\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. From chapter submission and review, to approval and revision, copy-editing and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. A unique name with a unique work ethic right at your service."}},relatedBooks:[{type:"book",id:"8450",title:"Beta Thalassemia",subtitle:null,isOpenForSubmission:!1,hash:"976f72013cd8e78d8f65bfb1f51f0146",slug:"beta-thalassemia",bookSignature:"Marwa Zakaria and Tamer Hassan",coverURL:"https://cdn.intechopen.com/books/images_new/8450.jpg",editedByType:"Edited by",editors:[{id:"187545",title:"Prof.",name:"Marwa",surname:"Zakaria",slug:"marwa-zakaria",fullName:"Marwa Zakaria"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7084",title:"Contemporary Pediatric Hematology and Oncology",subtitle:null,isOpenForSubmission:!1,hash:"21ab490c2debd2992b2a0b45f778b785",slug:"contemporary-pediatric-hematology-and-oncology",bookSignature:"Marwa Zakaria and Tamer Hassan",coverURL:"https://cdn.intechopen.com/books/images_new/7084.jpg",editedByType:"Edited by",editors:[{id:"187545",title:"Prof.",name:"Marwa",surname:"Zakaria",slug:"marwa-zakaria",fullName:"Marwa Zakaria"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6550",title:"Cohort Studies in Health Sciences",subtitle:null,isOpenForSubmission:!1,hash:"01df5aba4fff1a84b37a2fdafa809660",slug:"cohort-studies-in-health-sciences",bookSignature:"R. 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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:"73854",title:"Treatment of Wastewater by Nanofiltration",doi:"10.5772/intechopen.94329",slug:"treatment-of-wastewater-by-nanofiltration",body:'Increased demands by limited water resources have triggered in worldwide for innovative water practices. Many processes are used to purify water contaminated with rare earths and heavy metals, such as solvent extraction, precipitation, ion exchange, absorption and liquid–liquid extraction. The underground water resources can be polluted by wastewaters [1].
There is a lot of proceed of separation which can be applied to the treatment of discharges, among these techniques we mention: chemical precipitation, coagulation–flocculation, flotation, ion exchange, and the membrane processes as supported membrane liquid [2, 3, 4], nanofiltration (NF) [5], ultrafiltration (UF) [6, 7], reverse osmosis (RO) [8] and microfiltration recently show by [9].
Nanofiltration has a lot of applications in industry [10]. Among membrane technologies, nanofiltration is the best opportunity to solve environmental problems, such as: desalination recently shown by [11], wastewater and ground water treatment [12, 13], and heavy metals elimination [14].
These methods are valid but have many drawbacks which require the use of organic solvents which are harmful to the environment and time consuming.
With technological development in industries and the differentiation in quantity and type of waste, the development of new, more efficient techniques has become necessary. Among these techniques, membrane processes.
Currently, membrane extraction is the most widely used method for treating industrial waste and purifying wastewater. It is a very active field in separation sciences and many companies are currently producing and developing new membrane extraction techniques.
Nanofiltration is ecological technique; this advantage is particularly linked to this operation without the need for organic solvents and also because the extraction requires little time to perform.
Currently, membrane techniques play a very important role in water purification and open up new possibilities for beneficial use for water sources. They were difficult to use before for technical and economic reasons.
Membrane methods are commonly used in the purification of water and the purification of wastewater [15, 16].
Using these techniques, every five years the creation of water purification plants is multiplied by ten [17].
The “naturalists” are the first who approached the selective transport of substances through membranes [18].
In order to explain the transfer of the solvent, Abbé Nollet supposes the presence of forces between the parts of the membrane, through the membranes the passage of substances is influenced by their molecular mass [19].
The use of membrane processes in industry began in the 1960s. There is a wide variety of membranes due to the existence of several fields of application for membrane processes.
The membranes are used in the separation and concentration of ionic species or molecules in the solution and/or to separate microorganisms (bacteria, viruses, etc.) or suspended matter.
Perm selective membranes are used in membrane processes [19, 20].
The selective displacement of certain components through a membrane, under the application of a force, is the concept of membrane separation [20, 21, 22].
All membrane processes use tangential filtration to limit the accumulation of material [20, 23].
