Comparison of T3 responsiveness between larval and adult myogenic systems.
\\n\\n
Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\\n\\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\\n\\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\\n\\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\\n\\nThank you all for being part of the journey. 5,000 times thank you!
\\n\\nNow with 5,000 titles available Open Access, which one will you read next?
\\n\\nRead, share and download for free: https://www.intechopen.com/books
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Preparation of Space Experiments edited by international leading expert Dr. Vladimir Pletser, Director of Space Training Operations at Blue Abyss is the 5,000th Open Access book published by IntechOpen and our milestone publication!
\n\n"This book presents some of the current trends in space microgravity research. The eleven chapters introduce various facets of space research in physical sciences, human physiology and technology developed using the microgravity environment not only to improve our fundamental understanding in these domains but also to adapt this new knowledge for application on earth." says the editor. Listen what else Dr. Pletser has to say...
\n\n\n\nDr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\n\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\n\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\n\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\n\nThank you all for being part of the journey. 5,000 times thank you!
\n\nNow with 5,000 titles available Open Access, which one will you read next?
\n\nRead, share and download for free: https://www.intechopen.com/books
\n\n\n\n
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"577",leadTitle:null,fullTitle:"Assistive Technologies",title:"Assistive Technologies",subtitle:null,reviewType:"peer-reviewed",abstract:"This book offers the reader new achievements within the Assistive Technology field made by worldwide experts, covering aspects such as assistive technology focused on teaching and education, mobility, communication and social interactivity, among others. 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Coordinator for Post Graduate programs of the Faculty of Business (March 2006-April 2014), Chairperson of Center for Globalization and Sustainability Research (CGSR) (March2009-April2014), Multimedia University (MMU), Melaka Campus, Malaysia, member of Research and Development, research grants panel and the Institute of Postgraduate Studies (IPS) Coordination Committee (ICC) MMU. He is currently teaching Advanced Research Methodology, Entrepreneurship and Commercialization, and Economics for Managers at the postgraduate level and economic subjects at the undergraduate level.\nHis research interests include development economics, productivity analysis, knowledge-based economy, productivity and environment (green productivity), Bioeconomy, Islamic finance and microfinance, economic growth, (environment, tourism) and Entrepreneurship. He is the book\\'s author (Green Productivity: Applications in Malaysia’s Manufacturing) in 2012. 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Amphibian metamorphosis provides an excellent model to study remodeling of the body. This phenomenon is characterized by overall remodeling of the body plan (i.e. larval body) which was once established in early embryogenesis. This metamorphic organ remodeling is induced by thyroid hormone (Gudernatsch, 1912; Kaltenbach, 1953) and a larval body is thus converted into an adult one (Ishizuya-Oka and Shi,Y.B, 2007; Miller, 1996). During this period, most of preexisted larval body organs, i.e., ‘larval-specific organs’ such as tail and gills degenerated (Nishikawa and Hayashi, 1995) and new ‘adult-specific organs’ such as fore- and hindlimbs formed (Brown et al., 2005). This cell replacement is thought to be essential for amphibian metamorphosis and deeply involved in various fundamental biological processes such as cell growth, programmed cell death, differentiation, morphogenesis and cell-cell and cell-environment interactions (Nishikawa, 1997; Shibota et.al., 2000; Shimizu-Nishikawa et al., 2002; Yamane et al., 2011). How are these remodeling-events regulated by metamorphic hormones, triiodothyronine (T3) and thyroxine (T4)? It will provide a great value for developmental and endocrinological research to understand the regulatory mechanism. This is because, thyroid hormone work not only for inducing amphibian metamorphosis but also for triggering metamorphosis in the fishes, such as flounder (Miwa and Inui, 1987) and conger eel (Kitajima et al., 1967), and also in sea urchin (Chino et al., 1994). The process of metamorphosis in the anuran is usually coupled with biphasic development (ancestral life-history). However, in species of direct developer such as the Puerto Rican tree frog,
The reason for adopting thyroid hormone as a metamorphosis-inducing trigger by many organisms is involved in the fact that thyroid hormone is a ligand for nuclear receptors (transcription factors) and can directly cause tissue-specific gene expression changes in the same way as steroid hormone work in insect metamorphosis. Thus, in many metamorphosing organisms, their rebuilding from larval to adult body were achieved through switching of gene expression from larval to adult program by regulation of hormonal concentration and spatiotemporal expression of the receptors. For example, in developing limb buds, the expression of thyroid hormone receptor (TR)-β increases at early metamorphic period but down-regulates at metamorphic climax stage. While, in the tail, the TR-β upregulation occurs at metamorphic climax when tail shortening occurs (Yaoita and Brown, 1990).
A key feature of thyroid hormone action during metamorphosis is the multifaceted nature. The hormone promotes some tissue cells to grow and differentiate but induces the other ones to stop proliferation and degenerate (cell death). Although it is obvious that each program (growth or death) is triggered by thyroid hormone action, it still unknown how it causes the different reactions, death or live, only to a particular (larval or adult-type) cells among many TR-β-expressing cells. This is one of the most important issues in developmental biology field. In other word, it is important to understand not only the thyroid hormone actions but also the mechanisms by which some cells are programmed to commit to a specific cell fate (larval or adult type cells). It would be important to focus on cell-to-cell interactions or cell-to-cellular environments for the analysis of regulatory mechanism of cell fates. The environmental factors include nutrients, growth factors, hormones, cytokines, morphogens and extracellular matrices. There are basically two types of the target cells for such factors, i.e. adult and larval type cells. The adult type cells (or adult precursor cells) start their adult gene program by the actions from such factors while the larval type cells respond to the same factors to stop larval program and activate cell death program. In order to clarify this completely different mode of hormonal actions in organ remodeling during metamorphosis, it would be necessary to fully analyze not only hormonal response of target cells but also the interaction between target cells and surrounding cells.
Muscle remodeling also occurs during anuran metamorphosis (Nishikawa and Hayashi, 1994). It is of great interest to study muscle remodeling from larval to adult type during anuran metamorphosis from the aspect of molecular and cellular interactions. This is because, during anuran metamorphosis there are three different muscle changes, 1) degeneration of larval muscle in the tail (Kerr et al., 1974), 2) formation of new muscle (secondary myogenesis) in developing limbs, and 3) conversion of muscles from larval-type to adult-type in the trunk region (Ryke, 1953), which provide a useful system for analyzing programmed muscle cell death and initiation of adult program of myogenesis. In addition to this, it is also important from the viewpoint of evolutionary adaptation of myogenesis in the transition from fish to tetrapod trunk (Glimaldi et al., 2004). Thus, this chapter concentrates on
In evolutionary history, amphibians are in the process of evolving from aquatic fishes into terrestrial vertebrates. There are many changes in body organs between aquatic and terrestrial species. The most obvious example of such change would be seen in the epidermal changes in the skin. The stratified and keratinized (or cornified) epidermis in whole body skin is one of the phenotypes macroevolutionaly-acquired in amphibians but not fishes and became a well-established characteristic feature of tetrapoda, i.e. terrestrial vertebrates. Since amphibians have an aquatic larval period, the skin of the larva is a fish type of non-cornified epidermis. During metamorphosis, differentiation of a terrestrial type epidermis (i.e. stratified and cornified epidermis) occurs and complete transformation of whole body skin with terrestrial-type cornified (keratinized) epidermis is achieved after metamorphosis. Thus, in the amphibian, it is a unique feature that macroevolutional (phylogenic) changes from fish to terrestrial type are replicated during metamorphic (ontogenic) changes. Other than skin, is there any organs that are converted from larval (or aquatic) to adult (or terrestrial) type during metamorphosis? Just as the skins had evolved so as to protect whole body from drying in a terrestrial environment, it would be needed for the muscles to evolve from aquatic to terrestrial type providing with increased muscle strength so as to overcome the intense gravitational force in the terrestrial environment.
