\r\n\t
",isbn:"978-1-83768-400-7",printIsbn:"978-1-83768-399-4",pdfIsbn:"978-1-83768-401-4",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"3e168136bc7435be0c6bbe1d7adec1f4",bookSignature:"Prof. Marwa Zakaria, Prof. Tamer Hassan and Prof. Laila Sherief",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/12194.jpg",keywords:"Beta Thalassemia Major, Transfusion Dependent Beta-Thalassemia, Microcytic Hypochromic Anemia, Mutations, Beta Thalassemia Intermedia, Non-transfusion Dependent Thalassemia, Hb E Disease, Alpha Thalassemia, Genetic Counseling, Newborn Screening, Prenatal Diagnosis, Gene Therapy",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 14th 2022",dateEndSecondStepPublish:"July 12th 2022",dateEndThirdStepPublish:"September 10th 2022",dateEndFourthStepPublish:"November 29th 2022",dateEndFifthStepPublish:"January 28th 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"a month",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Dr. Marwa Zakaria completed her post-graduate training in Pediatric Nutrition at Boston University School of Medicine, USA. She is an Associate Professor and senior consultant of Pediatrics in the Faculty of Medicine at Zagazig University and a member of the International Society of Pediatric Oncology (SIOP), the European Hematology Association (EHA), and the Egyptian Society of Hematology.",coeditorOneBiosketch:"Professor at Zagazig University and an active member at EHA, SIOP, HAA, and ESPHO. Dr. Hassan is a guest speaker at numerous pediatric oncology and hematology meetings and he had over 50 international research publications in Pediatrics and Pediatric Hematology and Oncology.",coeditorTwoBiosketch:"Professor at Zagazig University, president of Sharkia Thalassemia Association, and member of the Egyptian national guidelines committee (NEGC) for evidence-based clinical practice. Prof. Sherief has over 50 international publications and many national publications and is an editorial board member in 17 international journals and Peer Reviewer for more than 38 international journals.",coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"187545",title:"Prof.",name:"Marwa",middleName:null,surname:"Zakaria",slug:"marwa-zakaria",fullName:"Marwa Zakaria",profilePictureURL:"https://mts.intechopen.com/storage/users/187545/images/system/187545.png",biography:"Prof. Marwa Zakaria is an Associate Professor of Pediatrics and Pediatric Hematology and Oncology, Pediatric Department, Zagazig University, Egypt. She is an active member of the International Society of Pediatric Oncology (SIOP), European Hematology Association (EHA), and Egyptian Society of Pediatric Hematology and Oncology (ESPHO). She has participated in several professional trainings and workshops, including ICH GCP online training, EHA Master Class and Bite-size Master Class, and training from the Society of Neuro-Oncology (SNO). She completed a postgraduate training program in Pediatric Nutrition at the School of Medicine, Boston University, USA, in 2017. She completed several international preceptorships, including a thalassemia preceptorship and a hemophilia preceptorship. Dr. Zakaria is the recipient of a 2018 award from SIOP, and scholarships from EHA-HOPE in 2017 and 2018. She has participated in many international and national pediatric and hematology conferences, where she has also been a guest speaker. She has more than forty international research publications in pediatrics and pediatric hematology and oncology to her credit. She has edited three books and five book chapters. She is also a reviewer for several journals, including Medicine, Frontiers in Pediatrics, Molecular Medicine Reports, International Journal of Infectious Diseases, and others. Dr. Zakaria served as co-investigator for four hematology clinical trials and sub-investigator for five others.",institutionString:"Zagazig University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Zagazig University",institutionURL:null,country:{name:"Egypt"}}}],coeditorOne:{id:"106463",title:"Prof.",name:"Tamer",middleName:null,surname:"Hassan",slug:"tamer-hassan",fullName:"Tamer Hassan",profilePictureURL:"https://mts.intechopen.com/storage/users/106463/images/system/106463.jpg",biography:"Tamer Hassen is a Professor of Pediatrics, Faculty of Medicine, Zagazig University, Egypt. He is an active member of the European Hematology Association (EHA), International Society of Pediatric Oncology (SIOP), and Egyptian Society of Pediatric Hematology and Oncology (ESPHO), and has attended numerous national and international pediatric and hematology conferences held by these organizations and others. He has been a guest speaker at numerous pediatric oncology and hematology meetings and has published more than fifty international research publications in pediatrics and pediatric hematology and oncology. Dr. Hassan has edited two books and authored four book chapters. He has participated in many professional trainings and workshops. He received international scholarships from EHA-HOPE Cairo in 2017 and 2018, and an award from SIOP in 2016. He has completed several international preceptorships, including a hemophilia preceptorship at Saint Luc Hospital, Brussels, Belgium, and an immune-thrombocytopenia (ITP) preceptorship at Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia. Dr. Hassan is an editor and reviewer for many journals, including Hemophilia, Medicine, Oncology Letters, Child Neurology, and more. He was a primary investigator in four international clinical trials and a sub-investigator for ten others.",institutionString:"Zagazig University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Zagazig University",institutionURL:null,country:{name:"Egypt"}}},coeditorTwo:{id:"110940",title:"Prof.",name:"Laila",middleName:null,surname:"Sherief",slug:"laila-sherief",fullName:"Laila Sherief",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS1HqQAK/Profile_Picture_2022-05-19T09:40:38.jpg",biography:"Professor Laila Sherief has been a long-serving member of the Zagazig University community in Egypt. She first graduated with honours from the Zagazig University and then went on to do her internship and residency there before becoming a lecturer, an Associate Professor then a Professor in Paediatric in the Faculty of Medicine. Prof. Sherief has published extensively in national/international medical journals and at medical conferences. She has over 50 international publications and many national publications and acts as a Peer Reviewer for more than 38 international journals, including Pediatric Hematology and Oncology, Pediatrics International, Journal of Coagulation & fibrinolysis, Medicine, BMC Endocrinal Disorders, Transfusion Medicine and Cancer Chemotherapy & Pharmacology. She is editorial board member in 17 international journals as BMC Pediatric, Frontiers in Genetics, Hematology case reports, Archives of hematology case reports and reviews, and Annals of Medical case reports. She supervised 83 master and MD thesis in Pediatric, Pediatric Hematology & Oncology and Clinical pathology\r\nProf. Sherief frequently attends national and international conferences and maintains memberships in many professional societies as International Society of Paediatric Oncology (SIOP), International Society of Haemostatis and Thrombosis (ISTH)., Egyptian Society of Pediatric Haematology & Oncology (ESPHO) and Egyptian Societies of thalassemia. She is the president of Sharkia thalassemia Association, Egypt, and member of the Egyptian national guidelines committee (NEGC) for evidence- based clinical practice. She was a member of the scientific committee for promotion of professors of pediatrics in the Supreme Council of Universities in Egypt from 2013 to 2016.