The solution of the particles which do not pass through the membrane is called “retentat”, and “permeat”, the solution of the components which pass through the membrane [24].
Various advantages, among which:
Reliability and quality of the final product [20].
Low energy consumption [20].
The ability to treat water containing several metals.
Good selectivity [25].
It works without adding chemicals [26], and the ease and use of industrial integration [20].
It works without the need for secondary chemicals [27, 28, 29].
For these reasons, the water treatment sectors use these technologies [30].
The nanofiltration technique is located between ultrafiltration (UF) and reverse osmosis (OI), it is used to separate components of size close to the nanometer order.
This type of membrane does not retain non-ionized organic compounds with a molar mass of less than 200 g/mol and monovalent salts. On the other hand, non-ionized organic compounds with a molar mass greater than 250 g/mol and multivalent ionized salts (calcium, magnesium, aluminum, sulfates, etc.) are retained [31].
Nanofiltration has lower electrical energy consumption, because it requires lower pressures than reverse osmosis [32].
The nanofiltration technique (Figure 1) is based on two separation mechanisms, separation under the effect of electrical repulsion for charged species, and separation under the effect of size for uncharged solutes [33].
Selective membrane [
The comparison between membranes of the same type requires the evaluation of the performance of these membranes under real conditions.
Using a few criteria such as: selectivity, permeability and lifetime, one can consider that one membrane is more adequate than another to be separated [27]. The information provided by the membrane manufacturers is insufficient to compare the membranes. To understand these membranes, the acquisition of this information is essential in order to master the transfer mechanisms and improve their performance.
Two categories of parameters are often sought:
performance-related parameters:
Permeability.
Retention.
The concentration factor.
Parameters related to morphology:
The membrane thickness.
Pore sizes.
Distribution of pores.
The charge density.
Hydrophobicity.
The adsorption and absorption capacities.
Under the action of a pump, the fluid circulates parallel to the membrane from a reservoir (Figure 2) [29].
Tangential filtration [
The flow of the feed solution is perpendicular to the membrane (Figure 3) [17, 28].
Front filtration [
The processes responsible for membrane filtration are:
Sieving.
The friction on the walls of the pores.
The diffusion in the membrane material and in the pores of the membranes.
Repulsive or attractive surface forces.
Electrostatic repulsion.
According to their separation mechanisms, the membranes are classified:
Non-porous membranes: these membranes can be considered as dense media, the species are diffused in the volumes located between the molecular chains of the material.
Porous membranes: the effects of friction, sieving and surface forces are dominant in these membranes.
Ion-exchange membranes: consist of dense gels, it is a special type of non-porous membrane, they can be anion-exchange (with a positive charge) or cation-exchange (with a negative charge).
According to the geometry under which the membranes are manufactured, they are classified as:
Flates modules (Figure 4):
Spiral membranes (Figure 5):
Tubular modules (Figure 6): are membranes with an internal diameter greater than 3 mm.
Hollow fiber modules (Figure 7):
Flat module [
Spiral module [
Tubular module [
Hollow fiber module [
The membranes are synthesized from inorganic materials and organic polymers. There are also mixed membranes made from inorganic materials and polymers [38].
The majority of usable membranes are manufactured either from inorganic materials or from polymers.
The main polymers used for the manufacture of membranes are:
Cellulose derivatives: are inexpensive, considered more hydrophilic, this type of polymer has a low tendency to adsorb.
Polyamides: these polymers are very sensitive to chlorine, polyamides having chemical and thermal properties superior to those of cellulose derivatives.
Polysulfone and polyethersulfone, these polymers have good mechanical, and thermal.
Inorganic membranes are made of ceramic (zirconium, titanium, aluminum oxides). These membranes are expensive, have a mechanical, chemical and thermal stability superior to polymeric membranes, they are brittle [38].
According to their structure, the membranes can be classified:
Membranes with symmetrical structure (isotropic membranes): have the same structure over their entire thickness.
Membranes with asymmetric structure (anisotropic membranes): The structure of the membrane is different from one layer to another.
There are two subtypes of asymmetric membranes:
Membranes made from the same material.
Composite membranes: are mainly composed of two layers:
Skin: a layer with a very low thickness, this layer is responsible for the selectivity of the membrane.