From this point of view, Nishikawa and Hayashi (1994) analyzed electrophoretically the difference in profiles of muscle contractile protein between larval and adult dorsal muscles in the frog
Expression patterns of adult type muscle contractile proteins during
There are two possibilities for the dorsal muscle isoform conversion during metamorphosis (Fig.2A). In the hypothesis 1 (H1), the isoform transition occurs by cell replacement with anterior-posterior proliferation of adult-type myoblasts and death of preexisting larval–type fibers. On the other hands, in hypothesis 2 (H2), the switch in gene expression from larval to adult program occurs within the same cells without larval cell death. If the former (H1) is the case, myoblasts proliferation should occur with anterior-posterior gradient just before the isoform transition in dorsal muscles. Examination of this point by the assay of DNA synthetic activity (Nishikawa and Hayashi, 1994) and PCNA (proliferating cell nuclear antigen) expression (Kawakami et al., 2009) revealed that the cell proliferation activity is higher in the anterior than the posterior dorsal muscles during early metamorphosis just prior to the isoform changes.
Muscle conversion models (A) and the β-TM patterns in dorsal muscle during
Immunohistochemical analysis of metamorphosing
These proliferation activities are well-matched the observations that small portions expressing β-TM (adult muscle area) appeared first at dorsomedial (DM) parts of dorsal muscles and the area gradually expanded to overall dorsal muscles (Fig.3 A, B). The DM parts correspond to the “cord” of the tadpole axial muscles which is reported by Elinson et al. (1999). The “cords” in tail portion also express adult muscle isoforms but this (β-TM+) regions never increased during metamorphosis. On the other hands, in β-TM (-) regions, i.e larval muscle areas, many apoptotic dying muscle cells were observed (Fig.3 B, C). From these results, it has been found that the larval to adult muscle remodeling is achieved by cell replacement (H1: “cell replacement model”) with new proliferation of adult myoblasts and death of preexisting larval cells, not by changing gene expression program from larval to adult one within the same cells (H2) (Nishikawa and Hayashi, 1994).
In summary, we can understand the muscle remodeling in
Death of regenerating tails in anuran amphibians has attracted interests of many researchers and Kerr et al. are not exceptional, who define the specific term “apoptosis” for the processes of non-accidental and active cell death (Kerr et al., 1974). They observed the tail cell death in
Patterns of two different apoptotic bodies (A) and a TUNEL (DNA-nick end labeling) detection of apoptotic tail muscle cells during
Oligonucleosomal DNA fragmentation is thought to be a good biochemical evidence of the apoptotic cells (Kaufmann et al., 2000). Nishikawa and Hayashi (1995) detected electrophoretically the nucleosomal DNA fragmentation in
These are four cellular components, i.e. two types of myogenic stem cells (larval and adult myoblasts) and two types of muscle fibers (adult and larval muscles), and these are responsible primarily for the muscle conversion during
Another feature of the apoptotic processes is a phagocytosis by macrophages of the dying apoptotic bodies. In regenerating tail of
On the other hands, researchers in French (Demeneix’ group) have been greatly contributed to the finding of cell death regulators for the muscle cell death during metamorphosis. The method was developed by de Luze et al. (1993) to introduce genes directly into tail muscles and using this method Sachs et al. (1997) found that somatic gene transfer with a mouse
We can see from the above that cell-death signaling in the tail muscle of metamorphosing
Are the deaths of larval muscle fibers and myoblasts induced by the thyroid hormone during anuran amphibian metamorphosis? How are the cell division and differentiation for the adult muscle stem cells (i. e. adult myoblasts) regulated by thyroid hormone? To answer these questions, Shibota et al. (2000) established primary cell culture methods for adult- and larval-type myoblasts in the frog,
It was found that there were several significant differences (1-7) in the nature of isolated cells between larval and adult-type myogenic stem cells as described below. (1) The cell size just after isolation in the larval-type (15 μm) was larger than that in the adult-type (5 μm). The size of spreading cells 1 day after inoculation was also larger in the larval type cells (30-50 μm) than in the adult type cells (5-10 μm) (Fig.5A, e and a). (2) Both types of cells could adhere to the plastic culture dish with different adhesion ratios (larval type=30-50%; adult type=50-60%). Most of attached cells (88% larval and 81% adult cells) were desmin-positive, showing the isolated cells to be myoblast-rich populations. (3) The timings of start of myotube-differentiation were quite different between larval and adult types: Myotube-formation by myoblasts fusion started on day 2 or 3 in larval but on day 4 in adult cell cultures (Fig.5A, f and c). (4) There was large difference in growth activity between larval and adult cells: The larval myoblasts increased only 2.5-fold over 6 days of culture but the adult ones 5.5-fold (Fig.5 B). (5) The cultured larval myoblasts responded to the metamorphic hormone, T3, with decrease in the DNA synthetic activity (50%) (Fig.5 F). As the result, T3 decreased the cell numbers (sum of myotubes and myoblasts) in larval cell cultures to 56% of those of control cultures over 6 days (Fig.5 E). On the other hands, T3 did not have much influence on the total cell numbers in adult cultures (Fig.5 D). (6) T3 promoted dose-dependently the differentiation of adult myoblasts into myotubes but diminished that of larval cells by half (Fig.6 A and B). (7) Death of differentiated myotubes was promoted by T3 specifically in larval but not in adult cultures (Fig.5 C and\n\t\t\t\tFig.6 C). In addition to the myotubes death, double staining with TUNEL and anti-desmin (a myoblast marker) antibody showed that death of myoblasts (desmin+ cells) was induced by T3 specifically in larval but not adult cells (Fig.6 D). From the differences in cell sizes, the start-timing of differentiation and cell growth activity between larval and adult myogenic stem cells (1, 3 and 4), it is conceivable that adult myoblast have a more stemness phenotype than the larval myoblasts. This is to say, adult myoblasts cannot enter the myotube-forming stage without dividing many times, but in contrast, the larval myoblasts can immediately go into myotube-differentiation. From this point of view, it would be an important issue to examine differences in gene expression of early myogenic transcription factors, such as
Another essential difference (5-7) between larval and adult cells was found to be the difference in T3 responses (Table 1). It was thus evident that the conversion of a larval to adult myogenic system during metamorphosis becomes possible through totally specific control of cell division, cell differentiation and programmed cell death at a precursor cell level by T3. In studies using with a myoblast cell line (Yaoita and Nakajima, 1997) cloned from
Primary culture of adult and larval myoblasts (A and B) and the effect of thyroid hormone (T3) on cell growth (C-F).