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Zagazig University",institutionURL:null,country:{name:"Egypt"}}},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"466998",firstName:"Dragan",lastName:"Miljak",middleName:"Anton",title:"Mr.",imageUrl:"https://mts.intechopen.com/storage/users/466998/images/21564_n.jpg",email:"dragan@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2270",title:"Fourier Transform",subtitle:"Materials Analysis",isOpenForSubmission:!1,hash:"5e094b066da527193e878e160b4772af",slug:"fourier-transform-materials-analysis",bookSignature:"Salih Mohammed Salih",coverURL:"https://cdn.intechopen.com/books/images_new/2270.jpg",editedByType:"Edited by",editors:[{id:"111691",title:"Dr.Ing.",name:"Salih",surname:"Salih",slug:"salih-salih",fullName:"Salih Salih"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"57943",title:"Shock Compression of Porous Ceramics",doi:"10.5772/intechopen.72246",slug:"shock-compression-of-porous-ceramics",body:'\nShock wave loading is generated often at impact, collision, and blast. A shock wave is a powerful amplifier of defects in that it activates pre-existing defects (e.g., microvoids, cracks, and grain boundaries), extends cracks, and breaks media. The main challenge of porous ceramics in the application upon shock wave loading is its nonstationary behavior due to crack, damage, and fracture of the heterogeneous structure [1, 2, 3, 4]. Mechanical, electrical, and optical properties of ceramics are severely affected by shock waves, and consequently, it may deteriorate the designed functions of shocked ceramics, such as in the cases of high-strength ceramics for armor [5], piezoelectric and ferroelectric ceramics for converting mechanical energy to electrical energy [6, 7, 8] and transparent ceramics for optical measurements in shock experiments [9]. Hence, a good understanding of the dynamic response of porous ceramics under rapid impulsive loading is vital to the design, manufacture, and usage of these materials. To this objective, a two-dimensional lattice-spring model (LSM) has been newly established, and the shock compression behavior of porous ceramics is explored and the mechanisms and strategies for improving robustness are discussed.
\nDynamic response of porous ceramics under rapid impulsive loading relates to evolution of a crack network following the shock wave. Although some pioneer works have been conducted on modeling ceramic shock fracture via mesh-based computational methods [10, 11, 12, 13], such methods encounter significant difficulties when dealing with fracture and fragmentation induced by shock wave compression. The reason is that partial derivatives are used in mesh-based methods to represent the relative displacement and force between any two neighboring particles [14]. But, the necessary partial derivatives with respect to the spatial coordinates are undefined along the cracks and need to be redefined. However, the redefinition requires us to know where the discontinuity is located. This limits the usefulness of these methods in addressing problems involving the spontaneous formation of cracks, in which one might not know their location in advance [14]. In contrast, as a particle method, the lattice-spring model (LSM, also known as discrete-element method) [15, 16, 17, 18, 19, 20] could avoid various numerical difficulties caused by displacement discontinuity. In this section, details of the LSM model (lattice interactions, spring mapping procedure, fracture criterion, microstructures, loading) and its validation are introduced.
\nA two-dimensional LSM was established to explore the shock behavior of porous ceramics. In the LSM, continuum medium is described as discrete material particles. The nearest neighboring particles are interconnected and interact through springs. Evolution of this network can represent the global response of macroscopic materials, if the interactions of material particles are described accurately. Through simplifications of real materials and the model’s discrete nature, LSM has the advantage in treating fracture, fragmentation, and other dynamic damage processes of brittle materials subjected to tension, compression, shear, and other complex loading [17].
\nThe model established here has an elastic-brittle interaction, which ignores the small plasticity contribution to the response that possibly exists in brittle materials; only a linear elastic interaction is used. Particle interaction is shown in Figure 1. Between pairs of nearest-neighbor particles, indexed by
Particle interaction in the LSM model and schematic of the parameter mapping procedure.
An energy threshold based on Griffith’s energy balance principle [21] has been used as the fracture criterion. The summation of the deformation energy induced by tension in the normal spring and shear in the shear spring is calculated when the relative position between two neighboring particles changes. And the two springs break irreversibly to create a microcrack between the two particles, when the sum exceeds a certain threshold corresponding to the fracture energy. The deformation energy induced by compression in the normal spring will not be counted in this criterion, because it is assumed that hydrostatic compression would not cause fracture in the homogeneous media. When the microcrack forms between two particles, tension and shear interactions are removed; however, repulsion and friction interactions exist, when the broken particles come into collision.
\nThe parameters used in the interaction formulae of LSM were usually given empirically, resulting in a qualitative representation of mechanical properties of target materials. Several outstanding studies have been done to overcome this shortcoming [14, 15, 16, 22, 23, 24, 25]. Gusev proposed a parameter mapping procedure between finite-element method (FEM) and LSM [26]: consider a network that is both a LSM lattice and a FEM mesh; first, elastic constants of the target material are transformed into stiffness matrix of the FEM mesh; next, using the same network, the interaction-parameter conversion between FEM and LSM is performed (Figure 1).
\nTo obtain the deformation state for the FEM mesh, the force-displacement equations assembled from all elements need to be solved, that is,
\nwhere {
Since motion of translation would not change the strain energy of the whole system, Eq. (3) holds between elements of the matrix [
Using
The resultant internal force
where \n
In order to validate the parameter mapping procedure, dense and porous samples have been built and tested. Young’s modulus,
Shear wave speeds (
where \n
together with
To capture the influence of grain boundaries (GBs) on porous ceramics, polycrystalline sketching has been randomly produced using Voronoi tessellation [10]. As shown in Figure 2(a), particles (small circles) in the model are assigned into grains (large polygons). If two particles connected by springs belong to different grains, then the springs are assumed to be a small segment of a GB. Given that media on GBs have higher energy state than media in grains, the deformation energy required for creating a pair of new crack surfaces on GBs is smaller than that in grains. The energy threshold on GBs is given as \n
(a) Sketch of polycrystalline model. (b) Fracture energy set in the polycrystalline model. (c) Sketch of porous ceramics. White circles are randomly distributed voids and small colored dots are grains.
