas of lifetime neurotoxicity testing, differential vulnerable periods of exposure, non‐monotonic dose‐response effects and neurotoxic risk assessment. Neurotoxicity during central nervous system development results in permanent changes.
\nThe DOHaD hypothesis proposes an association of early fetal environment with adult size, later ischemic heart disease, hypertension, metabolism, diabetes and insulin resistance, which are risk factors for dementia, obesity and deficits in behavior and learning [89–91]. Aβ‐derived diffusible ligands (ADDL) also contribute to insulin deficits and insulin resistance in the brain of AD patients, and ADDL levels can be used to diagnose AD [92].
\nThe brain of patients with AD has deficits in cerebral glucose utilization due to insulin/IGF resistance associated with increased oxidative stress, DNA damage, reactive oxygen species and mitochondrial dysfunction. The consequences of insulin and IGF resistance in the brain compromise neuronal survival, energy production, gene expression, and cerebral plasticity [93]. Thus, inhibition of insulin/IGF signaling mediates AD neurodegeneration by an increase in activity of kinases which phosphorylate tau; accumulation of AβPP – Aβ; mitochondrial dysfunction; generation of reactive oxygen and nitrogen species, oxidative and endoplasmic reticulum stress, and signaling through pro‐inflammatory and pro‐apoptotic cascades [93, 94].
\nSince Hoyer [95] proposed that the deficits in cerebral glucose utilization and energy metabolism worsen with progression in cognitive impairment. In addition, Steen et al. proposed that chronic deficits in insulin signaling mediate the pathogenesis of AD [96]. Additionally, AD could be regarded as a brain disorder that has composite features of type 1 (insulin deficiency) and type 2 (insulin resistance) diabetes. Thus, AD could be referred to as “type 3 diabetes”, because both molecular and biochemical consequence overlap with type 1 and type 2 diabetes [94, 97]. Recently, experimental studies consider that glucose hypometabolism is an early and persistent sign of AD because brains present features of impaired insulin signaling, a model using intracerebroventricular streptozotocin injections (icv STZ model) to generate sporadic AD that emulates the AD characteristics of Aβ deposits on the wall of meningeal and cortical blood vessels, mitochondrial abnormalities and oxidative stress [98].
\nA major risk factor in patients who progress to dementia is aging, which is characterized by defects in energy metabolism and mitochondrial function. Mitochondrial dysfunction is a hallmark of aging, and it plays a central role not only in Alzheimer’s but also in Parkinson\'s disease [99]; it causes the accumulation of soluble and toxic Aβ‐aggregates and oxidative stress, and it is linked to the initiation of the tau cascade. In addition, signaling from the nucleus to mitochondria may be crucial for the regulation of mitochondrial function and aging, possibly contributing to the development of age‐associated diseases such as AD. Mitochondria not only play a central role in metabolic pathways, they also regulate cell fate through crosstalk between autophagy and apoptosis. Macroautophagy (autophagy) and apoptosis are intimately interconnected and determine whether cells survive or die [100].
\nOn the other hand, genes define a baseline mitochondrial function, where maternal mtDNA contributes more, and environmental factors determine the rate of mitochondrial function, with less durability producing faster brain aging. Mitochondrial function influences AD, APP expression and processing and Aß accumulation [101, 102]. Also in familiar AD (FAD), the impaired mitochondrial function is caused by PS (either PS 1 or PS 2) mutations, but about 10% are inherited, most of the cases are sporadic AD (SAD). Both FAD and SAD share the features of accumulated extra and intracellular Aβ plaques, as well as intracellular NFTs and cell atrophy and cell death, suggesting a common pathogenic origin on the basis of the intracellular Ca2+‐homeostasis disruption tested in a mutant PS with a mitochondrial dysfunction with potential cell death [103]. Xie et al. used APP/PS1 transgenic mice to study the temporal relationship among Aβ plaque deposition, oxidative stress, and cell death, identified Aβ as the mediator of oxidative stress and subsequent neurodegeneration. Oxidative stress began in neurites and was followed by the appearance of Aβ plaques in the surrounding tissue ultimately leading to oxidation in neuronal soma, but the oxidized neurites survived for several weeks. The oxidation in neuronal soma was associated with caspase‐dependent apoptosis [104]. In addition, intermediate cellular players, including astrocytes or microglia, responded to amyloid deposits with chemokine or cytokine signaling which, in turn, led to oxidation in neurites.
\nThe Glutamate (Glu) and mitochondria have a relationship in oxidative stress that underlies AD; Glu is an important neurotransmitter in neurons and glial cells, and is strongly dependent on calcium homeostasis and mitochondrial function [105]. Mitochondrial deficits occur early in AD, even before plaque formation [106]. Decreased expression of cytochrome c oxidase (COX) and pyruvate dehydrogenase (PDH) has also been detected in postmortem brain tissue of patients with AD, as well as in animal models. Substances used to maintain brain metabolism in the 3xTg‐AD mouse model, such as icariin active component of the traditional Chinese herbal medicine
Genetic and environmental factors are particularly important for the sporadic form of AD. Diets rich in saturated fatty acids and alcohol but deficient in antioxidants and vitamins appear to promote the onset of the disease. In contrast, diets rich in antioxidants, vitamins B6, B12 and folate, unsaturated fatty acids, and fish suppress its onset [108]. During the last decade, many investigations have shown metabolic disturbances (obesity and metabolic syndrome) to be risk factors for the development of dementias and even AD [109]. Obesity is related to vascular diseases, and there is increasing evidence linking vascular risk factors to dementia and AD [109]. Instead of exploring the effect of its subcomponents, several studies have assessed the relationship between metabolic syndrome as a whole and the risk of AD or cognitive decline [111–113]. The cellular mechanisms involved in the AD associated with metabolic alterations are now becoming more understandable. It is well known that an optimal supply of nutrients is necessary to maintain normal functioning of the brain. Thus, the impact of poor nutrition (overweight, obesity) on the development of AD and the importance of good nutrition as a preventive strategy to reduce the incidence of dementias and AD are clear.
\nMalnutrition is associated with increased morbidity and mortality in patients with AD, with sleep disturbances, psychological problems, immobility, falls and increased hospitalization risk [114]. Normal human aging is also associated with vitamin deficiencies. One study in an Alzheimer transgenic mouse (VCT2+/‐APP/PSEN1) found decreased ascorbic acid and increased oxidative stress in the brain as well as for Alzheimer’s disease [115].
\nAntioxidant nutrients may help to protect these affected brain regions. Plasma vitamin C levels are lower in subjects with dementia compared to controls, supporting the free radical theory of oxidative neuronal damage [116]. Despite years of scientific, medical and clinical advances in this area, much work remains to discover specific nutritional interventions for the prevention of AD. Promising agents such as vitamins, energy substrates, flavonoids, lipids and modified diets functioning as antioxidants, metabolic enhancers, immune modulators and direct disease‐modifying agents await further investigation [117].
\nIt is well known that adequate nutrition is an important factor in order to maintain cognitive function, particularly during aging. Malnutrition is among the risk factors for developing mild cognitive impairment and AD in which a cognitive decline is correlated with synaptic loss. The synapses are part of the neuronal membrane and are continuously being remodeled; therefore, ensuring the availability of sufficient levels of nutritional precursors (i.e., uridine monophosphate, choline and omega‐3 fatty acids) to make the phospholipids required to build neuronal membranes may reduce synaptic degeneration in AD. Also, B‐vitamins, phospholipids and other micronutrients act as cofactors to enhance the supply of precursors required to make neuronal membranes and synapses. Vitamin D has a role in brain physiology as well, for instance, by promoting neurotransmission, neurogenesis, synaptogenesis, amyloid clearance and preventing neuronal death [118].
\nUndernutrition during early life results in deficits in the spatial learning capacity of the animals [118], as shown by a wide variety of behavioral tests, and it is known to cause changes in the developing brain that affect the morphology, particularly in the granule cells of the dentate gyrus [120–122]. Prenatal malnutrition and chronic malnutrition in the aged rats cause abnormal mitochondrial, swollen Golgi membrane system, increase in multivesicular bodies and lypofuscine density in neurons of the hippocampus [123]. Since the mitochondrion is responsible for the production of ATP, its dysfunction induces a senescence response [124]. Furthermore, mitochondrial autophagocytosis is believed to be a major contributor to lipofuscin formation [125]. Autophagocytosis of mitochondria is also prominent in AD, because the accumulated autophagic vacuoles in dystrophic neurites contribute to the local production of Aβ within plaques, and the generalized increase in autophagy in the neuropil could be a significant source of Aβ overproduction in the AD brain. Thus, a link between mitochondrial dysfunction/oxidative stress and autophagy has been reported to occur in AD [126]. In addition, lipofuscin can be used as a biomarker to detect senescence [127], since it is one of the “age pigments”, autofluorescent cell products from lysosomes that diverge in number and size among brain regions.