As noted above, there were shown to be essential differences between larval and adult type myoblasts each isolated from tadpole tail and leg muscles. Also in the trunk dorsal muscles during metamorphosis, there should be two different (larval and adult) myogenic stem cells with a life-or-death fate. Do these cells really exist within trunk dorsal muscles? If this is the case, is there a possibility that they form heterokaryon myotubes (“chimeric fate” myotubes) with different two types of cells other than myotubes consisting only of larval or adult cells? In such chimeric myotubes, which fates, a death-fate or a life-fate, possibly be selected in response to T3? In the next section, the study about cell interaction mechanism which regulates the myotubes fate (life-or-death) in the dorsal muscle during metamorphosis of
Effect of T3 on differentiation and death of
↓: suppression; ↑: induction or promotion; n.e.: no effect. In the presence of T3, larval type myogenic system of
Comparison of T3 responsiveness between larval and adult myogenic systems.
It was expected that there should be two types of myoblasts (larval- and adult-type muscle stem cells) in trunk dorsal muscles because both larval and adult-type muscles coexist within the same regions. As a first indirect approach for proving the real existence of different two types of myogenic precursor cells in the same trunk muscle, Shimizu-Nishikawa et al. (2002) compared the enhancement of cell death activity in response to T3 among three parts of the muscles, i.e., tadpole trunk, tail and limb muscles, each of which has a different muscle fate (Fig.7 A).
The results showed that the TUNEL+ dying myoblasts were induced by T3 strongly in the tail cells (10-fold induction; from 1.3% to 13%) and moderately in the trunk cells (2-fold; 2.5% to 5%), but not in the limb cells (1% to 1%). The value of cell death induction in trunk cells was between those of tail and limb cells, suggesting the possibility that two types of myogenic stem cells (i.e. T3-inducible and non-inducible cells) are mixed in the trunk muscles. As the second approach, for further direct evidence, isolation of two types (larval and adult) of myoblasts from the trunk dorsal muscles was tried on the basis of their physical natures. The cells dissociated with enzyme-digestion from tadpole trunk dorsal muscles were pre-cultured for three days in high-serum (growth promoting) medium, harvested with trypsin-digestion and used for two-steps cell isolation with a percoll-density gradient centrifugation (a buoyant density-sensitive method) and an albumin-unit gravity sedimentation (a size-sensitive method)(Fig.7 B). The results showed that two different cell types, large (Lg) and small (Sm) cells, were isolated from dorsal muscle at 1:1 (Sm : Lg) ratio. For comparison, the result from the fractionation of the tail muscle cells with the same procedures showed that the two types of cells (Sm and Lg) were also obtained from the tail muscle but their ratio was 5 : 1 (Fig.7 C). Cultivation of these cells (Sm and Lg) revealed that Lg-cells could grow rapidly and T3 decreased the number of Sm-cells but not that of Lg-cells (Fig.7 D). These results suggest that Lg-cells are the adult myoblasts and the Sm-cells are
Cell type-dependent patterns of T3-induced myoblast death.
larval myoblasts. Thus, it was shown that the trunk dorsal muscles contain almost the same number of two different (larval and adult) myoblasts. Interestingly, there were Lg-cells (adult type myoblasts) even in the tail muscle with a small ratio (1/5 of that in the dorsal muscle). In other words, there are many adult type muscle stem (AMS) cells with high growth activity in the dorsomedial (DM) portions of the trunk dorsal muscle but, on the other hands, a small number of AMS cells in the tail DM portions. These results suggest that the life-or-death fates of trunk and tail muscles are determined primarily by the differential distribution of adult myoblasts within the muscles. On the other hand, from the fact that tail muscle does not convert to adult type even though they contain AMS cells, it is conceivable that during metamorphosis the growth and differentiation of AMS cells is specifically activated in the trunk DM portions but suppressed in the tail DM portions. As to this spatial control, Yamane et al. (2011) suggested the possibility that the trunk-specific adult myogenesis is regulated by two cell-interactive mechanisms: a promotion by spinal cord (SP) cells and a suppression by notochord (Nc) cells (see section 6).
It is well known that myoblasts at first proliferate, then stop cell divisions and finally fuse among themselves to form multinuclear myotubes toward terminal differentiation. Unlike this, however, there is an exceptional uninuclear myotube formation without myoblast fusion during somitic myogenesis in
In the trunk dorsal muscles of
Formation of heterokaryon myotubes between adult and larval myoblasts.
Then, is there a possibility that the larval muscle fibers in tadpole are rescued from their T3-mediated death by fusing with the adult type myoblasts and transform into adult muscle fibers? If this is the case, such cell-fate conversion may accelerate the speed of adult myogenesis because such tadpoles do not have to use much more energy for destroying a lot of differentiated larval muscles. So, does a fusion-mediated fate-change really occur? For the clarification of this point, it was examined using an in vitro co-culture system whether chimeric myotubes with both adult and larval myoblasts respond to T3 to die or not (Fig.8 B). As the result, it was clarified that both larval and adult myoblasts randomly fuse to each other to make heterokaryon and the rescue from their T3-mediated death occur only when the proportion of adult nuclei number was higher than 80 % within the myotube. Since the rescue from larval cell death thus requires incorporation of so many adult cells, the rescue of the trunk myotubes would occur at a very low rate and most of larval type cells would usually die during metamorphosis by the action of T3. Interestingly, an apoptotic feature (DNA fragmentation) was not observed in any larval nuclei within the surviving heterokaryon myotubes (i.e. adult nuclei ratio ≥ 80%). This mean that the larval nuclei were protected from apoptotic death and their death fate was converted to a life fate (Fig.8 C). However, because a lot of adult cell fusion are needed for preexisting larval muscles to increase the adult-nuclear ratio up to 80%, it is reasonable in vivo situation that adult dorsal muscle conversion by the rescue of the larval myotubes seldom occurs or it occurs only at very few fibers in the anterior portion of body axis with high growth activity. Accordingly, it would never occur in the tail portion where the growth activity of myoblasts is very low (Fig.9). In essence, adult conversion of the trunk dorsal muscles is mainly carried out by the new myotubes formation rather than the old myotubes rescue.
Then, not involving the rescue mechanism, another mechanism which promotes the adult myoblasts differentiation should be needed in order to make efficiently the adult muscles in dorsal muscle region. In order to know whether such promotion of adult myogenesis involves some kinds of cell-cell interactions, experiments with “separated co-culture” of two types of (adult and larval) myoblasts were conducted (Shimizu-Nishikawa et al., 2002). In this experiment, adult (frog leg muscle) and larval (tadpole tail muscle) type myoblasts were separately inoculated in the two different areas in the same culture dish in order to avoid a direct adult-to-larval cell interaction (“separated co-culture”) and their differentiation activity was compared with that in control cultures with either one of the two types by counting myotube and myotube-nuclei numbers within each areas. In this “separated co-culture” system, two types of myoblasts can communicate only through culture medium but through direct cell-to-cell interactions. The result clearly showed that differentiation of adult myoblasts into myotubes was promoted by larval myoblasts but that of larval myoblasts was not affected by adult cells (Fig.10 A).
A model for myotubes formation during
Effects of separated co-culture and serum concentration on myoblast differentiation.
