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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:"3379",title:"Atrial Fibrillation",subtitle:"Mechanisms and Treatment",isOpenForSubmission:!1,hash:"33eb2e87586ea89705b55f1cfaeeb735",slug:"atrial-fibrillation-mechanisms-and-treatment",bookSignature:"Tong Liu",coverURL:"https://cdn.intechopen.com/books/images_new/3379.jpg",editedByType:"Edited by",editors:[{id:"157258",title:"Associate Prof.",name:"Tong",surname:"Liu",slug:"tong-liu",fullName:"Tong Liu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3435",title:"Ischemic Heart Disease",subtitle:null,isOpenForSubmission:!1,hash:"882248c482dce0e13a0cafa2a738032a",slug:"ischemic-heart-disease",bookSignature:"David C. 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1. Introduction
In nonpregnant females of various species, the components of the renin-angiotensin-aldosterone system (RAAS), i.e., prorenin, renin, angiotensin II (ANG-II), and aldosterone, are expressed in the tissues of reproductive organs, mainly the uterus and ovaries. These hormones have direct physiological relationships with specific reproductive functions, including folliculogenesis, oocyte maturation, ovulation, follicular atresia, corpus luteum development and luteolysis, steroidogenesis, angiogenesis, and expression of certain vasoactive substances [1, 2, 3, 4, 5, 6, 7, 8].
A great body of literature has confirmed an increase in plasma activity of renin (PRA) and plasma concentrations of ANG-II and aldosterone in women during the luteal compared to the follicular period of the estrous cycle [9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19]. The primary source of renin and aldosterone is progesterone (P4) secreted by the corpus luteum. The elevated P4 concentrations during the luteal period lead to increased renal plasma flow, glomerular filtration rate, and natriuresis. This natriuretic effect stimulates in a compensatory way the synthesis and release of renin, ANG-II, and aldosterone [10, 11, 12, 15, 16, 20, 21, 22, 23]. However, these results do not agree with those described by Szmuilowicz et al. [19], who suggested that the synthesis of aldosterone might be independent of renin and ANG-II at the ovarian level. Another physiological event that happens during the estrous cycle of the women is the preovulatory increase of renin [14, 24], ANG-II [25], and aldosterone [10, 12, 25, 26].
Similar results to those described in women have been reported in laboratory animals [27, 28, 29, 30]. A potential physiological mechanism related to these changes is the stimulatory effect exerted by estrogens (E2) on the synthesis of angiotensinogen [31]. Additional mechanisms could be the hemodynamic and renal blood flow variations, changes in Na concentrations at the macula densa in the kidney, alterations in local sympathetic activity, and release of corticotropin or adrenocorticotrophic hormone (ACTH). All of these mechanisms act as regulatory factors for aldosterone synthesis [17, 19, 32, 33].
During pregnancy, circulating and tissular RAASs interact closely in order to achieve a successful outcome of the pregnancy. The local RAASs involved in pregnancy are mainly located at the ovaries, uterus (both at the placenta and decidua), and intrarenal level. The nonrenal local RAAS systems have pivotal functions in the implantation and in the placentation as well as in the development of the uteroplacental and umbilical placental circulations. In addition, they contribute directly to the circulating RAAS of the pregnant female, determining in part the normal functionality of the cardiovascular and renal systems [34].
In this review, we summarize the state of the art of the current knowledge of the RAAS in reproductive mares. We provide comparative profiling of the hormones of this system with other species, mainly with women and laboratory animals. The results of our own investigations performed during the last 10 years have demonstrated that an activation of the RAAS happens around ovulation and during pregnancy in the reproductive mare, even though significant differences with the reports made for women and laboratory animals have been found.
2. Changes in the renin-angiotensin-aldosterone system during the estral cycle
2.1 A brief review of the estral cycle in the mare
An exhaustive review of the estral cycle of the mare and the neuroendocrine mechanisms associated has been published recently [35]. Briefly, the mean length of a mare’s estral cycle is 21 ± 3 days. The cycle is divided into two physiological periods: the estrous or follicular period and the diestrus or luteal period. The duration of the follicular period is approximately 6 days, but it can take 4–10 days depending on the mare. The luteal period has a duration of 15 days, ranging between 12 and 18 days. Ovulation can occur at any time during the follicular period, although it usually occurs 24–48 h before the end of this period. During the estral cycle, physiological changes in mares include follicular development, selection of the dominant follicle, release of the oocyte from follicle, formation of the corpus luteum, and production of P4. These physiological events are controlled by gonadotropin-releasing hormone (GnRH) that stimulates the hypophysis to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). These hormones control the development of the follicle and stimulate the secretion of E2 from the follicle to induce ovulation and corpus luteum establishment and development [35, 36].
2.2 Changes in the renin-angiotensin-aldosterone system during the luteal period
Most researchers have documented that aldosterone concentrations rise between 2 and 4 times during the luteal period [11, 37]. Presumably, this increase mirrors the increase experienced by ANG-II concentrations. However, this supposition has not always been supporting, and as a consequence, later it was suggested that the changes in ANG-II might be attributed to other ways independent of the RAAS [19]. Although this hypothesis is currently the most defended in the literature, some authors would not be able to confirm it [32, 38].
A variety of studies have shown that the relationship between PRA and aldosterone from the middle to the end of the luteal period can be adjusted to a linear model [9, 10, 16, 22, 37, 39, 40]. The researches performed in women with luteal insufficiency have helped to clarify complex issues, such as the involvement of the sex hormones in the modifications of the different RAAS components during the different period of the estral cycle. In this sense, several early investigations compared the concentrations of angiotensinogen, aldosterone, gonadotropins, ovarian steroids, and PRA in women with ovulatory cycles and in women with luteal insufficiency. While in physiological estral cycles the peak of PRA was closely related to the increase in aldosterone, in women with anovulatory cycles, these temporal relationships between renin and aldosterone or PRA and aldosterone were not found [9, 10, 41]. Subsequently, it was hypothesized that once the corpus luteum reaches functional maturity, it acts as the primary source of renin and aldosterone. Thereby, there was an explanation for the direct relationship between P4 and other compounds derived from the corpus luteum and the RAAS in physiological estral cycles, but not in women with ovulatory failure, because these women show a significant decrease in P4 concentrations [18, 21, 42].
P4 seems to be directly related to the luteal synthesis of aldosterone [15, 18, 21, 42]. Certain mechanisms dependent on P4, such as increased plasma flow, renal glomerular filtration rate, and Na and Cl excretion, result in natriuresis [16]. The initial natriuresis induced by P4 stimulates in a compensatory way the secretion of renin, ANG-II, and aldosterone [9, 10, 11, 20, 37]. The experimental administration of P4 results in natriuresis, which is followed by peaks of aldosterone secretion, aldosterone urinary excretion (AUE), and Na retention [11, 43]. Although PRA, ANG-II, and aldosterone increase after the administration of P4, the rises do not occur simultaneously [43]. These results have been explained in base of the competence between P4 and aldosterone for the mineralocorticoid receptor [12, 44, 45]. In physiological cycles, endogenously secreted P4 exerts a mild anti-aldosterone effect, avoiding an excessive retention of Na and water during the luteal period [46].
The E2 and P4 peaks during the luteal period lead to increases of PRA and ANG-II 2–3 times and also increases of AUE [17, 19]. However, the increase of E2 that happens during the first half of the estral cycle does not result in substantially raised PRA and AUE. Perhaps these events are mediated by the expression of aldosterone receptor protein and angiotensinogen in the absence of changes in ANG-II [46, 47, 48]. The lack of correlation between aldosterone and E2, as well as the lack of stimulation of aldosterone production in in vitro cultures of glomerulosa cells, could be other findings that might exclude E2 from the synthesis of aldosterone during the luteal period [19].
However, there are additional mechanisms involved in the synthesis of aldosterone independently of the P4 concentrations, such as the uptake of proteins and Na in the diet [49, 50] or a peripheral vasodilation [16]. It is difficult to interpret these findings without considering the intake of Na, since this electrolyte determines primarily the production of aldosterone via RAAS [49]. However, many previous studies did not control or did not report Na concentrations, which is a limiting factor in the proper interpretation of the results. More recently, Szmuilowicz et al. [19] showed that circulating and urinary levels of aldosterone increase significantly during the luteal period in response to the infusion of ANG-II in women with high Na concentrations. In these situations, positive correlations between P4 and aldosterone have been found, without parallel changes in PRA and ANG-II. On the contrary, in women with low Na concentrations, these interrelationships do not occur, even though the restriction of Na in the diet is a powerful stimulus for the activation of RAAS [49]. In Na-restricted diets, PRA and aldosterone respond independently between each other, and therefore, the absence of modifications in PRA and ANG-II could rule out that the increase in aldosterone is modulated via RAAS activation during the luteal period.
Another mechanism that has been related to the synthesis of renin and aldosterone during the luteal period is the release of angiotensinogen and prorenin. However, the studies conducted in this field have provided contradictory results. The expression of angiotensinogen is regulated transcriptionally by E2 [31], and consequently, the administration of different ovarian stimulation treatments in women increases the concentrations of E2 and renin [15]. Therefore, the activation of the RAAS during the luteal period could be partially related to the increased synthesis of angiotensinogen [21] or be a direct consequence of the vasodilatory effects of E2 [51]. However, early studies have not revealed variations in angiotensinogen during the luteal period of physiological estral cycles [10, 52, 53]. The combined use of E2 and P4 during the luteal period in ovariectomized rats resulted in increases in PRA without significant simultaneous changes in angiotensinogen [54]. The lack of a significant relationship between PRA and angiotensinogen might rule out E2 as a cause of the modifications in renin concentrations, despite its involvement in the secretion of aldosterone [10, 53, 55].
Although the main source of circulating active renin is the kidney, the ovaries appear to be the source of the cyclic increase of prorenin during the estral cycle [14, 56]. In fact, the release of LH triggers an increase of three times the concentrations of prorenin, remaining elevated during the first half of the luteal period, even though the decrease in P4 at the end of the luteal period reduces simultaneously the prorenin levels [18, 21, 42, 56].