Support layer: it is a layer with a much greater permeability than that of the skin layer, which is thicker and which retains the mechanical resistance.
In order to increase the permeability of the membrane, the majority of commercial membranes are manufactured with an asymmetrical structure [39].
The performance of filtration is characterized by the observed retention and permeates flow. Retention is expressed as follows [40]:
Cp: Concentration in permeat and C0: Concentration in feed.
This parameter characterizes the effectiveness of the treatment. It quantifies the retention of a target compound.
It represents the volume or mass flow crossing the membrane per unit of membrane area.
Permeability is a function of temperature and pressure.
According to Darcy’s law, the flow of solvent (Jv) is proportional to the transmembrane pressure.
The hydraulic permeability (Lp) is given by the following equation, this equation is valid for all membranes.
The permeate flow (Jv) characterizes the productivity and is expressed as follows:
The permeability of the membrane is deduced from the slope to the right of the permeate flow Jv as a function of the transmembrane pressure ΔP.
This is the resistance of the membrane to the flow of the fluid to be filtered; the resistance is related to the permeability by Eq. (3).
μ is the viscosity of the permeate (water).
The resistance can be calculated from the permeate flow through the membrane and the transmembrane pressure.
The SC of a membrane is the molecular weight above which the membrane retains at least 90% of the molecules. It is expressed in g/mol or in Dalton [40].
The cutoff is used in the characterization of membranes, but from a scientific point of view it is not rigorous, as it depends on the operating conditions and the characteristics of the solute.
This is a characteristic of the membrane, because beyond which the membrane will no longer be effective [41].
The conversion rate is the flow rate fraction of the liquid passing through the membrane [41]:
μ is the viscosity of the permeate.
The resistance can be calculated from the permeate flow through the membrane and the transmembrane pressure.
Depending on the chemical nature of the membrane, there are interactions between the membrane and the solutes to be filtered, in particular at the level of clogging [20].
Hydrophobicity and hydrophilicity:
Hydrophilicity depends on the ionized or polar groups of the polymers used, by nature organic membranes are hydrophobic [20].
Due to their hydrophilic properties, regenerated cellulosic membranes are widely used in ultrafiltration [42, 43].
Surface electrical charge:
Organic membranes have two functional groups one is amine (basic) and the other is carboxylic (acid) having positive or negative charges respectively.
Due to the partial hydrolysis of the amide functions, NF membranes are negatively charged, inorganic membranes have amphoteric surfaces.
The clogging phenomenon (Figure 8) occurs when dissolved or suspended matter is deposited on the outer surface or inside the pores [43]. Due to clogging, the performance of the membrane decreases [45].
Clogging mechanisms [
Upon contact between the membrane and the particles of the solution, a reversible or irreversible modification of the membrane was caused [40]. After this modification, the membrane needs to be replaced or cleaned [45].
The clogging mechanisms are linked to:
The adsorption of particles through the pores (partial blockage).
Complete blockage of the membrane pores.
Internal blockage of the membrane pores.
Formation of a deposit of particles on the membrane surface (forming a cake) [40, 45].
In view of the nature of the sealant, we can distinguish the type of plugging:
Clogging by precipitation of soluble salts (scale)
Bio-clogging (biofilm formation)
Clogging by colloidal substances [43].
The clogging reduces the flow of water at constant pressure, so a cleaning of the clogged membrane must be applied in order to recover its initial characteristics.
Clogging is a function of:
Type of membrane,
The nature and concentration of solutes and solvents,
The characteristics of the membrane surface,
Membrane materials. The hydrodynamics of the module.
Distribution of pore size.
The accumulation of solutes retained on the surface of the membrane leads to the phenomenon of concentration polarization [43], which causes an increase in the concentration of solute at this surface [41].
When the driving force is interrupted and the permeate flow quenched, the concentration polarization is invisible [45].
Assuming that the true concentration is unidirectional along an axis perpendicular to the membrane, the total permeation flux is the sum of the retro-diffusive flux and the convective flux [44].
To remove the clogging elements, cleaning with chemicals (acids and bases) and/or physical (or mechanical) cleaning and/or by using a specific cleaning solution containing appropriate detergents [46].
Physical cleaning is used to remove and loosen the material accumulated on the membrane.