This effect should be caused by some humoral factors which released from larval myoblasts but not by a direct cell-to-cell contact, because it occurred at a certain distance in the “separated” areas. So, it was examined whether the activity which promotes adult differentiation was observed in conditioned medium (CM). The result indicated that the activity was found only in a larval myoblast CM but not in an adult myoblast CM, suggesting that larval cell secreted a factor(s) for adult muscle differentiation. This putative factor was found to be in the retentate (R) fraction with molecular weight (MW) more than 10,000 through ultra filtration (MW 10,000 cut-off). The ultra filtration also revealed the inverse activity that inhibits the adult myoblast differentiation in the R fraction of control culture medium, suggesting that control medium (maybe serum components in medium) intrinsically contains a factor(s) which antagonizes with the factor(s) in L-CM to inhibit the adult myoblast differentiation. Thus, in order to examine if such inhibitory factor is from serum components of the culture medium, each adult and larval myoblasts were cultured in various conditions with different fetal calf serum (FCS) concentrations and their differentiation (myotube formation) activities were measured (Fig.10 B). As a result, differentiation of adult myoblasts was found to be suppressed dose-dependently by FCS but that of larval cells not to be affected. Taken from these results, it is conceivable that adult differentiation promoting factor(s) being released from larval cells functions through antagonistic regulation of the adult differentiation-inhibitory factor(s) in the control medium (i.e. serum). It was suggested from a work with mouse myogenic cells (Cusella-DeAngelis et al., 1994) that the differentiation inhibitory factor(s) in serum could possibly be some kind of molecules related to TGF-β. Because, interestingly, TGF-β dose-dependently suppressed the differentiation of mouse fetal (but not embryonic) myoblasts in the same way as FCS dose-dependently suppressed that of
In summary, it was found for the first time that the
The adult muscle differentiation occurs in the trunk (but not the tail) during
Therefore, it is reasonable to hypothesize for the trunk-specific adult muscle differentiation that adult myoblast differentiation is promoted by the spinal cord but suppressed by the notochord. So, according to this hypothesis, each of adult (from hindlimb) and larval (from tail) myoblasts was co-cultured with the spinal cord (or notochord) cells so as to compare their responses to two axial cells (i.e. spinal cord and notochord cells)(Fig.12). The result clarified the expected opposite roles of the two axial cells: The spinal cord cells increased twice the myotubes-forming activity of adult myoblasts but did not increase that of larval cells. On the other hands, the notochord cells strongly suppressed the myotube-formation by adult myoblasts but did not suppress that by larval cells (Fig.12 G-L). Thus, there is a high possibility that two contrasting mechanisms, i.e. the “spinal cord (SC)-promotion” and the “notochord (Nc)-suppression” on adult myogenesis, are involved in the trunk-specific adult muscle conversion (Fig.13).
Cross-sectional proportion of spinal cord to notochord in
Effect of spinal cord (SC) cells and notochord (Nc) cells on adult and larval myogenic cells in vitro.
A model for the trunk-specific adult muscle differentiation during
Sonic hedgehog (Shh) distribution in notochord and spinal cord of the trunk and tail regions during
As to the former mechanism, i.e. the “SC-promotion”, the involvement of sonic hedgehog (Shh) signaling is expected, because the spinal cord and notochord expresses Shh and positively regulates the early embryonic myogenesis (Munsterberg and Lassar, 1995, Stern and Hauschka, 1995, Blagden et al., 1997). In fact, the analysis with antibody staining revealed that the N-terminal fragment (active form) of Shh proteins is present in the spinal cord and notochord regions throughout metamorphosis of
Effect of a Shh inhibitor, cyclopamine, on the differentiation of
On the other hands, as to the “Nc suppression”, the causing factor(s) remains to be unknown. However, another interesting feature of the notochord cells was found by a “separated co-culture” experiment. In the “separated co-culture”, when the notochord cells and adult myoblasts were placed each in separated two areas on the same culture dish in order to avoid direct cell-cell interaction between them, the notochord cells lost their ability to suppress adult myogenesis but rather promoted the adult myoblast differentiation (Fig.16). Interestingly, the same effect (promotion of adult myogenesis) was also observed in a “separated co-culture” with a whole notochord tissue instead of isolated notochord cells. Thus, it was found that notochord cells have a long-distance promotive effect for adult myogenesis (i.e. the “notochord promotion”) other than the “notochord suppression” effect appearing at a short distance. Since the notochord also expresses Shh throughout metamorphosis (Fig.14) and Shh is also known to positively regulate early embryonic myogenesis (Munsterberg and Lassar, 1995), this molecule is possibly be a major candidate molecule for the “notochord promotion”.
Notochord suppression on adult differentiation requires a direct cell-to-cell interaction between notochord (Nc) cells and adult myoblasts (Ad-mbs).
As described above, the multiple cell-to-cell interactions coordinately regulate in diverse ways the trunk-specific promotion and the tail-specific suppression of adult myogenesis during metamorphosis. The molecular features of such cell interactions have not fully characterized. Especially, it should be primarily emphasized as an important future work to get insight into the molecular mechanism for the “notochord suppression”. Hebrok et al. (1998) reported with chick embryo that factors from notochord, such as fibroblast growth factors (FGF) and activin, suppress the prepancreatic dorsal endoderm Shh expression and thereby permit early pancreatic development. Such a FGF (or activin)-like molecule(s) might be a factor(s) responsible for the “notochord suppression”. Further investigations are needed for clarifying this question.
Secondary, it is also very important issue to clarify the signaling cascade for the “SC promotion” of adult myogenesis. The “SC promotion” shows adult-specific effect on the muscle differentiation and Shh is expected to be a responsible factor for this phenomenon. As detailed above (section 4), adult myoblasts proliferate many times as undifferentiated stem cells and then after few days stop cell divisions to transit to the differentiation steps (Shibota et al., 2000). Therefore, it is reasonable that the “SC promotion” is involved in the transition step from the undifferentiated stemness stage of the adult cells to the more committed differentiation stage. Borycki et al. (1999) reported that Shh, produced by the notochord and floor plate, control epaxial muscle determination through
The clarification of the cell-cell interaction mechanisms and their molecular cascades for the adult muscle differentiation during
Nishikawa and Hayashi firstly examined the larval-to adult-muscle isoform transition and put forward a new model, the “cell replacement model”, that clearly explains the larval-to-adult myogenic conversion during frog metamorphosis. In this model, larval-to-adult conversion of tadpole dorsal muscles was achieved through the cell replacement by both death of larval-type myogenic cells and proliferation and differentiation of adult-type myogenic cells. The death of tadpole trunk dorsal muscles was found to occur through apoptotic processes including nucleosomal DNA-fragmentation, apoptotic body formation and phagocytosis by macrophages.
In subsequent research, larval- and adult-type myogenic precursor cells (myoblasts) were isolated each from
Finally, co-culture system using myogenic cells (larval and adult myoblasts) and non-myogenic axial cells (notochord and spinal cord cells) was developed to examine how adult myogenesis is promoted in the trunk muscle region but suppressed in the tail muscle region through the interactions between myogenic and non-myogenic cell or environmental signals. The results revealed the suppression of adult myogenesis by notochord cells (“notochord suppression”), promotion of adult myogenesis by spinal cord cells (“spinal cord promotion”) and upregulation of adult myogenesis by sonic hedgehog (Shh)-signaling. These results present a model for the region-specific regulatory mechanism of adult myogenesis by cell-cell interactions, i.e., “spinal cord promotion” and “notochord suppression”, during X. laevis metamorphosis.
