\r\n\tThis publication will aim to collect those projects and research that seek to make buildings, including urban environments, self-sufficient in terms of energy, focusing here on the solutions for HVAC and the energy systems they require and doing so from a double point of view: \r\n\t- Complexity. As is the case with the automobile and aeronautics industries, buildings have become human-inhabited spaces with an ever-increasing technological load, which will presumably also be used in other ways, as the pandemic associated with COVID-19 has shown. In these scenarios, will HVAC systems be considered as before, or will new solutions have to be considered for new challenges? \r\n\t- Disruptive technologies. In the coming years, the implementation of technologies such as hydrogen fuel cells, polygeneration of energy, the use of second-use electric batteries in buildings to accumulate energy from renewable energies, or the resolution of constructive solutions with 3D printing will become widespread in buildings. In this scenario, what will be the answers given by those responsible for HVAC systems? \r\n\tIn addition, concepts such as artificial intelligence, technology transfer, biomimicry, or stigmergy will undoubtedly provide high-value solutions to new and refurbished buildings that society demands.
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1. Introduction
Nowadays, Atherosclerosis is the most important source of morbidity and mortality in the world, and is detected by the accumulation of lipids deposits (mainly cholesterol) in macrophages located not only in large but also in medium sized arteries. Currently, the association between atherosclerosis and heightened oxidative stress is widely accepted. Nevertheless, despite numerous efforts the role of oxidative stress in the progression of Atherosclerosis is still not clear.
Oxidation is a biochemical process of loss of electrons, which is essential for life due to its involvement in the production of cellular energy. However, when oxidation is excessive causing cellular damage is when Oxidative Stress appears. This process is complex; therefore, it cannot be measured or defined by a single parameter. For this reason, currently the interest lies on developing antioxidant therapies and diets enriched with antioxidants that prevent or at least decrease cellular damage and atheromatous plaque formation originated by the excess of oxidative stress.
Aim. The aim of this review is to analyze the state of the art on oxidized LDL role within the pathogenesis of atherosclerosis.
This chapter will be developed according to the following titles,
Oxidative stress and atherosclerosis.
LDL Oxidation
OxLDL in atheromatous plaque formation
Study Models
OXIDATIVE STRESS AND ATHEROSCLEROSIS
The word “Atherosclerosis” comes from the ancient Greeks where "sclerosis” means hardening and “athere” is gruel or accumulation of lipid. The physiopathological process is characterized by the aggregation of cholesterol, infiltration of macrophages and the proliferation of smooth muscle cells (SMCs) as accumulation of connective tissues and thrombus creation. In early stages of the disease, the growth of the lesion starts in the sub endothelial space and its progress may even cause total cessation in blood flow with intermittent periods of quiescence. The accumulation of lipids and other organic molecules lead to a proliferation of certain cell types within the arterial wall that gradually impinge the vessel lumen and block up the blood flow in large and medium sized arteries. Furthermore, this disease tends to be more common in white than black men [1]. The magnitude of this problem is deep, because atherosclerosis claims more lives than all types of combined cancer and economic costs are considerably high[2]. Currently, the idea that atherosclerosis constitutes a state of high levels of oxidative stress is widely accepted and this phenomenon is associated with lipid and protein oxidation in the vascular wall[3, 4].
Despite the countless efforts made to explain the role of oxidative stress in progression of atherosclerosis, its predictive role is still not clear. Goldstein and Brown discovered the LDL incorporation process in peripheral cells as fibroblasts, macrophages and others -which meant for them the Nobel Prize- has been the basis for a series of subsequent discoveries, from 1979 up to now, which have intended to explain the development of the atherosclerosis’ process [5-8]. The hypothesis of oxidative modification in atherosclerosis, reviewed by Steinberg and others in several opportunities argues that the oxidation of low-density lipoprotein (LDL) is an early stage of the disease and that oxidized LDL (OxLDL) would contribute to atherogenesis [9-12].
Until 1991, the strength of the scientific evidence regarding the role of the oxidation of LDL in the phenomenon of atherosclerosis was such that the National Heart, Lung and Blood Institute recommended the initiation of clinical trials [8, 13-17]. In relationship to this hypothesis, based on in vitro assays, the evidence showed the following relevant aspects: 1) the LDL oxidation is the first event in the foam cell formations [18, 19] the LDL lipids in human arterial lesions are extensively oxidized and 3) the presence of Ox LDL is evident in vivo[20]. On the other hand, the existence of several structurally unrelated compounds such as probucol and vit E that inhibit atherosclerosis in animals, prevent the initiation of the disease due to a reduction of the oxidization of LDL [21]. In relationship to probucol, It seems to be a more effective protection against lesion formation on an early-stage of the disease than the statin-mediated lipid-lowering effects [22].
The events involving the process of atherosclerosis begin with LDL oxidation in the vascular wall. This happens due to the production of reactive oxygen species (ROS) and nitrogen species (NOS) by endothelial cells, therefore, oxidative modifications would be crucial in the clinical aspect of coronary artery disease such as endothelial dysfunction and plaque disruption [23].
Although it is known by scientific evidence that LDL oxidation plays a central role in the pathophysiology of atherosclerosis, up to now there is no convincing proofs related to the protective effect of antioxidant therapy as a way to prevent the damage caused by that process on vital macromolecules such as lipids, proteins and DNA.This may be due to the discrepancies between human and animal studies that use antioxidant therapies either to try or to limit the atherosclerotic process and cardiovascular events. It is not clear if oxidative stress is cause or consequence of the atherogenic process. In this sense, it has been proposed that inflammation could be considered as a primary process and oxidative stress as a secondary event of atherosclerosis [24].
2. LDL oxidation
Oxidation is a biochemical process of loss of electrons, which is essential for life due to its involvement in the production of cellular energy. Oxidative stress appears when oxidation is excessive. This apparently simple process is actually complex in all biological levels, and cannot be measured or defined by a single parameter.
The oxidation process of lipids and proteins is the result of an excess of free radical and other oxidant species derived from oxygen, nitrogen and other chemical elements in the body. Chemically, the oxidative stress is associated with an increased production of oxidizing species or a significant decrease in the effectiveness of antioxidants defenses such as reduced glutathione, catalase, peroxidases and others. The cell proliferation and death are key processes in the progression of atherosclerosis and severe oxidative stress can cause cell death and even mild oxidation can trigger cellular stress and apoptosis, while more intense stress may cause necrosis [25].
There is a constant production of ROS and other oxidative species derived from the normal and xenobiotic metabolism, ionizing radiation and smoke snuff exposure, among others. Oxidative molecules can exert positive or negative effects over cells and tissues, depending on their concentration. ROS plays an important role in several physiological cell processes, such as signaling and regulation cascades, however excesses can induce chemical and structural modifications which has been proven that alter the function of cellular components, inhibit protein function, induce DNA damage, viral activation and lipid peroxidation which can promote cell death (Figure 1).
In addition, redox systems such as gluthation peroxidase, thioredoxine reductase and pyridine nucleotide redox status can change their physiological function when modified by ROS and others reactive species, affecting the normal cell signaling including apoptotic cell death [26].
Figure 1.
The figure shows some sources and consequences of oxidative stress.
Today there are clear proofs that LDL oxidation plays a significant role in atherogenesis. In fact, this has been demonstrated throughout time. So, between 1985 and 1989, 62 papers about OxLDL were published; between 1992 and January 1997, the number of publications related to OxLDL went up to 727, and up to day only considering PubMed entry, it is possible to find over 7000 publications associated with the key words Oxidized LDL. This growing interest is supported by the large amount of evidence which confirms that oxidative modification of LDL plays a pivotal role in atherosclerosis and hence, makes it an obvious target for therapeutic approaches [10, 27].
In 2002, Friedman et al. showed that the oxidized lipids from OxLDL are biologically active. Specifically, polyunsaturated fatty acids (PUFA) either free or bound to an ester from phospholipid are converted into hydroperoxides, which break down to form highly reactive molecules, such as malondialdehyde and 4-hydroxynonenal among other metabolic products. These reactive aldehydes can then form Schiff-bases, covalent Michael-type adducts with lysine residues of apolipoprotein B in LDL molecules. Besides, the sn-2 oxidized fatty acid fragments which can remain attached via ester bridges may also contain terminal reactive aldehydes. However, this reactive phospholipid also called "aldehyde phospholipid core" may also form adducts with Schiff-base lysine residues of apolipoprotein B and presumably also with other proteins and amines-containing phospholipids, such as phosphatidylethanolamine and phosphatidylserine (Figure 2).Finally, the authors proved that when LDL presents substantial oxidative modifications, a great number of neoepitopes are generated transforming it in a highly immunogenic LDL. Indeed, there are a variety of autoantibodies directed to epitopes of OxLDL derived from specific oxidation in animals and human, that appear to increase in individuals with clinical and morphological signs of atherosclerosis [28].
Figure 2.
Oxidative modifications in ApoB present in lipoproteins.
On the contrary, OxLDL is thought to promote atherosclerosis through complex inflammatory and immunologic mechanisms that lead to lipid dysregulation and foam cell formation. Matsuura et al (2006) proposed that in the intima of atherosclerotic lesions, the OxLDL forms complex with the Beta 2 glycoprotein I (beta2GPI) and / or C-reactive protein (CRP). In patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS), anti-OxLDL/beta2GPI complex autoantibodies have been found which has been significantly related to arterial thrombosis. In a non-immunized animal model of APS (NZWxBXSB F1 mice), it was demonstrated that anti-OxLDL/beta2GPI complex IgG autoantibodies can emerge spontaneously. Moreover, a monoclonal autoantibody (WB-CAL-1; IgG2a) against a complex beta-2-GPI was derived from the same mice. WB-CAL-1 significantly increased the in vitro uptake of OxLDL/beta-2-GPI complex by macrophages, suggesting that these IgG auto antibodies are pro-atherogenic. As opposed, IgM antibodies to OxLDL found in pro- atherogenic mice ApoE (-/-) and LDL -R (-/-) seemed to be protective. In human beings it has been widely reported the presence of IgG anti-Ox - LDL antibodies, but their clinical significance is not clear yet [29].
In the beginning, OxLDL was characterized by its biological properties, specifically for being a ligand for acetyl LDL receptor instead of a native LDL receptor. The Acetyl LDL receptor, present in macrophages, uptakes the OxLDL much faster than the native receptors, favoring the excessive intracellular accumulation of cholesterol. LDL oxidation and its uptake can be accomplished in vitro by an overnight incubation with macrophages cultured on an appropriate medium with 5 - 10 μM Cu2 + (oxidant) for 8-16 h allowing the study of the mechanism and kinetics of OxLDL.[30]
LDL oxidative modification, produces numerous structural changes, resulting in an increment of electrophoretic mobility, higher density, a polipoprotein B degradation, hydrolysis of phosphatidylcholine, changes on the amino groups of lysine residues and generation of fluorescent adducts caused by the covalent binding of lipid oxidation products to Apo B[31].
In vitro assays have shown that oxidative modification of LDL can be mutated by cultured endothelial cells or by cupric ions, which results in an increase of the lipoprotein uptake into macrophages [32, 33]. Therefore, it seems to be obvious that LDL oxidation is a crucial step for macrophage-derived foam cells formation in early stages of an atherosclerotic lesion. Moreover, LDL can be oxidized by specific enzymes such as lipooxygenase and phopholipase A2, even when these modifications are not necessarily identical to the endothelial cells-dependent modifications, they are still useful for studying oxidative alterations of LDL. In fact, in 1998, it was demonstrated that the oxidative modification of LDL by specific enzymes leads to an increased recognition by macrophages [32]. In conclusion, it is possible to say that oxidation of LDL in cells depends on at least three possibilities: (a) lipid oxidation by the action of lipoxygenase within the cells followed by the LDL exchange on its medium; (b) direct lipoxygenase-dependent lipid oxidation during cell contact with LDL and (c) both possibilities mentioned above [34].
It is has been reported that the in vitro addition of acetyl groups to LDL (acetylation), generates a modified LDL which can induce cholesterol accumulation in macrophages. Indeed, acetylated LDL is incorporated by “scavenger receptors” (SRA), which in contrast to the normal LDL receptor, are not “down regulated”, so they induce a great intracellular lipid accumulation. Thus, acetylated LDL increases the formation of foam cells [35].
Another process that needs to be taken into account is the autoxidation of glucose or the early glycation products (carbonyl compounds) generated by oxygen free radicals (superoxide and hydroxyl) and hydrogen peroxide that can cause oxidative damage. Baynes et al in 1991 introduced the “glycoxidation hypothesis”, which proposes that oxidative stress concomitant to glycation plays an important role in the stage of advanced glycation of proteins. Modifications of lipoproteins by glycation and oxidation alter their structure to make them sufficiently immunogenic. In type 2 diabetes, high titles of antibodies have been found against glicosylated-LDL and glicosylated-OxLDL. Immunogenic properties of glycosilated-OxLDL induce immune complex formation. It has been shown that glycosilated-OxLDL is trapped in the artery wall in situ [36-40].
Various pathologies can be originated by oxidative stress-induced apoptotic signaling which is a consequence of an increase of ROS and a decrease of other oxidative species and/or antioxidants, disruption of intracellular redox homeostasis and irreversible oxidative modifications of lipids, proteins or DNA. A better understanding of redox control over the development of apoptotic process in the cell, could better guide the course of the therapeutic strategies associated with disorders related to oxidative stress [25].
A great number of diseases have been related to oxidative stress and generation of free radicals, for this reason, antioxidant therapies and diets (such as Mediterranean diet) rich or enriched with antioxidants are thought to be a promising way to prevent or at least to attenuate the organic deterioration originated by the excessive oxidative stress.
3. OxLDL in atheromatous plaque formation
Atherosclerosis is a chronic inflammatory disease of the arterial wall that culminates with the atheromatous plaque formation. At present, there is a consensus that oxidation of LDL in the endothelial wall is an early event in atherosclerosis, according to the oxidative hypothesis [24]. First, the circulating LDL particles are transported from the vascular space into the arterial wall, mainly across trancytosis[41]. LDL is retained in the extracellular matrix of subendothelial space, through the binding of basic aminoacids in a polipoprotein B100 to negatively charged sulphate groups of proteoglycans in the extracellular matrix (ECM) [42, 43], where it is prone to be oxidized by oxidative stress, generating OxLDL[21], as we previously mentioned in this article.
It is known that OxLDL participates actively in atheromatous plaque formation, where it is retained. Multiple studies provide evidence suggesting OxLDL contribute in atherosclerotic plaque formation in several ways. In fact, at least four mechanisms have been proposed, being they complementary to each other: a) endothelial dysfunction, b) foam cell formation, c) SMCs migration and proliferation and c) induction of platelet adhesion and aggregation.
3.1. Endothelial dysfunction
The Endothelial dysfunction is a pathological condition in which the endothelium presents an impairment of anti-inflammatory, anti-coagulant and vascular regulatory properties. Nowadays, it is considered a key event in the atherosclerosis development. OxLDL formed and retained in the sub-entothelial space, activates endothelial cells (ECs) through the induction of the cell surface adhesion molecules which in turn, induce the rolling and adhesion of blood monocytes and T cells. It is reported that OxLDL induces the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular-cell adhesion molecule-1 (VCAM-1), increasing the adhesive properties of endothelium in a similar manner to the effects of pro-inflammatory cytokines as interleukin 1 beta [44].