\nThe increase in lipid components is possibly due to modifications in neuronal metabolism with age [128]. In Ref. [129], Giacone et al. proposed the “lipofuscin hypothesis of AD”, in which the first step in the genesis of senile plaques is the release of lipofuscin free into the neuropil, where it cannot be rapidly degraded due to its biochemical characteristics. Therefore, the lipofuscin may persist in the extracellular milieu, giving rise to a focal impairment that can initiate the senile plaque and serving as a source of Aβ oligomers for a prolonged period of time. This idea is supported by the hydrophobic and insoluble characteristics of lipofuscin, which mimic those of substances that are the most effective in inducing an innate immune response [130]; the rate of lipofuscin formation is also closely related to oxidative stress [131].
\nCellular senescence is a terminal phase of mitotic cells characterized by permanent cell‐cycle arrest; it can be induced by a variety of stressors, including reactive oxygen species. One hypothesis is that senescent cells contribute to aging by altering cells and its secretory phenotype, as well as to the development of age‐associated diseases such as AD [132].
\nIt has been suggested that neuroinflammation, mediated by the brain’s innate immune system, contributes to AD neuropathology and exacerbates the course of the disease. Some studies found that a systemic immune challenge during late gestation predisposes mice to develop AD‐like neuropathology during aging when there are elevated levels of inflammatory cytokines and hippocampal amyloid precursor protein (APP), altered tau phosphorylation and missorting to somatodendritic compartments. All these effects produced significant impairments in working memory in old age [34]. Also, AD and brain aging share common molecular changes, and AD could be a form of accelerated brain aging. In addition, in AD senescent mechanisms are present in all cells, including glia and neurons. Evidence indicates that vascular impairment is a fundamental contributor to AD pathology, and platelets are generally considered a key element because they represent the link between Aβ deposition, peripheral inflammation and endothelial senescence. AD is superimposed onto the normal process of aging and one important facet of aging is the accumulation of senescent cells that lose the ability to proliferate, and also release cytokines and proteases, collectively known as the senescence‐associated secretory phenotype, which contribute to the chronic inflammatory environment seen in the old age [133]. In brain, astrocytes clearly play a role in modulating neuronal function and survival in health but in disease are senescent [134]. Also, human astrocyte lines expressing the toxic form of Aβ rapidly reached a senescent state in vitro [135].
\nIn the other hand, observations suggest that chronic systemic inflammation induces in middle‐aged rats intense neuroinflammation evoked by senescent‐type microglia and may contribute to the initiation and progression of AD, resulting in cognitive impairment. Also, with chronic inflammatory bone disorders, pro‐inflammatory blood cells and bacterial components including lipopolysaccharides (LPS), activate the receptors localized on the surface of leptomeningeal cells, which in turn activate brain‐resident microglia to evoke neuroinflammation [136]. Furthermore, the maternal immune response predisposes the offspring to develop neuropsychiatric disorders and can prime microglia cells to produce high levels of cytokines with a second stimulus [137]. Prenatal immune activation of offspring changes the integrity of the gastrointestinal barrier [138], which probably increases exposure to antigens with pathogen‐associated molecular patterns, such as LPS. Exposure to Poly (I:C) on the late gestational day can alter cognitive performance in the adult or aged animals [34, 139]. High‐fat diets can also cause metabolic endotoxemia (an increased LPS concentration in plasma from microbiota in the gut) with a pro‐inflammatory response [140]. This gut microbiota LPS accelerates aging, with an increase in the concentration of pro‐inflammatory cytokines and of protein 16 (p16), which is a senescence biomarker in the colon [141]. The senescent cells produce chemokines, cytokines, growth and differentiation factors and matrix‐remodeling enzymes, collectively known as the senescence‐associated secretory phenotype [142, 143], which can contribute to tissue dysfunction [142] as Alzheimer\'s diseases [144]. The possible mechanism is that chronic systemic inflammatory challenges induce differential age‐dependent microglial responses. Microglia are the resident immune cells in the brain, providing its first line of defense and initiating the release of pro‐inflammatory mediators to trigger neuroinflammation in response to autoimmune injury, infection, ischemia, toxic insults and trauma. They recognize a broad spectrum of molecular targets, such as glycolipids, lipoproteins, nucleotides, abnormally processed peptides, modified or aggregated proteins (i.e., Aβ), inflammatory cytokines, and damaged neurons, which are the strongest inducers of microglia activation [145]. In Ref. [99], Wu et al. propose a strong relationship between nutrients, microglia, aging and brain based on the concept of “microglia ageing.” This concept considers microglia as the key contributor to the acceleration of cognitive decline, which is the major sign of brain aging. Senescent microglia display morphological changes: fewer and shorter processes, increased soma volume, and formation of spheroid swellings, collectively referred to as “dystrophic microglia.” Furthermore, inflammation induces oxidative stress and DNA damage, leading to the overproduction of reactive oxygen species, including macrophages and microglia and promoting aging. Therefore, providing early treatment of inflammatory disorders and controlling microglia aging, may delay the onset and limit the severity and/or progression of AD [136].
\nAnimal models are used to test changes in microglia. For example, in adult APP/PS1 mice, exercise enhances memory test performance and is associated with increased numbers of cholinergic and serotoninergic neurons, and reduced Aβ levels and microglia activation [146]. Dietary restriction also appears to attenuate age‐related activation of microglia, resulting in beneficial effects on neurodegeneration and cognitive decline [147]. Dietary restriction suppresses LPS‐induced secretion of inflammatory cytokines, and shifts hypothalamic signaling pathways to an anti‐inflammatory bias [148].
\nThe study of the aging organism allowed selection of a group of neurodegenerative diseases which have a similar mechanism of pathogenesis, including the pathological processes of protein aggregation and deposition in nerve tissue. The AD pathogenesis in β‐amyloidopathy is a manifestation of proteinopathy leading to cytotoxicity, neurodegeneration and the development of pathological apoptosis activated by the formation of intracellular Aβ [166].
\nProteinopathy‐induced cell senescence is caused by the accumulation of misfolded proteins and activation of the innate immune system, with the production of pro‐inflammatory cytokines, chemokines and oxidative stress that trigger chronic inflammation and ultimately, senescence. Components of SASP and proteinopathy can induces more senescent cells. These cells are resistant to apoptosis, but can die by autophagy. Senescent cells can be the link between Aß and secondary proteinopathies such as tau, α‐synuclein and TDP‐43 [149]. Indirect evidence that infection could be a cause of AD has been reported, and it was suggested that invasion by a virus could cause activation of microglia and pericytes and ultimately, amyloid deposition [150].
\nSystemic infections and persistent neuroinflammation are risk factors for developing AD [151]. Mice injected on gestational day 17 with poly I:C (a mimic of virus exposure) show, at 15 months, an increase in APP and its proteolytic fragments, hyperphosphorylation of tau without NFTs and the absence of significant Aβ accumulation, but these parameters have not yet been determined in aged mice [34]. Indirect evidence that infection could be a cause of AD has been reported by Wisniewski et al., who suggested that invasion by a virus could cause activation of microglia and pericytes and ultimately, amyloid deposition [152].
\nThe infectious hypothesis is suggested by the altered blood‐brain barrier and the activation of neuroinflammation in the brain, which could decrease Aß peptide clearance. For example, infection by
The amyloid cascade hypothesis postulates that memory deficits are caused by increased brain levels of Aβ peptide, which are derived from the larger amyloid precursor protein (APP) by sequential proteolytic processing [154]. This hypothesis is a neuron‐centric, linear and quantitative model postulating direct cause and consequences in a cascade initiated by Abfix deposition and leading progressively to Tau pathology, synaptic dysfunction, inflammation, neuronal loss and ultimately, to dementia. Earlier AD mouse models have generated a wealth of information that has significantly improved our knowledge about AD; however, the amyloid cascade hypothesis remains controversial, because the majority of these models are based on transgenic overexpression of APP in combinations with different familial AD‐associated mutations in APP or PS 1. Overexpression of APP generates elevated Aβ levels to mimic the Aβ amyloidosis of AD brains, but concomitant with this it produces non‐physiological effects and a number of undesirable side effects. One strategy is to introduce mutations into the mouse APP gene and new models (APPNL‐F and APPNLG‐F) that develop robust Aβ amyloidosis, which induces synaptic degeneration and memory impairments [155].