Mortars are among the first building materials used in constructions, even from prehistoric times. Their study reveals a great source of information regarding the evolution of their technological characteristics and application techniques, the availability and exploitation of raw materials, as well as the wider socioeconomic aspects of each era. In any case, it seems that ancient masons were fully aware of the significant role of mortars in constructions and could exploit the raw materials that were available along with the application techniques [1]. In particular, the role of the quality of aggregates on the properties of old mortars has been known since, at least, Roman times. Natural sands of different origins and nature (river, quarry, sea) and crushed bricks combined with binders which were usually lime-based, were used for many centuries (Figure 1). These mortars were of different types and served as bedding, renders or plasters, floors, and mosaics’ substates forming masterpieces of the world cultural heritage [2].
Coarse aggregates of natural origin in bedding mortars of the fourth century AD (left) and crushed brick as aggregates in a bedding mortar of the sixth century AD (right).
It is evident from the classic authors that the Romans preferred sharp sands to rounded sands, as they knew that these would produce stronger mortars; for example, Palladius, Pliny, and Vitruvius refer to recipes and guidelines for criteria that can be used for sand selection in the mixtures [3, 4, 5]. Among the requirements they mention, the origin, the shape, and the cleanness of the sand are the ones that prevail. They noticed the direct relation of the sand quality to the setting and strength of the mortars, and they gave precise directions to avoid, for example, sea sand due to salt contamination that can accelerate the weathering of the mortar. Manufacturing mortar was the first milestone in building history which has been continuously evolved up to the modern concrete. The materials used for mortar manufacture since antiquity were binders (clay, lime, pozzolan, brick/tile dust), aggregates (sand, gravel, crushed brick, pumice), and materials that were less frequently found and used (such as chopped straw, egg whites, reeds, blood, palm fibers, milk, and goat hair.). In Akrotiri of Thera, Greece (1700–1400 BC), structural mortars were made of local origin clay, mixed with gravel, charcoal, and straw [6]. In Hellenistic monuments, such as Dilos residences (second century BC), lime-pozzolan mortars were mainly found, with aggregates of natural origin and of granulometry mainly 0–8 mm [7]. During the Roman period (second century BC–third century AD), the use of lime and pozzolan dominated in constructions, while brick dust and crushed brick also started to be used [8]. The systematic and in high proportion use of brick dust and crushed brick in lime or lime-pozzolan mortars were expanded during the Byzantine era fourth–fifteenth century AD [9]. Aggregates (natural origin and crushed brick) were of gradation 0–8 mm to 0–16 mm, with a B/A ratio 1/2–1/3 [10]. The effectiveness of the adhesion between the binder and the crushed brick aggregates achieved in those cases was impressive. During the Ottoman period (fifteenth–nineteenth century AD), structural mortars were manufactured by using the available raw materials [11]. They were mainly lime-based (pure lime or lime with clay), while in specific constructions demanded in resistance to humidity (baths, cisterns), pozzolan and brick dust were also added. Aggregates were of natural origin (in some cases crushed brick was also added), of 0–8 mm granulometry, and of B/A ratio 1/2 [12]. In Medieval times (fifteenth–nineteenth century AD), structural mortars mainly consisted of lime (in some cases pozzolan was added), natural or crushed aggregates, and crushed brick in gradations 0–4 mm to 0–8 mm and B/A ratio 1/1–1/2 [13]. During the nineteenth and beginning of the twentieth century, structural mortars varied depending on the building type and the local constructional tradition. Aggregates were usually of the natural origin of 0–8 mm gradation [14]. Later, scholars such as Lanas [15] referred to the importance of the binder/aggregate interface as a zone that requires special attention. From the historic research of the components of mortars, it is obvious that the presence of sand was catalytic and continuous. In relation to the origin of the sand used, it was mainly local, from streams or rivers, and in special cases, crushed bricks or tiles in different gradation were added [16, 17]. Aggregates are the most ubiquitous materials in construction. Nowadays, the building industry uses aggregates as materials for construction, mainly in their bound state with cement to form concrete, bitumen to form asphalt, or as components for composite materials. Nevertheless, the utilization of aggregates has a long history in construction technology and especially in mortars. Over the last decades, due to the increasing cost of raw materials and the continuous reduction of natural resources, the recycling of industrial waste has become an interesting option for the building industry. Nowadays, many large industries use manufactured sand alone for producing mortar by partially replacing river sand. In these complex systems, the aim seems to be first, the utilization of low-cost materials from local resources and second ensuring the quality and performance of materials for specific applications. Therefore, there is still a continuous usage of sand in construction works. Alternative approaches to completely replacing sand in mortars have intensified over the last decades [18]. At the moment, the increasing awareness of society about safeguarding heritage buildings and at the same time protecting the environment promotes strategies of combining principles of restoration with environmental friendly materials and techniques.
Composites are materials made by combining two or more other materials. These materials are important in the construction sector as building technology has been favored by the advanced properties that composites can offer. The development of composite materials along with related design and manufacturing technologies constitute one of the most important advances in the history of materials. Composites are multifunctional materials having unprecedented mechanical and physical properties that can be tailored to meet the requirements of a particular application [19]. Thus, new achievements have been constructed as the innovative composites could add new possibilities to the engineers’ imagination.
Mortars are a specific type of composite material, which consists mainly of three phases—paste as the matrix, interface transition zone (ITZ), and aggregates. The properties of mortars are influenced by:
Aggregates (type, percentage, shape)
Binders (activity, percentage)
Their contact surface area
Mixing water
The maintenance conditions of the applied specimens
At fresh state, mortar should be workable (do not break and do not flow), plastic (to have consistency to hold and not flow on overload loads) and it should show volume stability (do not cause contractions or expansions). At harden state, it should have the required strength and the required porosity. Aggregates constitute the strongest phase, hold a significant percentage in the volume of mortar and are frequently used in sand size (up to 4 mm). Conditions for the use of aggregates in mortars is the health of both the parent rock and the grains (without breaks, cracks, impurities), low porosity—small absorption index, homogeneous granulometric grade, percentage of the fines (<0.075 mm) should not exceed 5% [20]. The presence of fines in lime-based mortars can cause considerable alterations to the properties of the mortars. Their presence significantly reduces the strength and increases the volume shrinkage of mortars [21]. Furthermore, the porosity can be increased, and the same can also happen with capillarity when fine aggregates are participating in excess. Additionally, the type of fines also seems to play a role in their behavior in relation to the basic binder. For example, the strength is decreased in compositions with clay fines while porosity is affected mainly by limestone fines [22]. Capillarity also seems to be affected by the type of fines as the compositions containing fines 10–15% presented low absorption probably because fines block capillary pores [23].
In the case of mortars, as composite materials and keeping in mind that aggregates retain the inherent properties of the rocks from which they are derived, it can explain that the color, the chemical and physical characteristics of the aggregates directly affect the specific weight, the measure of elasticity, the volume stability, the appearance, and the mechanical and physical properties of mortars. The addition of sand to a binding system in mortars technology has proved to confer technical advantages as they contribute to volume stability, durability, and structural performance [16]. The gradation of the aggregates was wide, but the most adequate part was sand of 0–4 mm. Coarse aggregates up to 1 cm were used in thick joints [10] and also combined with sand for structural mortars while sand or finer aggregates (0–2 mm) are usually the constituents of the renders or plasters [24]. Usually, aggregates are obtained after the gentle grinding and sieving (based on EN1015-1) [25]. Even homogeneous distribution of grains is usually obtained as shown in Figure 2 in a typical bedding mortar.