The blood leukocytes recruited migrate into the tunica intima, guided by chemokines. Indeed, OxLDL stimulates ECs and SMCs to secrete monocyte chemotactic protein-1 (MCP-1) and monocyte colony stimulating factor (mCSF) that induce the recruitment of monocytes into the endothelial wall [45-47]. On another hand, OxLDL can be chemotactic itself for monocytes and T lymphocytes (since it possesses lyso-phosphatidylcholine) and also for macrophages [48].
Nitric oxide (NO), is recognized as an important cardiovascular protective molecule, because exerts vasodilator properties and inhibits the adhesion of leucocytes and platelets to endothelium. This is generated in the vasculature by endothelial NO sythase (eNOS); the impairment of NO production and secretion by ECs is considered one of the most important characteristic of endothelial dysfunction [49].
The NO production from ECs is inhibited by OxLDL, given that the OxLDL is able to induce cholesterol depletion in the plasma membrane invaginations called caveolae, which causes the translocation of the protein caveolin and eNOS from the membrane domains, inhibiting eNOS activity in ECs [50]. Besides, another mechanisms to explain the inhibitory effect of OxLDL over NO production in ECs, has been proposed. It has been reported that OxLDL leads to an increased oxidative stress in ECs, producing significant amounts of superoxide, which chemically inactivates NO, forming peroxynitrite [51].
Lectin-like oxidized LDL receptor-1 (LOX-1), identified as the mayor OxLDL receptor in ECs, is expressed in several pro-inflammatory conditions and seems to play a crucial role in endothelial dysfunction induced by OxLDL[52]. Indeed, in human atherosclerotic lesions, LOX-1 overexpression in ECs has been reported, especially in the early stage of plaque formation [53]. It has been observed that the knockdown of LOX-1, inhibits the MCP-1 expression in human ECs stimulated with OxLDL and mitogen-activated protein kinase (MAPK) pathway would play a critical role [54]. Also, up-regulation of endothelial adhesion molecules as ICAM-1 and VCAM-1, can be induced by OxLDL in a LOX-1-dependent manner and this is mediated by the nuclear factor κB (NF-κB) [55]. Furthermore, the inhibitory effects of OxLDL over endothelial NO productions has been associated with LOX-1 function [51, 56]. Finally, it has been proposed that OxLDL can induce endothelial cell death through the activation of NF-κB and AP-1 pathways [57], worsening endothelial dysfunction and promoting the progression of the atherosclerotic plaque.
Figure 3.
Role of OxLDL in endothelial dysfunction.
3.2. Foam cell formation
Once inside the sub-endothelial ECM, monocytes differentiate into macrophages that express several scavenger receptors (SRs) such as SR-AI/II, SR-BI, cluster of differentiation 36 (CD36) and LOX-1, and toll-like receptors (TLRs). It is important to remark that this phenotypic change, since the internalization of native LDL, occurs at a very low rate to account for foam cells formation and this process is prone to suffer down regulation of LDL receptor. In contrast, scavenger receptors have high affinity for OxLDL and they are not down regulated, leading to a massive intracellular lipid accumulation [20], which results in the foam cells formation [58, 59]. This differentiation into macrophages that promotes pro-inflammatory milieu, is part of a “macrophage trapping”, a vicious circle that involves cell retention, oxidation of new LDL and the recruitment of more monocytes [18].
OxLDL also induce the expression of a number of genes associated to inflammation in macrophages: MCP-1, serum amyloid A, ceruloplasmin and hemeoxigenase-1 [60]. Moreover, macrophage activation induces the release of pro-inflammatory cytokines (interleukin 1-β, tumor necrosis factor), reactive oxygen species (ROS) and metalloproteases, which are associated with progression of inflammation [58].
Internalized OxLDL provides oxidized lipids as ligands for PPAR-γ pathway, upregulating CD36 expression, facilitating in turn, the internalization of more OxLDL[61, 62]. This internalization activates the macrophage, inducing the secretion of cytokines that recruits immune cells to intima and the secretion of the enzymes myeloperoxidase and 12/15-lipoxigenase, which are thought to participate in the oxidization of new LDL, increasing the local pool of OxLDL[63, 64]. Also, the internalization of OxLDL by CD36 seems to induce the inhibition of macrophage migration, favoring cell spreading and the activation of focal adhesion kinase, in a process mediated by src-kinases and oxidative stress [65]. Besides, OxLDL-CD36 interaction induces the loss of cell polarization in macrophages, an essential process to cell migration [66]. Thus, the evidence suggests that OxLDL not only participates in monocyte differentiation and macrophage activation, but also macrophage retention.
As mentioned, LOX-1 is one of the SRs expressed in macrophages and when it occurs by the influence of pro inflammatory cytokines, OxLDL or other stimuli, the OxLDL uptake increases significantly favoring the foam cells formation [67, 68]. The accumulation of OxLDL can lead to foam cell apoptosis or necrosis, forming cellular debris deposited in the core of the atherosclerotic plaque and contributing to inflammatory progression.
Figure 4.
Role of OxLDL in foam cell formation.
3.3. Smooth muscle cell migration and proliferation
The migration and subsequent focal proliferation of SMCs in tunica intima are some of the hallmarks of the atheromatous phenomenon and they play a critical role on it. The SMCs migrate from tunica media to the subendothelial space, where they proliferate in response to growth factors. The proliferation of SMCs can be stimulated by OxLDL, since these particles enhance platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) expression and secretion [69, 70] by ECs and macrophages. On the other hand, OxLDL also induces the secretion of a variety of other growth factors and their receptors: insulin-like growth factor-1(IGF-1) and epidermal growth factor (EGF), all with mitogenic effects inducing SMCs proliferation [71].
OxLDL has also been shown to induce changes directly in SMCs. OxLDL increases migration and leads to changes in SMCs phenotype making them to produce large amounts of ECM [72]. The production of interstitial collagen and elastin leads to the building of a fibrous cap that covers the developing atherosclerotic plaque, forming a “necrotic core” containing foam cells, cellular debris, extracellular lipids and lysosomal enzymes [73]. Thus, OxLDL participate in the expansion of the atherosclerotic lesion size.
OxLDL also induce LOX-1 expression in SMCs and recently, it has been proposed that many of the named effects of OxLDL are mediated by LOX-1[71]. Another important effect mediated by LOX-1 is the increment of ROS generation induced by OxLDL in SMCs, which can induce the cell death, contributing to plaque instability and rupture in the final stage of atherosclerosis [74]. Taken together, the evidence suggests that OxLDL has a crucial role in the plaque instability and hence, in the development of its complications.
Figure 5.
Role of OxLDL in smooth muscle cells proliferation and migration.
3.4. Induction of platelet adhesion and aggregation
Platelets are important players in atherosclerosis plaque development, especially after the plaque rupture, where they promote thrombus formation. In this process, OxLDL also is implicated. The impairment of endothelial NO production by OxLDL has been associated with an increase in prostaglandin secretion and thus, platelet aggregation [73]. CD36 is expressed in resting platelets and its interaction with OxLDL has been implicated with platelet activation, evidenced by P-selectin expression and the activation of integrin αIIbβ3[75].
OxLDL seems to induce a hyperactive state in platelets, since when they are cultured with OxLDL, they show more sensitivity to the classic platelet-activator ADP, in a process mediated by JNK and Vav family members [76, 77]. OxLDL is able to promote shape change and fast platelet activation through the action of Src kinases and Rho kinase-signaling pathways [78]. The effects of OxLDL over platelets could account also for additional pro-atherogenic phenomena. Platelets exposed to OxLDL release chemokines that favors atherosclerotic development [79] and promote endothelial dysfunction and foam cells formation [80, 81].
LOX-1 is expressed in platelets once they are activated [82], where it contributes to OxLDL internalization together with CD36. Since LOX-1 is able to binds anionic phospholipids as the present in the surface of activated platelets, has been proposed that endothelial LOX-1 mediates platelet adhesion to ECs [68]. Indeed, platelet binding to LOX-1 enhances endothelin-1 (ET-1) release from ECs [83] and induces oxidative inactivation of NO in ECs [56], suggesting that LOX-1 participates in endothelial dysfunction also through activated platelets. Thus, OxLDL seems to play a pivotal role in the pro-atherosclerotic behavior of activated platelets.
Figure 6.
Role of OxLDL in pro-atherosclerotic function of platelets.
4. Mouse models for atherosclerosis
Given the importance of knowing the role of oxidized LDL in the process of atherosclerotic plaque formation, the study of animal models has been an important tool, where the examination of genetically modified mice has significantly contributed towards a better understanding of the mechanisms involved in this pathology.
It is worth noting that the use of small animals in research benefits from easy availability and low cost compared to large animals like primates. In addition, working with small animals reduces ethical concerns and limits the quantity of new agents needed for in vivo studies.
Transgenic and knockout mouse models for atherosclerosis have also been instrumental in evaluating existing, finding and testing new atherosclerotic drugs [84]. Small-animal models have the advantage of a well-defined genetic characterization which opens the possibility to transform them into transgenic and gene knockout animals [85].
Atherosclerosis is it not developed by wild-type mice; in fact they have high levels of anti-atherogenic high-density lipoprotein (HDL) and low levels of pro-atherogenic LDL and very-low-density lipoprotein (VLDL). Furthermore, mice do not express cholesteryl ester transfer protein (CETP), a plasma protein known to transfer cholesteryl ester from HDL particles and other lipoprotein fractions to pro-atherogenic apolipoprotein-B-containing lipoproteins LDL, VLDL and intermediate low-density lipoproteins (ILDL).
The current mouse models of atherosclerosis are based on disorders on the metabolism of lipoproteins through diets or genetic manipulations [84]. These perturbations have been made thanks to the current availability of genetic information, a variety of inbred strains and the development of molecular biology technics [86]. Atherosclerotic mice were first reported by Thompson et al., 1969, [87] using C57BL/6 inbred mice fed for five weeks with a diet containing a 50% of fat, whereas control mice were fed with a regular diet of 5% of fat. Nevertheless, this diet had a high percentage of mortality [86]. Paigen et al. modified the diet proposed by Thompson supplementing it with a regular diet containing 1.25% of cholesterol, 0.5% of cholic acid and 15% of fat. Nowadays, this diet is named the “Paiged diet” [88]. However, Ignatowski et al., [89] reported in 1980 the first evidence of atherosclerosis in the aorta of a rabbit model fed with a diet containing animal proteins like meat, eggs and milk.
Nowadays, the most used model of atherosclerosis in mice is based on the alteration of genes that codify the low-density lipoprotein receptor (LDLr) and the apolipoprotein E (ApoE), being both key elements for the lipid metabolism.
The ApoE, is a glycoprotein found in almost every lipoprotein with the exception of LDL. The purpose of this glycoprotein mainly synthesized in the brain and liver is to serve as a ligand for receptors that removes the VLDL and chylomicrons remnants. Since the ApoE can also be synthesized by macrophages and monocytes in the atherosclerotic vessels, is thought to have an important role on inflammatory processes and on the cholesterol homeostasis [90]. Moreover, it has been reported that ApoE may function in the biliary excretion and in dietary absorption of cholesterol [91].
Plump et al., [92] in 1992, produced the first mice models deficient in apolipoprotein E (ApoE-/-). These animals were fed with a diet of 4.5% fat to develop a strong atherosclerosis model. This became an important tool in the research of atherosclerosis.
To inactivate the mice’s ApoE gene, a homologous recombination of genes was made in embryonic stem cells. Two plasmids (pNMC109 and pJPB63) with a neomycin-resistance gene were used to disrupt the structure of the ApoE gene. Chimeric mice were generated by blastocyst injection with targeted lines [93]. The fact that homozygous animals were born at the expected frequency and that they appeared to be healthy, was of significant importance.
Currently, the ApoE-/-mice are available on Jackson Laboratories which are direct descendants of the original ApoE-/- mouse created by the Maeda group (002052 B6.129P2-Apoetm1Unc).
Under a normal chow-fed diet, the mice developed a fatty streak observed in the aorta as early as a 3-month-old [93]. Foam cells at 10 weeks of age under the same diet were observed using a light microscopy. At 15 weeks of age, lesions containing SMCs and foam cells were observed, and at 20 weeks of age, fibrous plaques could be seen. It is worth mentioning that when a Western diet is used, the process is accelerated [94].
Although it is known that this model of ApoE-/- has considerable limitations, it has been used widely, because of the rapid development of atherosclerosis. A major drawback of the complete absence of ApoE protein is that most plasma cholesterol is confined to VLDL and not to LDL particles as in humans.
6. LDL receptor-deficient (LDLr-/-) mice
In humans, mutations in the LDLr gene cause familial hypercholesterolemia. The LDLr-/-mouse has a milder lipoprotein alteration than ApoE-/-mice when fed standard low-fat chow, with plasma cholesterol levels around 250 mg/dL due mainly to the accumulation of LDL [95].
In 1993, LDLr-/- mice were created by gene targeting of embryonic stem cells [96]. By feeding them with a 10% fat diet, an increase of total cholesterol level (2-fold) was observed on these mice, due mainly to the high levels of VLDL and LDL. When fed on a high-fat/high-cholesterol diet, LDLr-/- mice showed a rapid increase in the severity of hypercholesterolemia and atherosclerotic lesion development throughout the coronary arteries, aortic root, and aorta [85, 97]. The plasma lipoprotein profile of LDLr-/- mice resembled the one of humans, with the cholesterol being confined mainly to the LDL fraction. Nevertheless, this mice model of atherosclerosis is very responsive to the diet. In fact, their cholesterol levels rose up to 1500 mg/dL when they were under the Paigen diet [98]. The lesions produced in LDLr-/- mice were similar to the lesions produced in the ApoE-/- mice, in terms of their development of plaques in a time-dependent manner. On the contrary, the LDLr-/- mouse produced a more moderate murine model of atherosclerosis than the ApoE-/- mouse. This characteristic is produced mainly due to a milder degree of hyperlipidemia [99].
In 1998, a mouse model deficient in the Apo B mRNA editing activity (Apobec1-/-) and LDL receptor (LDLr-/-) were generated by Powell-Braxton et al [100]. The lipoprotein profile of this animal model resembles the human familial hypercholesterolemia and when fed with a chow diet, exhibited atherosclerosis at its 8-month of age. The characteristics of this animal model provided an advantage to study the interactions between the environment (high fat diet) and the gene response in the onset of atherosclerosis [101].
7. ApoE3-leiden transgenic mice
Mutations in the gene encoding ApoE can lead to a binding-defective ApoE, which mediates the binding of lipoproteins to LDL receptor and is an essential ligand for the receptor-mediated uptake of chylomicron and VLDL remnants by hepatic lipoprotein receptors. This results in a disturbed receptor-mediated clearance of lipoprotein remnants by the liver, as has been described for patients with familial dysbetalipoproteinemia[102]. Premature atherosclerosis is produced by a genetic disorder named familial dysbetalipoproteinemia, which presents high levels of plasmatic triglycerides and cholesterol, mainly due to the increase in the VLDL remnants and chylomicron. The ApoE3-Leiden, a genetic variant of ApoE, is related with an inherited familial dysbetalipoproteinemia [103].
The ApoE3-Leiden mutation it is characterized by a rare dominant-negative tandem duplication of codons 120 to 126 in human ApoE3 gene. Introducing a human ApoE3-Leiden gene construct into C57BL/6 mice has generated the ApoE3-Leiden transgenic mice. The ApoE3-Leiden gene consists of a construct with the ApoC1and ApoE genes with a promoter element to regulate the expression. While, this mice model of atherosclerosis still expresses ApoE protein, the clearance of lipoproteins containing ApoE is impaired, being less dramatic than the ApoE-/- mice model of atherosclerosis. The introduction of the ApoC1 gene in transgenic mice has exhibited elevated levels of cholesterol and triglycerides owing to an accumulation of VLDL-size particles in the circulation, increasing plasma lipid levels by diminished lipolysis and VLDL uptake through both the LDLr and low density lipoprotein receptor-related protein (LRP) [84, 104].The ApoE3-Leiden mice have a hyperlipidemic phenotype, develop atherosclerosis on being fed cholesterol, and are more sensitive to lipid-lowering drugs than ApoE-/- and LDLr-/- mice [105]. The ApoE3-Leiden mice model is very responsive to diets containing sugar, fat and cholesterol, developing high levels of plasma triglycerides and cholesterol, with a prominent increase in LDL and VLDL lipoproteins.