2.3 Changes in the renin-angiotensin-aldosterone system during the follicular period
Preovulatory increases of angiotensinogen, prorenin, PRA, renin, ANG-II, and aldosterone have been reported in women [11, 14, 25, 26] and laboratory animals [29]. According to other authors, the increase in aldosterone concentrations appears to be transient [11], or it is not constant in all cycles [37].
The origin of the preovulatory aldosterone peak is unknown, but it has been speculated that the increase in E2 could exert a stimulatory effect on angiotensinogen in the liver, and this, in turn, increases PRA and aldosterone [52, 53, 55]. Other researches, on the contrary, failed to find any relationship between angiotensinogen, PRA, and aldosterone in physiological cycles [11, 17, 19, 57], ruling out some type of significant influence of endogenous E2 on PRA and AUE during the periovulatory period [9, 10, 41]. Despite these contradictory results, the hypothesis that the increase in angiotensinogen is the cause of PRA and aldosterone peaks is still commonly accepted.
A transient peak of prorenin has been described simultaneously with the elevation of gonadotropins, mainly LH, toward the moment of the ovulation. It has been speculated that this prorenin peak will be responsible later for the increase of active renin [58]. However, prorenin and LH are not always related to active renin [14, 15], because the most striking effects of this precursor appear toward the middle of the luteal period [18, 21, 42].
Because ACTH is one the main regulators of aldosterone secretion, the preovulatory peak of PRA might be related to the stimulatory effect of E2 on the adrenal gland and to the increase of the 17α-P4-enzyme, which also shows a preovulatory peak. This enzyme catalyzes the conversion of pregnenolone into 17-α-hydroxypregnenolone, which is a precursor of the sexual steroids [59]. However, although an experimental infusion of ACTH triggers an elevation in PRA [60], the absence of changes in cortisol (CORT) concentrations in physiological cycles could refute these hypotheses [17, 19, 32]. Other factors, including hemodynamic changes in renal blood flow, local sympathetic activity, and variation in Na concentrations at the macula densa level, have also been associated with the preovulatory peak of renin and aldosterone [33, 61].
In broodmares, Satué et al. [62] evaluated the changes in circulating RAAS components around ovulation, considering the 5 days before ovulation (from day 5 to day 1), the day of the ovulation (day 0), and the 5 days immediately after ovulation (from day 1 to day 5). A summary of the main endocrine changes, including those of the RAAS, is presented in Figure 1.
Figure 1.
Representative scheme of the hormonal changes that occur in the mare during the 5 days before ovulation (preovulatory period), the day of the ovulation, and the last first 5 days after ovulation (postovulatory period) (ACTH, adrenocorticotrophic hormone; E2, estrogens; CORT, cortisol; P4, progesterone).
A progressive increase in plasma renin concentrations was found before ovulation, peaking at the day of the ovulation [62] (Figure 2). The increase in plasma renin before ovulation in other species, as has been previously attributed to the release of LH or to the stimulating effect of human chorionic gonadotropin (hCG) [24]. Another plausible explanation for this rise in plasma renin before ovulation was the increase in E2 concentrations, since a positive correlation between both variables has been found in mares (r = 0.744) [62] (Figure 3). These results in mares agree with the data provided by Sealy et al. [15] in women with ovarian stimulation, in whom significant simultaneous increases in renin and E2 were detected. Another explanation for the rise in renin concentrations in the mares could be a mild hypovolemia associated with the presence of interstitial fluid in abdominal cavity during ovulation. Even though changes in Na and Cl concentrations at the renal juxtaglomerular apparatus significantly influence the release of renin [63], the correlations between renin and these electrolytes appear to be low in mares before ovulation [62]. In the same way, Roussel et al. [64] described cyclic patterns of plasma Na and aldosterone concentrations in cow, but without significant correlations with the components of the RAAS.
Figure 2.
Plasma renin concentrations during the 5 days before ovulation, the day of the ovulation, and the first 5 days after ovulation in mares (numbers indicate the days between which significant differences were found at p < 0.05).
Figure 3.
Significant positive correlations between plasma estrogens (E2) and renin concentrations in mares before ovulation (r = 0.744).
After ovulation, a sharp decrease in plasma renin concentrations was detected in mares (Figure 2). Similar changes have been reported in women [17]. Ounis-Skali et al. [18] attributed these results to the release of renin from the corpus luteum, reflecting a direct relationship between P4 and renin after ovulation, and similar hypotheses might be extrapolable to the mare. Two studies performed by our research team demonstrated low correlations between P4 and renin, suggesting other factors different from P4 might be considered in order to explain the non-significant trend toward an increase in renin concentrations during the first days after ovulation [65, 66].
Plasma ANG-II concentrations did not show significant variations before ovulation, but it experienced a sharp and progressive decrease after ovulation [62] (Figure 4). On the contrary, significant increases in ANG-II have been previously observed in sows [11] and in rats [29] before ovulation. ANG-II concentrations in women after ovulation were almost the double of the values found before ovulation [17, 18, 19]. This increase in women was attributed to the modulation of the flow in the ovarian blood vessels during oocyte maturation [15]. The reason why ANG-II concentrations decrease in the mares after ovulation, which is an opposite change to this described for women and laboratory animals, is not currently known.
Figure 4.
Plasma angiotensin-II concentrations during the 5 days before ovulation, the day of the ovulation, and the first 5 days after ovulation in mares (numbers indicate the days between which significant differences were found at p < 0.05).
Plasma aldosterone concentrations increased progressively from the fifth day before ovulation until the day of the ovulation. After this moment, aldosterone concentrations did not change and persisted to be significantly higher than before ovulation [62] (Figure 5). Because an increase in renin was also found the day of the ovulation in mares and ANG-II was higher during the 5 days before ovulation, it was speculated that the increased renin was the starting point to activate RAAS, resulting in increased aldosterone concentrations. This hypothesis was proven when the correlations between hormones before and after ovulation were assessed (Figure 6). A positive significant correlation (r = 0.756) was found between renin and aldosterone concentrations before ovulation. Surprisingly, ANG-II and aldosterone concentrations did not present a significant correlation before ovulation (Figure 6). These data might indicate a dissociation between ANG-II and aldosterone before ovulation in the mare. In this case, the synthesis of aldosterone might have occurred in addition via other pathways independent from the activation of the RAAS [62].
Figure 5.
Plasma aldosterone concentrations during the 5 days before ovulation, the day of the ovulation, and the first 5 days after ovulation in mares (numbers indicate the days between which significant differences were found at p < 0.05).
Figure 6.
Correlations between the three main components of the renin-angiotensin-aldosterone system in mares before (A) and after ovulation (B).
The relationships between the diameter of the predominant follicle and the hormones of the RAAS have also been investigated in mares [62] (Figure 7). A significant positive correlation was found between renin and aldosterone concentrations and the diameter of the follicle before ovulation in the mares (r = 0.742 and 0.804, respectively) [62] (Figure 7). In other species, RAAS regulates the development and growth of the antral follicles. Receptors AT1 and AT2 for ANG-II have been found in the granulosa cells of the antral follicles and in the primordial primary and secondary follicles of sows [67]. Administration of an ANG-II inhibitor in cows avoided the growth of the predominant follicle and also induced a reduction in the concentrations of E2 [68, 69]. In the same way, in women subjected to ovarian stimulation with human menopausal gonadotropin (HMG), concentrations of ANG-II were positively correlated with E2 and the diameter of the predominant follicle [70]. In our research in mares, however, correlations between the diameter of the predominant follicle and ANG-II were very low (r = 0.366), despite the significant correlations between this diameter and the concentrations of renin and aldosterone [62] (Figure 7). Our results might suggest that circulating ANG-II concentrations do not exert a transcendental effect on the development of the ovarian follicle or, alternatively, some antagonist peptides of the ANG-II might be produced before ovulation in mares [65, 66].
Figure 7.
Correlations between the diameter of the predominant follicle (DPF) and the concentrations of renin, angiotensin II, and aldosterone before ovulation in mares.
3. Changes in the renin-angiotensin-aldosterone system during the pregnancy
Plasma concentrations of prorenin increase by 5–10 times during the first 10 weeks of pregnancy in women. This increase is simultaneous with the increase in hCG and after, both decreased until the moment of the delivery. Although prorenin is mainly synthesized in the renal juxtaglomerular cells, there are other extrarenal sources, such as the ovary, follicular fluid, and placenta [71]. The prorenin concentrations also increase when the LH concentrations peak at the moment of the ovulation [71, 72]. The combined administration of LH and FSH causes a 390% increase in plasma prorenin, while hCG increases above 1000% [13, 73]. An early study speculated that prorenin could act as a hormone with functions independent of the active renin [13]. Until now, to the authors’ best knowledge, the prorenin concentration in plasma/serum has not been quantified in mares.
A substantial increase in the circulating concentrations of angiotensinogen has also been documented during the first weeks of pregnancy in women [74]. Angiotensinogen concentrations remain elevated throughout pregnancy, peaking at term. In sheep, a bimodal pattern of secretion of this hormone has been described, with a first peak at the beginning of the pregnancy, concomitant with the period of the maximum placental growth. The second peak occurs at term, suggesting an association between plasma angiotensinogen and fetal growth [75].
The increased synthesis of angiotensinogen has been attributed to the stimulating effect of E2 at hepatic level [16, 17, 76]. However, the relationships between angiotensinogen and E2 are not always positive [77]. In nonpregnant women undergoing estrogen treatments, angiotensinogen and ANG-II increased in blood, whereas renin concentrations tended to decrease because of the negative feedback exercised by angiotensinogen [76]. However, the angiotensinogen concentrations have not been measured in mares yet.
The total concentration of circulating renin, both its active and inactive forms, increases during pregnancy in women. However, the contribution of the physiologically inactive renin to the total renin is greater than that of the active renin [78]. During the first third period of the pregnancy, renin concentrations increased between 2 and 4 times above baseline [79, 80]. After it reaches a plateau, around the fifth month of pregnancy and after that, the concentrations remained unchanged until the end of the pregnancy [81], being the main reason involved in the rise of PRA during the first and second thirds of the pregnancy, respectively [11, 80, 82, 83, 84]. Toward the end of the pregnancy, the renin concentration decreases intensely [78]. Even though the increased renin release contributes greatly to the ANG-II synthesis, the renin concentrations could decrease because of a negative feedback mechanism [15, 85].