Typical gradation of old structural mortar.
The ratio of binder to aggregates (B/A) ranges widely but it could be said that for most of the structural mortars, it is 1:2.5 or 1:3 while for the renders and plasters are richer in binder content and the ratio is mostly 1:1 or 1:1.5 [23]. Apart from the different types of aggregates, as their mineralogy and origin are concerned, the volume content in the mixture, the maximum size, and their gradation influences the structure of a binder—aggregate mixture and the performance of mortars overall [10]. The added aggregates strengthen the composite, and the associated interface weakens it. These two opposite effects offset each other, and the combination of them leads to declined strength. Generally, a strong cohesion between the mortar binder and coarse aggregate confirms the good masonry properties. On the other hand, the increase of aggregate content reduces the workability of a mix and thus, reduces the strength as well [26]. It has been mentioned before that aggregate plays a role in restraining the shrinkage of cement paste, and that the shrinkage of the aggregate itself can be neglected [27]. It has been found in various composite materials that a certain amount and proper size of the aggregate are beneficial to the strength and fracture energy of the composite [28]. For mortar specimens, aggregates have a significant influence on both rheological and mechanical properties. Their specific gravity, particle size distribution, shape, and surface texture influence markedly the properties of mortars in the fresh state. On the other hand, the mineralogical composition, toughness, elastic modulus, and degree of alteration of aggregates are generally found to affect the properties of mortars and in the hardened state [29]. The drying shrinkage strains in investigated mortars are changed significantly by different kinds of fine aggregate materials. The water content of the mortar mix proportion is a major factor in drying shrinkage evolution. Increasing the unit water content can result in an increase in the amount of capillary water, and hence more shrinkage strain would be obtained. The bonding stress of the weak interface zone between the coarse aggregate and paste can be improved when a chemical reaction between the aggregates and the paste [30].
More recently, the role of the recycled sand from waste demolition, when examined in mortars, revealed that it was more beneficial in lime mortars rather than in stronger lime-pozzolan or lime-pozzolan and cement mortars as a decrease in their performance were recorded in the latter cases due to the mortars’ structure [31]. It seems that two competitive mechanisms acted in these mortars; high porosity (due to high water content and the nature of the aggregates) which assists toward low strength and durability and the chemical reaction due to the presence of reactive components which creates a strong structure. This chemical reaction is a stronger mechanism in the case of lime mortars and prevails in relation to the competitive mechanisms of the higher porosity [32].
In an effort to test different aggregate-related properties to hydraulic lime mortar, Pavia et al. suggested [33] that an increase in the calcite content of the aggregate lowers the flexural and compressive strength of the mortar. At the same time, they proved that sharp aggregate, as well as aggregate with small average particle size, tends to increase the mechanical strength and bulk density of a mortar simultaneously reducing porosity, water absorption, and capillary suction. Additionally, they concluded that aggregates containing particles of a wide size range can increase the mechanical strength and bulk density of the hardened mortar diminishing porosity, water absorption, and capillary suction.
The role of aggregates on the structure and behavior of lime-based mortars is examined by studying the influence of the aggregate content, type, and grain size on the strength, porosity, and volume stability of the mortars. Trying to understand how the properties of the sands influence important macroscopic properties of pure lime mortar, threes sands that were available in the market were selected and analyzed in the laboratory. All of them were river origins of siliceous content (Figure 3).
(a) Black sand, (b) yellow sand, and (c) blonde sand.
X-ray diffraction analysis (XRD) using a D2 Phaser 2nd generation, Bruker instruments, indicated that blonde sand was containing quartz, feldspar, magnetite, calcite, hornblende. Yellow sand contained quartz, feldspar, magnetite and black contained quartz, feldspars, biotite, and hornblende. Physical properties, such as water absorption, specific gravity, and sand equivalent (S.E.), are shown in Table 1 while the chemical analysis revealed the silicic nature of the sands (Table 2).
Water absorption % | Specific gravity g/cm3 | S.E. | |
---|---|---|---|
Blonde | 0.70 | 2.36 | 90.5 |
Black | 1.46 | 2.35 | 98.0 |
Yellow | 1.09 | 2.34 | 75.0 |
Physical properties of sands.
Soluble in acids % b.w. | Soluble salts % b.w. | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Sample | Na2O | K2O | CaO | MgO | Fe2O3 | Al2O3 | SiO2 | L.I.% | Cl− | NO3− | SO42− |
Black sand | 3.24 | 2.63 | 3.05 | 1.28 | 3.66 | 13.83 | 68.37 | 3.45 | 0.19 | 0.08 | <0.01 |
Blonde sand | 2.97 | 1.76 | 3.16 | 1.87 | 5.69 | 14.17 | 66.00 | 4.23 | 0.09 | 0.11 | 0.04 |
Yellow sand | 7.82 | 0.94 | 0.73 | 0.46 | 1.02 | 18.71 | 67.14 | 2.88 | 0.01 | <0.01 | 0.31 |
Chemical analysis of sands.
Lime mortars were prepared using lime CL90 (based on EN459) [34] and the compositions were produced, as shown in Table 3. The workability was measured with a flow table as described in EN1015-3 [35].
Composition | Lime | Blond sand | Black sand | Yellow sand | W/B | Workability (cm) |
---|---|---|---|---|---|---|
L-blond | 1 | 3 | — | — | 0.758 | 15.0 |
L-black | 1 | — | 3 | — | 0.800 | 14.5 |
L-yellow | 1 | — | — | 3 | 0.750 | 14.8 |
Composition of trial mortar mixtures.
The samples were cured based on EN456 and at 28 days, the compressive strength and the open porosity were recorded (Table 4).
Composition | Compressive strength (MPa) | Porosity % (RILEM CPC11.3) |
---|---|---|
L-blond | 1.14 | 26.42 |
L-black | 1.03 | 27.11 |
L-yellow | 0.98 | 30.79 |
Properties of the produced mortars at 28 days.
The results show that there are different properties recorded in the produced mortars even when siliceous sands are used. The different properties, such as S.E. and the water absorption capacity of the sand grains, influence both the fresh (workability) and the hardened properties (porosity, strength) of the produced mortars.
The natural sands can be of similar origin with the crushed but weathering not only rounded the particles but also changed the proportions and removed most of the light minerals, such as the flaky micas. Due to these differences, mixtures with crushed sand often display higher water demand and lower workability than the corresponding composite with glaciofluvial sand. Additionally, crushed sand has a positive impact on long-term strength. It seems that, when rough-grained sand is used, strong cohesion with the binder can be achieved, as shown in Figure 4, where mortars with rounded and crushed sand were examined under scanning electron microscopy (SEM) [17].
SEM examination of rounded sand grain (left) where there is a gap in the contact zone and angular grain with strong cohesion (right).
The mechanical features, particle shape, grading, and physical properties, such as moisture absorption, sand equivalent value, are what can be labeled as properties of interest in the aggregates when used in mortars. Some of these most important properties are shown in Table 5.