Compared with ApoE-/- and LDLr-/- mice, ApoE3-Leiden mice represent a moderate mouse model for hyperlipidemia. Therefore, diets and drugs that influence the production of VLDL and chylomicron also show parallel effects on plasma levels of triglycerides and cholesterol. In this sense, the ApoE3-Leiden mice are more responsive to hypolipidemic compounds than the LDLr-/- and ApoE-/- mice [84, 106].
8. Double knockout mice models
A model that develops severe hyperlipidaemia and atherosclerosis was obtained with an ApoE and LDLr double knockout (ApoE-/-/ LDLr-/- / DKO) [98]. It has been observed that, even on a regular chow diet, the atherosclerosis progression is generally more considerable than in mice only deficient in ApoE [107, 108]. Hence, the ApoE-/-/, LDLr-/-/, DKO mouse is appropriate to study the effect of compounds with anti-atherosclerotic activity without the need of atherogenic diets.
Besides, the role of the ApoE and the LDLr in the development of the atherosclerosis and dysregulation of the NOS system leading to impairment of NO bioavailability, has been documented for some time in atherosclerotic vessels of both experimental animals and humans [109]. To study the contribution of endothelial eNOS to lesion formation, Kuhlencordt et al. [110] created ApoE-/-/ eNOS-/-/double knockout mice (ApoE-/-/ eNOS-/- / DKO), which presents a more pronounced atherosclerosis than ApoE-/- mouse model. Besides, eNOS absence favors the development of peripheral coronary disease, chronic myocardial ischemia, heart failure and an array of other vascular complications not detected in ApoE-/- mice [111].
Additionally, key structural proteins like apoB100 and apoB48, are needed to assemble lipoproteins rich in triacylglycerol; moreover, these proteins are part of all classes of atherogenic lipoproteins [112]. Veniant et al., 1998, characterized LDLr-/- and ApoE-/- mice which were homozygous to the ApoB-100 allele, founding that the LDLr-/-/ApoB100/100 mice model develop an extensive atherosclerosis, even when were fed with a normal chow diet, [113]
In summary, the experimental evidences show that the oxidative stress plays a pivotal role in atherogenesis, having OxLDL as a crucial player. Nevertheless, the clinical trials that used antioxidants strategies have shown poor results in relationship to the development of atherosclerosis, besides strong discrepancies between the different studies to establish the correlation between oxidative stress and atherogenic process. Therefore, the achievement of a successful therapy in humans based on the oxidative modification hypothesis is still a major challenge.
\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/47808.pdf",chapterXML:"https://mts.intechopen.com/source/xml/47808.xml",downloadPdfUrl:"/chapter/pdf-download/47808",previewPdfUrl:"/chapter/pdf-preview/47808",totalDownloads:5034,totalViews:4687,totalCrossrefCites:18,totalDimensionsCites:29,totalAltmetricsMentions:10,impactScore:20,impactScorePercentile:99,impactScoreQuartile:4,hasAltmetrics:1,dateSubmitted:"April 23rd 2014",dateReviewed:"September 30th 2014",datePrePublished:null,datePublished:"September 17th 2015",dateFinished:"November 11th 2014",readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/47808",risUrl:"/chapter/ris/47808",book:{id:"4477",slug:"hypercholesterolemia"},signatures:"E. Leiva, S. Wehinger, L. Guzmán and R. Orrego",authors:[{id:"153453",title:"MSc.",name:"Elba",middleName:null,surname:"Leiva",fullName:"Elba Leiva",slug:"elba-leiva",email:"eleivam@utalca.cl",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. LDL oxidation",level:"1"},{id:"sec_3",title:"3. OxLDL in atheromatous plaque formation",level:"1"},{id:"sec_3_2",title:"3.1. Endothelial dysfunction",level:"2"},{id:"sec_4_2",title:"3.2. Foam cell formation",level:"2"},{id:"sec_5_2",title:"3.3. Smooth muscle cell migration and proliferation",level:"2"},{id:"sec_6_2",title:"3.4. Induction of platelet adhesion and aggregation",level:"2"},{id:"sec_8",title:"4. Mouse models for atherosclerosis",level:"1"},{id:"sec_9",title:"5. Apolipoprotein E-deficient (Apo E\n\t\t\t\t-/-) mice",level:"1"},{id:"sec_10",title:"6. LDL receptor-deficient (LDLr-/-) mice",level:"1"},{id:"sec_11",title:"7. 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Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell 71:343-353; 1992.'},{id:"B93",body:'Piedrahita, J. A.; Zhang, S. H.; Hagaman, J. R.; Oliver, P. M.; Maeda, N. Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embryonic stem cells. Proc Natl Acad Sci U S A 89:4471-4475; 1992.'},{id:"B94",body:'Reddick, R. L.; Zhang, S. H.; Maeda, N. Atherosclerosis in mice lacking apo E. Evaluation of lesional development and progression. Arterioscler Thromb 14:141-147; 1994.'},{id:"B95",body:'Ishibashi, S.; Goldstein, J. L.; Brown, M. S.; Herz, J.; Burns, D. K. Massive xanthomatosis and atherosclerosis in cholesterol-fed low density lipoprotein receptor-negative mice. J Clin Invest 93:1885-1893; 1994.'},{id:"B96",body:'Ishibashi, S.; Brown, M. S.; Goldstein, J. L.; Gerard, R. D.; Hammer, R. E.; Herz, J. 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I.; Won, W. B.; Ross, J.; Dybdal, N.; Zlot, C. H.; Young, S. G.; Davidson, N. O. A mouse model of human familial hypercholesterolemia: markedly elevated low density lipoprotein cholesterol levels and severe atherosclerosis on a low-fat chow diet. Nat Med 4:934-938; 1998.'},{id:"B101",body:'Dutta, R.; Singh, U.; Li, T. B.; Fornage, M.; Teng, B. B. Hepatic gene expression profiling reveals perturbed calcium signaling in a mouse model lacking both LDL receptor and Apobec1 genes. Atherosclerosis 169:51-62; 2003.'},{id:"B102",body:'Marais, A. D.; Solomon, G. A.; Blom, D. J. Dysbetalipoproteinaemia: a mixed hyperlipidaemia of remnant lipoproteins due to mutations in apolipoprotein E. Crit Rev Clin Lab Sci 51:46-62; 2014.'},{id:"B103",body:'Murase, T.; Ebara, T.; Okubo, M. Hepatic lipase activity is decreased in Japanese patients with type III hyperlipoproteinemia. Clin Chim Acta 414:185-187; 2012.'},{id:"B104",body:'Jong, M. C.; Hofker, M. H.; Havekes, L. M. Role of ApoCs in lipoprotein metabolism: functional differences between ApoC1, ApoC2, and ApoC3. Arterioscler Thromb Vasc Biol 19:472-484; 1999.'},{id:"B105",body:'van Vlijmen, B. J.; van den Maagdenberg, A. M.; Gijbels, M. J.; van der Boom, H.; HogenEsch, H.; Frants, R. R.; Hofker, M. H.; Havekes, L. M. Diet-induced hyperlipoproteinemia and atherosclerosis in apolipoprotein E3-Leiden transgenic mice. J Clin Invest 93:1403-1410; 1994.'},{id:"B106",body:'Vainer, B.; Nielsen, O. H. Correlation between circulating soluble ICAM-1 and prednisolone-induced amelioration of ulcerative colitis. Scand J Gastroenterol 38:283-287; 2003.'},{id:"B107",body:'Witting, P. K.; Pettersson, K.; Ostlund-Lindqvist, A. M.; Westerlund, C.; Eriksson, A. W.; Stocker, R. Inhibition by a coantioxidant of aortic lipoprotein lipid peroxidation and atherosclerosis in apolipoprotein E and low density lipoprotein receptor gene double knockout mice. FASEB J 13:667-675; 1999.'},{id:"B108",body:'Kostogrys, R. B.; Franczyk-Zarow, M.; Maslak, E.; Gajda, M.; Mateuszuk, L.; Jackson, C. L.; Chlopicki, S. Low carbohydrate, high protein diet promotes atherosclerosis in apolipoprotein E/low-density lipoprotein receptor double knockout mice (apoE/LDLR(-/-)). Atherosclerosis 223:327-331; 2012.'},{id:"B109",body:'Perrotta, I.; Brunelli, E.; Sciangula, A.; Zuccala, V.; Donato, G.; Tripepi, S.; Martinelli, G. L.; Cassese, M. Inducible and endothelial nitric oxide synthase expression in human atherogenesis: an immunohistochemical and ultrastructural study. Cardiovasc Pathol 18:361-368; 2009.'},{id:"B110",body:'Kuhlencordt, P. J.; Gyurko, R.; Han, F.; Scherrer-Crosbie, M.; Aretz, T. H.; Hajjar, R.; Picard, M. H.; Huang, P. L. Accelerated atherosclerosis, aortic aneurysm formation, and ischemic heart disease in apolipoprotein E/endothelial nitric oxide synthase double-knockout mice. Circulation 104:448-454; 2001.'},{id:"B111",body:'Wang, Y. X. Cardiovascular functional phenotypes and pharmacological responses in apolipoprotein E deficient mice. Neurobiol Aging 26:309-316; 2005.'},{id:"B112",body:'Veniant, M. M.; Kim, E.; McCormick, S.; Boren, J.; Nielsen, L. B.; Raabe, M.; Young, S. G. Insights into apolipoprotein B biology from transgenic and gene-targeted mice. J Nutr 129:451S-455S; 1999.'},{id:"B113",body:'Veniant, M. M.; Zlot, C. H.; Walzem, R. L.; Pierotti, V.; Driscoll, R.; Dichek, D.; Herz, J.; Young, S. G. Lipoprotein clearance mechanisms in LDL receptor-deficient "Apo-B48-only" and "Apo-B100-only" mice. J Clin Invest 102:1559-1568; 1998.'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"E. Leiva",address:"eleivam@utalca.cl",affiliation:'
Interdisciplinary Excellence Research Program on Healthy Aging (PIEI-ES), Universidad de Talca, Talca, Chile
Interdisciplinary Excellence Research Program on Healthy Aging (PIEI-ES), Universidad de Talca, Talca, Chile
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Yarotskaya and Gennady T.\nSukhikh",authors:[{id:"193025",title:"Ph.D.",name:"Marina",middleName:null,surname:"Ziganshina",fullName:"Marina Ziganshina",slug:"marina-ziganshina"},{id:"196923",title:"Dr.",name:"Lyubov V.",middleName:null,surname:"Krechetova",fullName:"Lyubov V. Krechetova",slug:"lyubov-v.-krechetova"},{id:"196924",title:"Prof.",name:"Lyudmila V.",middleName:null,surname:"Vanko",fullName:"Lyudmila V. Vanko",slug:"lyudmila-v.-vanko"},{id:"196925",title:"Prof.",name:"Zulfiya S.",middleName:null,surname:"Khodzhaeva",fullName:"Zulfiya S. Khodzhaeva",slug:"zulfiya-s.-khodzhaeva"},{id:"196926",title:"Dr.",name:"Ekaterina L.",middleName:null,surname:"Yarotskaya",fullName:"Ekaterina L. Yarotskaya",slug:"ekaterina-l.-yarotskaya"},{id:"196927",title:"Prof.",name:"Gennady T.",middleName:null,surname:"Sukhikh",fullName:"Gennady T. Sukhikh",slug:"gennady-t.-sukhikh"}]},{id:"53441",title:"Pathogenic Angiogenic Mechanisms in Alzheimer's Disease",slug:"pathogenic-angiogenic-mechanisms-in-alzheimer-s-disease",signatures:"Chaahat Singh, Cheryl G. Pfeifer and Wilfred A. Jefferies",authors:[{id:"193311",title:"Prof.",name:"Wilfred",middleName:null,surname:"Jefferies",fullName:"Wilfred Jefferies",slug:"wilfred-jefferies"},{id:"196143",title:"Dr.",name:"Singh",middleName:null,surname:"Chaahat",fullName:"Singh Chaahat",slug:"singh-chaahat"},{id:"196144",title:"Dr.",name:"Cheryl G",middleName:null,surname:"Pfeifer",fullName:"Cheryl G Pfeifer",slug:"cheryl-g-pfeifer"}]},{id:"53523",title:"Hypoxia, Angiogenesis and Atherogenesis",slug:"hypoxia-angiogenesis-and-atherogenesis",signatures:"Lamia Heikal and Gordon Ferns",authors:[{id:"195461",title:"Dr.",name:"Lamia",middleName:null,surname:"Heikal",fullName:"Lamia Heikal",slug:"lamia-heikal"},{id:"199995",title:"Prof.",name:"Gordon",middleName:null,surname:"Ferns",fullName:"Gordon Ferns",slug:"gordon-ferns"}]},{id:"54134",title:"Coronary Collateral Growth: Clinical Perspectives and Recent Insights",slug:"coronary-collateral-growth-clinical-perspectives-and-recent-insights",signatures:"Bhamini Patel, Peter Hopmann, Mansee Desai, Kanithra Sekaran,\nKathleen Graham, Liya Yin and William Chilian",authors:[{id:"192680",title:"Dr.",name:"Wiliam M.",middleName:null,surname:"Chilian",fullName:"Wiliam M. 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Renna, Rodrigo Garcia, Jesica Ramirez and Roberto M.\nMiatello",authors:[{id:"192616",title:"Dr.",name:"Nicolás",middleName:null,surname:"Renna",fullName:"Nicolás Renna",slug:"nicolas-renna"},{id:"202536",title:"Dr.",name:"Rodrigo",middleName:"Damián",surname:"García",fullName:"Rodrigo García",slug:"rodrigo-garcia"},{id:"202537",title:"Dr.",name:"Jesica",middleName:null,surname:"Ramirez",fullName:"Jesica Ramirez",slug:"jesica-ramirez"},{id:"202539",title:"Dr.",name:"Roberto M.",middleName:null,surname:"Miatello",fullName:"Roberto M. Miatello",slug:"roberto-m.-miatello"}]},{id:"53018",title:"Tumor Angiogenesis: A Focus on the Role of Cancer Stem Cells",slug:"tumor-angiogenesis-a-focus-on-the-role-of-cancer-stem-cells",signatures:"Keiko Fujita and Masumi Akita",authors:[{id:"26281",title:"Prof.",name:"Masumi",middleName:null,surname:"Akita",fullName:"Masumi Akita",slug:"masumi-akita"},{id:"192582",title:"Dr.",name:"Keiko",middleName:null,surname:"Fujita",fullName:"Keiko Fujita",slug:"keiko-fujita"}]},{id:"53461",title:"VEGF-Mediated Signal Transduction in Tumor Angiogenesis",slug:"vegf-mediated-signal-transduction-in-tumor-angiogenesis",signatures:"Lucia Napione, Maria Alvaro and Federico Bussolino",authors:[{id:"193680",title:"Ph.D.",name:"Lucia",middleName:null,surname:"Napione",fullName:"Lucia Napione",slug:"lucia-napione"},{id:"196917",title:"Dr.",name:"Maria",middleName:null,surname:"Alvaro",fullName:"Maria Alvaro",slug:"maria-alvaro"},{id:"196992",title:"Prof.",name:"Federico",middleName:null,surname:"Bussolino",fullName:"Federico Bussolino",slug:"federico-bussolino"}]},{id:"54103",title:"Noncoding RNAs in Lung Cancer Angiogenesis",slug:"noncoding-rnas-in-lung-cancer-angiogenesis",signatures:"Ioana Berindan-Neagoe, Cornelia Braicu, Diana Gulei, Ciprian\nTomuleasa and George Adrian Calin",authors:[{id:"193102",title:"Dr.",name:"Ioana",middleName:null,surname:"Berindan-Neagoe",fullName:"Ioana Berindan-Neagoe",slug:"ioana-berindan-neagoe"},{id:"193316",title:"Dr.",name:"Cornelia",middleName:null,surname:"Braicu",fullName:"Cornelia Braicu",slug:"cornelia-braicu"},{id:"193317",title:"Dr.",name:"Ciprian",middleName:null,surname:"Tomuleasa",fullName:"Ciprian Tomuleasa",slug:"ciprian-tomuleasa"},{id:"193318",title:"BSc.",name:"Diana",middleName:null,surname:"Gulei",fullName:"Diana Gulei",slug:"diana-gulei"},{id:"193319",title:"Prof.",name:"George Adrian",middleName:null,surname:"Calin",fullName:"George Adrian Calin",slug:"george-adrian-calin"}]},{id:"53402",title:"Recent Advances in Angiogenesis Assessment Methods and their Clinical Applications",slug:"recent-advances-in-angiogenesis-assessment-methods-and-their-clinical-applications",signatures:"Imran Shahid, Waleed H. AlMalki, Mohammed W. AlRabia,\nMuhammad Ahmed, Mohammad T. Imam, Muhammed K. Saifullah\nand Muhammad H. Hafeez",authors:[{id:"188219",title:"Prof.",name:"Imran",middleName:null,surname:"Shahid",fullName:"Imran Shahid",slug:"imran-shahid"},{id:"191256",title:"Prof.",name:"Waleed",middleName:null,surname:"Almalki",fullName:"Waleed Almalki",slug:"waleed-almalki"},{id:"191259",title:"Dr.",name:"Muhammad",middleName:null,surname:"Hassan Hafeez",fullName:"Muhammad Hassan Hafeez",slug:"muhammad-hassan-hafeez"},{id:"195198",title:"Prof.",name:"Muhammad",middleName:null,surname:"Ahmed",fullName:"Muhammad