The synthesis of renin, in addition to renal juxtaglomerular cells, can also be carried out in other extrarenal tissues, as the uterus. This organ is the priority organ of renin synthesis during pregnancy, leading to the so-called hyperreninemia of the pregnancy [80, 86]. The renin at the level of the fetal membranes and the uterus is found predominantly in the form of prorenin, and although it is supposed that it can be released into the maternal circulation, the degree of contribution to the maternal circulating levels is unknown. Both active renin and inactive renin have been identified in the uterus, placenta, and myometrium in women and in some laboratory animals [87]. Despite this, amniotic fluid seems to be the main source of renin produced by the chorionic cells during pregnancy [74].
The placenta appears to be the major source for the conversion of angiotensin I into ANG-II, since the prorenin, active renin, angiotensin converting enzyme (ACE), and ANG-II have been identified in the chorion and in the placenta [88]. The physiological roles of these components have not been completely clarified, but it has been speculated that they might participate in the regulation of the blood flow [89, 90, 91, 92].
The increase in renin concentrations during pregnancy has also been attributed to the loss of electrolytes as a consequence of the increase in the glomerular filtration rate as well as of the secretion of P4, due to the antagonic effects of the hormone on aldosterone, because P4 induces natriuresis [74, 76, 93]. On the other hand, the positive influence of E2 on the synthesis of angiotensinogen has also been considered a plausible reason for the renin peak during pregnancy [76]. Surprisingly, it is possible to find increased renin concentrations without a simultaneous increase of ANG-II concentrations. In addition, the sequestration of Na and water at the uterus might be another triggering factor for the release of renin during pregnancy, as documented in pregnant bitches [94].
In pregnant mares, Satué et al. [95] described a significant increase in the renin from the seventh month of pregnancy (Figure 8). In pregnant women, as stated before, the increase in renin concentrations occurs earlier than in the pregnant mares [79, 80, 84]. At present, it is unknown if the origin of these differences is the different animal species or it could be due to the influence of other physiological factors. In the mare, ANG-II concentrations did not vary significantly during pregnancy (Figure 9), despite the changes in renin concentrations (Figure 8). These data might suggest that there is a dissociation between renin and ANG-II during pregnancy in the mares. In pregnant women, it has been shown that the increase in ANG-II exerts a negative feedback effect on renin secretion [74, 85, 96]. In addition, it has been proposed that the peak of renin during pregnancy is in part associated with the release of estrogens, which act on the production of angiotensinogen in the liver [15, 76, 97]. Moreover, Satué et al. [98] found a dissociation between renin and E2, in agreement with previous results described for pregnant women [77, 99].
Figure 8.
Mean (maximum and minimum indicated in bars) concentrations of renin in mares during pregnancy (significant differences between months indicated with numbers at p < 0.05).
Figure 9.
Mean (maximum and minimum indicated in bars) concentrations of angiotensin II in mares during pregnancy.
On the contrary to the data found for ANG-II in mares [95], most of the investigations performed in women and laboratory animals showed that during pregnancy, circulating concentrations of ANG-II increased up to two and even three times from nonpregnant values [74, 78, 100, 101]. This increase in women appears from the beginning of the pregnancy, peaking at the seventh month and persisting to be elevated until the moment of the delivery [102].
Pregnant mares showed a marked increase in circulating aldosterone concentrations during pregnancy, with mean values that exceed almost 12 times the physiological reference range for healthy adult horses [103] (Figure 10). Similar results have been reported in pregnant women [74, 84, 104], bitches [105, 106, 107], and some species of laboratory animals [108]. In pregnant bitches, Robb et al. [94] and in rats, Brochu et al. [106] attributed the increase in aldosterone concentrations to a higher activity of the enzyme aldosterone-synthase and to an increased synthesis of mRNA in the cells of the zona glomerulosa, these cells being the only production site, without fetal and/or placental participation, on the contrary of what appears to happen in women [78].
Figure 10.
Mean (maximum and minimum indicated in bars) concentrations of aldosterone in mares during pregnancy (significant differences between months indicated with numbers at p < 0.05).
In mares, our team has found lower aldosterone concentrations during the second month of pregnancy, compared to the fifth, sixth, and seventh months of pregnancy (Figure 10). The highest values were observed in the fifth month of pregnancy. In the eighth, ninth, and tenth months of pregnancy, aldosterone concentrations were significantly lower than the mean values found in the fifth month. In pregnant women, it has been speculated that the increased release of aldosterone would occur in an attempt to conserve Na and water to favor the expansion of the fetoplacental unit. In this way, the adequate supply of nutrients to the fetus, the maintenance of the ideal oxygen tension for fetal development, as well as the homeostasis and appropriate blood pressure between the mother and the fetus would be guaranteed [108, 109].
Although the evolution of aldosterone concentrations during pregnancy is similar in women, laboratory animals, and mares, there are temporary differences in the moment in which the peaks of concentrations are reached. In women and laboratory animals, the maximum increase in aldosterone appears in the second third of pregnancy, followed by a decrease in the third period of pregnancy. In the mare, on the contrary, as shown in Figure 10, the maximum concentrations were found in the fifth month.
The increase in aldosterone during pregnancy in women has been attributed, firstly, to the increase in the sensitivity of the cells of the adrenal gland to the increased synthesis and release of renin [74, 110] and, secondly, to the increase in ANG-II concentrations, a finding that has been associated with an increase in placental lactogen [74]. In women, it is known that placental lactogen plays a regulatory role in metabolic homeostasis, triggering an increase in ANG-II receptors during the second period of the pregnancy [111, 112]. It has also been speculated in women that the increase in the concentrations of aldosterone during pregnancy could be a decisive physiological event in order to prevent the massive natriuresis that could arise from an enhanced glomerular filtration rate. In these cases, aldosterone shows a physiological action opposite to the natriuretic effect of P4 at the level of the distal convoluted tubule, avoiding excessive loss of Na and allowing its gradual accumulation in the fetoplacental and in the extracellular maternal fluids [113]. However, the antagonism between both mineralocorticoids, i.e., aldosterone and P4, during pregnancy does not seem to be constant [114, 115].
4. Conclusions
Our results obtained in healthy reproductive mares demonstrated that there is an activation of the RAAS around the time of ovulation, as indicated by the increased plasma renin and aldosterone concentrations. After ovulation, the rapid decrease in plasma renin and ANG-II concentrations might indicate a modulation of the previously activated RAAS, even though plasma aldosterone concentrations increased during this period, suggesting a dissociation of the components of this system.
In the pregnant mare, there is also an increased activity of various components of the RAAS. Pregnant mares show a progressive increase in circulating renin, with fluctuating changes in aldosterone, peaking at fifth month of pregnancy and without significant changes in ANG-II. The reason for the apparent dissociation between the three main hormones of the RAAS at determined moments of the pregnancy remains unclear. The data obtained in pregnant mares regarding the RAAS seems to indicate that renin is a more intense stimulus for the increased synthesis of aldosterone than ANG-II.
Acknowledgments
The authors would like to express their gratitude to the owners who have allowed, over a period of more than 10 years, the participation of their mares in the studies carried out by our research team.
Conflict of interest
The authors declare that they have no conflicts of interest.