Voids are set by removing portions of the model particles (Figure 2(c)). In the model, the balance distance between nearest neighbor particles is 1 μm, characteristic size of the grains is 10 μm, and the diameter of a round void is 50 μm. The length of the model along the shock direction is 1.6 mm. The model is illustrated schematically in Figure 3. A piston composed of two columns of particles is set on the left-hand side of the model; it moves with piston velocity (
Schematic of the shock wave compression model for porous ceramics.
A shock wave relates to a high-power pulse, in which stress and the energy are sufficient to vanquish toughness of ceramics. It would activate pre-existing defects (e.g., microvoids, cracks, and grain boundaries), extends cracks, and breaks media. Mechanical, electrical, and optical properties of ceramics are severely affected by shock waves [28, 29, 30], and consequently, it may deteriorate the designed functions of ceramics. Hence, revealing the mechanisms of damage and deformation in shocked porous ceramics would be a foundation for modulation of shock behavior and enhancement of robustness of the porous ceramics involving shock applications. In this section, the effects of voids and grain boundaries on the mesoscopic deformation features of shocked porous ceramics have been explored and compared with shock experiments with the recovery of shocked porous ceramics. Microscope photographs of voids in the recovered sample have been analyzed and compared with computational results. A novel mechanism of slippage and rotation deformation has been revealed, which contributes to and enhances inelastic deformation of the shocked brittle materials. As the pressure increases, the rotational deformation becomes a universal and important mechanism for relieving shear stress and dissipating strain energy.
\nSimulations reveal that void collapse is initiated from severe shear stress concentrations around the void after the shock sweeps through. When media far from the void experience a mild shear stress, media in four corners around the void achieve the fracture criterion. Figure 4 shows an isolated void that swept by a shock wave. Four shear cracks extend from the void, and broken fragments fill into void along shear cracks and occupy the free volume.
\nMesoscopic mechanisms of shock plasticity in porous brittle material. (a) Distribution of the maximum resolved shear stress when shock wave has just swept through a void. (b) A snapshot of shear cracks extension around the void after shock wave has swept through. (c) Relative slippage and rotational deformation revealed in post-shocked region.
To validate the computational results, shock experiments with the recovery of shocked porous ceramics have been implemented [31]. The lead zirconate titanate (PZT) ceramic has been used, which is a ferroelectric ceramic and generates megawatts of electrical power in a short period of time via a ferroelectric-to-antiferroelectric phase transformation driven by the shock wave from a high-explosive. Unpoled samples have been used, which have no bound charge and charge releasing under the shock experiments. Voids in the ceramics were introduced during fabrication by adding spherical polymethyl methacrylate particles. As shown in Figure 5(a), the voids in sintered ceramics have diameters of ~50 μm. Bulk density of the samples is determined using the Archimedes method, and the sample porosity is calculated from the ratio of the bulk density to the theoretical density (
(a) Microscopic observation of a void in initial porous lead zirconate titanate ceramic. (b) A schematic of the shock experiment with recovery of the shocked porous ceramics. (c) Cross section of a recovered sample.
In the recovery experiment, one wants to recover porous ceramic that contains shock compression fracture, and this fracture should only be produced by high-speed impact between the flyer and the target. Therefore, a momentum trap (Figure 5(b)), which has the same shock impedance as the ceramic, is needed to bear the intense dynamic tension produced by rarefaction waves and to fly away alone carrying most of the momentum input by the flyer. Figure 5(c) shows an incised sample: an integral recovered ceramic (yellow) is conserved in a brown brass packet. Samples are polished and acid etched before scanning electron microscopy (SEM) studies.
\nFigure 6 shows comparison of void collapse features observed in the model with an isolated void and recovered porous ceramics. Long-distance extended cracks that are emitted from voids are an important feature in the model (Figure 6(a)). Figure 6(b) shows representative long cracks in the recovery sample subjected to 3.3 GPa compression. The extended crack directions deviate from those around the modeled isolated void (Figure 6(a)), and only two cracks are emitted. In Figure 6(c), no long crack exists around this void; instead, a thick crevice forms at the top left corner of the void. It can be deduced that numerous grains in this area were damaged by multicracks and were scaled off during polishing to form such a feature. Many cracks that advance along GBs of porous PZT ceramic have been observed (Figure 6(d)). Hence, a more complex model, including multivoid and GBs, would be needed to reproduce these damaged features.
\n(a) Shear cracks emit from the void because of shear stress concentrations after the exposure to a shock wave. (b) Long-distance extended cracks and (c) thick cranny are observed representative mesoscopic deformation features. (d) Minor crack advances along GBs.
Features of void collapse and shear fracture obtained from the polycrystalline model containing multivoid have been analyzed. In Figure 7(a), fragments of grains fill a damaged void, and long shear cracks extend from the void. All fragments have been removed in Figure 7(b) to compare with experimental observations (Figure 7(c)). In Figure 7(d), a wide area on the bottom left corner of the void has been damaged during crack evolution. When all fragments have been removed, a thick crevice is visible (Figure 7(e)), which is comparable with the deformation feature observed experimentally (Figure 7(f)). Figure 7(g–i) compares damage features between two voids. A few minor cracks, which are similar to the intergranular crack in Figure 6(d), exist around all the voids in the polycrystalline model.
\nComparison of deformation features observed in the polycrystalline model and recovery sample. (a)–(c) Representative long-distance extended shear cracks. (d)–(f) Representative thick crevices. (g)–(i) Crack transfixion between two voids.
The polycrystalline model also reveals the evolution of long cracks and thick crevices. For long cracks, an initially transgranular crack translates into an intergranular cracks after a certain propagation range. The translation should occur when the crack-driving force is decreased to a value that cannot support transgranular fractures. This fracture mode is termed “transgranular-to-intergranular crack mode.” However, intergranular cracks branch from the main transgranular crack during main crack propagation to form thick crevices. This fracture mode is termed “main (transgranular) crack and branching (intergranular) cracks mode.” Media in a wide area will be damaged in this fracture mode, and a thick crevice becomes visible after fragments have been removed.
\nWhat is the dominant factor that leads to these two different fracture modes? As shown in Figure 7(d), the main crack comminutes media in a wide area during its propagation. The thickness of the main transgranular crack is ~10 μm. The violent extension of the main crack implies that the crack-driving force is very strong. The branching of numerous intergranular cracks from the main transgranular crack may be attributed to the need for more effective shock energy dissipation.
\nA novel mechanism of slippage and rotation deformation, which contributes to and enhances inelastic deformation of the shocked brittle materials, has been revealed by this model. In shocked porous ceramic, numerous shear cracks are emitted during void collapse, forming a crack network. As a consequence, the media are comminuted into scattered tiny shatters by interlaced cracks. When the field of the relative velocity in these comminuted regions is drawn (Figure 8), the arrows (which indicated the relative velocities and directions of media) revealed complex vortex structures, showing that the shatters were slipping and rotating under shock [17]. The complex vortex structures indicate that the network composed of shear cracks takes a similar role to that of shear bands in high-strength high-toughness metallic glasses [32, 33]. They provide the precondition for relative slippages of media and irreversible deformation of the sample.