\nThe quantitative aspects of the hypothesis imply that reducing the number of Aβ‐plaques or the concentration of Aβ‐oligomers should be sufficient to halt progression of AD. Thus, a minor increase in the Aβ42:Aβ40 ratio stabilizes toxic oligomeric species with intermediate conformations. The toxic impact of these Abfix species on the synapse but can spread into cells, producing neuronal death; Kuperstein et al. [156], suggest that there is a dynamic equilibrium between toxic and non‐toxic intermediates.
\nIn addition, it is well known that diffusible Aβ oligomers are the major toxic agents in AD, and both monomers and oligomers are important for the early diagnosis of dementia because they are potential predictors for the progression of AD and are useful to evaluate new drugs against AD [157, 158].
\nA quarter to a third of older people has amyloid burdens without symptoms of dementia [159]. Various APP transgenic mice do not have all the characteristics of AD: they exhibit little or no neuron loss and not all of them develop cognitive impairments, even if for three‐quarters of their lives they have deposits of amyloid, suggesting that Aβ alone is not sufficient. Thus, they are a model of asymptomatic AD [159, 160].
\nAD investigations have been conducted traditionally by studying human brains (autopsy) or by producing specific brain lesions in mice. The generation of animal models is particularly relevant, because they have been designed to test neurodegeneration with characteristics similar to those in the human brain, allowing us to design new therapeutic approaches. These models are key tools for in‐depth studies of neurodegenerative diseases like AD.
\nMany studies of AD are based on experimental models in mice since their genome is nearly 99% homologous with human [161]. Transgenic mouse models recapitulate the major hallmarks of AD and have been utilized since the early 1990s to explore in detail mechanisms underlying the disease pathology; they have provided excellent opportunities to analyze the bases for the temporal evolution of AD brains and to delineate the basic mechanisms that cause cellular dysfunction.
\nAt present, there are many transgenic mouse and knockout models to analyze certain aspects of AD pathology, allowing the exploration of uncharted territories; they have revealed new pathogenic possibilities, many of which have not yet been demonstrated in humans. On the other hand, some discrepancies between the data obtained in the mice and in man remain unexplained [162]. Mice lack certain important aspects of AD; for example, age is an important factor in AD, but these animals have a short life, between 2 and 4 years. Also, the amyloid protein in mice, derived from proteolysis of the APP precursor, is different from that in human [163]. In spite of that, diverse studies in this mouse model showed the presence of soluble Aβ oligomers at prefibrillar stages that can act as toxic ligands at postsynaptic compartments, driving the synaptic in neuronal populations localized in similar areas to those affected in the human pathology with memory alterations. They have also been instrumental in validating dug targets in special cerebral areas to control memory.
\nThe triple transgenic (3xTg‐AD) mouse, which develops pathologies associated with AD, was created in 2003 (Figure 1). To produce this model, Oddo’s team simultaneously microinjected two genes (APP and tau) into single‐cell PS1M146V mouse embryos (transgenic mice that overexpress human or wild‐type APP, and are hybrids from the 129/C57BL6 strain). These mice develop both amyloid plaques and NFT‐like pathology in a progressive and age‐dependent manner associated with anatomical and temporal analogously to that observed in the human AD brain [16]. In this 3xTg‐AD, Aβ deposits initiate in the cortex and progress to the hippocampus with aging (Figure 2). Amyloid accumulation is localized in the basal neocortex as well as in entorhinal areas, but this accumulation can also expand into the hippocampus. The conformational or hyperphosphorylation changes characteristic of tau pathology occur particularly in pyramidal neurons of the hippocampal CA1 subfield and in cortical structures (Figure 3) and evolve in the AD brain [164].
Triple transgenic mouse (3xTg‐AD).
Photomicrographs of the amyloid beta in triple transgenic mouse in the cerebral cortex of 11‐month‐old female showing the staining for amyloid beta aggregates mice stained by immunohistochemistry using a BAM‐10 antibody.
Photomicrographs of the cerebral cortex of an 11‐month‐old female mouse stained by immunohistochemistry using 499 tau antibody, showing the presence of human tau protein in two magnifications.
Another characteristic of the 3xTg‐AD mouse is that the brain regions severely affected, including the hippocampus, entorhinal cortex, amygdala, neocortex, and some subcortical areas such as basal forebrain where the acetylcholine (Ach) neurotransmitter is altered in the brains of individuals with mild AD due to low choline acetyltransferase (ChAT) activity [165–167].
\nThe 3xTg‐AD mouse has fewer ChAT‐immunopositive neurons in the Meynert nucleus (primary source of cholinergic neurons), as well as a reduced density of ChAT‐positive cholinergic fibers projecting to the primary motor cortex and the CA1 area of the hippocampus [168]. These cognitive dysfunctions are caused by massive loss of cholinergic neurons in the anterior basal brain, the area most vulnerable to the development of the pathological characteristics associated with AD. Alterations in cholinergic neurotransmission in the patients’ neocortex and hippocampus are associated with the early stages of memory loss [168]. We also found a 50% reduction in nest‐building quality (a task controlled by the hippocampus), associated with a significant increase in damaged neurons in the CA1 hippocampal area (26%) compared to wild‐type mice [170]. The decreased ability to carry out activities of daily living (humans) or to perform nest building correctly (3xTg‐AD mice) are behavioral symptoms that can be studied and related to anatomical and morphological signs in the complex Alzheimer’s disease syndrome.
\nA variety of animals can serve as experimental models of AD, which are valuable tools for the design of new therapeutic strategies and to explore some other aspects of the disease, as some specimens develop amyloid plaques in their brain and cognitive dysfunctions similar to those of AD. Like humans, dogs develop amyloid plaques in their brains with advancing age, and some specimens suffer sporadic cases of Alzheimer’s disease, age‐related cognitive impairment with loss of short‐term memory or working memory, changes in behavior, irritability, incontinence, and orientation problems [171]. Sarasa cloned and sequenced the canine APP, finding it virtually identical to human APP, including the peptide sequence corresponding to β‐amyloid peptide. They analyzed the presence and distribution of amyloid plaques in the brains of healthy young and old dogs with severe cognitive dysfunction. With specific antibodies against AB40 and AB42, they found that the old demented animals had many amyloid and more mature plaques than older control dogs [163].
\nA nontransgenic rodent
Sparks and Schreurs proposed studying AD in rabbits fed a diet rich in cholesterol and copper. These animals develop amyloid plaques in their brains and deficiencies in learning complex tasks. They exhibit increased immunoreactivity to amyloid β in neurons, the presence of extracellular plaques in the meninges, microgliosis, apoptosis, vascular activation of SOD, rupture of the blood‐brain barrier and elevated brain levels of cholesterol; these data provide strong support for the suggestion that copper is implicated in the accumulation of Abfix [173].
\nAlzheimer\'s disease is of special interest to neuroscientists, not only because it is the most common of the brain degenerations but also because it is a multifactorial disorder of unknown etiology. In addition, recent evidence supports the hypothesis that persistent chronic infections produce increased Aβ (amyloidosis) in brain, and may be mediated by a response of the innate immune system. This hypothesis may give an explanation of the common pathogenic mechanisms and inflammatory gene polymorphisms involved in both AD and type 2 diabetes. In both diseases amyloidosis, that is, the accumulation of insoluble aggregates of fibrillar proteins, occurs in various organs and is often associated with bacterial infections [174]. Thus, the accumulation of intraneuronal amyloid‐β peptide (Aβ) appears to be an early event in AD, suggesting its important role in the neurodegenerative process of AD, because Aβ aggregates, particularly oligomers, may lead to synaptic dysfunction and neuronal loss, which are associated with memory and neural plasticity loss. Transgenic animal models are established to study the pathological role of intracellular Aβ and to screen for drugs against Aβ aggregation and associated toxicity, and they suggest that soluble, nonfibrillar Aβ oligomers may induce synaptic failure early in AD. Despite their undoubted value, the transgenic models rely on genetic manipulations that represent the inherited and familial but not the most abundant, sporadic form of AD [175].