\n',keywords:"estrous cycle, mare, pregnancy, renin, angiotensin, aldosterone",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/68048.pdf",chapterXML:"https://mts.intechopen.com/source/xml/68048.xml",downloadPdfUrl:"/chapter/pdf-download/68048",previewPdfUrl:"/chapter/pdf-preview/68048",totalDownloads:1011,totalViews:0,totalCrossrefCites:1,dateSubmitted:"March 7th 2019",dateReviewed:"June 14th 2019",datePrePublished:"September 9th 2019",datePublished:"August 19th 2020",dateFinished:"July 10th 2019",readingETA:"0",abstract:"In women and laboratory animals, local and circulating components of the renin-angiotensin-aldosterone system (RAAS) are related to specific reproductive functions that occur during the estrous cycle, such as folliculogenesis, ovulation, corpus luteum development, and steroidogenesis. Also, in pregnant females of these species, maternal cardiovascular and renal systems undergo intense modifications, with the aim of matching the increased energy requirements of the fetus and fetoplacental unit. Some of these changes can be the origin, and others the consequence of a new endocrine environment. The fetus and the placenta induce endocrine changes, with modifications in the protein, lipid, carbohydrate, and mineral metabolism, together with simultaneous cardiovascular changes derived from the uterine growth and its content. The participation of RAAS during this period is of vital importance to regulate these cardiovascular, hemodynamic, hematological, and metabolic adjustments imposed by pregnancy because they will have a direct influence on the correct development and viability of the fetus. In mares, our research team has been investigating the changes of RAAS in mares during the estral cycle and during pregnancy, and these results are presented in the current chapter, comparing with the data previously reported for women and laboratory animals.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/68048",risUrl:"/chapter/ris/68048",signatures:"Katy Satué and Ana Muñoz",book:{id:"7848",type:"book",title:"Selected Chapters from the Renin-Angiotensin System",subtitle:null,fullTitle:"Selected Chapters from the Renin-Angiotensin System",slug:"selected-chapters-from-the-renin-angiotensin-system",publishedDate:"August 19th 2020",bookSignature:"Aleksandar Kibel",coverURL:"https://cdn.intechopen.com/books/images_new/7848.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-78985-422-0",printIsbn:"978-1-78985-421-3",pdfIsbn:"978-1-78985-554-8",isAvailableForWebshopOrdering:!0,editors:[{id:"183303",title:"Dr.",name:"Aleksandar",middleName:null,surname:"Kibel",slug:"aleksandar-kibel",fullName:"Aleksandar Kibel"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"125292",title:"Dr.",name:"Katy",middleName:null,surname:"Satué Ambrojo",fullName:"Katy Satué Ambrojo",slug:"katy-satue-ambrojo",email:"ksatue@uchceu.es",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/125292/images/system/125292.jpeg",institution:{name:"CEU Cardinal Herrera University",institutionURL:null,country:{name:"Spain"}}},{id:"159022",title:"Dr.",name:"Ana",middleName:null,surname:"Muñoz",fullName:"Ana Muñoz",slug:"ana-munoz",email:"pv1mujua@uco.es",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Changes in the renin-angiotensin-aldosterone system during the estral cycle",level:"1"},{id:"sec_2_2",title:"2.1 A brief review of the estral cycle in the mare",level:"2"},{id:"sec_3_2",title:"2.2 Changes in the renin-angiotensin-aldosterone system during the luteal period",level:"2"},{id:"sec_4_2",title:"2.3 Changes in the renin-angiotensin-aldosterone system during the follicular period",level:"2"},{id:"sec_6",title:"3. Changes in the renin-angiotensin-aldosterone system during the pregnancy",level:"1"},{id:"sec_7",title:"4. Conclusions",level:"1"},{id:"sec_8",title:"Acknowledgments",level:"1"},{id:"sec_11",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Schauser KH, Nielsen AH, Dantzer V, Poulsen K. Angiotensin-converting enzyme activity in the bovine uteroplacental unit changes in relation to the cycle and pregnancy. Placenta. 2001;22:852-862. 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Renal segmental tubular response to salt during the normal menstrual cycle. Kidney International. 2002;61:425-431. DOI: 10.1046/j.1523-1755.2002.00158.x'},{id:"B33",body:'Sealey JE, Laragh JH. Plasma renin activity enzyme-kinetic assay: Protection of angiotensin I from bacterial degradation. Clinical Chemistry. 2011;57(3):529-530. DOI: 10.1373/clinchem.2010.156596'},{id:"B34",body:'Lumbers ER, Pringle KG. Roles of the circulating renin-angiotensin-aldosterone system in human pregnancy. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2014;306(2):91-101. DOI: 10.1152/ajpregu.00034.2013'},{id:"B35",body:'Satué K, Gardón JC. A review of the estrous cycle and the neuroendocrine mechanisms in the mare. Journal of Steroids and Hormonal Science. 2013;4:115. DOI: 10.4172/2157-7536.1000115'},{id:"B36",body:'McKinnon AO, Squires EL, Vaala WE, Dickson DV. Equine Reproduction. 2nd ed. Ames, IA: Wiley Blackwell; 2011. pp. 3288-3299. ISBN: 978-0-813-81971-6'},{id:"B37",body:'Katz FH, Romfh P. Plasma aldosterone and renin activity during the menstrual cycle. The Journal of Clinical Endocrinology and Metabolism. 1972;34:819-822. DOI: 10.1210/jcem-34-5-819'},{id:"B38",body:'Parry BL, Javeed S, Laughlin GA, Hauger R, Clopton P. Cortisol circadian rhythms during the menstrual cycle and with sleep deprivation in premenstrual dysphoric disorder and normal control subjects. Biological Psychiatry. 2000;48(9):920-931'},{id:"B39",body:'Michelakis AM, Yoshida H, Dormois JC. Plasma rennin activity and plasma aldosterone during the normal menstrual cycle. American Journal of Obstetrics and Gynecology. 1975;123(7):724-726'},{id:"B40",body:'Stachenfeld NS, DiPietro L, Kokoszka CA, Silva C, Keefe DL, Nadel ER. Physiological variability of fluid-regulation hormones in young women. Journal of Applied Physiology. 1999;86:1092-1096. DOI: 10.1152/jappl.1999.86.3.1092'},{id:"B41",body:'Sundsfjord JA. Plasma renin activity and aldosterone excretion during prolonged progesterone administration. Acta Endocrinologica. 1971;67(3):483-490'},{id:"B42",body:'Garcia MJ, Martinez-Martos JM, Mayas MD, Carrera MP, De la Chica S, Cortes P, et al. Hormonal status modifies renin-angiotensin system regulating aminopeptidases and vasopressin-degrading activity in the hypothalamus-pituitary-adrenal axis of female mice. Medicinal Chemistry. 2008;4:336-347'},{id:"B43",body:'Stachenfeld NS, Taylor HS. Oestrogen effects on urine concentrating response in young women. The Journal of Physiology. 2003;1(3):869-880. DOI: 10.1113/jphysiol.2003.046920'},{id:"B44",body:'Myles K, Funder JW. Progesterone binding to mineralocorticoid receptors: In vitro and in vivo studies. The American Journal of Physiology. 1996;270(4):601-607. DOI: 10.1152/ajpendo.1996.270.4.E601'},{id:"B45",body:'Quinkler M, Meyer B, Bumke-Vogt C, Grossmann C, Gruber U, Oelkers W, et al. Agonistic and antagonistic properties of progesterone metabolites at the human mineralocorticoid receptor. European Journal of Endocrinology. 2002;146(6):789-799'},{id:"B46",body:'Keam S, Wagstraff A. Ethinylestradiol/drospirenone. A review of its use as an oral contraceptive. Treatments in Endocrinology. 2002;2(1):1-23'},{id:"B47",body:'Nowaczynski W, Murakami T, Richardson K, Genest J. Increased aldosterone plasma protein binding in women on combined oral contraceptives throughout the menstrual cycle. Journal of Clinical Endocrinology and Metabolism. 1978;47(1):193-199. DOI: 10.1210/jcem-47-1-193'},{id:"B48",body:'Williamson PM, Buddle ML, Brown MA, Whitworth JA. Ambulatory blood pressure monitoring (ABPM) in the normal menstrual cycle and in women using oral contraceptives. Comparison with conventional blood pressure measurement. American Journal of Hypertension. 1996;9(1):953-958. DOI: 10.1016/0895-7061(96)00150-1'},{id:"B49",body:'Adler GK, Moore TJ, Hollenberg NK, Williams GH. 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The relationship of the renin-angiotensin-aldosterone system to plasma gonadotropin, prolactin, and ovarian steroid patterns during the menstrual cycle. Archiv für Gynäkologie. 1978;225:179-200'},{id:"B58",body:'Bouhnnik J, Feherentz JA, Galen FX, Seyer R, Evin G, Castro B, et al. Immunologic identification of both plasma and human renal inactive renin as prorenin. The Journal of Clinical Endocrinology and Metabolism. 1985;60(2):399-401. DOI: 10.1210/jcem-60-2-399'},{id:"B59",body:'Strott CA, West CD, Nakagawa K, Kondo T, Tyler FH. Plasma 11-deoxycorticosteroid and ACTH response to metyrapone (plasma metyrapone test). The Journal of Clinical Endocrinology and Metabolism. 1969;29(1):6-11. DOI: 10.1210/jcem-29-1-6'},{id:"B60",body:'Kem DC, Gomez-Sanchez C, Kramer NJ, Holland OB, Higgins JR. Plasma aldosterone and renin activity response to ACTH infusion in dexamethasone-suppressed normal and sodium-depleted man. The Journal of Clinical Endocrinology and Metabolism. 1975;40(1):116-124. 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Association between aldosterone and cortisol levels during ovulatory period in Spanish purebred mares. Reproduction, Fertility, and Development. 2014;26:146. DOI: 10.1071/RDv26n1Ab65'},{id:"B66",body:'Satué K, Gardon JC, Montesinos P. Relationship between oestradiol-17beta and renin concentrations during preovulatory period in Spanish purebred mares. Reproduction in Domestic Animals. 2012;47(3):111. DOI: 10.1111/j.1439-0531.2012.02044.x'},{id:"B67",body:'Shuttleworth G, Hunter MG, Robinson G, Brouhton Pipkin F. Immunocytochemical localization of angiotensin II receptor subtypes 1 and 2 in the porcine fetal, prepubertal and postpubertal ovary. Journal of Anatomy. 2002;201:267-274. DOI: 10.1046/j.1469-7580.2002.00091.x'},{id:"B68",body:'Ferreira R, Gasperin B, Rovani M, Santos J, Barreta M, Bohrer R, et al. Angiotensin II signaling promotes follicle growth and dominance in cattle. Endocrinology. 2011;152(12):4957-4965. 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Prolonged HCG action affects angiogenic substances and improves follicular maturation, oocyte quality and fertilization competence in patients with polycystic ovary syndrome. Human Reproduction. 2005;20:1562-1568. DOI: 10.1093/humrep/deh789'},{id:"B73",body:'Itskovitz J, Sealey JE, Glorioso N, Rosenwaks Z. Plasma prorenin response to human chorionic gonadotropin in ovarian-hyperstimulated women: Correlation with the number of ovarian follicles and steroid hormone concentrations. Proceedings of the National Academy of Sciences of the United States of America. 1987;84(20):7285-7289. DOI: 10.1073/pnas.84.20.7285'},{id:"B74",body:'Alhenc-Gelas F, Tache A, Saint-Andre JP, Milliez J, Sureau C, Corvol P, et al. The renin-angiotensin system in pregnancy and parturition. Advances in Nephrology from the Necker Hospital. 