Ahmed",slug:"muhammad-ahmed"},{id:"195199",title:"MSc.",name:"Muhammed",middleName:null,surname:"Saifullah",fullName:"Muhammed Saifullah",slug:"muhammed-saifullah"},{id:"195200",title:"Prof.",name:"Mohammad",middleName:null,surname:"Imam",fullName:"Mohammad Imam",slug:"mohammad-imam"},{id:"195201",title:"Prof.",name:"Mohammed",middleName:null,surname:"Al Rabia",fullName:"Mohammed Al Rabia",slug:"mohammed-al-rabia"}]},{id:"53313",title:"Novel Methods to Study Angiogenesis Using Tissue Explants",slug:"novel-methods-to-study-angiogenesis-using-tissue-explants",signatures:"Tomoko Takahashi, Keiko Fujita and Masumi Akita",authors:[{id:"26281",title:"Prof.",name:"Masumi",middleName:null,surname:"Akita",fullName:"Masumi Akita",slug:"masumi-akita"},{id:"192582",title:"Dr.",name:"Keiko",middleName:null,surname:"Fujita",fullName:"Keiko Fujita",slug:"keiko-fujita"},{id:"192585",title:"MSc.",name:"Tomoko",middleName:null,surname:"Takahashi",fullName:"Tomoko Takahashi",slug:"tomoko-takahashi"}]},{id:"53219",title:"Therapeutic Angiogenesis: Foundations and Practical Application",slug:"therapeutic-angiogenesis-foundations-and-practical-application",signatures:"Pavel Igorevich Makarevich and Yelena Viktorovna Parfyonova",authors:[{id:"75221",title:"Prof.",name:"Yelena",middleName:null,surname:"Parfyonova",fullName:"Yelena Parfyonova",slug:"yelena-parfyonova"},{id:"192434",title:"Dr.",name:"Pavel",middleName:null,surname:"Makarevich",fullName:"Pavel Makarevich",slug:"pavel-makarevich"}]},{id:"53828",title:"Platelet Lysate to Promote Angiogenic Cell Therapies",slug:"platelet-lysate-to-promote-angiogenic-cell-therapies",signatures:"Scott T. Robinson and Luke P. Brewster",authors:[{id:"193297",title:"Dr.",name:"Luke",middleName:null,surname:"Brewster",fullName:"Luke Brewster",slug:"luke-brewster"},{id:"193532",title:"Dr.",name:"Scott",middleName:null,surname:"Robinson",fullName:"Scott Robinson",slug:"scott-robinson"}]},{id:"53483",title:"Anti-VEGF Therapy in Cancer: A Double-Edged Sword",slug:"anti-vegf-therapy-in-cancer-a-double-edged-sword",signatures:"Victor Gardner, Chikezie O. Madu and Yi Lu",authors:[{id:"40915",title:"Dr.",name:"Yi",middleName:null,surname:"Lu",fullName:"Yi Lu",slug:"yi-lu"},{id:"195224",title:"Mr.",name:"Victor",middleName:null,surname:"Gardner",fullName:"Victor Gardner",slug:"victor-gardner"},{id:"195226",title:"Dr.",name:"Chikezie",middleName:null,surname:"Madu",fullName:"Chikezie Madu",slug:"chikezie-madu"}]},{id:"53575",title:"Antiangiogenic Therapy for Hepatocellular Carcinoma",slug:"antiangiogenic-therapy-for-hepatocellular-carcinoma",signatures:"Kosuke Kaji and Hitoshi Yoshiji",authors:[{id:"192883",title:"Dr.",name:"Kosuke",middleName:null,surname:"Kaji",fullName:"Kosuke Kaji",slug:"kosuke-kaji"},{id:"195636",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Yoshiji",fullName:"Hitoshi Yoshiji",slug:"hitoshi-yoshiji"}]},{id:"53335",title:"MCAM and its Isoforms as Novel Targets in Angiogenesis Research and Therapy",slug:"mcam-and-its-isoforms-as-novel-targets-in-angiogenesis-research-and-therapy",signatures:"Jimmy Stalin, Lucie Vivancos, Nathalie Bardin, Françoise Dignat-\nGeorge and Marcel Blot-Chabaud",authors:[{id:"192897",title:"Dr.",name:"Jimmy",middleName:null,surname:"Stalin",fullName:"Jimmy Stalin",slug:"jimmy-stalin"},{id:"195979",title:"Ms.",name:"Lucie",middleName:null,surname:"Vivancos",fullName:"Lucie Vivancos",slug:"lucie-vivancos"},{id:"195980",title:"Prof.",name:"Nathalie",middleName:null,surname:"Bardin",fullName:"Nathalie Bardin",slug:"nathalie-bardin"},{id:"195981",title:"Prof.",name:"Francoise",middleName:null,surname:"Dignat-George",fullName:"Francoise Dignat-George",slug:"francoise-dignat-george"},{id:"195982",title:"Dr.",name:"Marcel",middleName:null,surname:"Blot-Chabaud",fullName:"Marcel Blot-Chabaud",slug:"marcel-blot-chabaud"}]}]}],publishedBooks:[{type:"book",id:"940",title:"Atherogenesis",subtitle:null,isOpenForSubmission:!1,hash:"65accab87dc266373e16c0a9b1298a28",slug:"atherogenesis",bookSignature:"Sampath Parthasarathy",coverURL:"https://cdn.intechopen.com/books/images_new/940.jpg",editedByType:"Edited by",editors:[{id:"139179",title:"Dr.",name:"Sampath",surname:"Parthasarathy",slug:"sampath-parthasarathy",fullName:"Sampath Parthasarathy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"947",title:"Cardiac Arrhythmias",subtitle:"New Considerations",isOpenForSubmission:!1,hash:"450b96aa2d0bc75977a827e0fc5bae13",slug:"cardiac-arrhythmias-new-considerations",bookSignature:"Francisco R. 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1. Introduction
Hydroponic techniques have been developed to facilitate cultivation under diverse environments and to improve farming practices using soilless methods. In this novel world, hydroponic farming makes efficient use of fertilizers and water, increases productivity, and provides better crop quality; Table 1 shows the difference in productivity between soil and soilless culture for different crops. Also, due to the risks of soil and water contamination in metropolitan areas, this technique has a potential alternative to agricultural production in cities. Hydroponic systems irrespective of their scale reduce dependence on the soil as a substrate and instead derive nutrition directly from the hydroponic solution comprising of water and nutrients [2]. Because hydroponics provides better control of plant growth, it is possible to achieve high quality and productivity through careful management of—nutrient composition, dissolved O2 concentration, temperature, pH, and electrical conductivity (EC) of the nutrient solution. Nutrient supply in hydroponics can significantly influence the nutrition, taste, texture, color, and other characteristics of fruit and vegetable crops [3]. In hydroponics, essential nutrient elements are dissolved in appropriate concentrations and relative ratios to achieve the normal growth of plants [4]. It is well known that the productivity and quality of crops grown in hydroponic systems are markedly dependent on the extent of the plant nutrients acquisition from the growing medium [5]. Due to this, nutrient solution and its management are the cornerstone for a successful hydroponics system and are the most important determining factors of crop yield and quality.
Crop
Hydroponic system production (Kg/ha)
Open-field production (Kg/ha)
Rice
13,456.56
841.03–1009.25
Maize
8971.0
1682.07
Peas
15,699.32
2242.76
Tomato
403,335.81
11,203.75–22,407.47
Potato
156,852.29
17,925.98
Cabbage
20,184.84
14,577.94
Cucumber
31,398.64
7849.66
Lettuce
23,548.98
10.092.42
Table 1.
Yield comparisons for different crops between hydroponic and open field cultivation.
Plant nutrients used in hydroponics are dissolved in water and are mostly in inorganic and ionic forms. All the essential elements for plant growth are supplied using different chemical combinations and establishing a nutrient solution that provides a favorable ratio of ions for plant growth and development is considered an important step in cultivating crops in hydroponic systems [6]. Plant uptake of nutrients can only proceed when they are present in an available form for absorption, and in most situations, nutrients are absorbed in an ionic form. Ions are electrically charged forms of each nutrient, some are cations (positively charged) and others are anions (negatively charged). For example, nitrogen is absorbed as ammonium (NH4+, a cation) or nitrate (NO3−, an anion); Table 2 shows the available form of each nutrient and different nutrient solution formulas which have been established by many scientists. There are various standard nutrient solutions, such as the Hoagland and Snyder [13], Hoagland and Arnon [11], Steiner [14] Bollard [15], and others. These standard solutions are good as a general guideline but are not adapted to specific growing conditions. The function of a hydroponics nutrient solution is to supply the plant roots with water, oxygen, and essential mineral elements in soluble form. A nutrient solution usually contains inorganic ions from soluble salts of essential elements required by the plant. However, some organic compounds such as iron chelates may be present [16]. A total of 17 elements are considered essential for most plants, these are carbon, hydrogen, oxygen, nitrogen, phosphorus, potassium, calcium, magnesium, sulfur, iron, copper, zinc, manganese, molybdenum, boron, chlorine, and nickel [17]. An essential element has a clear physiological role, and its absence prevents the complete plant life cycle [18]. Among the minerals, N, P, and K are the most decisive elements in plants [6]. Some other elements such as sodium, silicon, vanadium, can stimulate growth, or can compensate for the toxic effects of other elements, or may replace essential nutrients in a less specific role. Tahereh et al. [19] reported that the plants grown in the absence of silica would be weak and show abnormal growth, and proper application of this nutrient can increase consistency and disease resistance, reduce the outbreak of nutrient deficiencies, improve product quality and increase crop yield. In hydroponics, all the nutrients are in a balanced ratio which is directly supplied to the plants, and composition must reflect the uptake ratio of individual elements by the crop, as the demand between species differs, and must be specific for each crop [20]. It is very important to keep ionic balance in the nutrient solution since plant growth and productivity can be negatively affected by the improper relationship between the essential nutrients, that is, the ratio of anions: NO3−, H2PO4− and SO42−, and the cations K+, Ca2+, Mg2+ [21], and a change in the concentration of one ion must be accompanied by either a corresponding change for an ion of the opposite charge, a complementary change for other ions of the same charge, or both [12]. However, for most common crop plants, critical levels for most nutrients have been determined [22].
Element
Form taken up by plants
Hoagland & Arnon
Hewitt
Cooper
Steiner
mg L−1
Nitrogen
NH4+, NO3−
210
168
200–236
168
Phosphorus
HPO4−2, H2PO4−
31
41
60
31
Potassium
K+
234
156
300
273
Calcium
Ca2+
160
160
170–185
180
Magnesium
Mg2+
34
36
50
48
sulfur
SO42−
64
48
68
336
Iron
Fe2+, Fe3+
2.5
2.8
12
2–4
Copper
Cu2+
0.02
0.064
0.1
0.02
Zinc
Zn2+
0.05
0.065
0.1
0.11
Manganese
Mn2+, Mn4+
0.5
0.54
2
0.62
Boron
H3BO3, BO3−, B4O72−
0.5
0.54
0.3
0.14
Molybdenum
MoO42−
0.01
0.04
0.2
Not considered
Table 2.
Nutrient’s form taken up by plants and nutrients compositions as suggested by different scientists.
Source: Salisbury and Ross [7]; Cooper [8]; Steiner [9]; Windsor and Schwarz [10]; Hoagland and Arnon [11]; Hewitt [12].
2.1 Plant nutrients interaction
Nutrients in the nutrient solution have great interactions that may gain either positive or negative effects on crop production, depending on crop growth stages, amounts, combinations, and balance [23]. Inadequate or excessive concentrations of minerals or an imbalanced ion composition in the nutrient solution may inhibit plant development, resulting in toxicity or nutrient-induced deficiencies [24]. In crop plants, the nutrient interactions are generally measured in terms of growth response and change in concentration of nutrients. Nutrient interactions may be positive or negative and also possible to have no interactions. Interaction between nutrients occurs when the supply of one nutrient affects the absorption and utilization of other nutrients. This type of interaction is most common when one nutrient is in excess concentration in the growth medium. Upon the addition of two nutrients, an increase in crop yield that is more than adding only one, the interaction is positive (synergistic). Similarly, if adding the two nutrients together produced less yield as compared to individual ones, the interactions are negative (antagonistic). When there is no change, there is no interaction. However, most interactions are complex and better understanding of nutrient interactions may be useful in understanding the importance of a balanced supply of nutrients and consequently improvement in plant growth or yields [25]. According to Marschner [26], at the level of the nutrient acquisition mechanisms, competitive or antagonistic phenomena among elements can occur, for example, the interaction between NH4+ and K+, and this could be crucial for NH4+ fed plants when exposed to a suboptimal/unbalanced availability of K+ because the competition could induce/exacerbate K+ deficiency [27], and it is more relevant when the additional application of NH4+ is of pivotal role to achieve specific qualitative objectives of the edible fruits [28]. The interactions between K+/Na+ and Cl−/NO3− could represent a limiting factor for soilless cultivation of crop plants, especially in a semiarid environment characterized by saline water. NaCl interferes with the uptake processes of both K+ and NO3−, since K+ is sensitive to Na+ in the external environment, while the uptake of NO3− is inhibited by Cl− [29]. This phenomenon could be even more pronounced in hydroponic solutions particularly when used in a closed system, where monitoring the ratio between Ca2+, Mg2+, and K+ in the solutions is very important to avoid K+/Ca2+ induced Mg2+ deficiency. Calcium, magnesium, and potassium compete with each other and the addition of any one of them will reduce the uptake rate of the other two [26]. Unbalanced fertilization practice, with a high level of K+ and Ca2+, can induce Mg2+ deficiency in crop plants, Schimansky [30] suggested that the excessive availability of K+ and Ca2+ could inhibit Mg2+ uptake by roots. Similarly, very high rates of Mg2+ fertilizers will depress K+ absorption by plants, but this antagonism is not nearly as strong as the inverse relation of K+ on Mg2+ [31]. Also, the uptake of nitrogen, sulfur, and iron is not exclusively dependent on its availability in the hydroponic solution but also on the presence of other elements. The uptake of NO3− was hampered by the shortages of iron and sulfur, and the effect on the assimilation process seems to play a dominant role in determining the NO3− accumulation at the leaf level. In the case of nitrogen and sulfur, the lacking one represses the assimilation of the other and induces physiological changes aiming at re-balancing the contents in the plant [32]. One of the greatest issues concerning hydroponic productions is sulfur starvation due to a consistent accumulation of NO3− in plant leaves [33]. The anion which is taken up relatively slowly can also reduce the uptake speed of its counter-ion, as observed for SO42− on K+ uptake [26].