\nThis review poses a historical overview of the pathology of Alzheimer’s disease and provides an up to date of its features. Then, a molecular and histological follow‐up of the proteins most strongly associated with this pathology is delivered. Finally, the diverse molecular and cellular current hypotheses seeking to disentangle the mechanisms of Alzheimer’s disease and supported by research in animal models are analyzed. These models have been extremely useful in elucidating the mechanisms of Alzheimer’s disease, including the numerous factors and conditions that contribute to the pathogenesis, which may have important implications providing new insight for current and future strategies to treat Alzheimer’s disease and to reduce or delay its onset by preventing infection, inflammation and amyloidosis.
\nThe authors would like to thank Azucena Aguilar for technical assistance, genotyping and colony management; special thanks to INB Units (Proteogenomics, Vivarium, Microscopy and Behavior). They also thank Dr. Dorothy Pless for proofreading of this manuscript. This work was supported in part by CONACYT: CB2012/178841, CB‐2015‐01/255399 and DGAPA‐UNAM IN203616 and IN203616 to SDC.
\nThe constant increase in the production of sludge from wastewater treatment plants presents a major environmental problem. Compared to traditional means such as landfill or incineration, agricultural sludge spreading appears to be the most cost-effective option for sludge disposal [1]. The use of sludge in agriculture appears among the most sustainable environmental solutions in their disposal. In fact, sludge potential fertilizer and the high cost of mineral fertilizers promote sludge use in agriculture. Nevertheless, their metallic trace elements content (ETM) presents a real disadvantage in their use. Actually, metallic elements retained by the sludge during wastewater treatment can cause high metallic charges accumulation in soil [2]. Metals can be found in the form of sulphites, oxides, hydroxides, silicates, phosphates, carbonates and insoluble salts. They can also be adsorbed or associated with the organic matter of the sludge. The amount of metals in the sludge depends on the origin of the wastewater and the treatments it has undergone [3, 4]. It is, therefore, necessary to try to understand the mechanisms and factors involved in the transfer of these elements into the soil and their effects on the plant following the addition of sludge. The behavior of heavy metals in soils and their absorption by plants depend on the quality of the sludge, the nature of the metal, the physico-chemical properties of the soils and the plant species. Plants differ in their ability to absorb and accumulate metals [2, 3]. From the perspective of an agricultural recovery of sludge, we have tried to contribute to the study of the impact of sludge on the transfer of metallic trace elements in the sludge-soil–plant system. Therefore, a field experiment was carried out in Oued Souhil (Tunisia). In this context, we propose to study the effect of two types of urban and industrial sludge on the distribution and compartmentalization of metallic trace elements in the different organs of two species (durum wheat and rapeseed) chosen according to their absorption capacity.
The experimental protocol was installed in the field to the Agricultural Experiment Station of Oued Souhil - Nabeul, situated about 60 kilometers from Tunis and belonging to the National Institute for Research in Rural Engineering Water and Forest.
The urban mud used in this study is taken from the wastewater treatment plant in Korba with a treatment system at low load activated sludge followed by maturation. Sludge from this station underwent a stabilization in aerobic followed by drying on beds. The dry sludge is removed from the drying bed.
The industrial mud is provided from wastewater treatment plant Bou Argoub which hosts two big companies, the Tunisian beverage manufacturing company (SFBT) specialized in the food industry, and Assad company specialized in the electrical industry. Sludge from this station underwent a stabilization in aerobic followed by drying on beds. This sludge is loaded with heavy metals especially lead and chromium.
The plant materials that were used in this experiment are the rapeseed (
Experimentation was carried out on two juxtaposed plots reserved for each crop (wheat or rapeseed). For each type of sludge, four doses (5, 25, 50 and 100 t ha−1) were used. Results were compared to a control soil without any treatment.
Sludges were manually dug into the soil. Before utilization, the sludge was analyzed.
The soil was analyzed before the application of sludge and after the harvest. Sampling was conducted between the lines using an auger at four depths (0–10, 10–20, 20–40 and 40–60 cm).
In the laboratory, soil samples were dried in open air and sieved to 2 mm or 0.2 mm depending on the type of analysis required. The main measured parameters were particle size, total calcium, conductivity, carbon, organic matter, total nitrogen and heavy metals concentration. For the particle size, we used the method of the International pipette Robinson, which is essentially based on the destruction of organic matter in the soil using H2O2 and the dispersion of clays by sodium hexametaphosphate. Clays and silts are measured in the suspension of land following the decay time that depends on particle diameter (NF X 31–107). The settling velocity was measured by the formula of Stokes. The Mud and soil samples were analyzed by XRF (X-Ray Fluorescence) and ICP-AES (Inductive Coupled Plasma Atomic Emission Spectrometry Activa–Horiba Jobin Yvon Spectrometer) in the Geosciences and environment Department of National School of Mines in Saint Etienne. The Soil pH was measured by using a 1:2 soil to water ratio. Plant samples were washed with tap water and rinsed three times with distilled water, then separated into leaves, stems and roots, dried at 40°C to constant weight, crushed and sieved at 2 mm. Moreover, the digestion of plant samples was performed using nitric concentrated acid, according to [5, 6, 7, 8]. The plant extracts were analyzed by ICP-AES.
The sowings were performed with 50 seeds m2–1 for rapeseed and 350 seedsm2–1 for wheat. The rapeseed harvest was performed after the formation of slices. We weighed the aerial part and the root. The same work was done to wheat. The samples were subsequently dried and crushed ore to determine the mix of metals in different parts of the plant. The different parts of the plant were dried at 80°C to constant weight and then crushed to a fine powder using a porcelain mortar to prevent metal contamination. Digestion is done at high temperature (70°C) with aqua regia. For histological analysis, preparing the samples carefully for transmission microscopy was essential for obtaining reliable results. Therefore, samples were set at 4°C with a solution of 20.5% glutaraldehyde, pH was maintained at 7.4 with a solution of sodium cacodylate (0.1 M). The samples were then washed with sodium cacodylate buffer (0.1 M) and post-fixed in a solution of 1% osmium tetroxide in veronal buffered (0.1 M) [9]. After several washes in distilled water, the samples were dehydrated with a graded ethanol series of increasing concentrations going from 30 to 100%. The final inclusions were made from a mixture of resin [10]. Only the sections with interference colors are gray or silver, that is to say (thickness of 600 to 900A° (1A° = 0.1 nm)) were collected and deposited on a copper grid with 3 mm diameter. The ultrathin sections were mixed using an alcoholic solution of uranyl acetate and 7 by 1% lead citrate [11]. On top of that, observations were made using a Hitatchi H800 electron microscope.
The data were subjected to analysis of variance. The comparison of means at 5% level of significance was performed by the Newman–Keuls test using the Statistica 7 software.
The amount of heavy metal in sludge is not a good indicator for metal availability for
BCF = Metal content (mg kg−1) in root/metal content (mg kg−1) in sludge (1)
BAF = Mean metal content (mg kg−1) in shoot (root+straw+spike)/metal content (mg kg−1) in sludge (2)
TF = Mean metal Content (mg kg−1) in shoot (root+straw+spike) /metal content (mg kg−1) in root (3)
XRD analyzes have shown that industrial sludge has high levels of chromium and lead. These elements mainly exist as Daubreelite Cr2FeS4, Brezininaite Cr3S4, Wattersite Hg5CrO6, Crocoite PbC2O4, Pheonicochroite Pb2O (CrO4) and lead oxalate PbC2O4. As for urban sludge, we note the absence of chromium and the presence of lead in the form of Macphersonite Pb4 (CO3)2(SO4) and Lanarkite Pb2O (SO4).
The results of the XRD spectrum (Figure 1) were confirmed by those obtained by the chemical and mineralogical analysis (SEM) shown in Table 1. Thus, industrial sludge from BouArgoub has very high levels of chromium, lead and cadmium. These contents are higher than the limit values of the Tunisian standard NT-106, which is not the case of urban sludge of Korba. Both types of sludge are rich in organic matter and nutrients, especially nitrogen and phosphorus.
XRD spectrum of sludge from urban (a) and industrial (b) wastewater treatment plants.