1986;15:25-33'},{id:"B75",body:'Dandrea J, Cooper S, Ramsay M, Keller-Woods M, Broughton Pipkin F, Symonds M, et al. The effects of pregnancy and maternal nutrition on the maternal renin angiotensin system in sheep. Experimental Physiology. 2002;87(3):353-359'},{id:"B76",body:'Oelkers W. The renin–aldosterone system and drospirenone. Gynecological Endocrinology. 2002;16:83-87'},{id:"B77",body:'Weinberger MH, Kramer NJ, Grim CE, Petersen LP. The effect of posture and saline loading on plasma renin activity and aldosterone concentration in pregnancy, non-pregnant and oestrogen treated women. The Journal of Clinical Endocrinology and Metabolism. 1977;44:69-77. DOI: 10.1210/jcem-44-1-69'},{id:"B78",body:'Carr B, Gant N. The endocrinology of pregnancy induced hypertension. Clinics in Perinatology. 1983;10:737-761'},{id:"B79",body:'Tapia HR, Johnson CE, Strong CG. Renin angiotensin system in normal and in hypertensive disease of pregnancy. Lancet. 1972;2:847-850. DOI: 10.1016/S0140-6736(72)92211-8'},{id:"B80",body:'Skinner SL. The renin system in fertility and normal human pregnancy. In: Robertson JIS, Nicolls MG, editors. The Renin Angiotensin System. London: Gower Medical Publishing; 1993. pp. 1-16'},{id:"B81",body:'Langer B, Grima M, Coquard C, Bader AM, Schlaeder G, Imbs JL. Plasma active renin, angiotensin I, and angiotensin II during pregnancy and in preeclampsia. Journal of Obstetrics and Gynaecology. 1998;91:196-202'},{id:"B82",body:'Weinberger MH, Kramer NJ, Petersen LP, Cleary RE, Young PC. Sequential changes in the renin-angiotensin-aldosterone systems and plasma progesterone concentration in normal and abnormal human pregnancy. Perspectives in Nephrology and Hypertension. 1976;5:263-269'},{id:"B83",body:'Sullivan C, Matrin J. Sodium and pregnancy. Clinical Obstetrics and Gynecology. 1994;37:558-573'},{id:"B84",body:'Bentley-Lewis MD, Graves SW, Seely EW. The renin aldosterone response to stimulation and suppression during normal pregnancy. Hypertension in Pregnancy. 2005;24:1-16. DOI: 10.1081/PRG-45765'},{id:"B85",body:'Broughton Pipkin F, Morrison R, O’Brien PMS. The effect of prostaglandin E1 upon the pressor and hormonal response to exogenous angiotensin II in human pregnancy. Clinical Science. 1987;72:351-357'},{id:"B86",body:'Lindheimer MD, Katz AI. Renal physiology and disease in pregnancy. In: Seldin DW, Giebisch G, editors. The Kidney: Physiology and Pathophysiology. New York: Raven; 1992. pp. 3371-3432'},{id:"B87",body:'Skinner SL, Lumbers ER, Symonds EM. Renin concentration in human fetal and maternal tissues. American Journal of Obstetrics and Gynecology. 1968;101:529-533'},{id:"B88",body:'Kalenga MK, Thomas K, de Gasparo M, De Hertogh R. Determination of renin, angiotensin converting enzyme and angiotensin II levels in human placenta, chorion and amnion from women with pregnancy induced hypertension. Clinical Endocrinology (Oxf). 1996;44:429-433'},{id:"B89",body:'Pringle KG, Tadros MA, Callister RJ, Lumbers ER. The expression and localization of the human placental prorenin/renin-angiotensin system throughout pregnancy: Roles in trophoblast invasion and angiogenesis? Placenta. 2011;32:956-962. DOI: 10.1016/j.placenta.2011.09.020'},{id:"B90",body:'Lumbers ER, Wang Y, Delforce SJ, Corbisier de Meaultsart C, Logan PC, Mitchell MD, et al. Decidualisation of human endometrial stromal cells is associated with increased expression and secretion of prorenin. Reproduction of Biological Endocrinology. 2015;13:129. DOI: 10.1186/s12958-015-0127-8'},{id:"B91",body:'Pepin E, Dehboneh SS, Raguema N, Esfandarani MT, Lavoie JL. Role of the renin-angiotensin system in healthy and pathological pregnancies, renin-angiotensin system—Past, present and future. In: Anna Naidenova Tolekova. IntechOpen; 2017. DOI: 10.5772/66748'},{id:"B92",body:'Khlestova GV, Romanov AY, Nizyaeva NV, Karapetyan AO, Baev OR, Ivanets TY. Dynamics of renin, angiotensin II, and angiotensin (1-7) during pregnancy and predisposition to hypertension-associated complications. Bulletin of Experimental Biology and Medicine. 2018;165:438-439. DOI: 10.1007/s10517-018-4188-5'},{id:"B93",body:'Jeyabalan A, Conrad KP. Renal function during normal pregnancy and preeclampsia. Frontiers in Bioscience. 2007;12:2425-2437'},{id:"B94",body:'Robb CA, Davis JO, Johnson JA, Blaine EH, Schneider EG, Baumber JS. Mechanisms regulating the renal excretion of sodium during pregnancy. The Journal of Clinical Investigation. 1970;49:871-880. DOI: 10.1172/JCI106306'},{id:"B95",body:'Satué K, Domingo R. Longitudinal study of the renin angiotensin aldosterone system in purebred Spanish broodmares during pregnancy. Theriogenology. 2011;75(7):1185-1194. DOI: 10.1016/j.theriogenology.2010.11.029'},{id:"B96",body:'Laragh JH, Sealey JE. The plasma renin test reveals the contribution of body sodium-volume content (V) and renin-angiotensin (R) vasoconstriction to long-term blood pressure. American Journal of Hypertension. 2011;24(11):1164-1180. DOI: 10.1038/ajh.2011.171'},{id:"B97",body:'Brosnihan AL. Systemic and uteroplacental renin–angiotensin system in normal and pre-eclamptic pregnancies. Therapeutic Advances in Cardiovascular Disease. 2008;2:349-362. DOI: 10.1177/1753944708094529'},{id:"B98",body:'Satué K, Domingo R, Redondo JI. Relationship between progesterone, oestrone sulphate and cortisol and the components of renin angiotensin aldosterone system in Spanish purebred broodmares during pregnancy. Theriogenology. 2011;76(8):1404-1415. DOI: 10.1016/j.theriogenology.2011.06.009'},{id:"B99",body:'Weir RJ, Brown JJ, Fraser R, Lever AF, Logan RW, McIlwaine GM, et al. Relationship between plasma renin, renin substrate, angiotensin II, aldosterone and electrolytes in normal pregnancy. The Journal of Clinical Endocrinology and Metabolism. 1975;40:108-115. DOI: 10.1210/jcem-40-1-108'},{id:"B100",body:'Symonds EM. The renin angiotensin system in pregnancy. Obstetrics & Gynecology Annual. 1981;10:45-67'},{id:"B101",body:'Van Dijk DJ, Boner G, Giler S, Erman A. Increased serum angiotensin converting enzyme activity and plasma angiotensin II levels during pregnancy and postpartum in the diabetic rat. JRAAS. 2001;2:193-198. DOI: 10.3317/jraas.2001.027'},{id:"B102",body:'Godard C, Gaillard R, Vallotton MB. The renin angiotensin aldosterone system in mother and fetus at term. Nephron. 1976;17:353-360. DOI: 10.1159/000180741'},{id:"B103",body:'McKeever KH, Hinchcliff KW, Schmall LM, Reed SM, Lamb DR, Muir W III. Plasma renin activity, aldosterone, and vasopressin during incremental treadmill exercise in horses. American Journal of Veterinary Research. 1992;53:1290-1293'},{id:"B104",body:'McCance DR, McKnight JA, Traub AI, Sheridan B, Roberts G, Atkinson AB. Plasma atrial natriuretic factor levels during normal pregnancy and pregnancy complicated by diabetes mellitus and hypertension. Journal of Human Hypertension. 1990;4:31-35'},{id:"B105",body:'Brochu M, Gauvin JP, St. Louis J. Increase of aldosterone secretion in adrenal cortex suspensions derived from pregnant rats. Proceedings of the Society for Experimental Biology and Medicine. 1996;212:147-152'},{id:"B106",body:'Brochu M, Lehoux JG, Picard S. Effects of gestation on enzymes controlling aldosterone synthesis in the rat adrenal. Endocrinology. 1997;138:2354-2358. DOI: 10.1210/endo.138.6.5198'},{id:"B107",body:'Brochu M, Roy-Clavel E, Picard S, St-Louis J. In vivo regulation of enzymes controlling aldosterone synthesis in pregnant rats. The Journal of Endocrinology. 1998;24:575-579'},{id:"B108",body:'Abou-Samra AB, Pugeat M, Dechaud H. Increased plasma concentration of N terminal beta lipotrophin and unbound cortisol during pregnancy. Clinical Endocrinology. 1984;20:221-228'},{id:"B109",body:'Jensen E, Wood CH, Keller-Wood M. The normal increase in adrenal secretion during pregnancy contributes to maternal volume expansion and fetal homeostasis. Journal of the Society for Gynecologic Investigation. 2002;9:362-371'},{id:"B110",body:'Wilson M, Morganti AA, Zervoudakis I, Letcher RI, Romns BM, Von Oeyon P, et al. Blood pressure, the renin aldosterone system and sex steroids throughout normal pregnancy. The American Journal of Medicine. 1980;68:97-104'},{id:"B111",body:'Petit A, Guillon G, Tence M, Jard S, Gallo-Payet N, Bellabarba D, et al. Angiotensin II stimulates both inositol phosphate production and human placental lactogen release from human trophoblastic cells. The Journal of Clinical Endocrinology and Metabolism. 1989;69(2):280-286'},{id:"B112",body:'West CA, Sasser JM, Baylis C. The enigma of continual plasma volume expansion in pregnancy: Critical role of the renin-angiotensin-aldosterone system. American Journal of Physiology. Renal Physiology. 2016;311:1125-1134. DOI: 10.1152/ajprenal.00129.2016'},{id:"B113",body:'Hayslett JP. A new role for progesterone: An agonist for mineralocorticoid receptor activation and pregnancy-related hypertension. The American Journal of Kidney Diseases. 2001;38:893-895. DOI: 10.1053/ajkd.2001.27723'},{id:"B114",body:'Bay W, Ferris T. Factors controlling plasma renin and aldosterone during pregnancy. Hypertension. 1979;1:410-415'},{id:"B115",body:'Smeaton TC, Andersen GJ, Fulton JS. Study of aldosterone levels in plasma during pregnancy. The Journal of Clinical Endocrinology and Metabolism. 1977;44:1-7. DOI: 10.1210/jcem-44-1-1'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Katy Satué",address:null,affiliation:'
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Rice cultivation in India is confronted with diverse agro-climatic conditions, varying soil types, and several biotic and abiotic constraints. Among major fungal diseases of Rice in India, the blast caused by Magnaporthe oryzae is the most devastating disease, with the neck blast being the most destructive form. Most of the blast epidemic areas in India have been identified with a mixture of races blast fungus resulting in the resistance breakdown in a short period. At present, a more significant number of the rice varieties cultivated in India were bred by conventional breeding methods with blast resistance conferred by a single resistance gene. Therefore, the blast disease in India is predominantly addressed by the use of ecologically toxic fungicides. In line with the rest of the world, the Indian scientific community has proven its role by identifying several blast resistance genes and successfully pyramiding multiple blast resistance genes. Despite the wealth of information on resistance genes and the availability of biotechnology tools, not a great number of rice varieties in India harbor multiple resistance genes. 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UK Research and Innovation (former Research Councils UK (RCUK) - including AHRC, BBSRC, ESRC, EPSRC, MRC, NERC, STFC.) Processing charges for books/book chapters can be covered through RCUK block grants which are allocated to most universities in the UK, which then handle the OA publication funding requests. It is at the discretion of the university whether it will approve the request.)