In hydroponic solutions, interactions among solutes cannot be neglected and therefore ion activity should be used in calculations instead of concentrations [34]. The high ionic concentrations can disrupt membrane integrity and function, as well as internal solute balance and nutrient absorption, resulting in nutritional deficiency symptoms similar to those observed when nutrient concentrations are below the required levels [24]. In addition, the root physiological process is not only affected by the availability levels of the nutrients, but also by the nutrient sources and/or by the interactions among the different nutrients [35]. The chemical forms of a nutrient are also very important, for example, plants can use a wide variety of nitrogen forms, ranging from the inorganic, namely NH4+ and NO3−, to the organic ones, like urea and amino acids [36]. Ammonium is an attractive nitrogen form for root uptake due to its permanent availability and the reduced state of the nitrogen; nevertheless, when both nitrogen forms are supplied to the nutrient solution, plant roots may absorb preferentially one of them, depending on the heredity of each specie [37]. Pure NH4+ nutrition caused the development of toxicity symptoms in many herbaceous plants, as well as inhibited NO3− uptake [38]. Therefore, a balanced nitrogen diet is clearly beneficial for several plant species as compared to that based exclusively on NO3− [39]. Tomato root growth was optimal when NO3− and NH4+ were supplied in a 3:1 ratio; on the contrary, when NH4+ concentration was too high, a strong inhibition in the root development was observed [40]. However, the form of nitrogen suitable for obtaining the maximum production for each species and its cultivation conditions has not yet been defined [37]. Also, the plant species and environmental conditions are two critical factors that affect the optimum NO3−/NH4+ ratio, which can affect not only root development and morphology but also the overall root biomass. According to [41], the chemical quality of nutrient solutions can affect plant yield and bioactive compounds.
Several physical-chemical phenomena can alter the nutrient availability for plants, the most important of which are—precipitation, co-precipitation, and complexation. Precipitation reactions may occur when cations and anions in an aqueous solution combine to form a precipitate. It is known that phosphate availability can be reduced at pH above 7 mostly due to precipitation with calcium and different calcium-phosphate minerals can potentially form above this pH [42], and precipitation of phosphates must be avoided in hydroponic solutions because it is not only depleting phosphorus from the nutrient solution, but it may also reduce the solubility of other nutrients, such as calcium, magnesium, iron, and manganese. Also, sulfur availability can be limited by precipitation with calcium, as calcium-sulfate minerals [43]. Co-precipitation also may strongly reduce the solubility of nutrients added at trace concentrations, such as copper, zinc, manganese, and nickel, when insoluble compounds, such as iron hydroxides, calcium carbonates, or calcium phosphates, are formed [44]. In hydroponic solutions, a complex chemical compound is formed when a metal nutrient is bound by one or more neutral molecules or anions, either of organic or inorganic nature. The resulting complex can be a neutral compound, a cation, or an anion, depending on whether positive or negative charges prevail. These reactions diminish the concentration of the free ions in the nutrient solution, changing elemental bioavailability. The addition, organic ligands, such as: ethylenediaminetetraacetic acid (EDTA), Diethylenetriamine Penta acetic Acid (DTPA), Ethylenediamine (O-Hydroxyphenyl acetic) Acid (EDDHA), and citrate, can increase the stability of certain elements in solution, especially iron, copper, and zinc [45].
3. PH level of the nutrient solution
The pH value of the nutrient solution greatly affects plants’ growth. This is because the nutrients added to the nutrient solution are available for the uptake by the plant are soluble in water only at particular pH levels, as shown in Figure 1. According to Mayavan et al. [47], the plants require a range of pH values to be maintained to ensure the availability of all the nutrients for uptake by the plants. Nutrient solution pH is typically managed between 5.5 and 6.5, and it seems to be a range where almost all hydroponically grown crops exhibit normal growth and nutrient uptake, and the optimum pH range for different crops grown hydroponically are shown in Table 3. However, species-specific pH responses of leafy greens grown in liquid culture hydroponic systems are largely unexplored [49]. However, the optimum pH for maximum growth differs not only between species, but also between cultivar, climatic conditions, and soil, substrate, or nutrient solution conditions [50]. Frick and Mitchell [51] indicated that the pH of a hydroponic nutrient solution fluctuates because of the unbalanced anion and cation exchange reaction with roots and there is no buffering capacity in hydroponics. The changes in the pH of a nutrient solution depend on the difference in the magnitude of nutrient uptake by plants, in terms of the balance of anions over cations. When the anions are up taken in higher concentrations than cations, for example, nitrate, the plant excretes OH− or HCO3− anions, to balance the electrical charges inside, which produces increasing in the pH value and this process is called physiological alkalinity [52]. Nutrient disorders and thereby growth reduction occur when pH is outside the optimum range, and several studies suggested that the direct effect of pH seems to be detrimental only at the extreme ends of acidity and alkalinity, and growth reductions and nutrient disorders outside of the conventional pH ranges can typically be attributed to pH-dependent factors [49, 53]. The growth response to pH is species-specific and further studies to investigate responses to pH of commercially important cultivars and species grown hydroponically need to be done [49]. In general, the pH of the plant root environment is affecting nutrient uptake, nutrient availability, ion antagonism, ionic species present, and solubility of fertilizer salts [50, 54]. Due to this, it is important to measure and maintain the pH value to the required level because a little drift in the pH value can make a lot of nutrients unavailable for the plants [47].
Figure 1.
The availability of different nutrients at the different pH bands is indicated by the width of the white bar: The wider the bar, the more available is the nutrient. Source: Truog [46].
Crop
Optimum pH range
Tomato
6.0–6.5
Pepper
5.5–6.0
Egg plant
6.0
Cucumber
5.0–5.5
Strawberry
6.0
Courgettes
6.0
Banana
5.5–6.5
Ficus
5.5–6.0
Spinach
6.0–7.0
Lettuce
6.0–7.0
Cabbage
6.5–7.0
Broccoli
6.0–6.8
Asparagus
6.0–8.0
Bean
6.0
Basil
5.5–6.0
Sage
5.5–6.5
Table 3.
The optimum range of pH values for different crops grown hydroponically.
Precipitation/dissolution phenomena are often promoted by pH changes and, therefore, pH must be continuously controlled or buffered. Cations may form insoluble hydroxides at alkaline pH or other insoluble precipitates by reacting with other anionic nutrients. PH values above 7 may cause the precipitation of iron, zinc, copper, nickel, and manganese as insoluble hydroxides [55]. Also, at high pH values and high dissolved CO2 concentrations, macronutrients like calcium and magnesium can precipitate as carbonates. As the pH increases above 7, most of the dissolved phosphorus reacts with calcium forming calcium phosphates. Gradually, reactions occur in which the dissolved free phosphate species form insoluble compounds that cause phosphate to become unavailable [56]. According to Resh [57], slightly acidic pH is optimum for hydroponic production because iron, manganese, calcium, and magnesium may form precipitates and become unavailable at pH above 7. Bugbee [58] also reported that availability of potassium and phosphorus is slightly reduced in a nutrient solution with high pH. The reason for the reduction in phosphorus uptake at a high pH level is explained by the reduction in the concentration of H2PO4−, which is the substrate of the proton-coupled phosphate symporter in the plasma membrane, in the pH range of 5.6–8.5; conversely, a decrease in pH can increase the activity of proton-coupled solute transporters and enhance anion uptake [59]. Because pH affects nutrient availability and nutrient uptake across the plasma membrane, it is difficult to determine whether growth inhibition and nutrient disorders observed at low pH of the nutrient solution are a result of the direct effect of excessive hydronium ion concentration or pH-dependent factors affecting nutrient availability and uptake. At acidic pH, for example, in uncontrolled hydroponic systems under anoxic conditions, some elements might also precipitate as insoluble sulfides. Also, it is very important to note that, the addition of nutrients in the form of salts to hydroponic solutions may lead to hydrolysis reactions, which may result in the acidification or alkalinization of the medium. For example, nitrogen supply may alter solution pH, if nitrogen is added only in the form of NO3− (alkalinization) or NH4+ (acidification) [60].
In general, stabilizing the pH of a nutrient solution is necessary for optimum crop productivity in hydroponics [51], and maintaining an adequate nutrient solution and pH level are often cited as major obstacles to hydroponic production [61]. Despite the fact that the optimal pH in the root zone of most crops grown hydroponically ranges from 5.5 to 6.5, although values as low as 4.0 have been proposed for preventing the incidence of infections from Pythium and Phytophthora spp. [13, 49]. Low pH in the rhizosphere poses abiotic stress, resulting directly (i.e., high H+ injury of roots) or/and indirectly (i.e., limited availability of phosphorus) in restricted plant growth and crop yield. The value of pH changes as the plant absorbs nutrients from the solution, the plants give hydrogen ions into the nutrients in exchange for the ions of elements they require, and they do this to be electrically neutral. The hydrogen ions that the plants get are a result of photosynthesis. These hydrogen ions combine with water to produce hydronium ions which increases the pH of the water. This has to be counteracted by adding acids like phosphoric acid into the nutrient solution to ensure the solubility of all the elements in the nutrients [47]. Various acids or bases used to adjust pH may also provide some interacting factors on the plants. For example, potassium hydroxide, sodium hydroxide, phosphoric acid, and acetic acid are commonly used to maintain the pH of the nutrient solution. The presence of these acids or bases may have had small impacts through the addition of minerals such as potassium, phosphorus, and/or sodium and the increased concentration of acetates. Other nonmineral nutrients containing acids (carbonic, formic, citric, acetylsalicylic, etc.) could be used for pH adjustment, but their potential toxicity and interactions with the nutrient solutions would need careful consideration and study. Overall, it would be ideal to have a solution where pH could be maintained easily within a small pH range without the addition of mineral nutrients [62]. Wang et al. [63] found that a mixture of three (HNO3, H3PO4, and H2SO4) acids was much more effective than only single acid for maintaining an optimal solution pH of 5.5–6.5. The management of nutrient solution pH is an important challenge in soilless systems, since not only it may determine plant growth but also it influences dry matter production, root rhizosphere, and apoplastic pH [13]. However, in soilless culture, when maintaining marginal values of the optimum pH range, the risk of exceeding or dropping below them for some time increases due to the limited volume of nutrient solution per plant that is available in the root zone, and most plants, when exposed to external pH levels >7 or < 5, show growth restrictions. When soilless substrates are used instead of liquid-based hydroponics, pH in the nutrient solution interacts with substrates [64], and micronutrient toxicity occurs rather than deficiency. Therefore, the evaluation of the plant’s pH response must consider the growing systems employed.
4. Nutrient solution electrical conductivity
In soilless culture, the total salt concentration of a nutrient solution must be considered, and the nutrient solution EC is an index of salt concentration and an indicator of electrolyte concentration of the solution and is related to the number of ions available to plants in the root zone. The EC is a measure of the total salts dissolved in the hydroponic nutrient solution. It is used for monitoring applications of fertilizers. However, EC reading does not provide information regarding the exact mineral content of the nutrient solution. It is an important factor that reflects the total content of macro- and micro-elements available to plants [6], and it is an easy and accurate method of measuring total salt concentration. Inadequate management of the nutrient solution, such as the use of a too high or a too low concentration of the nutrient solution, or an imbalanced ion composition could inhibit plant growth due to either toxicity or nutrient-induced deficiency [65]. In hydroponic production systems, EC management is one of the most important and manageable cultural practices that affects the visual, nutritional, and phytochemical quality of leafy vegetables [4]. However, managing the EC in moderately high levels—either by using low-quality water that contains residual ions, such as Cl−, Na+ and SO4−, or by adding major nutrients through stock solutions—is a cultivation management technique that provides great potential to achieve high dietary and organoleptic quality in fresh vegetables [24]. Each plant species has a proper uptake rate of the nutrient solution; excessively high or low levels of the nutrient solution have a negative effect on plants. For many leafy vegetables, there are already specific formulations used on a commercial scale for hydroponics, and the optimum EC levels for different crops grown hydroponically are shown in Table 4. Although the plants were supplied with suitable ion ratios, plants can easily suffer from nutrient deficiency or excess if the nutrient solution concentration is low or high. Therefore, it is crucial to determine the suitable EC level of nutrient solutions with favorable ion ratios for growing plants [6]. The optimal EC is crop specific and depends on environmental conditions [66]. Thus, the determination of the most favorable nutrient ratio for each species under diverse climatic conditions is of major importance.
Crop
EC (dSm−1)
Tomato
2.0–4.0
Pepper
0.8–1.8
Egg plant
2.5–3.5
Cucumber
1.7–2.0
Strawberry
1.8–2.2
Courgettes
1.8–2.4
Banana
1.8–2.2
Ficus
1.6–2.4
Spinach
1.8–2.3
Lettuce
1.2–1.8
Cabbage
2.5–3.0
Broccoli
2.8–3.5
Asparagus
1.4–1.8
Bean
2.0–4.0
Basil
1.0–1.6
Sage
1.0–1.6
Table 4.
Optimum range of EC values for different crops grown hydroponically.
Many studies have reported that EC levels of nutrient solutions affect the growth of various crops. The optimal EC level range should be from 1.5 to 3.5 dS m−1 for most hydroponic crops, but this value varies between crop species and phenological stages [6]. However, the upper levels of EC in nutrient solutions must be considered for each species, since excessive EC values may decrease the osmotic potential of the nutrient solution and consequently result in delays in water transport from roots to fruits, with negative effects on fruit expansion and yield [24]. The EC levels showed a considerable influence on the ratio of ions as well as the uptake content of individual minerals. Too low and too high EC would reduce yields, visual quality, phytochemical compounds and lead to a less attractive color and taste to consumers, and enhance the negative health effects due to nitrate accumulation [4]. Increasing conductivity in nutrient solution may reduce water absorption by plants and decrease photosynthesis [67]. Also, higher EC means plants are exposed to salinity stress and high levels of nutrients, which hinders nutrient uptake and induces osmotic stress, ion toxicity, nutrient imbalance, wastes nutrients, and increases the discharge of more nutrients into the environment, resulting in environmental pollution. At the extreme EC level, plants are not able to take up any more water, and water will move backward out of the nutrient solution, which makes plants withered. The elevated EC may have negative effects on yield but can also positively affect the quality of the fresh produce, thus compromising any yield losses through the production of products with a high added value [24]. As an example, the yield of tomatoes under the hydroponic system increased as EC of the nutrient solution increased from 0 to 3 dS m−1 and decreased as the EC increased from 3 to 5 dS m−1 due to an increase in water stress [68]. Lower EC values mean the supply of some nutrients to the crop may be inadequate are mostly accompanied by nutrient deficiencies and decreasing yield [69]. So, appropriate management of EC in hydroponics technique can give an effective tool for improving vegetable yield and quality [48].