Contents | Industrial sludge | Urban sludge | Tunisian standard |
---|---|---|---|
pH | 6.3 | 6.7 | <6 |
MO % | 57.9 | 66.6 | 50–70% |
N % | 4.3 | 5.2 | 3–9% |
C % | 31.9 | 39.0 | ND |
C/N | 7.5 | 7.4 | 5–12 |
Fe2O3% | 1.02 | 1.88 | ND |
MnO % | 0.03 | 0.02 | <1% |
MgO % | 0.8 | 1.22 | ND |
CaO % | 8.51 | 13.4 | ND |
P2O5% | 2.18 | 3.24 | 4–5% |
Cd mg kg−1 | 11 | 3 | 20 |
Co mg kg−1 | 18 | 28 | ND |
Cu mg kg−1 | 68 | 158 | 1000 |
Fe mg kg−1 | 8300 | 10,700 | ND |
Mn mg kg−1 | 81 | 152 | ND |
Ni mg kg−1 | 49 | 78 | 200 |
Pb mg kg−1 | 577 | 63 | 800 |
Zn mg kg−1 | 360 | 440 | 2000 |
Cr mg kg−1 | 8030 | 155 | 500 |
Chemical contents (mg kg−1) of industrial sewage sludge, urban sewage sludge and Tunisian standard values [12].
According to [13, 14, 15, 16, 17, 18] sludge is a good source of nutrients for plant growth, it can improve the physical properties of the soil. Vlamis et al. [19, 20] reported that sludge can replace mineral fertilization. Phosphorus in sludge is as effective as phosphorus in fertilizers in increasing the extractable phosphorus in the soil to the level required for crop growth. Likewise, calcium carbonate in sludge increases soil pH more effectively than agricultural lime.
Our results made it possible to highlight the action of the sludge on the behavior of the plant in qualitative and quantitative terms. During the first year of experimentation, the productions obtained were generally higher than those obtained on the control plots. A dose-effect was very clear. The dose of 100 t ha−1 records the highest production whatever the crop. Similar results are obtained by other authors. A clear improving action of sludge on English Ray Grass production [21, 22, 23]. Zaier et al. [24] showed that the sludge significantly stimulates the biomass production of B. napus. Similar results have been demonstrated by [25] who showed that the biomass production of durum wheat was significantly improved by 18% with the addition of 40 t ha−1 of sewage sludge. Pasqualone et al. [26] found positive effects of increasing sludge doses on durum wheat productivity, 12 kg ha−1 of sludge was demonstrated to can effectively replace mineral fertilization. Boudjabi et al. [27] found a significant increase in the number of tillers, ears and kernels per ear of barley in amended soils. This has been linked to an improvement in the physical and chemical properties of soils. This beneficial effect has been observed on several crops such as wheat, sorghum, maize, chili peppers, barley and potatoes [21, 28, 29, 30, 31].
For the two types of sludge, the results of the second application show a positive effect on rapeseed production at the doses of 5 t ha−1 and 25 t ha−1. However, in this second application, industrial sludge causes an increase in the concentration of metals in the soil, especially chromium, cadmium and lead. The cumulative application of industrial sludge generates an excessive accumulation of heavy metals [32, 33] which could be harmful to soil fertility, affecting the ecosystem and human health [34]. Marchiol et al. [35] observed that
During the experimentation, the plants presented a normal appearance but some rapeseed leaves cultivated in plots having received 200 t ha−1 of industrial sludge show spots of necrosis and a purplish color. In the literature, these symptoms are described as due to phosphate deficiency. Soil rich in iron or zinc can reduce the absorption capacity of phosphate ions, which could occur as a result of adding sludge to the soil [36]. In this context, [37] have also shown that the presence of high levels of lead can cause the formation of precipitate of lead phosphates, which cannot be assimilated by plants and consequently a phosphorus deficiency can occur. For rapeseed, we have seen a delay in germination in certain plots following a cumulative effect of industrial sludge. Also, germination appeared to be inhibited by the presence of urban sludge. Laboratory experiments confirmed this effect, but showed that germination was not permanently inhibited, but simply delayed. The latency period is dose-dependent, so it increases depending to the amount of sludge added. A similar effect was induced by heavy metals (Cu, Ni, Zn) in aqueous solution [38]. Also, germination is positively correlated with the degree of stability of the sludge and the organic matter contents [39]. The observed delay of germination was restored after one month and the development cycle resumed normally.
A study by [40] showed that sludge causes the late maturity of wheat. This was not the case in our experimentation where the wheat development cycle was not disrupted. An increase in crop yield resulted in an increase in the number of seed in our study. We also mentioned that urban sludge increases the oil yield of rapeseed after the 1st spreading. Similarly, [41] has shown that urban sludge considerably increases the productivity of sunflower oil. The use of urban sludge as a fertilizer has been considered for years given its richness in organic matter and nutrients [41, 42]. However, sludge contains phytotoxic metals which can cause certain problems at high levels [43]. The response of plants to these metals varies considerably from one species to another [44, 45, 46] and the results obtained are disparate. Other factors including edaphic can intervene. In our work, we have shown that whatever the site of culture (control, contaminated, heavily contaminated), wheat has a lower concentration of heavy metals than rapeseed. However, these differences are minimal on the control site and are accentuated with the addition of sludge, especially in the presence of industrial sludge. This finding is not the same for the seed since, on the control site, the wheat seems to concentrate more heavy metals than rapeseed, but this is only due to the high zinc contents of wheat seeds. If we disregard the zinc, we find the same result. In fact, Brassicaceae are generally considered to be metal accumulators that can tolerate high concentrations [47] unlike cereals [48]. However, the accumulating power of rapeseed remains low to consider phytoremediation [49]. It is important to note that both rapeseed and durum wheat were able to survive on a site treated with sludge loaded with heavy metals. This capacity may be due both to the existence of tolerance strategies in the plant making the assimilation of metal limited and also to the strong metal bonds in the sludge and the soil rich in matter organic. Most heavy metals can also be stored and detoxified in root tissues with minimal translocation to leaves whose cells are sensitive to phytotoxic effects [50, 51, 52, 53, 54].
Actually, the extent of metal contamination depends both on the concentration of the metal in the environment and on the intrinsic factors of the metal. The concentrations of the main tracemetalic elements are represented in Figure 2. In the control environments and those treated by urban sludge, the Zn contents are higher than the other metals while cadmium was the least abundant. The concentrations founded were as following: Zn > > Cr > Cu > Ni > Pb > Co > Cd. For the environments treated by industrial sludge, the amounts of trace elements were completely different, reflecting an increase in chromium and lead amounts. The concentrations founded in these environments were as following: Cr > > Zn > > Pb > Cu > Ni > Co > Cd.
Effect of metal on some of metal trace element concentrations in the plant.
The presence of metals in the soil can influence the uptake of essential nutrients for plant growth [55, 56]. The essential divalent cations such as Ca2+, Mn2+, Zn2+, Mg2+ compete with toxic metals such as Cd. Therefore, the increase in the contents of these elements can reduce the absorption of metals such as Cd [57, 58, 59]. However, in our experimentation, for the rapeseed, we noted a synergy between a non-essential metal Cd and a trace element Zn. Also, the increase of Cd absorption decreases the absorption of iron and manganese by the root (Figure 3). These observations are explained by competitions between these different cations for surface complexation sites in the root and for the unspecific carriers of major cations or trace elements. Other works have shown that treatment with cadmium can cause deficiencies in iron, copper and manganese [57, 60].
Influence of cadmium on the absorption of zinc, iron and manganese in rapeseed roots.
For wheat, the absorption of iron, manganese and zinc increases according to the doses (Figure 4) of the sludge and probably plays a non-negligible beneficial role on the Phyto availability of non-essential elements such as cadmium, an antagonistic effect could have taken place, which could explain the negligible Cd contents found in wheat [61].
Effect of industrial sludge on the absorption of zinc, iron and manganese in the roots of durum wheat.
Sludge application causes a high accumulation of metallic trace elements in the soil, these metallic elements are then driven to the roots and finally to the aerial part. The addition of industrial sludge causes a significant contamination of the soil and the roots by heavy metals while the degree of contamination at the level of the aerial part is lower as shown in Figure 5. For urban sludge, the accumulation of heavy metals is high but much less than that of industrial sludge. The comparison between contaminated and uncontaminated environments shows that the more the environment is polluted with ETM (Trace Metal Elements), the higher the contents of these elements in the plant.