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Metallurgical properties of sinter and pellets (reducibility, strength, softening and melting temperatures) with different contents of red mud in iron ore raw materials are also presented, including the technology of red mud usage in ferrous metallurgy carried out through industrial and laboratorial tests. Additionally, the main technical and economic indicators of blast furnace smelting (productivity, coke consumption, chemical composition of pig iron and slag, etc.) are presented. The possibility and expediency of utilisation of red mud in a blast furnace are shown.",book:{id:"7557",slug:"recovery-and-utilization-of-metallurgical-solid-waste",title:"Recovery and Utilization of Metallurgical Solid Waste",fullTitle:"Recovery and Utilization of Metallurgical Solid Waste"},signatures:"Andrey Dmitriev",authors:null},{id:"37118",doi:"10.5772/33969",title:"Size Reduction by Grinding as an Important Stage in Recycling",slug:"comminution-as-an-important-stage-in-recycling",totalDownloads:5409,totalCrossrefCites:3,totalDimensionsCites:6,abstract:null,book:{id:"2254",slug:"post-consumer-waste-recycling-and-optimal-production",title:"Post-Consumer Waste Recycling and Optimal Production",fullTitle:"Post-Consumer Waste Recycling and Optimal Production"},signatures:"Marek Macko",authors:[{id:"98075",title:"Dr.",name:"Marek",middleName:null,surname:"Macko",slug:"marek-macko",fullName:"Marek Macko"}]}],mostDownloadedChaptersLast30Days:[{id:"77881",title:"Chemical Recycling of Polyolefins (PE, PP): Modern Technologies and Products",slug:"chemical-recycling-of-polyolefins-pe-pp-modern-technologies-and-products",totalDownloads:391,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Chemical recycling is one of the most intensively developed potential solutions for the global plastic waste issue. This broadly defined term covers several different technologies that lead to many diverse products. Polyolefins (polyethylene and polypropylene) can be chemically recycled by pyrolysis (cracking) or gasification. These polymers’ chemical composition and structure make them a great potential source of valuable hydrocarbons or carbon atoms for syngas production. Thermal and catalytic cracking of polyethylene and polypropylene can be optimised to maximise specific types of hydrocarbons that, after optional additional processing, such as hydrotreatment, steam cracking or distillation, can be used as intermediates in petrochemical plants, fuels or fuel components, monomers for polymerisation of new, virgin polymers or as specialty chemicals (final market products). Gasification of plastic waste transforms polymers into a mixture of hydrogen, carbon monoxide and carbon dioxide, which can be further used as a source of these gasses, transformed into chemicals and fuels, or used directly to produce energy. This chapter presents all of these process paths with examples of existing technologies and their level of technology readiness and perspectives for scale-up.",book:{id:"10855",slug:"waste-material-recycling-in-the-circular-economy-challenges-and-developments",title:"Waste Material Recycling in the Circular Economy",fullTitle:"Waste Material Recycling in the Circular Economy - Challenges and Developments"},signatures:"Daria Frączak",authors:[{id:"353408",title:"Dr.Ing.",name:"Daria",middleName:null,surname:"Frączak",slug:"daria-fraczak",fullName:"Daria Frączak"}]},{id:"77840",title:"Recent Advances in Pre-Treatment of Plastic Packaging Waste",slug:"recent-advances-in-pre-treatment-of-plastic-packaging-waste",totalDownloads:321,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"There is an urgent need to close the loop of plastic waste. One of the main challenges towards plastic packaging waste recycling is the presence of a variety of contaminants. These contaminants include organic residues, additives, labels, inks and also other plastic types that can be present in the waste stream due to missorting or in multimaterial structures (e.g. multilayer films in packaging). In this context, pre-treatment processes are a promising route to tackle the difficulties that are encountered in mechanical and chemical recycling due to these contaminants. This chapter gives better insight on the already existing pre-treatment techniques and on the advances that are being developed and/or optimized in order to achieve closed-loop recycling. Some of these advanced pre-treatments include chemical washing to remove inks (deinking), extraction methods to remove undesired plastic additives and dissolution-based pre-treatments, such as delamination and dissolution-precipitation techniques.",book:{id:"10855",slug:"waste-material-recycling-in-the-circular-economy-challenges-and-developments",title:"Waste Material Recycling in the Circular Economy",fullTitle:"Waste Material Recycling in the Circular Economy - Challenges and Developments"},signatures:"Rita Kol, Martijn Roosen, Sibel Ügdüler, Kevin M. Van Geem, Kim Ragaert, Dimitris S. Achilias and Steven De Meester",authors:[{id:"95620",title:"Dr.",name:"Dimitris S.",middleName:null,surname:"Achilias",slug:"dimitris-s.-achilias",fullName:"Dimitris S. 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Van Geem"}]},{id:"63364",title:"Comprehensive Utilization of Iron-Bearing Converter Wastes",slug:"comprehensive-utilization-of-iron-bearing-converter-wastes",totalDownloads:1099,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Basic oxygen furnace (BOF) sludge is composed of not only valuable iron but also impurities like Zn, Pb, and some alkaline oxides. It is collected from wet cleaning system in steelmaking plants. How to deal with these double identity wastes? Will the traditional landfill treatments result in environmental pollution? What technologies have been developed recently, and is it actually useful? In this chapter, physical-chemical properties and mineralogical phases of converter sludge were characterized, and different recycling technologies were introduced. The proven metalized pellet-producing process would be highlighted that green pellets made from iron-bearing sludge are dried and preheated in a traveling grate firstly, and then reduced at high temperature in a rotary kiln or a rotary hearth furnace (RHF) to get direct reduced iron (DRI), served as a good iron source for blast furnace.",book:{id:"7557",slug:"recovery-and-utilization-of-metallurgical-solid-waste",title:"Recovery and Utilization of Metallurgical Solid Waste",fullTitle:"Recovery and Utilization of Metallurgical Solid Waste"},signatures:"Hu Long, Dong Liu, Lie-Jun Li, Ming-Hua Bai, Yanzhong Jia and Wensheng Qiu",authors:null},{id:"77937",title:"An Evaluation of Recycled Polymeric Materials Usage in Denim with Lifecycle Assesment Methodology",slug:"an-evaluation-of-recycled-polymeric-materials-usage-in-denim-with-lifecycle-assesment-methodology",totalDownloads:259,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Today, World economy is only 8.6% circular, which creates a huge potential in materials reuse. To close the Emission Gap by 2032, this percentage needs to be doubled. The circular economy ensures that with less virgin material input and fewer emissions. With the help of effective recycling technologies, virgin material use can be decreased and especially petroleum based materials impact can fall within planetary boundaries. This book chapter analyzes different chemical and biological recycling technologies, their advantages and challenges in denim production. Moreover, Life Cycle Assessment (LCA) analysis will be used to evaluate the environmental impact of recycled polymeric materials usage in denim fabrics. Finally, it concludes by challenges and the future of chemically recycled materials in denim production and opportunities to evaluate waste as a raw material to design circular systems.",book:{id:"10855",slug:"waste-material-recycling-in-the-circular-economy-challenges-and-developments",title:"Waste Material Recycling in the Circular Economy",fullTitle:"Waste Material Recycling in the Circular Economy - Challenges and Developments"},signatures:"Sedef Uncu Aki, Cevza Candan, Banu Nergis and Neslihan Sebla Önder",authors:[{id:"172112",title:"Prof.",name:"Cevza",middleName:null,surname:"Candan",slug:"cevza-candan",fullName:"Cevza Candan"},{id:"304795",title:"Prof.",name:"Banu",middleName:null,surname:"Nergis",slug:"banu-nergis",fullName:"Banu Nergis"},{id:"320710",title:"Ms.",name:"Neslihan Sebla",middleName:null,surname:"Önder",slug:"neslihan-sebla-onder",fullName:"Neslihan Sebla Önder"},{id:"357366",title:"Dr.",name:"Sedef",middleName:null,surname:"Uncu Aki",slug:"sedef-uncu-aki",fullName:"Sedef Uncu Aki"}]},{id:"63272",title:"Treatments and Recycling of Metallurgical Slags",slug:"treatments-and-recycling-of-metallurgical-slags",totalDownloads:1379,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Steelmaking plants continuously strive to reduce the environmental load in the steelmaking process, resulting in the recycling of energy, water, and other byproducts. In this chapter, techniques for the treatment and recycling of metallurgical slags are described. Metallurgical slags are considered secondary raw materials and are used or added during the process to improve steelmaking practice. Steelmaking slag added into ladle slags makes it possible to minimize slag line wear. BOF-converter slags are also applied in buildup, foaming, or slag splashing practices carried out to prolong the lifespan of refractory lining. Also, EAF slags are commonly used to avoid refractory wear and decrease energy consumption. It is known that cement concrete is one of the most common building materials. Blast furnace crystallized slags are used in cement production, in different percentages. In this sense, understanding the properties of slags is a prerequisite to apply them in different functions. This chapter deals with the measurement and modeling of thermochemical properties of slags, thermophysical properties, and interproperty correlations. Different experimental tests applied in slag characterization are also detailed.",book:{id:"7557",slug:"recovery-and-utilization-of-metallurgical-solid-waste",title:"Recovery and Utilization of Metallurgical Solid Waste",fullTitle:"Recovery and Utilization of Metallurgical Solid Waste"},signatures:"Elena Brandaleze, Edgardo Benavidez and Leandro Santini",authors:null}],onlineFirstChaptersFilter:{topicId:"889",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[],lsSeriesList:[],hsSeriesList:[],sshSeriesList:[],testimonialsList:[]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"May 18th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:27,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:49,paginationItems:[{id:"80495",title:"Iron in Cell Metabolism and Disease",doi:"10.5772/intechopen.101908",signatures:"Eeka Prabhakar",slug:"iron-in-cell-metabolism-and-disease",totalDownloads:1,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Iron Metabolism - Iron a Double‐Edged Sword",coverURL:"https://cdn.intechopen.com/books/images_new/10842.