EC is modified by plants as they absorb nutrients and water from the nutrient solution. When a nutrient solution is applied continuously, plants can uptake ions at very low concentrations, and a high proportion of the nutrients are not used by plants. However, in particular situations, too low concentrations do not cover the minimum demand for certain nutrients. On the other hand, high concentrated nutrient solutions lead to excessive nutrient uptake and therefore toxic effects may be expected. Therefore, a decrease in the concentration of some ions and an increase in the concentration of others is observed simultaneously, both in close and open systems. It was observed, in a closed hydroponic system with a rose crop, that the concentration of iron decreased very fast, while that of Ca2+, Mg2+, and Cl− increased; moreover, concentrations of K+, Ca2+, and SO42− did not reach critical levels [70]. Providing the most suitable nutrient solution and EC level for growing vegetables and crops in hydroponic systems helps to avoid the waste of nutrient solution, which contributes to saving production costs for growing crops in plant factories and preventing environmental pollution, and the value of EC is required to be controlled to ensure nutritional elements needed by plants is fulfilled.
5. Nutrient solution temperature
Nutrient solution temperature is considered as one of the most important determining factors of crop yield and quality in hydroponic production systems [71]. The temperature of the nutrient solution affects the physiological process in the root, such as the absorption of water and nutrients, and the thermal regulation of hydroponic solution can contribute to improving and optimizing plant physiological processes [72]. Nutrient uptake for plants grown in glasshouses may be positively and adversely affected by manipulating the hydroponic solution temperature to the optimum level [73]. It is also possible that the increased temperature facilitated solubility of minerals and increase uptake since the rate of dissolving of solutes increases with increase in temperature [74], and the nutrient solution temperature tends to determine the concentration of nutrients absorbed by the plant, as more nutrients are dissolved at higher temperatures and less at lower temperatures, consequently influencing the efficiency of the photosynthetic apparatus [75]. Calatayud et al. [76] revealed that, in most plant species, nutrient uptake by roots decreased at low temperatures. Increasing nutrient temperatures increased nutrient uptake in cucumber and enhanced plant growth leading to a significant increase in yield [77]. The uptake rate of N, P, K, Na, Fe, Mn, and Zn in Jojoba was significantly reduced at low temperatures [78]. While, in cucumber, uptake of N, P, K, Ca, and Mg was increased when the temperature was raised in a closed hydroponic system from 12 to 20°C [77]. It has been reported that commercial growers experience a lower level of ornamental plant production in winter than in summer due to the low temperature of the solution [79, 80]. Also, the production of various plant metabolites is influenced by the temperature of the root zone in many plants, including leafy vegetables [67].
The chemical equilibrium of the solution is affected by nutrient temperature, and this is particularly crucial for areas where the over warming of the nutrient solution often occurs, impacting also all the physiological processes in the plant [81]. Generally, the cold solution increased NO3− uptake and thin-white roots production but decreased water uptake and it also influenced the photosynthetic apparatus. The temperature of the nutrient solution also has a direct relation to the amount of oxygen consumed by plants, and an inverse relation to the oxygen dissolved. It is of paramount importance to regulate hydroponic solution temperatures in situations whereby, plants are grown in a controlled environment during winter months. Optimizing solution temperature can be achieved by warming the nutrient solution and this showed success in a variety of crops [82, 83]. High temperature in the root zone is one of the most significant limiting factors for lettuce cultivation in tropical hydroponics. Instead of cooling the entire greenhouse air, the root zone cooling system could be an energy-efficient cooling system for a greenhouse for tropical hydroponics. Therefore, it is very important to study the optimum nutrient temperature requirements for different crops grown in climates with adverse winter conditions.
6. Dissolved oxygen levels in nutrient solution
Maintaining enough dissolved O2 in a nutrient solution in a hydroponic system is crucial for plant health. Oxygen availability to roots grown in soilless culture can become limiting in case O2 demand exceeds O2 supply, inducing a reduction in root growth rate, ion, and water uptake, eventually reducing plant production [84]. Plants grown in hydroponic systems can quickly deplete the dissolved O2 in the nutrient solution resulting in poor root aeration, especially when greenhouse temperatures are high, Table 5 shows O2 solubility in pure water at different temperatures. Jong et al. [86] noticed that cucumber growth was significantly affected by root-zone aeration. Roosta et al. [87] found improve eggplant growth with rising O2 levels in the nutrient solution in floating hydroponic cultures and higher O2 levels seemed to alleviate signs of ammonium toxicity among the tested plants. Root respiration also decreases when O2 supply in the root environment falls below a critical O2 concentration [88]. The sensitivity of roots to low O2 concentration depends on its effect on mitochondrial respiration because it supplies most of the energy required for root function. Reduction in O2 levels in the nutrient solution could lead to poor roots, an increase in the incidence of diseases and pests, and a reduction in plant growth. Oxygen around a plant’s roots affects the beneficial microorganisms that provide protection from pathogens and improve nutrient uptake. Tomato plant roots would be much more susceptible to Pythium infection if root zone O2 dropped below 2.8 mg/L [89]. Dissolved O2 concentration, is strongly dependent on solution temperature and flow rate near the root zone, as well as on the growth rate of the crop, and may be influenced by the bacterial community present in the solution. The temperature has a direct relationship to the amount of oxygen consumed by the plant and a reverse relationship with dissolved oxygen from the nutrient solution. The consumption of O2 increases when the temperature of the nutrient solution increases. Consequently, it produces an increase in the relative concentration of CO2 in the root environment if the root aeration is not adequate [90]. For overcoming the limited oxygen exchange between the atmosphere and the nutrient solution in static deep water culture hydroponics, the nutrient solution is aerated by an air bubbler connecting with the pump to provide adequate root oxygenation [6]. Roots of loose-leaf lettuce grown in a floating raft hydroponic system were found to have a better condition with oxygen enrichment done in nutrient solution up to aeration pressure of 0.012 mPa and concentration of 600 ppm, with indicators of increasing length and total root surface area [68]. So, it is important to make sure the nutrient solution is properly aerated to maintain enough oxygen for the plant cells found in the root mass since this is crucial to the function of the plant’s cells and the microbial world.
Temperature (oC)
Oxygen solubility (mg L−1)
10
11.29
15
10.08
20
9.09
25
8.26
30
7.56
35
6.95
40
6.41
45
5.93
Table 5.
Solubility of oxygen in pure water at various temperatures.
An optimized and well-balanced supply of nutrients is a prerequisite for efficient use of the resources by hydroponically grown vegetables, not only to ensure a high yield but also to guarantee the quality of the edible tissues. In hydroponics, because of the limited nutrient-buffering capacity of the system and the ability to make rapid changes, careful monitoring of the system is necessary. The frequency and volume of the nutrient solution applied depends on the type of substrate, the crop and growth stage, the size of the container, the irrigation systems used, and the prevailing climatic conditions. Depending on the stage of plant development, some elements in the nutrient solution will be depleted more quickly than others and as water evaporates from the nutrient solution, the fertilizer becomes more concentrated and can burn plant roots. In hydroponics, nutrient management is very important and must be done as highly efficient as possible to improve productivity without harming the environment. Nutrient management included- application the right fertilizers source (e.g., ammonium or nitrate as nitrogen source), balanced nutrient solution according to plants needs and according to plant growth stages and climatic conditions. The main principle of crop nutrient management is to prevent overapplication of nutrients, which prevents loss due to low yield from toxicities of some nutrients resulting from the unnecessary use of fertilizers. It was reported that the strong difference between the ion ratios presented in the nutrient solution and those absorbed by plants led to the accumulation of certain ions in the nutrient solution, which caused an imbalance of mineral elements in the nutrient solution and created more energy to absorb the suitable ions [6]. Recycling exhausted solutions may also represent an efficient strategy to prevent groundwater and environmental pollution. However, the main problem with the reuse of exhausted nutrient solutions is the shortage of some key macro and micronutrients [91] and their increased salinity [92] causing, in turn, problems for crops [93, 94]. Thus, it is very important to develop management practices/tools that reduce salinity in recycled solutions and/or minimize the physiological impact of salinity on plants. The salinity increase could be contrasted by treating the recycled water with appropriate osmotic systems, including forward and reverse osmosis.
In closed hydroponic systems, accumulation of potentially toxic organic compounds released by the roots of cultivated plants may occur and to overcome this issue, several treatment techniques have been proposed for root exudates degradation or removal. However, for the treatment to be effective, it should be able to remove root exudates without interfering with the inorganic mineral nutrients in the solution. As above-mentioned, the regulation of the solution flow rate in hydroponic production affects plant growth, which in turn affects crop yield and quality. The influence of nutrient solution flow rate on plant growth is related to the plants’ physical environment. The flow of nutrient solution not only promotes nutrient ion diffusion but also increases the kinetic energy available to plant roots Therefore, adjusting the flow rate can improve plant yield and a reasonable flow pattern must be carefully selected. Because increasing the flow means increasing electricity consumption, it increases the cost of operation. Therefore, it is important to balance plant yield, nutrient management, and energy utilization. According to Baiyin et al. [95], determining the ideal flow rate for hydroponic production may help to increase yield. However, such a determination requires a specific analysis of each crop and growing environment. The hydroponic nutrient solution is the sole source of nutrients to the plant; therefore, it is imperative that a balanced solution, containing all the right plant nutrients, is applied.
8. Conclusion
Hydroponic cultivation is revolutionizing agricultural crop production techniques all over the world owing to its minimal environmental footprint, enhanced pest control, and provide high crop yield. It allows more accurate control of environmental conditions that offer possibilities for increasing production and improving the quality of crops. The rapid development of computers and controllers has enabled the opportunity to apply the controller in hydroponics. The microcontroller could be used to control these nutrient solution parameters by using relevant sensors. It monitors the conductivity and pH throughout 24 h during the whole cycle of production. Also, it helps in monitoring temperature, nutrient atomization, EC, and pH fluctuations and level of nutrient solution in the nutrient reservoir. However, although the comprehension of the multi-level interactions among the various mineral elements is considered crucial to understanding the different sensing and signaling pathways induced by a single or multiple shortage/s, the impact of these nutrients’ interactions on crop performance is largely unknown [32].
Some hydroponic growers use more than the required amounts of nutrients for crop growth to minimize the chances of nutrient deficiency. But one of the most important factors for a successful hydroponics system is the use of the appropriate nutrient solution, and it is important to control the amount of nutrients to allow or deny plants the nutrient accumulation. While hydroponic systems are considered to represent a sustainable method for growing plants, the nutrient solution used in hydroponic systems is based on chemical fertilizers which are mined from scarce and non-renewable resources. Recently, there has been an increased interest in organic hydroponics, as the market for organic food continues to grow and some studies have reported the possibility of growing vegetables using an organic nutrient solution. For optimizing the utilization of organic waste for hydroponic plant growth, a solubilization step is required to break down organic matter and mobilize nutrients [96]. For example, the direct use of organic fertilizers in hydroponic systems may inhibit plant growth due to the high biological oxygen demand in the root zone caused by the presence of dissolved organic carbon compounds. Additionally, most of the nutrients in organic sources, such as waste material from the agricultural and aquacultural industry, are not in ionic forms and, hence, are not directly available for plants. Also, the last decade has seen increasing interest in using wastewater as a source of hydroponic nutrition. This aims at a dual benefit of optimizing water reuse as well as a practical end point for wastewater management. Untreated domestic rinse water obtained from washing machine second-cycle rinse can effectively be used for indoor hydroponic cultivation of plants without the need for any additional fertilizer. It also entails the benefits of significant savings in water use, sewage disposal, ecosystem protection, and the possibility to produce economically viable food crops [97]. Nowadays, hydroponic farming technology is extensively used in producing ornamental plants and flowers. Controllable application of fertilizers, the ability to change nutrients in different weather conditions and different plant growth stages, reduction of fertilizer leaching from the root zone, reduction of contamination, environmental protection, and enhancement of the quality and quantity of products are becoming some of the advantages of this technology.
\n',keywords:"nutrient solution, pH, EC, solution temperature, nutrient management",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/80089.pdf",chapterXML:"https://mts.intechopen.com/source/xml/80089.xml",downloadPdfUrl:"/chapter/pdf-download/80089",previewPdfUrl:"/chapter/pdf-preview/80089",totalDownloads:264,totalViews:0,totalCrossrefCites:0,dateSubmitted:null,dateReviewed:"November 12th 2021",datePrePublished:"January 18th 2022",datePublished:null,dateFinished:"January 17th 2022",readingETA:"0",abstract:"Hydroponics is a profitable, sustainable agricultural method and environmental friendly technology for growing plants without soil. It is the fastest-growing agriculture sector, rapidly gaining momentum and popularity, and could dominate food production in the future. Nutrient solution and its management are the cornerstone of a successful hydroponic system and are the most important determinant of crop production and quality, which is largely dependent on the extent to which plant nutrients are acquired from the nutrient solution. All nutrients in the solution in balanced ratio are supplied directly to the plants and the composition of the solution must reflect the uptake ratio of individual elements by the crop. A balanced supply of nutrients is a prerequisite for the efficient use of resources, and stabilization of the solution pH, electrical conductivity, O2 level, and temperature is essential for optimum crop yield in hydroponic systems. In this chapter, the composition of the nutrient solution, nutrient availability which is affected by many factors, and the management of the nutrient solution are discussed.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/80089",risUrl:"/chapter/ris/80089",signatures:"Moaed Ali Al Meselmani",book:{id:"11093",type:"book",title:"Soilless Culture",subtitle:null,fullTitle:"Soilless Culture",slug:null,publishedDate:null,bookSignature:"Prof. Metin Turan, Associate Prof. Sanem Argin, Prof. Ertan Yildirim and Dr. Adem Güneş",coverURL:"https://cdn.intechopen.com/books/images_new/11093.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80355-169-2",printIsbn:"978-1-80355-168-5",pdfIsbn:"978-1-80355-170-8",isAvailableForWebshopOrdering:!0,editors:[{id:"140612",title:"Prof.",name:"Metin",middleName:null,surname:"Turan",slug:"metin-turan",fullName:"Metin Turan"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Plant nutrients",level:"1"},{id:"sec_2_2",title:"2.1 Plant nutrients interaction",level:"2"},{id:"sec_4",title:"3. PH level of the nutrient solution",level:"1"},{id:"sec_5",title:"4. Nutrient solution electrical conductivity",level:"1"},{id:"sec_6",title:"5. Nutrient solution temperature",level:"1"},{id:"sec_7",title:"6. Dissolved oxygen levels in nutrient solution",level:"1"},{id:"sec_8",title:"7. Nutrient solution management",level:"1"},{id:"sec_9",title:"8. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Singh S, Singh BS. Hydroponics – A technique for the cultivation of vegetables and medicinal plants. In: Proceedings of 4th Global Conference on Horticulture for Food, Nutrition and Livelihood Options. Bhubaneshwar, Odisha, India; 2012. p. 220'},{id:"B2",body:'Sundara KMR, Nayagi DS, Jeevitha R, Veena K. Design and development of automatic robotic system for vertical hydroponic farming using IOT and big data analysis. 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Salt tolerance and salinity effects on plants: A review. Ecotoxicology and Environmental Safety. 2005;60:324-349. DOI: 10.1016/j. ecoenv.2004.06.010'},{id:"B95",body:'Baiyin B, Tagawa K, Yamada M, Wang X, Yamada S, Yamamoto S, et al. Effect of the flow rate on plant growth and flow visualization of nutrient solution in hydroponics. Horticulturae. 2021;7:225. DOI: 10.3390/horticulturae7080225'},{id:"B96",body:'Ezziddine M, Liltved H, Seljåsen R. Hydroponic lettuce cultivation using organic nutrient solution from aerobic digested aquacultural sludge. Agronomy. 2021;11:1484. DOI: 10.3390/agronomy11081484'},{id:"B97",body:'Sundar P, Jyothi K, Sundar C. Indoor hydroponics: A potential solution to reuse domestic rinse water. Biosciences Biotechnology Research Asia. 2021;18(2):373-383'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Moaed Ali Al Meselmani",address:"m.almeselmani@sheffield.ac.uk",affiliation:'
Grantham Centre for Sustainable Futures, The University of Sheffield, Sheffield, UK
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Dr. Kashou has also spent more than seventeen years in both pediatric and adult clinical brain imaging. \n\nAs an academic, Professor Kashou has developed and taught several courses: Biomedical Computation (MATLAB), Medical Imaging (PET, SPECT, CT, US, MRI), Processing of Medical Images, and Nuclear Magnetic Resonance Imaging in Medicine. In these courses he emphasized the clinical imaging end goal as he taught computer software, physics, engineering, and physiology. During this time, he focused on developing a research program and implementing an academic vision. This included establishing and directing two brain research labs, revitalizing, and sustaining an otherwise nonexistent graduate (MS & PhD) medical imaging program. 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In 2004, he did a research in biomedical engineering at the National High Magnetic Field Lab, Florida, and the Center of Nanobiotechnology at Florida State University, Tallahassee. Dr. Sharma is affiliated with the Department of Medicine, Columbia University, New York, from 2000. His research interests are tissue differentiation and development of imaging techniques.",institutionString:null,institution:{name:"Florida State University",institutionURL:null,country:{name:"United States of America"}}}]},generic:{page:{slug:"our-story",title:"Our story",intro:"
The company was founded in Vienna in 2004 by Alex Lazinica and Vedran Kordic, two PhD students researching robotics. While completing our PhDs, we found it difficult to access the research we needed. So, we decided to create a new Open Access publisher. A better one, where researchers like us could find the information they needed easily. The result is IntechOpen, an Open Access publisher that puts the academic needs of the researchers before the business interests of publishers.