Accumulation of metallic trace elements in the soil spread by sludges and in the different parts of the plant.
The difference in behavior between aerial organs and roots with respect to heavy metals is reflected in the ultrastructure. From a cytological point of view, the number of cells in apoptosis is higher in the roots. This suggests the existence of much more effective bio protection modalities in the root. The high doses of the sludge cause ultrastructural changes in the roots, but the nucleus retains its integrity and the chromatin is evenly distributed. As for the cytosol, it has a contracted appearance with grouping of ribosomes into polysomes. Mitochondria change their shape and have swollen ridges (Figure 6).
(a) central cylinder of control roots in longitudinal section (Gr * 40). (b) central cylinder of a control root in cross section (c) Cross section of a root treated with 100 t ha−1 BU (Gr * 40). (d, e) Central cylinder of a root of treatment 100BI (Gr * 40). Cp: Parenchymal cell; X: xylem; RL: Woody rays; CC: central cylinder; P: periderm.
Fragmentation of the vacuole into many small vacuoles is also observed (Figure 6). The plasma membranes appear damaged. The best-known strategy is to interfere with the entry of heavy metals into root cells by trapping them in the apoplasm where they associate with organic acids [62] or anionic groups in cell walls [63]. Once inside the plant, most heavy metals are held in deep cells, where they are detoxified by complexing with amino acids, organic acids or peptides and or they are sequestered in vacuoles [51]. This greatly limits translocation to aerial organs, thus protecting the leaf tissues, and in particular the metabolites of photosynthetic cells against possible damage. Another defense mechanism generally adopted by plants exposed to heavy metals is the improvement of cellular antioxidant systems which would limit oxidative stress [52, 53].
The export of metals to the aerial part is accompanied by physiological disturbances. A decrease in chlorophyll could be induced by excess zinc and cadmium [64]. Our results confirm this fact as shown in Figure 7. Likewise, a decrease in the level of carotenoids can be linked to an excess of cadmium [65] or to an excess of copper [66].
(a) Variation of heavy metals in the leaf as a function of treatment. (b): Effect of cadmium on the biosynthesis of chlorophyll, proline, and MDA in the leaves of rapeseed.
Metals alter electron transport and inhibit the activity of Calvin cycle enzymes [67]. High doses of industrial sludge also weaken photosynthetic activity [68, 69] and cause a gradual decrease in photochemical quenching (qp) [70, 71] accompanied by a significant increase in non-photochemical quenching (NPQ).
Chromium directly inhibits one of the key enzymes in chlorophyll biosynthesis NADPH [72]. Likewise, several metals such as Cd, Pb, Cu, Zn, and Ni can replace Mg in chlorophylls, resulting in inactive molecules [73, 74, 75]. In the leaf, excess metals can also induce changes in membrane stiffness, permeability and stability [76]. At the cellular level, rearrangements were observed (Figures 8 and 9). The damage produced at mitochondria and chloroplasts is more severe than that of the nucleus.
Observation under a transmission electron microscope of cross sections of root cortical cells of a control plant (2a and 2b) and of a plant treated with 100 t ha−1 industrial sludge (2c to 2f). 2 a: Plasmalemma (pl) of a cortical cell of a control root 2 b: Cell organelles of a control root with homogeneous distribution of ribosomes (r). 2 c: Retraction of the cytoplasm with detachment of the plasmalemma and formation of a periplasmic space (ep). 2 d-e: Vesicular formations (vf) and membrane formations (fm). 2 f: Degradation of the primary (PI) and secondary (PII) wall.Pp.: Pectocellulosic wall, m: Mitochondria Ag: Golgie apparatus, cy: Cytoplasm, pr: Polyribosome.
Observation under a transmission electron microscope of the cortical zone of a rapeseed stem from the control treatment (a and b) (a: General appearance of the cell and b: Appearance of the nucleus (N) and after a contribution of 100 t ha−1 BI (c, d and e) (c: Detachment of the plasma membrane (pl) and formation of periplasmic space; d: Irregularly shaped nucleus divided into small nucleoli (nu); e: Vesicle surrounded by a single membrane and containing certain cellular organelles (nucleus, mitochondria and peroxisome (p) and in the presence of 100 t ha−1 BU (f) with pairing of Golgian saccules forming a dictyosome (Ag) and releasing Golgian vesicles giving rise to lysosomes. (di): Cytoplasmic digitation.
In the leaves of plants cultivated in the presence of high doses of industrial sludge loaded with metals, the number of chloroplasts has decreased. Similar results have been reported by [77]. Other structural damage is also frequently observed such as swelling of chloroplasts, rupture of the envelope, deformation of thylakoids. The thylakoid membranes lose their parallel arrangement, the grana become disorganized and the thylakoid surface is reduced. These ultra-structural changes are accompanied by an increase in the degree of membrane lipid peroxidation, appreciated by the production of malondialdehyde. We have also observed an enlargement of the mitochondria, the disintegration of the membranes, the disappearance of the ridges and a clear vacuolation. The intensity of toxicity actually varies from cell to cell.
The attenuation of toxicity could be due, for example, to the retention of metals on the cell wall [78] or their sequestration in the vacuole [79] or their storage in inactivated on specific proteins, amino amines or peptides.
The study of the risks of ETM (Trace Metal Elements) associated with the spreading of sludge requires not only knowledge of the total metal content, but also of the metal content in the various compartments that make up the soil. Nevertheless, assessing the total stock of an element is a good approach to study the degree and extent of soil contamination by a metallic element. Our results have shown that in general, heavy metals are preferentially localized in the surface horizon and this for different media (Figure 10). However, on the control medium, the difference in accumulation between the 3 horizons is minimal and the contents are more or less comparable. The more the environment is polluted, the greater the difference in accumulation between the horizons. In fact, the level of accumulation of heavy metals depending on the pollution of the environment is much greater at the surface horizon than for the underlying horizons.
Accumulation of heavy metals in the different horizons of the soil.4.
The second addition of sludge increases the ETM (Trace Metal Elements) content in the soil of the two crops. The surface layer (0-10 cm) appears the richest in cadmium, chromium and lead. After the second harvest, the cultivated wheat soil has higher ETM (Trace Metal Elements) contents than those of the rapeseed plots (Figure 11). This is due to the low extracting power of wheat compared to rapeseed. In a study on Brassica napus, [80] reported that in the presence of sewage sludge the extraction of heavy metals by this species increases significantly due to its hyperaccumulation power, but its use in phytoremediation is a very long process.
Comparison of heavy metals in the different horizons of the soil (between 0 and 10 cm and 10 and 20 cm) after the first and second harvest.
To assess the risk associated with heavy metals in the case of spreading waste products (sludge, compost, wastewater, etc.), one of the most widely used methods is to prevent the accumulation of trace elements in the soil [81, 82]. Only the soil and sludge contents, as well as the quantities of sludge added are taken into account. Taking into account all our data, we tried to make a balance in order to assess the risk of saturation of the soil by heavy metals provided by the different types of sludge in the case of our experiment. The results obtained are shown in Table 2. It emerges from this table that for all the heavy metals, the soil reaches saturation much more quickly with the input of industrial sludge than for urban sludge and this is easily explained by the respective quality of sludge. For urban sludge, the probable duration of saturation varies between 361 and more than 160,000 years depending on the sequence: Cd >> > Ni > Pb > Cr > > Cu > Zn. This is in favor of the use of urban sludge given that the risk of soil contamination is low, in particular for toxic metals (Cadmium, Chromium and Lead) and that the elements which arrive first at the thresholds are copper and zinc which are trace elements essential to the plant. The problem arises differently with the spreading of industrial sludge highly loaded with heavy metals. Indeed, in this case the risk of contamination is present since the saturation time drops to very low levels for toxic heavy metals to reach less than 10 years for cadmium and chromium and 30 years for lead. The sequence found is: Ni > Cu > Zn > Pb > Cd > Cr.
Cd | Cu | Cr | Ni | Pb | Zn | |
---|---|---|---|---|---|---|
Heavy metals soil standard (ppm) | 3 | 140 | 150 | 75 | 150 | 300 |
Wheat and rapeseed soil (ppm) | ||||||
Average annual contribution per BU of 5 t ha −1 year−1 (g ha−1 year−1) | ||||||
Increase due to sludge | ||||||
Average annual contribution per Industrial Sludge 5 t Ha−1(g ha−1 year−1) | ||||||
Increase due to sludge | ||||||
Assessment of the risk of soil saturation by heavy metals provided by the different types of sludge.