\nSlippage and rotation of shatters induced by extending shear cracks.
The rotational deformations of different types of materials have been reported in shock and static high-pressure investigations carried out by experiments and simulations [34, 35, 36, 37, 38]. For example, nickel nanoparticles were found to rotate in a diamond anvil cell when the pressure rose from 3 GPa to more than 38 GPa. When the particle sizes were various from 500 nm down to 3 nm, the measurements indicated that more active grain rotation occurs in the smaller nickel nanocrystals. Investigations here and in literatures about rotational deformation of various materials and loading conditions indicate that it becomes a universal and important deformation mechanism under high pressure to help the loaded systems to relieve shear stress and dissipate strain energy, when other usual deformations (e.g., dislocation, twinning) are absent or repressed [38, 39].
\nPre-existing defects in ceramics induce shock wave compression fractures and may lead to the failure of designed functions. One traditional strategy for failure prevention has been by sintering “defect-free” ceramics (e.g., a large, perfect single-crystal sample). However, such treatment by sintering is difficult in practice and costly in expense, and more importantly, it only increases the critical emergence stress of shock fracture rather more than eliminating the probability of shock failure. Adopting an approach that is the opposite of creating defect-free ceramics, one may be able to control shock fracture and avoid the shock failure of ceramics by properly introducing defects. The control of shock fracture by introducing defects may seem counterintuitive. However, under quasi-static loading, there have already been many successful cases in which defects are introduced to avoid catastrophic fracture. In nature, highly mineralized natural materials owe their exceptional toughness and quasi-ductility to microscopic building blocks, weak interfaces and architecture [40, 41, 42]. In engineering, the fracture toughness of “hard and brittle” glass and metal glasses has been increased by properly introducing microcracks and voids [43, 44, 45]. These mechanisms can be summarized as crack shielding, deflection, and bridging, which effectively reduce the crack-driving force [46]. In shock applications, however, the difference is that a shock wave relates to a high-power pulse. The stress and the energy input are sufficient to vanquish various toughening strategies. Hence, numerous cracks nucleate and grow inevitably. In this case, strategies for toughening brittle materials cannot be duplicated. Instead, a novel approach in addressing shock fracture is proposed, i.e., modulating the propagation of crack network in shocked ceramics by deliberately adding pores.
\nMesoscopic damage and deformation evolutions (void collapse, shear fracture, and rotational deformation) induced significant stress relaxation, leading to macroscopic “plastic” response, although the model particles and springs did not contribute to plasticity (only a linear elastic interaction was set in springs of the model). Note that here plasticity is taken in its broadest sense; it is identified not by dislocation movements, but by the macroscopic stress-strain curve and irreversible deformations. Figure 9 shows the correlation between macroscopic plasticity and mesoscopic damage evolution. Initially, a steep shock front is induced by the impact of the piston. The shock front broadens and splits into two waves during propagation inside a sample. The precursor wave is an elastic wave, which propagates with longitudinal acoustic speed. The second wave, which corresponds to an irreversible deformation, is usually termed the deformation wave (it is called plastic wave in ductile metals). The propagation speed of the deformation wave is slower than the elastic wave; thus, a plateau is produced between these two waves. After the deformation wave, the final equilibrium state, namely the Hugoniot state, is achieved. The deformation wave and the following plateau (the Hugoniot state) correspond to a “severely fractured state (SFS),” where shear fracture, void collapse, and rotational deformation of comminuted media are processed abundantly [10]. Note that the deformation wave and the SFS propagate synchronously. If the deformation wave is unloaded, then, without enough energy to maintain damage evolution, the SFS would be “frozen.” This is the foundation for modulating shock fracture.
\nComparison of (a) shock wave profiles and (b–d) damage distributions in dense, 5, and 12% porous ceramics, respectively.
Figure 10 shows schematics of controlling shock fracture. A traditional strategy for doing it is sintering “fully dense” ceramics (Figure 10(a)). Evolution of a dense sample with only 0.5% porosity was therefore simulated; Figure 10(c) shows that its average degree of damage is reduced to ~0.1, but the damage is distributed throughout the sample. An alternative approach is worth looking for. Instead of sintering fully dense ceramics, a new idea is to make use of the pores. As shown in Figure 10(b), voids are deliberately added in the ceramic; Figure 10(d) shows the degree of damage of a porous sample with 9.3% porosity (it is the porosity of PZT ceramics used in experiments) after sufficient evolvement: half of the porous sample has an average damage of ~0.4, and the other half of the sample is almost intact. A “shielded region” is acquired at the cost of severe fracture in the other parts of the sample (the “damaged region”).
\nSchematic of short pulse evolutions in (a) dense ceramic (with 0.5% porosity) and (b) porous ceramic (with 9.3% porosity). Degrees of damage of (c) dense and (d) porous samples at 800 ns after impact.
The design of controlling fractured region is based on the following mechanism: (1) the deformation wave would be slowed down by the deliberately increased porosity; (2) if the pulse is short compared with the thickness of the sample, then a rarefaction wave (the “trailing edge” of a stress pulse of shock) would catch up and unload the slow deformation wave; (3) the SFS would be frozen after the deformation wave vanishes, rather than sweep through the entire sample. After that, the ceramic will undergo elastic compression and stay in a mildly damaged state.
\nFigure 11(a) shows the configuration of the model to investigate whether voids can protect part of a sample away from the SFS. In one of the simulation runs, the porosity of the sample is 9.3% and the velocity of the flyer
Mechanism of earning a shielded region where the severely fractured state will not enter. (a) Configuration of the model. T refers to a very long momentum trap. (b) Damage distribution in the sample at 800 ns. (c) Stress wave evolution at three midterm times.
Damage evolutions of dense, 5, and 12% porous ceramics have been further simulated and their ultimate damage distributions after the flyer impact at 300 m/s are compared. Figure 12 plots the void collapse ratio
Comparison of collapse ratios of dense and porous samples with different porosities under the same shock stress and pulse width.