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81799",title:"Cross Talk of Purinergic and Immune Signaling: Implication in Inflammatory and Pathogenic Diseases",doi:"10.5772/intechopen.104978",signatures:"Richa Rai",slug:"cross-talk-of-purinergic-and-immune-signaling-implication-in-inflammatory-and-pathogenic-diseases",totalDownloads:7,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81764",title:"Involvement of the Purinergic System in Cell Death in Models of Retinopathies",doi:"10.5772/intechopen.103935",signatures:"Douglas Penaforte Cruz, Marinna Garcia Repossi and Lucianne Fragel Madeira",slug:"involvement-of-the-purinergic-system-in-cell-death-in-models-of-retinopathies",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81756",title:"Alteration of Cytokines Level and Oxidative Stress Parameters in COVID-19",doi:"10.5772/intechopen.104950",signatures:"Marija Petrusevska, Emilija Atanasovska, Dragica Zendelovska, Aleksandar Eftimov and Katerina Spasovska",slug:"alteration-of-cytokines-level-and-oxidative-stress-parameters-in-covid-19",totalDownloads:8,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Chemokines Updates",coverURL:"https://cdn.intechopen.com/books/images_new/11672.jpg",subseries:{id:"18",title:"Proteomics"}}}]},overviewPagePublishedBooks:{paginationCount:27,paginationItems:[{type:"book",id:"7006",title:"Biochemistry and Health Benefits of Fatty Acids",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7006.jpg",slug:"biochemistry-and-health-benefits-of-fatty-acids",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Viduranga Waisundara",hash:"c93a00abd68b5eba67e5e719f67fd20b",volumeInSeries:1,fullTitle:"Biochemistry and Health Benefits of Fatty Acids",editors:[{id:"194281",title:"Dr.",name:"Viduranga Y.",middleName:null,surname:"Waisundara",slug:"viduranga-y.-waisundara",fullName:"Viduranga Y. Waisundara",profilePictureURL:"https://mts.intechopen.com/storage/users/194281/images/system/194281.jpg",biography:"Dr. Viduranga Waisundara obtained her Ph.D. in Food Science and Technology from the Department of Chemistry, National University of Singapore, in 2010. She was a lecturer at Temasek Polytechnic, Singapore from July 2009 to March 2013. She relocated to her motherland of Sri Lanka and spearheaded the Functional Food Product Development Project at the National Institute of Fundamental Studies from April 2013 to October 2016. She was a senior lecturer on a temporary basis at the Department of Food Technology, Faculty of Technology, Rajarata University of Sri Lanka. She is currently Deputy Principal of the Australian College of Business and Technology – Kandy Campus, Sri Lanka. She is also the Global Harmonization Initiative (GHI) Ambassador to Sri Lanka.",institutionString:"Australian College of Business & Technology",institution:null}]},{type:"book",id:"6820",title:"Keratin",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6820.jpg",slug:"keratin",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Miroslav Blumenberg",hash:"6def75cd4b6b5324a02b6dc0359896d0",volumeInSeries:2,fullTitle:"Keratin",editors:[{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}}]},{type:"book",id:"7978",title:"Vitamin A",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7978.jpg",slug:"vitamin-a",publishedDate:"May 15th 2019",editedByType:"Edited by",bookSignature:"Leila Queiroz Zepka, Veridiana Vera de Rosso and Eduardo Jacob-Lopes",hash:"dad04a658ab9e3d851d23705980a688b",volumeInSeries:3,fullTitle:"Vitamin A",editors:[{id:"261969",title:"Dr.",name:"Leila",middleName:null,surname:"Queiroz Zepka",slug:"leila-queiroz-zepka",fullName:"Leila Queiroz Zepka",profilePictureURL:"https://mts.intechopen.com/storage/users/261969/images/system/261969.png",biography:"Prof. Dr. Leila Queiroz Zepka is currently an associate professor in the Department of Food Technology and Science, Federal University of Santa Maria, Brazil. She has more than fifteen years of teaching and research experience. She has published more than 550 scientific publications/communications, including 15 books, 50 book chapters, 100 original research papers, 380 research communications in national and international conferences, and 12 patents. She is a member of the editorial board of five journals and acts as a reviewer for several national and international journals. Her research interests include microalgal biotechnology with an emphasis on microalgae-based products.",institutionString:"Universidade Federal de Santa Maria",institution:{name:"Universidade Federal de Santa Maria",institutionURL:null,country:{name:"Brazil"}}}]},{type:"book",id:"7953",title:"Bioluminescence",subtitle:"Analytical Applications and Basic Biology",coverURL:"https://cdn.intechopen.com/books/images_new/7953.jpg",slug:"bioluminescence-analytical-applications-and-basic-biology",publishedDate:"September 25th 2019",editedByType:"Edited by",bookSignature:"Hirobumi Suzuki",hash:"3a8efa00b71abea11bf01973dc589979",volumeInSeries:4,fullTitle:"Bioluminescence - Analytical Applications and Basic Biology",editors:[{id:"185746",title:"Dr.",name:"Hirobumi",middleName:null,surname:"Suzuki",slug:"hirobumi-suzuki",fullName:"Hirobumi Suzuki",profilePictureURL:"https://mts.intechopen.com/storage/users/185746/images/system/185746.png",biography:"Dr. Hirobumi Suzuki received his Ph.D. in 1997 from Tokyo Metropolitan University, Japan, where he studied firefly phylogeny and the evolution of mating systems. He is especially interested in the genetic differentiation pattern and speciation process that correlate to the flashing pattern and mating behavior of some fireflies in Japan. He then worked for Olympus Corporation, a Japanese manufacturer of optics and imaging products, where he was involved in the development of luminescence technology and produced a bioluminescence microscope that is currently being used for gene expression analysis in chronobiology, neurobiology, and developmental biology. Dr. Suzuki currently serves as a visiting researcher at Kogakuin University, Japan, and also a vice president of the Japan Firefly Society.",institutionString:"Kogakuin University",institution:null}]}]},openForSubmissionBooks:{},onlineFirstChapters:{},subseriesFiltersForOFChapters:[],publishedBooks:{},subseriesFiltersForPublishedBooks:[],publicationYearFilters:[],authors:{paginationCount:617,paginationItems:[{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNVJQA4/Profile_Picture_2022-03-07T13:23:04.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. His research interests include biochemistry, oxidative stress, reactive species, antioxidants, lipid peroxidation, inflammation, reproductive hormones, phenolic compounds, female infertility.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Associate Prof.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/15648_n.jpg",biography:"Dr. Mohd Aftab Siddiqui is currently working as Assistant Professor in the Faculty of Pharmacy, Integral University, Lucknow for the last 6 years. He has completed his Doctor in Philosophy (Pharmacology) in 2020 from Integral University, Lucknow. He completed his Bachelor in Pharmacy in 2013 and Master in Pharmacy (Pharmacology) in 2015 from Integral University, Lucknow. He is the gold medalist in Bachelor and Master degree. He qualified GPAT -2013, GPAT -2014, and GPAT 2015. His area of research is Pharmacological screening of herbal drugs/ natural products in liver and cardiac diseases. He has guided many M. Pharm. research projects. He has many national and international publications.",institutionString:"Integral University",institution:null},{id:"255360",title:"Dr.",name:"Usama",middleName:null,surname:"Ahmad",slug:"usama-ahmad",fullName:"Usama Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255360/images/system/255360.png",biography:"Dr. Usama Ahmad holds a specialization in Pharmaceutics from Amity University, Lucknow, India. He received his Ph.D. degree from Integral University. Currently, he’s working as an Assistant Professor of Pharmaceutics in the Faculty of Pharmacy, Integral University. From 2013 to 2014 he worked on a research project funded by SERB-DST, Government of India. He has a rich publication record with more than 32 original articles published in reputed journals, 3 edited books, 5 book chapters, and a number of scientific articles published in ‘Ingredients South Asia Magazine’ and ‘QualPharma Magazine’. He is a member of the American Association for Cancer Research, International Association for the Study of Lung Cancer, and the British Society for Nanomedicine. Dr. Ahmad’s research focus is on the development of nanoformulations to facilitate the delivery of drugs that aim to provide practical solutions to current healthcare problems.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. Dr. Khullar has a keen research interest in genetics of hypertension, and is currently studying pharmacogenetics of hypertension.",institutionString:"Post Graduate Institute of Medical Education and Research",institution:{name:"Post Graduate Institute of Medical Education and Research",country:{name:"India"}}},{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",biography:"Xianquan Zhan received his MD and Ph.D. in Preventive Medicine at West China University of Medical Sciences. He received his post-doctoral training in oncology and cancer proteomics at the Central South University, China, and the University of Tennessee Health Science Center (UTHSC), USA. He worked at UTHSC and the Cleveland Clinic in 2001–2012 and achieved the rank of associate professor at UTHSC. Currently, he is a full professor at Central South University and Shandong First Medical University, and an advisor to MS/PhD students and postdoctoral fellows. He is also a fellow of the Royal Society of Medicine and European Association for Predictive Preventive Personalized Medicine (EPMA), a national representative of EPMA, and a member of the American Society of Clinical Oncology (ASCO) and the American Association for the Advancement of Sciences (AAAS). He is also the editor in chief of International Journal of Chronic Diseases & Therapy, an associate editor of EPMA Journal, Frontiers in Endocrinology, and BMC Medical Genomics, and a guest editor of Mass Spectrometry Reviews, Frontiers in Endocrinology, EPMA Journal, and Oxidative Medicine and Cellular Longevity. He has published more than 148 articles, 28 book chapters, 6 books, and 2 US patents in the field of clinical proteomics and biomarkers.",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",country:{name:"China"}}},{id:"297507",title:"Dr.",name:"Charles",middleName:"Elias",surname:"Assmann",slug:"charles-assmann",fullName:"Charles Assmann",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/297507/images/system/297507.jpg",biography:"Charles Elias Assmann is a biologist from Federal University of Santa Maria (UFSM, Brazil), who spent some time abroad at the Ludwig-Maximilians-Universität