Backwashing is the most common procedure: part of the permeate passes through the membrane in the opposite direction of flow.
This requires a membrane that must physically support the inverted pressure gradient, other practices use pulsed flows.
Air/gas scrubbing: used to inject air or gas into the membrane [47].
If the membrane is not fully restored, chemical cleaning is necessary.
Chemical cleaning contains two parts of acid and basic cleaning as well as rinsing.
Acid washing is used to dissolve the scale layers of metal oxides and thus prevent the formation of insoluble hydroxides that are difficult to remove [47].
The purpose of alkaline washing is to hydrolyze silica, inorganic colloids and organic and biological matter.
Surfactants are also used as cleaning solutions, they are used to:
Move the clogging elements in the surface.
Emulsified oils.
The solubilization of hydrophobic elements [47].
For example for polyether sulfonated membranes Tween 20 is used for cleaning [7].
Nanofiltration experiments were carried out with the separation unit illustrated in Figure 9. On an industrial scale, this unit is multiplied according to needs.
Experimental setup [
CA is the cartridge filter with activated carbon and 25 μm of wound cartridge filter. S is the safety valve (14 bars). B1 is the feed tank (100 L). B2 is the permeate tank (20 L). C2 is the nanofiltration membrane. FI1 is the upstream flow meter (100–1000 l/h). FI2 is the downstream flow meter of retentive. FI3 is the downstream flow meter of permeate. PI1 & PI2 are the manometers at upstream and downstream of module (0–16 bars). PI3 & PI4 are the monitoring manometers of filters state (0–2.5 bars). LSL1 is the low level sensor (pump safety). CE1 is the sensor of permeate conductivity measuring. Y is the emptying, CIT1 to the electrical display cabinet. V1–5, 7, 10, 11, 14–16, 19 & 22 are the pressure regulation valves for nanofiltration process. P is the multistage centrifugal pump (high pressure).
Analyzes of water are carried out on turbidimeter, pH meter, conductimeter, atomic absorption spectrophotometer, UV–visible, apparatus for measuring DBO5 and DCO, and ICP-MS.
With membrane techniques, gas separation is more economical.
Membrane processes are better for the environment because they work without chemicals.
Are easy and effective compared to other techniques.
A low investment cost for their systems.
The membranes do not require frequent regeneration.
The determination of various compounds [49].
During nanofiltration, the electromigration, diffusion and convection are the major transport mechanisms. The atoms ions can pass through the channels between the molecular groups in the molecular structure of the membrane. The selectivity of nanofiltration membrane was defined by nature and size of these passages, ionic size, shape, pore density, pore diameter, and membrane surface charge [50, 51].
The suitability of a thin film polyamide nanofiltration composite membrane (SNTE NF270–2540) to extract heavy metal ions (Zn (II), Cr (III), Cu (II), Fe (III), Cd (II), Pb (II), Co (II) & Ni (II)) from industrial wastewater was examined [52]. The operating conditions including feed pH value, feed metal concentration and pressure were optimized. The retention of iron at pH = 5.3 and nickel at pH = 7.2 for pressure from 6.0 to 13.5 bars was quantitative (100%). For lead at pH = 4.4 for pressure from 6.0 to 10 bars, the retention was quantitative (100%).
The influence of divalent cations on the rejection of trivalent cations was examined [52].
The membrane was characterized by using the ions transport model and the consumption energy was calculated. The effect of ionic concentration and the diffusion fluxes were studied [52].
The water purification by nanofiltration membrane techniques is presented, as well as the different classes of membranes. The influence of physico-chemical parameters is discussed.
The effect of pH on the adsorption capacity depends on the surface charge or zeta potential of the sorbent at different pH and presence of different electrolyte.
Purification by membrane filtration is highly dependent on the species present in water and properties of the membrane.
Membrane nanofiltration in combination with others techniques showed a high rejection.
NF membrane can be used in any types of water and it can treat organic or inorganic effluents.
For a given module, we observe that there is interest in working at a high conversion rate to limit heating of the solution (energy consumption). However, the solution to be treated is concentrated very quickly. Scaling of the cartridge will occur very quickly. We must find a compromise for the three parameters C0, Y and Qp.
We gratefully acknowledge the DGRSDT - Algeria for the financial support.
Epigenetics 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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