Figure 13(a) and (e) shows the fracture characteristics of the sample subjected to a compression of 3.3 GPa and that of 1.4 GPa, respectively. Each image is composed of 19 SEM frames, which are successively scanned along the “scanned area” marked in Figure 13(b). The image has a width of 766 μm and a length of nearly 8 mm. The direction of the shock wave propagation is from the left of the image to the right. The green circles represent the voids that are basically intact. Figure 13(c) shows that they are concavities that are almost hemispheric and show no sign of collapse. The red rectangles represent the voids that have collapsed. Figure 13(d) shows that they are hollows that are believed to have been voids, but no longer retains their hemispheric shape.
\nFracture character of porous ceramics in recovery experiments. (a) Voids evolution in the sample subjected to compression of 3.3 GPa. (b) Cross section of recovery sample. (c) Green circle represents basically intact void. (d) Red rectangle represents void which has collapsed. (e) Voids evolution in the sample subjected to compression of 1.4 GPa.
For the sample loaded by a 3.3 GPa shock wave, an elastic wave-deformation wave structure emerged once, then the deformation wave is unloaded. The shield ratio should be
The results obtained from simulations and experiments have a similar trend, except that about 40% of the voids were identified as collapsed void in the shielded region of the experimental sample. We attribute this “additional damage” in the shielded region of the recovered sample to two main reasons. First, there is roughness on the rear interface between the ceramic and the packet, which induced dynamic tensile stress after the shock wave has swept through and resulted in additional void damage. Second, the PZT ceramic is soft; a lot of grains are scaled off during polishing, which has a significant influence on the results counting. If one deducts the additional damage, then the experimental result is in good agreement with the simulation result.
\nWith the lattice-spring model simulation and the shock recovery experiment, mechanisms of damage evolution, including void collapse, shear fracture, and rotational deformation, are illuminated, and their contributions to the damage toleration of the shocked porous ceramics are demonstrated, which would be beneficial to the understanding of porous ceramics in application upon shock wave loading.
\nHere, adding pores deliberately does not mean to fabricate “foam ceramic.” As the porosity increases, the length of the shielded region increases accordingly, and it should be considered integrally when one designs porous ceramics.
\nEpigenetics coined by Dr. Conrad H. Waddington is a branch of biology that studies the changes occurring in organisms resulting from changes in gene expression instead of the genetic sequence. Epigenetic mechanisms, some of which are reversible, can thus alter the phenotype without affecting the genotype. Epigenetic mechanisms regulate gene expression by affecting mainly the availability of the DNA for transcription by chemical modifications of the DNA base pairs without directly altering the DNA sequence, by affecting the architecture of the chromatin, and by the activity of non-coding RNAs. The DNA undergoes modifications such as methylation, whereas histones undergo modifications such as acetylation, phosphorylation, SUMOylation, ubiquitylation, etc. These modifications and other mechanisms govern the architecture of the chromatin. The architecture of chromatin determines which portion of the DNA can be expressed, and this depends on histones and non-histone chromatin-associated proteins such as the High mobility group (HMG) proteins [1]. Non-coding RNAs such as microRNAs (miRNAs), long non-coding RNAs, and small interfering RNAs have also been shown to affect epigenetic mechanisms [2, 3, 4]. In a genome, the collection of all the modifications that regulate gene expression is called its epigenome.
The negatively charged DNA, where the negative charge is due to the phosphate groups of its sugar-phosphate backbone, is electrostatically attracted to the positively charged lysine of the histone proteins. Two of each H2A, H2B, H3, and H4 histone proteins come together to form a histone octamer [5]. The DNA forms a complex with histone octamer to form a nucleosome. The nucleosome consists of about 146 base pairs of DNAs wrapped around the histone octamer in a superhelical fashion [6, 7]. Upon addition of H1 histone to the nucleosome, it forms a chromatosome, which consists of around 166 base pairs of DNAs wound around it. Two chromatosomes are connected by linker DNA [8]. The C-terminal domains of H2A and H2B, as well as the N-terminal domains of H2A, H2B, H3, and H4 extend from the globular nucleosome core and are called histone tails [9]. The region of chromatin where nucleosomes are densely packed is called heterochromatin. It is inaccessible to the transcription factors and polymerases and thus is a transcriptionally inactive region. However, the region of chromatin where nucleosomes are loosely packed is called euchromatin. The DNA in this region is accessible to the transcription factors and polymerases and thus it can be transcribed. Various modifications to the histone proteins allow the nucleosomes to be densely or loosely packed. These modifications shall be discussed below. There exist a variety of cross-talk among various modifications. This cross-talk is facilitated by “writers”, “readers”, and “erasers”. Writers are enzymes that add a modification to histones or DNA, similarly, erasers are enzymes that remove the modification. However, readers have a domain that recognizes and interprets the modified or unmodified site [10]. Histone modifications can be studied using chromatin immunoprecipitation assays (ChIP). In the presence of high-quality antibodies, ChIP assays can analyze even minute changes in histone modification and nucleosome structure [11]. Distribution and levels of endogenous histone H3 lysine modifications can be monitored using Fabs (fluorescently labeled specific antigen-binding fragments), without disturbing cell growth and embryo development [12].
Histone acetylation and deacetylation play a significant role in gene regulation. The N-terminal tail projecting from the histone core of the nucleosome contains positively charged lysine residues that undergo acetylation or deacetylation catalyzed by histone acetyltransferase (HAT) and histone deacetylase (HDAC), respectively. Acetylation removes the positive charges on histones, thus weakening the electrostatic attraction between histones and the phosphate-sugar backbone of the DNA, resulting in relaxed chromatin, which is associated with gene expression. Hence, histone acetylation is generally considered as an active histone marker. Generally, hyperacetylation leads to more relaxed chromatin whereas hypoacetylation leads to more condensed chromatin. Histone acetyltransferase CBP (cyclic-AMP response element-binding protein) acts in conjugation with p300, forming CBP/p300 complex, which is capable of recruiting other HATs, like PCAF (p300/CBP-associated factor) [13]. As many as 25 HATs have been identified so far and classified into five families—CBP/p300, SRC, MYST, TAFII250, and Gcn5-related N-acetyl-transferase. All HATs use acetyl-coenzyme A as an acetyl group donor [14]. Most active gene enhancers have been observed to show high levels of the H3K122ac mark (Table 1) [15].
Enzymes/Writers | Residues modified |
---|---|
HAT1 | H4 (K5, K12) |
CBP/p300 | H3(K14, K18, K122) H4(K5,K8) H2A(K5) H2B(K12, K15) |
PCAF/GCN5 | H3 (K9, K14, K18) |
Humans show 18 HDACs, which are divided into four classes as shown in Table 2.