München (LMU, Germany). He has Masters Degree in Biochemistry (UFSM), and is currently a PhD student at Biochemistry at the Department of Biochemistry and Molecular Biology of the UFSM. His areas of expertise include: Biochemistry, Molecular Biology, Enzymology, Genetics and Toxicology. He is currently working on the following subjects: Aluminium toxicity, Neuroinflammation, Oxidative stress and Purinergic system. Since 2011 he has presented more than 80 abstracts in scientific proceedings of national and international meetings. Since 2014, he has published more than 20 peer reviewed papers (including 4 reviews, 3 in Portuguese) and 2 book chapters. He has also been a reviewer of international journals and ad hoc reviewer of scientific committees from Brazilian Universities.",institutionString:"Universidade Federal de Santa Maria",institution:{name:"Universidade Federal de Santa Maria",country:{name:"Brazil"}}},{id:"217850",title:"Dr.",name:"Margarete Dulce",middleName:null,surname:"Bagatini",slug:"margarete-dulce-bagatini",fullName:"Margarete Dulce Bagatini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217850/images/system/217850.jpeg",biography:"Dr. Margarete Dulce Bagatini is an associate professor at the Federal University of Fronteira Sul/Brazil. She has a degree in Pharmacy and a PhD in Biological Sciences: Toxicological Biochemistry. She is a member of the UFFS Research Advisory Committee\nand a member of the Biovitta Research Institute. She is currently:\nthe leader of the research group: Biological and Clinical Studies\nin Human Pathologies, professor of postgraduate program in\nBiochemistry at UFSC and postgraduate program in Science and Food Technology at\nUFFS. She has experience in the area of pharmacy and clinical analysis, acting mainly\non the following topics: oxidative stress, the purinergic system and human pathologies, being a reviewer of several international journals and books.",institutionString:"Universidade Federal da Fronteira Sul",institution:{name:"Universidade Federal da Fronteira Sul",country:{name:"Brazil"}}},{id:"226275",title:"Ph.D.",name:"Metin",middleName:null,surname:"Budak",slug:"metin-budak",fullName:"Metin Budak",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226275/images/system/226275.jfif",biography:"Metin Budak, MSc, PhD is an Assistant Professor at Trakya University, Faculty of Medicine. He has been Head of the Molecular Research Lab at Prof. Mirko Tos Ear and Hearing Research Center since 2018. His specializations are biophysics, epigenetics, genetics, and methylation mechanisms. He has published around 25 peer-reviewed papers, 2 book chapters, and 28 abstracts. He is a member of the Clinical Research Ethics Committee and Quantification and Consideration Committee of Medicine Faculty. His research area is the role of methylation during gene transcription, chromatin packages DNA within the cell and DNA repair, replication, recombination, and gene transcription. His research focuses on how the cell overcomes chromatin structure and methylation to allow access to the underlying DNA and enable normal cellular function.",institutionString:"Trakya University",institution:{name:"Trakya University",country:{name:"Turkey"}}},{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",slug:"anca-pantea-stoian",fullName:"Anca Pantea Stoian",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",biography:"Anca Pantea Stoian is a specialist in diabetes, nutrition, and metabolic diseases as well as health food hygiene. She also has competency in general ultrasonography.\n\nShe is an associate professor in the Diabetes, Nutrition and Metabolic Diseases Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. She has been chief of the Hygiene Department, Faculty of Dentistry, at the same university since 2019. Her interests include micro and macrovascular complications in diabetes and new therapies. Her research activities focus on nutritional intervention in chronic pathology, as well as cardio-renal-metabolic risk assessment, and diabetes in cancer. She is currently engaged in developing new therapies and technological tools for screening, prevention, and patient education in diabetes. \n\nShe is a member of the European Association for the Study of Diabetes, Cardiometabolic Academy, CEDA, Romanian Society of Diabetes, Nutrition and Metabolic Diseases, Romanian Diabetes Federation, and Association for Renal Metabolic and Nutrition studies. She has authored or co-authored 160 papers in national and international peer-reviewed journals.",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",country:{name:"Romania"}}},{id:"279792",title:"Dr.",name:"João",middleName:null,surname:"Cotas",slug:"joao-cotas",fullName:"João Cotas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/279792/images/system/279792.jpg",biography:"Graduate and master in Biology from the University of Coimbra.\n\nI am a research fellow at the Macroalgae Laboratory Unit, in the MARE-UC – Marine and Environmental Sciences Centre of the University of Coimbra. My principal function is the collection, extraction and purification of macroalgae compounds, chemical and bioactive characterization of the compounds and algae extracts and development of new methodologies in marine biotechnology area. \nI am associated in two projects: one consists on discovery of natural compounds for oncobiology. The other project is the about the natural compounds/products for agricultural area.\n\nPublications:\nCotas, J.; Figueirinha, A.; Pereira, L.; Batista, T. 2018. An analysis of the effects of salinity on Fucus ceranoides (Ochrophyta, Phaeophyceae), in the Mondego River (Portugal). Journal of Oceanology and Limnology. in press. DOI: 10.1007/s00343-019-8111-3",institutionString:"Faculty of Sciences and Technology of University of Coimbra",institution:null},{id:"279788",title:"Dr.",name:"Leonel",middleName:null,surname:"Pereira",slug:"leonel-pereira",fullName:"Leonel Pereira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/279788/images/system/279788.jpg",biography:"Leonel Pereira has an undergraduate degree in Biology, a Ph.D. in Biology (specialty in Cell Biology), and a Habilitation degree in Biosciences (specialization in Biotechnology) from the Faculty of Science and Technology, University of Coimbra, Portugal, where he is currently a professor. In addition to teaching at this university, he is an integrated researcher at the Marine and Environmental Sciences Center (MARE), Portugal. His interests include marine biodiversity (algae), marine biotechnology (algae bioactive compounds), and marine ecology (environmental assessment). Since 2008, he has been the author and editor of the electronic publication MACOI – Portuguese Seaweeds Website (www.seaweeds.uc.pt). He is also a member of the editorial boards of several scientific journals. Dr. Pereira has edited or authored more than 20 books, 100 journal articles, and 45 book chapters. He has given more than 100 lectures and oral communications at various national and international scientific events. He is the coordinator of several national and international research projects. In 1998, he received the Francisco de Holanda Award (Honorable Mention) and, more recently, the Mar Rei D. Carlos award (18th edition). He is also a winner of the 2016 CHOICE Award for an outstanding academic title for his book Edible Seaweeds of the World. In 2020, Dr. Pereira received an Honorable Mention for the Impact of International Publications from the Web of Science",institutionString:"University of Coimbra",institution:{name:"University of Coimbra",country:{name:"Portugal"}}},{id:"61946",title:"Dr.",name:"Carol",middleName:null,surname:"Bernstein",slug:"carol-bernstein",fullName:"Carol Bernstein",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61946/images/system/61946.jpg",biography:"Carol Bernstein received her PhD in Genetics from the University of California (Davis). She was a faculty member at the University of Arizona College of Medicine for 43 years, retiring in 2011. Her research interests focus on DNA damage and its underlying role in sex, aging and in the early steps of initiation and progression to cancer. In her research, she had used organisms including bacteriophage T4, Neurospora crassa, Schizosaccharomyces pombe and mice, as well as human cells and tissues. She authored or co-authored more than 140 scientific publications, including articles in major peer reviewed journals, book chapters, invited reviews and one book.",institutionString:"University of Arizona",institution:{name:"University of Arizona",country:{name:"United States of America"}}},{id:"182258",title:"Dr.",name:"Ademar",middleName:"Pereira",surname:"Serra",slug:"ademar-serra",fullName:"Ademar Serra",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/182258/images/system/182258.jpeg",biography:"Dr. Serra studied Agronomy on Universidade Federal de Mato Grosso do Sul (UFMS) (2005). He received master degree in Agronomy, Crop Science (Soil fertility and plant nutrition) (2007) by Universidade Federal da Grande Dourados (UFGD), and PhD in agronomy (Soil fertility and plant nutrition) (2011) from Universidade Federal da Grande Dourados / Escola Superior de Agricultura Luiz de Queiroz (UFGD/ESALQ-USP). Dr. Serra is currently working at Brazilian Agricultural Research Corporation (EMBRAPA). His research focus is on mineral nutrition of plants, crop science and soil science. Dr. Serra\\'s current projects are soil organic matter, soil phosphorus fractions, compositional nutrient diagnosis (CND) and isometric log ratio (ilr) transformation in compositional data analysis.",institutionString:"Brazilian Agricultural Research Corporation",institution:{name:"Brazilian Agricultural Research Corporation",country:{name:"Brazil"}}}]}},subseries:{item:{id:"23",type:"subseries",title:"Computational Neuroscience",keywords:"Single-Neuron Modeling, Sensory Processing, Motor Control, Memory and Synaptic Pasticity, Attention, Identification, Categorization, Discrimination, Learning, Development, Axonal Patterning and Guidance, Neural Architecture, Behaviours and Dynamics of Networks, Cognition and the Neuroscientific Basis of Consciousness",scope:"Computational neuroscience focuses on biologically realistic abstractions and models validated and solved through computational simulations to understand principles for the development, structure, physiology, and ability of the nervous system. This topic is dedicated to biologically plausible descriptions and computational models - at various abstraction levels - of neurons and neural systems. This includes, but is not limited to: single-neuron modeling, sensory processing, motor control, memory, and synaptic plasticity, attention, identification, categorization, discrimination, learning, development, axonal patterning, guidance, neural architecture, behaviors, and dynamics of networks, cognition and the neuroscientific basis of consciousness. 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