",metaTitle:"Our story",metaDescription:"The company was founded in Vienna in 2004 by Alex Lazinica and Vedran Kordic, two PhD students researching robotics. While completing our PhDs, we found it difficult to access the research we needed. So, we decided to create a new Open Access publisher. A better one, where researchers like us could find the information they needed easily. The result is IntechOpen, an Open Access publisher that puts the academic needs of the researchers before the business interests of publishers.",metaKeywords:null,canonicalURL:"/page/our-story",contentRaw:'[{"type":"htmlEditorComponent","content":"
We started by publishing journals and books from the fields of science we were most familiar with - AI, robotics, manufacturing and operations research. Through our growing network of institutions and authors, we soon expanded into related fields like environmental engineering, nanotechnology, computer science, renewable energy and electrical engineering, Today, we are the world’s largest Open Access publisher of scientific research, with over 4,200 books and 54,000 scientific works including peer-reviewed content from more than 116,000 scientists spanning 161 countries. Our authors range from globally-renowned Nobel Prize winners to up-and-coming researchers at the cutting edge of scientific discovery.
\\n\\n
In the same year that IntechOpen was founded, we launched what was at the time the first ever Open Access, peer-reviewed journal in its field: the International Journal of Advanced Robotic Systems (IJARS).
\\n\\n
The IntechOpen timeline
\\n\\n
2004
\\n\\n
\\n\\t
Intech Open is founded in Vienna, Austria, by Alex Lazinica and Vedran Kordic, two PhD students, and their first Open Access journals and books are published.
\\n\\t
Alex and Vedran launch the first Open Access, peer-reviewed robotics journal and IntechOpen’s flagship publication, the International Journal of Advanced Robotic Systems (IJARS).
\\n
\\n\\n
2005
\\n\\n
\\n\\t
IntechOpen publishes its first Open Access book: Cutting Edge Robotics.
\\n
\\n\\n
2006
\\n\\n
\\n\\t
IntechOpen publishes a special issue of IJARS, featuring contributions from NASA scientists regarding the Mars Exploration Rover missions.
\\n
\\n\\n
2008
\\n\\n
\\n\\t
Downloads milestone: 200,000 downloads reached
\\n
\\n\\n
2009
\\n\\n
\\n\\t
Publishing milestone: the first 100 Open Access STM books are published
\\n
\\n\\n
2010
\\n\\n
\\n\\t
Downloads milestone: one million downloads reached
\\n\\t
IntechOpen expands its book publishing into a new field: medicine.
\\n
\\n\\n
2011
\\n\\n
\\n\\t
Publishing milestone: More than five million downloads reached
\\n\\t
IntechOpen publishes 1996 Nobel Prize in Chemistry winner Harold W. Kroto’s “Strategies to Successfully Cross-Link Carbon Nanotubes”. Find it here.
\\n\\t
IntechOpen and TBI collaborate on a project to explore the changing needs of researchers and the evolving ways that they discover, publish and exchange information. The result is the survey “Author Attitudes Towards Open Access Publishing: A Market Research Program”.
\\n\\t
IntechOpen hosts SHOW - Share Open Access Worldwide; a series of lectures, debates, round-tables and events to bring people together in discussion of open source principles, intellectual property, content licensing innovations, remixed and shared culture and free knowledge.
\\n
\\n\\n
2012
\\n\\n
\\n\\t
Publishing milestone: 10 million downloads reached
\\n\\t
IntechOpen holds Interact2012, a free series of workshops held by figureheads of the scientific community including Professor Hiroshi Ishiguro, director of the Intelligent Robotics Laboratory, who took the audience through some of the most impressive human-robot interactions observed in his lab.
\\n
\\n\\n
2013
\\n\\n
\\n\\t
IntechOpen joins the Committee on Publication Ethics (COPE) as part of a commitment to guaranteeing the highest standards of publishing.
\\n
\\n\\n
2014
\\n\\n
\\n\\t
IntechOpen turns 10, with more than 30 million downloads to date.
\\n\\t
IntechOpen appoints its first Regional Representatives - members of the team situated around the world dedicated to increasing the visibility of our authors’ published work within their local scientific communities.
\\n
\\n\\n
2015
\\n\\n
\\n\\t
Downloads milestone: More than 70 million downloads reached, more than doubling since the previous year.
\\n\\t
Publishing milestone: IntechOpen publishes its 2,500th book and 40,000th Open Access chapter, reaching 20,000 citations in Thomson Reuters ISI Web of Science.
\\n\\t
40 IntechOpen authors are included in the top one per cent of the world’s most-cited researchers.
\\n\\t
Thomson Reuters’ ISI Web of Science Book Citation Index begins indexing IntechOpen’s books in its database.
\\n
\\n\\n
2016
\\n\\n
\\n\\t
IntechOpen is identified as a world leader in Simba Information’s Open Access Book Publishing 2016-2020 report and forecast. IntechOpen came in as the world’s largest Open Access book publisher by title count.
\\n
\\n\\n
2017
\\n\\n
\\n\\t
Downloads milestone: IntechOpen reaches more than 100 million downloads
\\n\\t
Publishing milestone: IntechOpen publishes its 3,000th Open Access book, making it the largest Open Access book collection in the world
We started by publishing journals and books from the fields of science we were most familiar with - AI, robotics, manufacturing and operations research. Through our growing network of institutions and authors, we soon expanded into related fields like environmental engineering, nanotechnology, computer science, renewable energy and electrical engineering, Today, we are the world’s largest Open Access publisher of scientific research, with over 4,200 books and 54,000 scientific works including peer-reviewed content from more than 116,000 scientists spanning 161 countries. Our authors range from globally-renowned Nobel Prize winners to up-and-coming researchers at the cutting edge of scientific discovery.
\n\n
In the same year that IntechOpen was founded, we launched what was at the time the first ever Open Access, peer-reviewed journal in its field: the International Journal of Advanced Robotic Systems (IJARS).
\n\n
The IntechOpen timeline
\n\n
2004
\n\n
\n\t
Intech Open is founded in Vienna, Austria, by Alex Lazinica and Vedran Kordic, two PhD students, and their first Open Access journals and books are published.
\n\t
Alex and Vedran launch the first Open Access, peer-reviewed robotics journal and IntechOpen’s flagship publication, the International Journal of Advanced Robotic Systems (IJARS).
\n
\n\n
2005
\n\n
\n\t
IntechOpen publishes its first Open Access book: Cutting Edge Robotics.
\n
\n\n
2006
\n\n
\n\t
IntechOpen publishes a special issue of IJARS, featuring contributions from NASA scientists regarding the Mars Exploration Rover missions.
\n
\n\n
2008
\n\n
\n\t
Downloads milestone: 200,000 downloads reached
\n
\n\n
2009
\n\n
\n\t
Publishing milestone: the first 100 Open Access STM books are published
\n
\n\n
2010
\n\n
\n\t
Downloads milestone: one million downloads reached
\n\t
IntechOpen expands its book publishing into a new field: medicine.
\n
\n\n
2011
\n\n
\n\t
Publishing milestone: More than five million downloads reached
\n\t
IntechOpen publishes 1996 Nobel Prize in Chemistry winner Harold W. Kroto’s “Strategies to Successfully Cross-Link Carbon Nanotubes”. Find it here.
\n\t
IntechOpen and TBI collaborate on a project to explore the changing needs of researchers and the evolving ways that they discover, publish and exchange information. The result is the survey “Author Attitudes Towards Open Access Publishing: A Market Research Program”.
\n\t
IntechOpen hosts SHOW - Share Open Access Worldwide; a series of lectures, debates, round-tables and events to bring people together in discussion of open source principles, intellectual property, content licensing innovations, remixed and shared culture and free knowledge.
\n
\n\n
2012
\n\n
\n\t
Publishing milestone: 10 million downloads reached
\n\t
IntechOpen holds Interact2012, a free series of workshops held by figureheads of the scientific community including Professor Hiroshi Ishiguro, director of the Intelligent Robotics Laboratory, who took the audience through some of the most impressive human-robot interactions observed in his lab.
\n
\n\n
2013
\n\n
\n\t
IntechOpen joins the Committee on Publication Ethics (COPE) as part of a commitment to guaranteeing the highest standards of publishing.
\n
\n\n
2014
\n\n
\n\t
IntechOpen turns 10, with more than 30 million downloads to date.
\n\t
IntechOpen appoints its first Regional Representatives - members of the team situated around the world dedicated to increasing the visibility of our authors’ published work within their local scientific communities.
\n
\n\n
2015
\n\n
\n\t
Downloads milestone: More than 70 million downloads reached, more than doubling since the previous year.
\n\t
Publishing milestone: IntechOpen publishes its 2,500th book and 40,000th Open Access chapter, reaching 20,000 citations in Thomson Reuters ISI Web of Science.
\n\t
40 IntechOpen authors are included in the top one per cent of the world’s most-cited researchers.
\n\t
Thomson Reuters’ ISI Web of Science Book Citation Index begins indexing IntechOpen’s books in its database.
\n
\n\n
2016
\n\n
\n\t
IntechOpen is identified as a world leader in Simba Information’s Open Access Book Publishing 2016-2020 report and forecast. IntechOpen came in as the world’s largest Open Access book publisher by title count.