Class | Enzymes/Erasers | Properties |
---|---|---|
Class I (Rpd3-like proteins) | HDAC1 to 3 HDAC8 | Catalyze zinc-dependent hydrolysis of acetylated histones |
Class II (Hda1-like proteins) | HDAC4 to 7 HDAC9 HDAC10 | Catalyze zinc-dependent hydrolysis of acetylated histones |
Class III (Sir2-like proteins) | SIRT (sirtuins) 1 to 7 | Utilize NAD+ during deacetylation to form nicotinamide and 2’- |
Class IV | HDAC 11 | Catalyze zinc-dependent hydrolysis of acetylated histones |
Various classes of HDACs and their general properties [13].
Inactivation of CBP, such as through chromosomal translocation or bi-allelic mutations, has been observed to be correlated with oncogenic effects, observed to be involved in leukemia [18]. However, inhibition of CBP/p300 has shown antitumorigenic properties in regard to gastric cancers [19]. TATA-box binding protein associated factor 9 (TAF9) increases fatty acid
Methylation of lysine residues of histone proteins (usually H3 and H4) is catalyzed by lysine methyltransferases (KMTs) and reversed by lysine demethylases (KDMs). This modification occurs post-transcriptionally. KDMs and KMTs also have shown roles in the regulation of the cell cycle [21]. In plants, DNA methylation tends to occur as a heritable epigenetic mark at the C-5 position of cytosine in the context of CG, CHG, and CHH (where H is A, C, or T) to form 5-methylcytosine.
Lysine methyltransferases (KMT) transfer a methyl group from S-adenosyl-L-methionine (SAM) onto the epsilon amino group of lysine residues of histone proteins. There are two classes of KMTs based on their catalytic domains: the SET domain-containing enzymes, and the one lacking SET domain. The latter is represented by KMT4, which is also known as Dot1L in humans. Both enzyme classes use S-adenosyl-L-methionine (SAM) as the methyl group donor [21]. The lysine of histone can be monomethylated, dimethylated, or trimethylated. For instance, trimethylated lysine 9 of histone H3 is represented as H3K9me3 and its monomethylated form is represented as H3K9me1.
Lysine demethylases remove the methyl group from the methylated epsilon amino group of lysine residues of histone proteins. KDM1A (also known as LSD1)—the first demethylase to be discovered—contains a flavin adenine dinucleotide-dependent monoamine oxidase domain that has been known to catalyze the demethylation of H3K4me2 and H3K4me1. Another class of KDMs employs jumonji (jmj) C domain to catalyze demethylation by oxidizing methyl groups. The cofactors of JmjC proteins are alpha-ketoglutarate, molecular oxygen, and Fe (II) [22]. Formaldehyde is one of the products of demethylase reactions (Table 3) [26].
Histone phosphorylation is a posttranslational modification instigated by DNA damage, entry into mitosis, or extracellular signals. It can trigger the binding of reader proteins and change the affinity of reader or writer proteins of other histone modifications [27]. Serine (S), threonine (T), and tyrosine (Y) are the sites of phosphorylation on histones. The mammalian 14–3-3 family of readers of the H3S10ph mark is composed of seven members that have been demonstrated to show interaction with around 700 different factors [28], including many chromatin-modifying proteins and transcriptional regulators, for instance, p53 [29]. 14–3-3 show increased affinity for the H3S10ph mark when the nearby lysine residues K9 or K14 are acetylated [30]. H3S10 is phosphorylated during mitosis by the action of Aurora B kinase, where data has suggested that this phosphorylation may function by displacing HP1 (Heterochromatin protein 1) from H3K9me, which otherwise plays a role in the compaction of chromatin. H3T3 phosphorylation catalyzed by Haspin kinase is required for appropriate metaphase chromosome alignment [31] (Table 4).
Histone residue (phosphorylated) | Kinase(s)/Writers | Function(s) of the phosphorylation mark |
---|---|---|
H1T18ph, | CDK2 | — |
H2AS1ph | Ribosomal protein S6 kinase alpha-5 | Transcription inhibition. |
H2AT119ph | NHK-1, Aurora B | Mitotic regulation of chromatin structure and function. |
H2BS32ph | Protein kinase C (PKC) | Probable role in apoptosis-related nucleosomal DNA fragmentation. |
H2BS36ph | AMPK | Direct transcriptional and chromatin regulatory pathways resulting in cellular response to stress. |
H3T3ph | Haspin | Proper localization of chromosomal passenger complex (CPC) at centromere. |
H3T11ph | Death associated protein-like kinase (Dlk) | Regulation of kinetochore assembly (during prophase to early anaphase) [34]. |
H3T6ph | PKC beta 1 | Hormone dependent gene activation: Phosphorylation-dependent on androgen prevents LSD1-mediated H3K4demethylation. |
H3S10ph | Aurora B | Dissociates HP1 from chromatin and prevents formation of condensed heterochromatin. Assists in condensation during cell-division; involved in transcription of certain genes. |
H3T41ph | JAK2 | Involved in hematopoietic differentiation. |
H3T45ph | Protein kinase -C, S-phase kinase Cdc7-Dbf4 | DNA replication, apoptosis, function in DNA damaged cells when DNA is nicked. |
H3Y41ph | Tyrosine-protein kinase JAK2 | |
H4S1 | CK II | Repair of DNA damage, chromatin assembly, and mitosis. |
H4H18 & H4H75 | Unknown | Destabilization of histone octamer to facilitate DNA replication. |
Chromatin structure and gene expression are also regulated by small ubiquitin-like modifier (SUMO) conjugation. Along with altering substrate-protein or substrate-DNA interactions, SUMO can also block ubiquitin attachment sites [35]. The reversible attachment of mature SUMO proteins to the lysine (K) side chains of substrate proteins are regulated by an enzyme pathway analogous to the ubiquitin pathway. SUMO is expressed in all eukaryotes and is evolutionarily conserved. Humans express five SUMO paralogs, SUMO-1, −2, −3, −4 and − 5.