Property | Regulation |
---|---|
Determination of rock compressive strength | ASTM C170 |
Determination of disintegration resistance (health) of aggregates (sodium sulfate method). | ASTM C88 AASHΤO Τ104) |
Determination of mineral hardness | the MOHS scale |
Determination of specific gravity of aggregates | BS 812/ ΑΑSΗΤΟ T 19. |
Determination of moisture absorption of aggregates. | AASHTO Τ85 |
Determination of granulometric analysis | AASHTO Τ27/ AASHTO T11/ ΕΝ933-1 |
Determination of ultra-fine crushed material by rinsing | Α8ΤΜ 0117 (AASHTO Τ37) |
Determination of equivalent sand | AASHTO Τ176 |
Determination of abrasion resistance of aggregates | BS 812/75 |
Determination of wear in aggregate crushing | BS 812/75 |
Determination of wear on the impact of aggregates | BS 812/75 |
Determination of plaque index | 88,812/75 Section 105.1 |
Important properties of aggregates to be used in mortar production.
The bond behavior in the interface between the binder and the aggregates has a strong effect on the mortar properties since the effectiveness of the reinforcement provided by the addition of particles depends on the interfacial bond (Figure 5). This is since the size, shape, and content of the particles predominantly control the morphological features of the internal structure of the composite.
Macroscopic examination of contact zones of natural aggregates and binders in old mortars. Despite the presence of cracks in the binder in the left image, the cohesion is strong. On the right, there are pores on the interface probably due to the high content in aggregates in relation to the binder.
The test results showed that with increasing volume fraction of aggregate, the compressive strength of the composite decreases, which is different from the prediction of conventional composite theories. The possible explanation of this result is based on the interface transition zone (ITZ) around the aggregate, which is the weak zone in composites (Figure 6) [15]. With more aggregate added into the mixtures, more interfaces are formed in the hardened material. The compatibility between the aggregate of the paste affects the development of strong cohesion at the aggregate-matrix interface in many cases and that usually indicates the good performance of the mortar. As aggregates are, by weight or by volume, the major component of mortars, they can be a source of silica, which can react in certain conditions with the binder, leading to the formation of reaction rims at the edge of the grains and recrystallization along with the pre-existing cracks (Figure 7).
Examination under SEM of natural aggregate and lime binder with weak ITZ (left) and crushed brick as aggregate and lime-pozzolan binder with strong ITZ (right).
Old mortars under the polarized microscope (x10). Reaction rim in the interfacial zone of the binders and the aggregates used.
Apart from the different types of aggregates as their mineralogy is concerned, the volume content in the mixture, the maximum size, and their gradation influences the structure of a binder—aggregate mixture [3, 5]. The analysis of mortars reveals that higher strength values are attained for lime mortars of low binder/aggregate (B/A) ratio (1:1.5, 1:2.5, and 1:3) which contained sand (0–4 mm). Coarse aggregates have contributed positively to the volume stability of lime mortars. The microstructure has recorded the restriction of volume changes in cases where coarse aggregates have been used in the structure of lime mortars (Figure 8).
Pores and cracks in the structure of lime mortar with coarse aggregates (polarized microscope, x15).
However, it is well recognized that coarse aggregate particles can act as crack arresters, as they restrict the shrinkage of the binder so that under an increasing load, extra energy is absorbed for the formation of a new crack (Figure 9) [36].
Cracks inside the binder where they meet the aggregate volume as the obstacle.
Usually, a detailed analysis of the authentic building materials is performed to establish an opinion about the materials and techniques used during the construction phase [2]. Based on the results of this analysis, the design and laboratory production of some materials follows [14, 37]. The destructive consequences from the use of incompatible repair materials are related to different physical, chemical, and elastic characteristics that many new materials possess in relation to the old lime-based ones. For this reason, the quality of the materials used in intervention works is of primary importance for the longevity and economy of interventions. However, standard test methods and recommendations have not yet been developed despite the effort at the European level.
As river sand remains as one of the most widely used fine aggregates due to its desirable properties an increased tendency to use and it is observed. With an increase in construction activities, the demand for river sand has also been increasing. As a result, it has been mined at a high rate, depleting its natural resources and causing serious environmental issues. Also, owing to the excess cost of transportation, the natural river sand has become expensive. Hence, industries are shifting to other materials, such as crushed sand. But as the demand for building materials will continue to increase, their sources for crushed sand might also get exhausted. Therefore, there is a need to replace the fine aggregate either completely or partially with an alternative material that can satisfy the properties required for concrete, which is cost-effective and at the same time sustainable. Finding an alternative material to river sand has now become imperative.
The incentive to use sand from building demolition in repairing mortars derives from different needs. Natural sand originating from rivers is becoming rare, while the extraction of aggregates from quarries carries an increased administrative cost due to new strict legislations.
Both practices are not considered environmental friendly and, thus, the criteria and legislation for sand extraction are becoming stricter and demanding, while in some places, good quality natural sands are not available. On the other hand, the increased waste production offers the availability of large volumes of recycled materials and public concern about the environment pushes toward their utilization. The possibility of incorporating fine recycled sand originating from construction and demolition waste in lime-based traditional mortars. The study showed that the recycled sand had an even grain distribution, without any hazardous material and low content of soluble salts [38]. The mortars mixtures with recycled sand showed increased water demand and reduced workability compared to mortars with natural sands, even when superplasticizer was used [39]. The mechanical strength measured at 28 and 90 days showed good results as the mortars with lime and recycled sand had higher compressive strength compared to mortars with natural sands [40].
Additionally, several industrial wastes, (fly ash, demolition waste, slag, glass, brick waste, and plastic), have been shown to be suitable as construction materials and readily follow the design requirements. The substitution of the siliceous aggregate with plastic sand leads to a decrease in mechanical properties, opportunities in the use of these materials are not affected, especially for applications that do not require a structural function [41].
The mechanical and physical properties of a mortar both at fresh state, but also long-term, depend on multiple factors, including binder type, curing time, binder—aggregate and binder—water ratios, nature, shape, and grading of aggregates, the compaction degree, and also the environment in which they function. As mortars are composite materials, each component has a special role in the ultimate quality of the material. Aggregates, being of great volume in the mortar mass, significantly influence the structure and the properties achieved in all states of mortar production. The analyses of old mortars revealed the continued presence of sand in the mortars from pre-history up to the cement era. Coarser grains were also used in the technology of mortars. Generally, it is accepted that the strongest mortar mixes are produced from well-graded, clean, and angular aggregates. Usually, they were of local origin following principles of ecology and economy.
The same principles should be applied today having the technological evolution as an alley to protect the environment and work on the benefit of the constructions. Understanding the mechanisms of action and the parameters affecting significant properties in mortars, a well-engineered mixture can be achieved utilizing alternative solutions to protect natural resources and at the same time bring to the market high-quality innovative mortars. Recycled sands are promising materials in construction as after specific tests, they can be utilized either in repairing old structures or even in preparing new cement-based mortars.
IntechOpen implements a robust policy to minimize and deal with instances of fraud or misconduct. As part of our general commitment to transparency and openness, and in order to maintain high scientific standards, we have a well-defined editorial policy regarding Retractions and Corrections.