\n
\n\n
2017
\n\n
\n\t
Downloads milestone: IntechOpen reaches more than 100 million downloads
\n\t
Publishing milestone: IntechOpen publishes its 3,000th Open Access book, making it the largest Open Access book collection in the world
\n
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This chapter tries to answer at least a few questions about corruption and the causes for it, its consequences and how to deal with it successfully.",book:{id:"6487",slug:"trade-and-global-market",title:"Trade and Global Market",fullTitle:"Trade and Global Market"},signatures:"Štefan Šumah",authors:[{id:"228073",title:"Mr.",name:"Stefan",middleName:null,surname:"Sumah",slug:"stefan-sumah",fullName:"Stefan Sumah"}]},{id:"55499",title:"Human Resources Management in Nonprofit Organizations: A Case Study of Istanbul Foundation for Culture and Arts",slug:"human-resources-management-in-nonprofit-organizations-a-case-study-of-istanbul-foundation-for-cultur",totalDownloads:2294,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The aim of this study is to investigate the efficiency and importance of human resources management in nonprofit organizations. The understanding was included to the literature as personnel management at the beginning of the twentieth century and it turned into an approach as human resources management in the 1980s. It could be observed that many organizations, which deem the human as the most critical stakeholder, adopt a traditional way of personnel management in operating human resources. The employees play a key role in the success of an organization. For this reason, subjects such as recruitment, training, development, career management, performance appraisal, occupational health, and safety are the fundamental functions of human resources management. The study examines to what extent these roles are evaluated through a case study. The subject matter of the study is the most powerful culture and art foundation in Turkey. Compared to many other nonprofit organizations, the foundation actively performs a variety of services within a year worldwide. The fact that the total number of employees might rise up to 800, including the field personnel, indicates the need of a good functioning human resources management. The human resources practices of the foundation are examined and evaluated within that scope.",book:{id:"5826",slug:"issues-of-human-resource-management",title:"Issues of Human Resource Management",fullTitle:"Issues of Human Resource Management"},signatures:"Beste Gökçe Parsehyan",authors:[{id:"189113",title:"Dr.",name:"Beste",middleName:null,surname:"Gokce Parsehyan",slug:"beste-gokce-parsehyan",fullName:"Beste Gokce Parsehyan"}]},{id:"59152",title:"Marketing Strategies for the Social Good",slug:"marketing-strategies-for-the-social-good",totalDownloads:1594,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Social network sites (SNS) have proven to be a good environment to promote and sell goods and services, but marketing is more than creating commercial strategies. Social marketing strategies can also be used to promote behavioral change and help individuals transform their lives, achieve well-being, and adopt prosocial behaviors. In this chapter, we seek to analyze with a netnographic study, how SNS are being employed by nonprofits and nongovernment organizations (NGOs) to enable citizens and consumers to participate in different programs and activities that promote social transformation and well-being. A particular interest is to identify how organizations are using behavioral economic tactics to nudge individuals and motivate them to engage in prosocial actions. By providing an understanding on how SNS can provide an adequate environment for the design of social marketing strategies, we believe our work has practical implications both for academicians and marketers who want to contribute in the transformation of consumer behavior and the achievement of well-being and social change.",book:{id:"6583",slug:"marketing",title:"Marketing",fullTitle:"Marketing"},signatures:"Alicia De La Pena",authors:[{id:"196878",title:"Dr.",name:"Alicia",middleName:null,surname:"De La Pena",slug:"alicia-de-la-pena",fullName:"Alicia De La Pena"}]}],onlineFirstChaptersFilter:{topicId:"4",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82387",title:"Kept Promises? The Evolution of the EU Financial Contribution to Climate Change",slug:"kept-promises-the-evolution-of-the-eu-financial-contribution-to-climate-change",totalDownloads:2,totalDimensionsCites:null,doi:"10.5772/intechopen.105541",abstract:"The chapter provides an overview of the public climate finance implemented under the UNFCCC by the EU as a whole and its Member States—in the chapter called EUplus—later taken over by SDG 13.a, for the period 2011–2018 (the latest year available). Through the analysis of the UNFCCC Biennial Reports, it is possible not only to highlight the amount allocated to the challenge against climate change, but also to break it down into its two meanings: mitigation and adaptation, as well as to identify the type of channel through which this support has been implemented. In this context, particular attention will be given to the two contribution channels: bilateral and multilateral, highlighting the type of support in different cases. The chapter shows an increase in contributions, especially since 2015, and how support has been increasingly shifted toward adaptation. This could mean that there is an awareness in a delay in achieving the stabilization of GHG emissions in the atmosphere.",book:{id:"11476",title:"Globalization and Sustainability - Recent Advances, New Perspectives and Emerging Issues",coverURL:"https://cdn.intechopen.com/books/images_new/11476.jpg"},signatures:"Cecilia Camporeale, Roberto Del Ciello and Mario Jorizzo"},{id:"82381",title:"Promotion of Science Learning through Science Content and Practical Assessment",slug:"promotion-of-science-learning-through-science-content-and-practical-assessment",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.105407",abstract:"Assessment is an integral part of the learning and teaching. Trends in International Mathematics and Science report reveals that in South Africa, grade 9 has the worst science skills. The objective of the study is to explore if teachers can promote science learning through science content and practical assessment. The descriptive survey design was utilized in the study. The study was informed by Vygotsky’s social constructivism. Thirty out of sixty-seven schools were selected using simple random sampling. Cronbach’s alpha test was used to ascertain the scale reliability of the questionnaire. The findings revealed the following: Data illustrates how educators assess Science Learning. Responses were agreed, neutral, disagree, and no response. Align with cognitive domains 86.7%; Principles of assessment 77%; Investigations 66.7%; Simulation 63.3%; Debates 50%; each among these: Assignment, Experiments, and Examinations 40%; Problem Solving 37%; Projects 34%; Presentation 23%; Roleplay 17%; Tests 13.3%; and Quiz 7%. Regarding Neutral, data validates that teachers need support as well as those who disagreed they lack content knowledge regarding strategies of assessment. We recommend teachers to value assessment and implement different strategies of assessment so that students can be able to apply both theory and the practical.",book:{id:"10662",title:"Pedagogy - Challenges, Recent Advances, New Perspectives, and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10662.jpg"},signatures:"Nomxolisi Mtsi, Shakespear M. Chiphambo and Nomaroma Kumanda"},{id:"82524",title:"Italy’s Small Exporting Companies: Globalization and Sustainability Issues",slug:"italy-s-small-exporting-companies-globalization-and-sustainability-issues",totalDownloads:0,totalDimensionsCites:0,doi:"10.5772/intechopen.105542",abstract:"Internationalization has gained momentum in the last few years as a strategy that may allow small enterprises to grow. Frequently, import and export activities represent the first step of the internationalized process and an important challenge for small business. Quite a number of studies have investigated and tried to solve the implied problems. Starting from the theoretical and empirical literature, this research focuses on the most relevant economic and financial constraints faced by small Italian import-export companies and is specifically aimed at analyzing the characteristics of their financial structure between 2011 and 2020, as well as their performance over the same period. We selected small Italian enterprises and identified the subset of import-export companies. We applied a set of performance indicators to reclassify financial statements to highlight the dynamics of investments, profitability, financial independence, and liquidity over the 10 years under analysis. The economic and financial characteristics of the small import-export companies are determined by comparing their performance with that of all Italian small enterprises. The findings show that small Italian exporting companies are not characterized by significant growth in turnover but present a situation that is certainly better in terms of economic and financial sustainability compared with non-internationalized companies.",book:{id:"11476",title:"Globalization and Sustainability - Recent Advances, New Perspectives and Emerging Issues",coverURL:"https://cdn.intechopen.com/books/images_new/11476.jpg"},signatures:"Roberta Pace and Francesca Mandanici"},{id:"82382",title:"A Cultural Approach in the Synchronous Class in English Teaching and Learning",slug:"a-cultural-approach-in-the-synchronous-class-in-english-teaching-and-learning",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.105553",abstract:"If culture is defined as a way of training to obtain knowledge through educational channels, the concept is associated with educability. Therefore, teaching cognitive, attitudinal, and procedural knowledge directly indicates teaching and learning culture to acquire norms and patterns of sociocultural behavior. The purpose of this study was: to debate about the way interaction among students and teachers in synchronous classes based on life’s materials, topics, and methods, and critical or reflective thinking can be adapted by the teacher to the students’ closest environment to communicate in English as an international language. If a language is taught, spoken, and learned in the country, culture surrounding the context is taught. If this language is not spoken in the place, the knowledge system also transmits norms and values, different from those of the language. So, the students get, culturally and socially, modes of action, principles, and knowledge through international language learning. Thus, teaching and learning English as an international language means the way possible interaction has opportunities for every student’s growth and the way their personality formation gets integral results. English taught and learned as an international language denotes reaching the students’ world and needs to communicate in English as a meaningful international language.",book:{id:"10662",title:"Pedagogy - Challenges, Recent Advances, New Perspectives, and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10662.jpg"},signatures:"Ned Vito Quevedo Arnaiz, Nemis García Arias and Fredy Pablo Cañizares Galarza"},{id:"82470",title:"The Effect of COVID-19 on the Quality of Life of Care Workers: Challenges for Social Services Leaders",slug:"the-effect-of-covid-19-on-the-quality-of-life-of-care-workers-challenges-for-social-services-leaders",totalDownloads:4,totalDimensionsCites:0,doi:"10.5772/intechopen.105603",abstract:"Stressful situations are likely to impact health and social care workers’ quality of life negatively. Indeed, mental, physical, and emotional health problems have been reported in relation to the effects of the COVID-19 pandemic on the quality of life of health care workers. Instead of health care workers’ reality, and despite the care sector’s relevance, studies of the effects of COVID-19 on the quality of life of care workers have not been sufficiently explored. Recognizing the effect of COVID on the quality of life of care workers will collaborate with leaders of organizations, social work practitioners, and academics in the design of policies that promote better working conditions. Therefore, during 2021, a study was carried out in Chile where 150 social services and care workers were surveyed in Chile using a version of COV19-QoL in Spanish. The impact of COVID on quality of life is described, and the challenges that this reality implies to social service leaders are presented.",book:{id:"11095",title:"Social Work - Perspectives on Leadership and Organisation",coverURL:"https://cdn.intechopen.com/books/images_new/11095.jpg"},signatures:"Magdalena Calderón-Orellana, Alejandra Inostroza and Paula Miranda Sánchez"},{id:"82448",title:"Virus World Vulnerability: A Critical Reading of Gender and Performance in Bo Burnham’s “Inside” (2021)",slug:"virus-world-vulnerability-a-critical-reading-of-gender-and-performance-in-bo-burnham-s-inside-2021",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.105182",abstract:"Through an engagement with the seminal work of Raewyn Connell on masculinities and hegemonic masculinity, this chapter argues for the hegemonic norm as producing behaviour among men that can be traced in multiple male subjectivities. The argument is that men respond to the prevailing masculine norm by enacting self-protective disavowal—a complex psychological process that involves the reordering of reality in the interests of the maintenance of power, and one that is seen in cases of both legitimate and imagined threats to the self and the body. Self-protective disavowal is at the core of the Same Shit phenomenon—the idea that while the experience of masculinity varies across culture and position in the gender order, self-protective disavowal is a constant that leads to predicable patterns among men. The discussion then explores deliberate vulnerability as a kind of anti-protective disavowal in Bo Burnham’s INSIDE, a complex, undefinable ‘special’ released on Netflix in 2021. The chapter considers Burnham’s work as a departure from self-protective disavowal and Same Shit masculinity through deliberate vulnerability and critically evaluates the value of this alternative, especially given the nihilism that reigns over the work and calls into question the validity of uncritically romanticization of alternatives.",book:{id:"10540",title:"Masculinity Studies - An Interdisciplinary Approach",coverURL:"https://cdn.intechopen.com/books/images_new/10540.jpg"},signatures:"Chris McWade"}],onlineFirstChaptersTotal:285},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:320,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:133,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:17,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517",scope:"Paralleling similar advances in the medical field, astounding advances occurred in Veterinary Medicine and Science in recent decades. These advances have helped foster better support for animal health, more humane animal production, and a better understanding of the physiology of endangered species to improve the assisted reproductive technologies or the pathogenesis of certain diseases, where animals can be used as models for human diseases (like cancer, degenerative diseases or fertility), and even as a guarantee of public health. Bridging Human, Animal, and Environmental health, the holistic and integrative “One Health” concept intimately associates the developments within those fields, projecting its advancements into practice. This book series aims to tackle various animal-related medicine and sciences fields, providing thematic volumes consisting of high-quality significant research directed to researchers and postgraduates. It aims to give us a glimpse into the new accomplishments in the Veterinary Medicine and Science field. By addressing hot topics in veterinary sciences, we aim to gather authoritative texts within each issue of this series, providing in-depth overviews and analysis for graduates, academics, and practitioners and foreseeing a deeper understanding of the subject. Forthcoming texts, written and edited by experienced researchers from both industry and academia, will also discuss scientific challenges faced today in Veterinary Medicine and Science. In brief, we hope that books in this series will provide accessible references for those interested or working in this field and encourage learning in a range of different topics.",coverUrl:"https://cdn.intechopen.com/series/covers/13.jpg",latestPublicationDate:"June 29th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:11,editor:{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"19",title:"Animal Science",coverUrl:"https://cdn.intechopen.com/series_topics/covers/19.jpg",isOpenForSubmission:!0,editor:{id:"259298",title:"Dr.",name:"Edward",middleName:null,surname:"Narayan",slug:"edward-narayan",fullName:"Edward Narayan",profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",biography:"Dr. Edward Narayan graduated with Ph.D. degree in Biology from the University of the South Pacific and pioneered non-invasive reproductive and stress endocrinology tools for amphibians - the novel development and validation of non-invasive enzyme immunoassays for the evaluation of reproductive hormonal cycle and stress hormone responses to environmental stressors. \nDr. Narayan leads the Stress Lab (Comparative Physiology and Endocrinology) at the University of Queensland. A dynamic career research platform which is based on the thematic areas of comparative vertebrate physiology, stress endocrinology, reproductive endocrinology, animal health and welfare, and conservation biology. \nEdward has supervised 40 research students and published over 60 peer reviewed research.",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null},{id:"20",title:"Animal Nutrition",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",isOpenForSubmission:!0,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"28",title:"Animal Reproductive Biology and Technology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/28.jpg",isOpenForSubmission:!0,editor:{id:"177225",title:"Prof.",name:"Rosa Maria Lino Neto",middleName:null,surname:"Pereira",slug:"rosa-maria-lino-neto-pereira",fullName:"Rosa Maria Lino Neto Pereira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9wkQAC/Profile_Picture_1624519982291",biography:"Rosa Maria Lino Neto Pereira (DVM, MsC, PhD and) is currently a researcher at the Genetic Resources and Biotechnology Unit of the National Institute of Agrarian and Veterinarian Research (INIAV, Portugal). She is the head of the Reproduction and Embryology Laboratories and was lecturer of Reproduction and Reproductive Biotechnologies at Veterinary Medicine Faculty. She has over 25 years of experience working in reproductive biology and biotechnology areas with a special emphasis on embryo and gamete cryopreservation, for research and animal genetic resources conservation, leading research projects with several peer-reviewed papers. Rosa Pereira is member of the ERFP-FAO Ex situ Working Group and of the Management Commission of the Portuguese Animal Germplasm Bank.",institutionString:"The National Institute for Agricultural and Veterinary Research. Portugal",institution:null},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:15,paginationItems:[{id:"82457",title:"Canine Hearing Management",doi:"10.5772/intechopen.105515",signatures:"Peter M. Skip Scheifele, Devan Marshall, Stephen Lee, Paul Reid, Thomas McCreery and David Byrne",slug:"canine-hearing-management",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg",subseries:{id:"19",title:"Animal Science"}}},{id:"82285",title:"Parvovirus Vectors: The Future of Gene Therapy",doi:"10.5772/intechopen.105085",signatures:"Megha Gupta",slug:"parvovirus-vectors-the-future-of-gene-therapy",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg",subseries:{id:"19",title:"Animal Science"}}},{id:"82170",title:"Equine Stress: Neuroendocrine Physiology and Pathophysiology",doi:"10.5772/intechopen.105045",signatures:"Milomir Kovac, Tatiana Vladimirovna Ippolitova, Sergey Pozyabin, Ruslan Aliev, Viktoria Lobanova, Nevena Drakul and Catrin S. Rutland",slug:"equine-stress-neuroendocrine-physiology-and-pathophysiology",totalDownloads:2,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Veterinary Anatomy and Physiology",coverURL:"https://cdn.intechopen.com/books/images_new/10665.jpg",subseries:{id:"19",title:"Animal Science"}}},{id:"81793",title:"Canine parvovirus-2: An Emerging Threat to Young Pets",doi:"10.5772/intechopen.104846",signatures:"Mithilesh Singh, Rajendran Manikandan, Ujjwal Kumar De, Vishal Chander, Babul Rudra Paul, Saravanan Ramakrishnan and Darshini Maramreddy",slug:"canine-parvovirus-2-an-emerging-threat-to-young-pets",totalDownloads:19,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg",subseries:{id:"19",title:"Animal Science"}}}]},overviewPagePublishedBooks:{paginationCount:11,paginationItems:[{type:"book",id:"7233",title:"New Insights into Theriogenology",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7233.jpg",slug:"new-insights-into-theriogenology",publishedDate:"December 5th 2018",editedByType:"Edited by",bookSignature:"Rita Payan-Carreira",hash:"74f4147e3fb214dd050e5edd3aaf53bc",volumeInSeries:1,fullTitle:"New Insights into Theriogenology",editors:[{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. 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He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"322007",title:"Dr.",name:"Maria Elizbeth",middleName:null,surname:"Alvarez-Sánchez",slug:"maria-elizbeth-alvarez-sanchez",fullName:"Maria Elizbeth Alvarez-Sánchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",country:{name:"Mexico"}}},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}},{id:"441116",title:"Dr.",name:"Jovanka M.",middleName:null,surname:"Voyich",slug:"jovanka-m.-voyich",fullName:"Jovanka M. Voyich",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Montana State University",country:{name:"United States of America"}}},{id:"330412",title:"Dr.",name:"Muhammad",middleName:null,surname:"Farhab",slug:"muhammad-farhab",fullName:"Muhammad Farhab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}}]}},subseries:{item:{id:"24",type:"subseries",title:"Computer Vision",keywords:"Image Analysis, Scene Understanding, Biometrics, Deep Learning, Software Implementation, Hardware Implementation, Natural Images, Medical Images, Robotics, VR/AR",scope:"The scope of this topic is to disseminate the recent advances in the rapidly growing field of computer vision from both the theoretical and practical points of view. Novel computational algorithms for image analysis, scene understanding, biometrics, deep learning and their software or hardware implementations for natural and medical images, robotics, VR/AR, applications are some research directions relevant to this topic.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",hasOnlineFirst:!0,hasPublishedBooks:!1,annualVolume:11420,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null,series:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403"},editorialBoard:[{id:"1177",title:"Prof.",name:"António",middleName:"J. 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