Once in the soil, some of these metals persist due to their immobile nature and the risk of crossing plants is low. Their in-depth migration is unlikely. On the other hand, the most mobile elements can transfer through the soil to the aquifer or be absorbed by the plant. Besides the intrinsic criteria of metals, their bioavailability and their transfer are more or less modified, in particular by edaphic factors such as pH, temperature and organic matter contents, hence the need to take into account all factors for success of a spreading project.
The decontamination of polluted soils can be considered but remains a rather long process requiring a lot of time [80] calculated that more than 1000 years would be needed to clean up a contaminated site. These results have been confirmed by [83]. Likewise, [84] studying the phytoextraction of
When metals migrate through plants and the food chain is involved, account must be taken of the amounts of the metals that can be transferred to consumers. As
An increase in the levels of metallic trace elements was indeed mentioned at seed level during the second campaign. We also detected a decrease in the oil content with the addition of industrial sludge. The composition of total lipids in fatty acids shows an increase in the percentage of oleic acid (C18: 1) at the expense of linoleic (C18: 2) and linolenic (C18: 3) acids under the effect of heavy metals provided by industrial sludge while no difference is recorded with urban sludge regardless of the dose. No significant difference in heavy metal content was observed with the contribution of different doses of urban sludge, even after two years of spraying. On the other hand, we detected increases in most of the heavy metals, in particular for the high doses of industrial sludge.
The cadmium contents increase significantly with the contribution of 100 t ha−1, it reaches 25 ppb following the cumulative contribution. For lead and chromium, the increase is especially visible at the 100 t ha−1 dose. These increases become more important during the second year. For nickel, the levels are higher compared to the control from the addition of 50 t ha−1 of industrial sludge for the two spreading operations. For wheat, the composition of the seeds in metallic trace elements is little or not affected by the contribution of sludge. The observed increases concerned only a few metals and for the excessive doses of industrial sludge. In order to assess the health risk linked to heavy metals via the consumption of products amended with sewage sludge, we tried to theoretically determine the daily exposure of consumers of these products to heavy metals (EJE) and to compare it with tolerable toxicological doses (TDI). The TDI is defined as the amount of contaminants that can be ingested daily without adverse health effects [86, 87]. The harmful potential of a product is the greater the lower the TDI value. In our calculations, we considered the seeds of wheat and rapeseed oil that are suitable for human consumption.
The daily exposure dose attributable to the consumption of these EJE products is calculated according to the formula [88]:
With: [C product]: Concentration of the metal in wheat grains or rapeseed oil; Product qty.: consumption of the product at the 95th percentile (g person−1 day−1) which is equal to 382 g day−1 for adult person weighing 60 kg for wheat [88] and 25 g day −1 for rapeseed oil [87]. For the trace and zero contents, we assimilated them to the detection limits of the dosing device.
The intake of sludge in its two forms has no effect on the theoretical exposure to Cd of high consumers of wheat, which is estimated at 3.8 μg person−1 day−1 for all the treatments (Table 3). These values are clearly lower than the TDI which is 60 μg person−1 day−1. The problem arises differently for Pb where the dose of sludge (urban and industrial) influences by increasing the level of exposure of consumers but the values obtained are all below the TDI (216 μg person−1 day−1). It should be noted that the higher the dose, the closer one gets to the TDI. For Ni, the intake of both types of sludge increases consumer exposure to this element but without a net dose effect. In addition, the values obtained remain below the TDI (720 μg person−1 day−1). Exposure to Cr is increased with the addition of industrial sludge. Nevertheless, the comparison with the TDI could not be made because the available TDI is fixed for Cr III and Cr IV while our data relate to total Cr.
Estimated exposure μg person−1 day−1 | EJE/DJT | ||||||||
---|---|---|---|---|---|---|---|---|---|
Control | 3,8 | 19,1 | 525,3 | 261,7 | 0,064 | 0,088 | — | 0,363 | |
5BU | 3,8 | 19,1 | 540,5 | 355,3 | 0,064 | 0,088 | — | 0,493 | |
25BU | 3,8 | 19,1 | 498,5 | 395,4 | 0,064 | 0,088 | — | 0,549 | |
50BU | 3,8 | 143,3 | 548,2 | 336,2 | 0,064 | 0,663 | — | 0,467 | |
100BU | 3,8 | 191,0 | 531,0 | 269,3 | 0,064 | 0,884 | — | 0,374 | |
5BI | 3,8 | 19,1 | 624,6 | 382,0 | 0,064 | 0,088 | — | 0,531 | |
25BI | 3,8 | 59,2 | 618,8 | 368,6 | 0,064 | 0,274 | — | 0,512 | |
50BI | 3,8 | 210,1 | 601,7 | 389,6 | 0,064 | 0,973 | — | 0,541 | |
100BI | 3,8 | 194,8 | 685,7 | 475,6 | 0,064 | 0,902 | — | 0,661 | |
Control | 0,003 | 0,005 | 0,0002 | 0,014 | 4,3E-05 | 2,52E-05 | — | 1,98E-05 | |
5BU | 0,003 | 0,005 | 0,0001 | 0,016 | 4,3E-05 | 2,44E-05 | — | 2,27E-05 | |
25BU | 0,003 | 0,006 | 0,0002 | 0,016 | 4,3E-05 | 2,60E-05 | — | 2,20E-05 | |
50BU | 0,003 | 0,005 | 0,0002 | 0,016 | 4,3E-05 | 2,44E-05 | — | 2,22E-05 | |
100BU | 0,003 | 0,005 | 0,0002 | 0,017 | 4,3E-05 | 2,52E-05 | — | 2,31E-05 | |
5BI | 0,003 | 0,005 | 0,0002 | 0,014 | 4,5E-05 | 2,44E-05 | — | 1,91E-05 | |
25BI | 0,005 | 0,006 | 0,0002 | 0,014 | 7,9E-05 | 2,60E-05 | — | 1,89E-05 | |
50BI | 0,016 | 0,006 | 0,0003 | 0,017 | 2,6E-04 | 2,83E-05 | — | 2,38E-05 | |
100BI | 0,055 | 0,014 | 0,0008 | 0,016 | 9,2E-04 | 6,61E-05 | — | 2,22E-05 |
Estimated exposure and calculated mean Hazard quotient.
The hazard quotient (QD) is defined by the ratio between the calculated EJE and the corresponding TDI, according to the formula of [89] i.e. QD = EJE/DJT If the hazard quotient is greater than 1, the occurrence of Adverse effects related to toxicants are potentially possible. Otherwise, the risk can be considered as theoretically non-existent. All the ratios calculated for wheat seed are less than 1, however it is important to note that the high doses, especially of industrial sludge, increase the QD which rapidly approaches 1 for Ni and in particular Pb. It is probable that ‘it is the same for Cr. Thus, it is imperative to note that whatever the quality of the sludge, the spreading must be done at suitable doses and must be controlled. For rapeseed oil, the estimated daily exposure is extremely low since the values are infinitely low and are much lower than the respective TDI. It should be noted that for Cd and Pb, the 100 t ha−1 BI increase EJE. From a metals point of view, the addition of sludge, especially urban sludge and at low doses, does not generate a health risk, however, it should not be forgotten that the metals can be introduced by other products which must be taken into account in the process risk assessment hence the need to monitor these situations.
The spreading of sludge from wastewater treatment plants increased the production of durum wheat and rapeseed. Their richness in nitrogen, phosphorus and potassium gives them a beneficial effect on crops. However, the application of sludge can induce increases in the concentration of metals in plant tissues. This increase can generate disturbances at the level of the cell and organelles like mitochondria and chloroplasts which can be altered. Repeated applications of sludge at the same site tend to increase the accumulation of heavy metals in the soil which can cause toxicities to soil microorganisms, animals and humans, via the food chain. However, it is important to note that these harmful effects mainly concerned industrial sludge, but the use of this sludge is strictly prohibited. In addition, the high doses used in our field experiments are clearly higher than those authorized in agricultural practice. Finally, the risk assessment by calculating both the level of exposure for the consumer and the number of years for a soil to be saturated shows that the use of urban sludge is safe, particularly in the short and medium term. Nevertheless, the quality of the sludge to be spread must be constantly checked. Other metallic trace elements such as mercury, boron brought in by the sludge must be taken into account.