Ubiquitination is the reversible process of transfer of ubiquitin to the histone core proteins (H2A, H2B, H3, H4). It is also known as ubiquitylation. Histone ubiquitination is involved in nearly all DNA-related processes such as DNA replication, transcription, and repair. Ubiquitin moiety consists of the 76-amino acid polypeptide, and hence is a bulky modification. In humans, ubiquitination of histone mainly occurs on the H2AK119ub1 and H2BK120ub1 catalyzed by an isopeptide bond formation between the carboxy-terminal glycine of ubiquitin and the epsilon-group of a lysine residue on the carboxy-terminal tail of histones. Ubiquitin transfer is an ATP-dependent process. The first step is adenylation of the C terminus of ubiquitin catalyzed by E1. Two of the known human ubiquitin E1 enzymes are UBA1 and UBA6. It was observed that UBA1 associates with DNA break by interacting with poly-ADP ribosylated proteins [39]. UBA1 might be the preferred nuclear E1 [40]. E2 enzyme receives ubiquitin moiety from E1 enzyme and conjugates it to the respective substrate. It has been observed that
DNA methylation includes the addition of a methyl group to the DNA at the 5′ position of the pyrimidine ring of cytosine residues. This results in 5-methylcytosine (5mC). DNA methylation usually takes place on CpG dinucleotide sequence. The region of the genome where CpG residues are concentrated is known as a CpG island. CpG islands are located on more than half of human gene promoters. Most CpG dinucleotides are methylated [43] whereas most CpG islands are unmethylated, especially those located in the promoter region of transcriptionally active genes. These CpG islands, upon undergoing methylation can lead to gene silencing through various mechanisms such as inhibiting or promoting the recruitment of regulatory elements to their respective binding sites. Cancer cells usually show hypermethylated CpG islands causing the silencing of tumor suppressor genes. The role of 5-mC does not merely depend on its abundance but also on its genetic context or surroundings, and its location within the different regions of a gene. Non-CpG methylation can be found in a context where CHH or a CHG are present (H being T, A, or C), which is found in plants and embryonic stem cells. Other DNA methylations such as N6-methyladenine is being studied as potential epigenetic mark [44]. 5mC is converted to 5hmC (5-hydroxymethyl cytosine). This has been observed to be catalyzed by ten-eleven translocation family proteins [45]. DNA is methylated by the action of DNA methyltransferases (DNMTs), of which DNMT 1 is ubiquitously expressed. It uses S-Adenosyl-L-methionine as a methyl group donor. Cytosine methylation patterns are inherited through cell division. This involves DNMT 1 having hemimethylated CpG dinucleotide specificity. Hence, based on the presence of methylation on the CpG dinucleotide in the complementary template strand, DNMT 1 can methylate CpGs in the newly synthesized DNA strand [43]. Studying DNA methylation is centered on three major approaches: (i) bisulfite conversion-based, (ii) methylation-sensitive-enzyme-restriction based (MSRE), and (iii) affinity enrichment based. The methylation signal generated by these assays is then analyzed by either DNA hybridization or sequencing. Bisulfite converted DNA is most commonly analyzed by microarray or Next Generation Sequencing [46]. Various techniques are employed for DNA methylation profiling such as pyrosequencing, bisulfite-PCR, ChIP seq (Chromatin Immunoprecipitation), bisulfite seq, and specialized RNA seq. Illumina sequencing of total genomic DNA known as whole-genome bisulfite sequencing (WGBS), is a high-throughput for DNA methylation analysis [47]. Since bisulfite sequencing results in the alteration of unmethylated cytosine into uracil, which upon PCR amplification is replicated as adenine, bisulfite-free approaches have gained traction attributing to their noninterference with the DNA sequence. Several bisulfite-free methods for the detection of methylation have been developed recently, such as TAPS (TET-assisted pyridine borane sequencing) [48] and
DNA methylation is capable of altering chromatin structure and by extension gene expression. Histone modifications, transcription factors, ncRNAs, etc. in concert with DNA methylation affect chromatin and regulate gene expression [52].
Although plants and mammals have significant morphological dissimilarities and a long evolutionary history, the similarities on a fundamental level are striking. Epigenetic mechanisms discovered in mammals or plants are mostly relevant to both [53]. Nutrition and environment play a crucial role in the development of phenotypic characters, from prenatal development to later on in life. The most widely studied effect of epigenetics on health is in terms of cancer biomarkers that are studied in the form of DNA methylation. However, epigenetics has a broader impact on health. Epigenetics also play a major role in plant growth, development, and reproduction, especially in plant breeding. Epigenetics of human health has gained traction in complex disorders such as allergies, autoimmune diseases, memory, cancer, behavior plasticity, and psychological and neurodegenerative disorders. Some epigenetic marks can be reversible, and this has funneled researchers’ interest in epigenetic therapy. Epidrugs are drugs that target epigenetic marks responsible for epigenetic alterations. An example of these is histone deacetylase inhibitors [54]. Histone deacetylase inhibitors are being used as cancer therapeutic agents, all while some have received U.S. F.D.A. approval for treatment of multiple myeloma, cutaneous and peripheral T-cell lymphoma. Additionally, HDAC inhibitors are being used as antifibrotic, anti-inflammatory, and antidiabetic agents.
Epigenetics play a significant role in various diseases such as cancers, autoimmune diseases, neurodegenerative diseases, congenital diseases, etc. HATs and HDACs modulate the transcriptional activity of nuclear factor-κB that results in downstream inflammatory gene expression levels that have been identified in the regulation of several diabetic key genes [55]. Cancer cells usually show hypermethylated CpG islands preceding promoters, and this leads to the silencing of tumor suppressor genes. This silencing allows cells to grow rapidly, leading to tumorigenesis. Imprinting, in genetics, delineates a condition where one of the two alleles for a gene pair is not expressed due to certain epigenetic modifications. This can lead to complications if the expressed allele is impaired, causing phenotypes such as susceptibility to certain microbes or chemical substances. Compared to healthy cells, malignant cells show decreased monoacetylated (H4ac) and trimethylated form of H4 (H4me3) [56]. DNA methylation patterns show a change in response to inherited genetic polymorphisms, exposures to environmental chemicals, and diet [57, 58, 59]. Histone acetylase inhibitors are a class of epidrugs. An epidrug Panobinostat, a non-selective histone deacetylase inhibitor, has been approved by the U.S. F.D.A. for the treatment of multiple myeloma [60].
Nutrition, being one of the most studied factors, has been understood to play an important role in epigenetics. Adverse antenatal nutritive conditions and postnatal health all have been observed to be correlated. Nutrients can either act directly by inhibiting epigenetic enzymes such as DNMT, HDAC, or by altering the substrate availability necessary for those enzymatic functions. Low dietary levels of folate, methionine, or selenium (all involved in methyl group donation or transfer) can lead to hypomethylation, which has been observed in neural tube defects, atherosclerosis, and cancer [61, 62, 63, 64, 65]. It has been observed that prenatal as well as early postnatal stress exposure have impacts on disease susceptibility [66]. DNA hypomethylation and histone acetylation are involved in the induction of gamma-globin expression [67]. A clinical trial is underway that deals with the down-regulation of BCL11A gene, which suppresses the production of fetal hemoglobin (HbF), resulting in an increase in the level of HbF, which has been shown to be therapeutic in patients with beta-hemoglobinopathies [68].