This work was supported by National Institute for Rural Engineering research, Water and Forestry, Tunis and Ecole Nationale Supérieure des Mines de Saint Etienne, France.
The authors of chapiter submitted for publication, we confirm that the results presented in this paper are real and original. The authors declare that they have no competing interests. The opinions expressed in this article are those of the authors and do not necessarily represent any agency determination or policy.
IntechOpen publishes different types of publications
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She is now a lecturer at the University of Witwatersrand, South Africa, and a principal researcher at the Health Economics and Epidemiology Research Office (HE2RO), South Africa. Dr. Moolla holds a Ph.D. in Psychology with her research being focused on mental health and resilience. In her professional work capacity, her research has further expanded into the fields of early childhood development, mental health, the HIV and TB care cascades, as well as COVID. She is also a UNESCO-trained International Bioethics Facilitator.",institutionString:"University of the Witwatersrand",institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419588",title:"Ph.D.",name:"Sergio",middleName:"Alexandre",surname:"Gehrke",slug:"sergio-gehrke",fullName:"Sergio Gehrke",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038WgMKQA0/Profile_Picture_2022-06-02T11:44:20.jpg",biography:"Dr. Sergio Alexandre Gehrke is a doctorate holder in two fields. The first is a Ph.D. in Cellular and Molecular Biology from the Pontificia Catholic University, Porto Alegre, Brazil, in 2010 and the other is an International Ph.D. in Bioengineering from the Universidad Miguel Hernandez, Elche/Alicante, Spain, obtained in 2020. In 2018, he completed a postdoctoral fellowship in Materials Engineering in the NUCLEMAT of the Pontificia Catholic University, Porto Alegre, Brazil. He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. In addition, he is also a Collaborating Professor in several Postgraduate programs at different universities all over the world.",institutionString:null,institution:{name:"Universidad Católica San Antonio de Murcia",country:{name:"Spain"}}},{id:"342152",title:"Dr.",name:"Santo",middleName:null,surname:"Grace Umesh",slug:"santo-grace-umesh",fullName:"Santo Grace Umesh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/342152/images/16311_n.jpg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"333647",title:"Dr.",name:"Shreya",middleName:null,surname:"Kishore",slug:"shreya-kishore",fullName:"Shreya Kishore",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333647/images/14701_n.jpg",biography:"Dr. Shreya Kishore completed her Bachelor in Dental Surgery in Chettinad Dental College and Research Institute, Chennai, and her Master of Dental Surgery (Orthodontics) in Saveetha Dental College, Chennai. She is also Invisalign certified. She’s working as a Senior Lecturer in the Department of Orthodontics, SRM Dental College since November 2019. She is actively involved in teaching orthodontics to the undergraduates and the postgraduates. Her clinical research topics include new orthodontic brackets, fixed appliances and TADs. She’s published 4 articles in well renowned indexed journals and has a published patency of her own. Her private practice is currently limited to orthodontics and works as a consultant in various clinics.",institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"323731",title:"Prof.",name:"Deepak M.",middleName:"Macchindra",surname:"Vikhe",slug:"deepak-m.-vikhe",fullName:"Deepak M. Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. His research interests include root canal morphology, functionally graded concept, dental biomaterials, epidemiology and dental education, biomimetic restoration, finite element analysis and endodontic regeneration. Dr. Madfa has numerous international publications, full articles, two patents, a book and a book chapter. Furthermore, he won 14 international scientific awards. Furthermore, he is involved in many academic activities ranging from editorial board member, reviewer for many international journals and postgraduate students' supervisor. Besides, I deliver many courses and training workshops at various scientific events. Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\r\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\r\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Orthodontist, Assoc Prof in the Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. After graduating from TED Ankara College in 1986, she attended the Hacettepe University, Faculty of Dentistry in Ankara. \nIn 1993 she attended the Gazi University, Faculty of Dentistry, Department of Orthodontics for her PhD education. After finishing the PhD education, she worked as orthodontist in Ankara Dental Hospital under the Turkish Government, Ministry of Health and in a special Orthodontic Clinic till 2011. Between 2011 and 2016, Dr. Deniz Uzuner worked as a specialist in the Department of Orthodontics, Faculty of Dentistry, Gazi University in Ankara/Turkey. In 2016, she was appointed associate professor. Dr. Deniz Uzuner has authored 23 Journal Papers, 3 Book Chapters and has had 39 oral/poster presentations. She is a member of the Turkish Orthodontic Society. Her knowledge of English is at an advanced level.",institutionString:null,institution:null},{id:"332914",title:"Dr.",name:"Muhammad Saad",middleName:null,surname:"Shaikh",slug:"muhammad-saad-shaikh",fullName:"Muhammad Saad Shaikh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jinnah Sindh Medical University",country:{name:"Pakistan"}}},{id:"315775",title:"Dr.",name:"Feng",middleName:null,surname:"Luo",slug:"feng-luo",fullName:"Feng Luo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sichuan University",country:{name:"China"}}},{id:"344229",title:"Dr.",name:"Sankeshan",middleName:null,surname:"Padayachee",slug:"sankeshan-padayachee",fullName:"Sankeshan Padayachee",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"315727",title:"Ms.",name:"Kelebogile A.",middleName:null,surname:"Mothupi",slug:"kelebogile-a.-mothupi",fullName:"Kelebogile A. 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The following concerns will be addressed in this Cell Physiology subject, which will consider all organ systems (e.g., brain, heart, lung, liver; gut, kidney, eye) and their interactions: (1) Neurodevelopment and Neurodevelopmental Disease (2) Free Radicals (3) Tumor Metastasis (4) Antioxidants (5) Essential Fatty Acids (6) Melatonin and (7) Lipid Peroxidation Products and Aging Physiology.
",coverUrl:"https://cdn.intechopen.com/series_topics/covers/11.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11407,editor:{id:"133493",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",profilePictureURL:"https://mts.intechopen.com/storage/users/133493/images/3091_n.jpg",biography:"Prof. Dr. Angel Catalá \r\nShort Biography Angel Catalá was born in Rodeo (San Juan, Argentina). He studied \r\nchemistry at the Universidad Nacional de La Plata, Argentina, where received aPh.D. degree in chemistry (Biological Branch) in 1965. From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). W inner of the Bimbo PanAmerican Nutrition, Food Science and Technology Award 2006 and 2012, South AmericaHuman Nutrition, Professional Category. 2006 award in pharmacology, Bernardo\r\nHoussay, in recognition of his meritorious works of research. Angel Catalá belongto the Editorial Board of Journal of lipids, International Review of Biophysical ChemistryFrontiers in Membrane Physiology and Biophysics, World Journal oExperimental Medicine and Biochemistry Research International, W orld Journal oBiological Chemistry, Oxidative Medicine and Cellular Longevity, Diabetes and thePancreas, International Journal of Chronic Diseases & Therapy, International Journal oNutrition, Co-Editor of The Open Biology Journal.",institutionString:null,institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},editorTwo:null,editorThree:null,series:{id:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261"},editorialBoard:[{id:"186048",title:"Prof.",name:"Ines",middleName:null,surname:"Drenjančević",slug:"ines-drenjancevic",fullName:"Ines Drenjančević",profilePictureURL:"https://mts.intechopen.com/storage/users/186048/images/5818_n.jpg",institutionString:null,institution:{name:"University of Osijek",institutionURL:null,country:{name:"Croatia"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"79615",title:"Dr.",name:"Robson",middleName:null,surname:"Faria",slug:"robson-faria",fullName:"Robson Faria",profilePictureURL:"https://mts.intechopen.com/storage/users/79615/images/system/79615.png",institutionString:null,institution:{name:"Oswaldo Cruz Foundation",institutionURL:null,country:{name:"Brazil"}}},{id:"84459",title:"Prof.",name:"Valerie",middleName:null,surname:"Chappe",slug:"valerie-chappe",fullName:"Valerie Chappe",profilePictureURL:"https://mts.intechopen.com/storage/users/84459/images/system/84459.jpg",institutionString:null,institution:{name:"Dalhousie University",institutionURL:null,country:{name:"Canada"}}}]},onlineFirstChapters:{paginationCount:10,paginationItems:[{id:"82112",title:"Comparative Senescence and Lifespan",doi:"10.5772/intechopen.105137",signatures:"Hassan M. 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