Endocrine Disrupting Chemicals (EDC), man-made chemicals known to alter endocrine functioning, that has been correlated with lower birth weight in children induce Adipogenesis. The epigenome is susceptible to the generation of new phenotypes in response to changes in environmental stimuli (Tables 5 and 6).
Year | Name of the scientist(s) | Conclusions drawn/discoveries made |
---|---|---|
1996 | Korenke et al. | Studied monozygotic identical twin for x-linked adrenoleukodystrophy (ALD) gene and concluded that some non-genetic factors might be responsible for the difference in ALD phenotype. [69] |
2005 | Fraga, M. et al. | Epigenetic variations arise during the lifetime of monozygotic twins. [70] |
Genes/diseases/disorders | Epigenetic observation | Note |
---|---|---|
Diabetes | HATs & HDACs modulate transcriptional activity of nuclear factor-Κb. | Show downstream inflammatory gene expression levels identified in the regulation of diabetic key genes. |
Cancer | Hypermethylated CpG islands preceding promoters. | Leads to the silencing of tumor-suppressing genes and hence tumorigenesis. |
Cancer | Decreased acetylation at H4ac and decreased methylation at H4me3. | Seen in malignant cells. [56] |
Neural tube defects, atherosclerosis, cancer | Hypomethylation | Caused due to Low dietary levels of folate, methionine, or selenium (all involved in methyl group donation or transfer) [61, 62, 63, 64, 65] |
Immunity | Alterations in levels of acetylation and methylation. | Required to alter DNA accessibility to allow recombination for antigen specific responses. [71] |
Endocrine Disrupting Chemicals (EDC) that have been correlated with lower birth weight in children induce Adipogenesis | DNA methylation variance was also observed along with adipogenesis in human. Mesenchymal stem cells [72] exposed to EDC. |
Epigenetic change of plant genomes resembles that of mammals in that there is an analogous profile of histone marks and the DNA can be methylated at cytosine residues. Still, plant epigenomes are more susceptible to environmental influence than those in animals. Transgenerational epigenetic inheritance has a requirement that the epigenetic marks can be passed to the progeny. The variation in methylation of the same gene among different plants is known as epialleles [73]. Stable and heritable stress-induced modifications that cannot be reversed are being referred to as the epigenetic “stress memory”. Epigenetic marks that are heritable may affect the inheritable phenotypic variation of plants, impacting fitness, and hence are subject to natural selection. However, unlike inheritable inheritance, the epigenetic changes show unstableness and are affected by the climate [74, 75]. DNA hypomethylation induced by pathogen infections acts as a part of plant defense response in many species including the model plant
Epigenetic observation | Note |
---|---|
DNA hypomethylation induced by pathogens infections | Part of plant defense response. |
Hypermethylated genome regions in | Tend to preferentially occur in shoots than in roots. [77] |
Few epigenetic observations and their role in plant health [77].
Scientists, Year | Observed effect | Probable Cause |
---|---|---|
Sano et al., 1990 | Induction of dwarf plants in rice | Demethylation of rice genomic DNA |
Burn et al., 1993 | Induction of flowering initiation | Vernalization treatments cause a reduction of DNA methylation levels. |
Epigenetic mechanisms play a crucial role in the phenotype of an organism. Epigenetic mechanisms include DNA modifications such as methylation, histone modifications such as SUMOylation, methylation, acetylation, phosphorylation, etc.—and action of non-coding RNAs. Recent technological advancements have made and will progressively make studying such modifications easier, more accurate, and cost-effective. Studying epigenetic modifications has provided insights into the inter-individual differences that genetics alone could not account for. Many phenotypes and diseases in humans and plants show underlying epigenetic marks at play from early on in the life of the organism, and some conditions or diseases can even manifest later on in life depending on their nutrition and environment. Histone modification reactivates gamma-globin gene expression in adults. Down-regulation of gamma-globin suppressing genes, which suppresses the production of fetal hemoglobin (HbF), results in an increase in the level of HbF, which has been shown to be therapeutic in patients with beta-hemoglobinopathies. Histone deacetylases are being used to treat various diseases such as multiple myeloma, cutaneous and peripheral T-cell myeloma. Epigenetics can be used for selective breeding of crops with desirable traits. As more would be understood about the various regulatory pathways involved in epigenetic mechanisms and more epigenetic modifications, it could revolutionize human disease prevention.
The authors would like to thank Dr. B.A. Mehere, Principal, and Dr. Utpal Dongre, Head of the Department of Biochemistry and Biotechnology, Dr. Ambedkar College, Deekshabhoomi, Nagpur, India, for providing research space and facility.
The authors declare no conflict of interest.
No fund was received for this work from any funding agencies.
CBP | Cyclic-AMP response element-binding protein |
CDK2 | Cyclin-dependent kinase 2 |
cfNOMe | Cell-free DNA-based Nucleosome Occupancy and Methylation profiling |
ChIP seq | Chromatin Immunoprecipitation |
CPC | Chromosomal passenger complex |
Dlk | Death associated protein-like kinase |
DNMTs | DNA methyltransferases |
DUBs | Deubiquitinating enzymes |
HAT | Histone acetyltransferase |
HbF | Fetal hemoglobin |
HDAC | Histone deacetylase |
HMG | High mobility group |
HP1 | Heterochromatin protein 1 |
jmj C | Jumonji |
KDMs | Lysine demethylases |
KMTs | Lysine methyltransferases |
miRNAs | microRNAs |
MSRE | Methylation-sensitive-enzyme-restriction based |
NAFLD | Non-alcoholic fatty liver disease |
ncRNAs | Non-coding RNAs |
PCAF | p300/CBP-associated factor |
PKC | Protein kinase C |
SUMO | Small ubiquitin-like modifier |
TAF9 | TATA-box binding protein associated factor 9 |
TAPS | TET-assisted pyridine borane sequencing |
USPs/UBPs | Ubiquitin specific proteases |
WGBS | Whole-genome bisulfite sequencing |
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\n\nWe have adopted the Protocol to increase the number of readers of our publications. All our Works are more widely accessible, with resulting benefits for scholars, researchers, students, libraries, universities and other academic institutions. Through this method of exposing metadata, IntechOpen enables citation indexes, scientific search engines, scholarly databases, and scientific literature collections to gather metadata from our repository and make our publications available to a broader academic audience.
\n\nAs a Registered Data Provider, metadata for published Books and Chapters are available via our interface at the base URL: http://mts.intechopen.com/oai/index.php
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