",metaTitle:"Retraction and Correction Policy",metaDescription:"Retraction and Correction Policy",metaKeywords:null,canonicalURL:"/page/retraction-and-correction-policy",contentRaw:'[{"type":"htmlEditorComponent","content":"IntechOpen’s Retraction and Correction Policy has been developed in accordance with the Committee on Publication Ethics (COPE) publication guidelines relating to scientific misconduct and research ethics:
\\n\\n1. RETRACTIONS
\\n\\nA Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
\\n\\nA formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
\\n\\nPublishing of a Retraction Notice will adhere to the following guidelines:
\\n\\n1.2. REMOVALS AND CANCELLATIONS
\\n\\n2. STATEMENTS OF CONCERN
\\n\\nA Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
\\n\\nIntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\\n\\n3. CORRECTIONS
\\n\\nA Correction will be issued by the Academic Editor when:
\\n\\n3.1. ERRATUM
\\n\\nAn Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
\\n\\nA published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\\n\\n3.2. CORRIGENDUM
\\n\\nA Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
\\n\\n4. FINAL REMARKS
\\n\\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\\n\\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\\n\\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
\\n\\nAny suggestions or comments on this Policy are welcome and may be sent to permissions@intechopen.com.
\\n\\nPolicy last updated: 2017-09-11
\\n"}]'},components:[{type:"htmlEditorComponent",content:'IntechOpen’s Retraction and Correction Policy has been developed in accordance with the Committee on Publication Ethics (COPE) publication guidelines relating to scientific misconduct and research ethics:
\n\n1. RETRACTIONS
\n\nA Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
\n\nA formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
\n\nPublishing of a Retraction Notice will adhere to the following guidelines:
\n\n1.2. REMOVALS AND CANCELLATIONS
\n\n2. STATEMENTS OF CONCERN
\n\nA Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
\n\nIntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\n\n3. CORRECTIONS
\n\nA Correction will be issued by the Academic Editor when:
\n\n3.1. ERRATUM
\n\nAn Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
\n\nA published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n3.2. CORRIGENDUM
\n\nA Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n4. FINAL REMARKS
\n\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\n\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\n\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
\n\nAny suggestions or comments on this Policy are welcome and may be sent to permissions@intechopen.com.
\n\nPolicy last updated: 2017-09-11
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After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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He obtained a Master’s degree in Public Health and PhD in Public Health and Epidemiology. He has a background in Clinical Medicine and has taken courses at higher diploma levels in public health from University of Transkei, Republic of South Africa, and African Medical and Research Foundation (AMREF) in Nairobi, Kenya. Dr. Kasenga worked in different places in and outside Malawi, and has held various positions, such as Licensed Medical Officer, HIV/AIDS Programme Officer, HIV/AIDS resource person in the International Department of Diakonhjemet College, Oslo, Norway. He also managed an Integrated HIV/AIDS Prevention programme for over 5 years. He is currently working as a Director for the Health Ministries Department of Malawi Union of the Seventh Day Adventist Church. Dr. Kasenga has published over 5 articles on HIV/AIDS issues focusing on Prevention of Mother to Child Transmission of HIV (PMTCT), including a book chapter on HIV testing counseling (currently in press). 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His research interest focuses on computational chemistry and molecular modeling of diverse systems of pharmacological, food, and alternative energy interests by resorting to DFT and Conceptual DFT. He has authored a coauthored more than 255 peer-reviewed papers, 32 book chapters, and 2 edited books. He has delivered speeches at many international and domestic conferences. He serves as a reviewer for more than eighty international journals, books, and research proposals as well as an editor for special issues of renowned scientific journals.",institutionString:"Centro de Investigación en Materiales Avanzados",institution:{name:"Centro de Investigación en Materiales Avanzados",country:{name:"Mexico"}}},{id:"76477",title:"Prof.",name:"Mirza",middleName:null,surname:"Hasanuzzaman",slug:"mirza-hasanuzzaman",fullName:"Mirza Hasanuzzaman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/76477/images/system/76477.png",biography:"Dr. Mirza Hasanuzzaman is a Professor of Agronomy at Sher-e-Bangla Agricultural University, Bangladesh. He received his Ph.D. in Plant Stress Physiology and Antioxidant Metabolism from Ehime University, Japan, with a scholarship from the Japanese Government (MEXT). Later, he completed his postdoctoral research at the Center of Molecular Biosciences, University of the Ryukyus, Japan, as a recipient of the Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship. He was also the recipient of the Australian Government Endeavour Research Fellowship for postdoctoral research as an adjunct senior researcher at the University of Tasmania, Australia. Dr. Hasanuzzaman’s current work is focused on the physiological and molecular mechanisms of environmental stress tolerance. Dr. Hasanuzzaman has published more than 150 articles in peer-reviewed journals. He has edited ten books and written more than forty book chapters on important aspects of plant physiology, plant stress tolerance, and crop production. According to Scopus, Dr. Hasanuzzaman’s publications have received more than 10,500 citations with an h-index of 53. He has been named a Highly Cited Researcher by Clarivate. He is an editor and reviewer for more than fifty peer-reviewed international journals and was a recipient of the “Publons Peer Review Award” in 2017, 2018, and 2019. He has been honored by different authorities for his outstanding performance in various fields like research and education, and he has received the World Academy of Science Young Scientist Award (2014) and the University Grants Commission (UGC) Award 2018. He is a fellow of the Bangladesh Academy of Sciences (BAS) and the Royal Society of Biology.",institutionString:"Sher-e-Bangla Agricultural University",institution:{name:"Sher-e-Bangla Agricultural University",country:{name:"Bangladesh"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",biography:"Kusal K. Das is a Distinguished Chair Professor of Physiology, Shri B. M. Patil Medical College and Director, Centre for Advanced Medical Research (CAMR), BLDE (Deemed to be University), Vijayapur, Karnataka, India. Dr. Das did his M.S. and Ph.D. in Human Physiology from the University of Calcutta, Kolkata. His area of research is focused on understanding of molecular mechanisms of heavy metal activated low oxygen sensing pathways in vascular pathophysiology. He has invented a new method of estimation of serum vitamin E. His expertise in critical experimental protocols on vascular functions in experimental animals was well documented by his quality of publications. He was a Visiting Professor of Medicine at University of Leeds, United Kingdom (2014-2016) and Tulane University, New Orleans, USA (2017). For his immense contribution in medical research Ministry of Science and Technology, Government of India conferred him 'G.P. Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. degree in chemistry in 2000 and Ph.D. degree in physical chemistry in 2007 from the University of Khartoum, Sudan. He moved to School of Chemistry, Faculty of Science, University of Sydney, Australia in 2009 and joined Dr. Ron Clarke as a postdoctoral fellow where he worked on the interaction of ATP with the phosphoenzyme of the Na+/K+-ATPase and dual mechanisms of allosteric acceleration of the Na+/K+-ATPase by ATP; then he went back to Department of Chemistry, University of Khartoum as an assistant professor, and in 2014 he was promoted as an associate professor. In 2011, he joined the staff of Department of Chemistry at Taif University, Saudi Arabia, where he is currently an assistant professor. His research interests include the following: P-Type ATPase enzyme kinetics and mechanisms, kinetics and mechanisms of redox reactions, autocatalytic reactions, computational enzyme kinetics, allosteric acceleration of P-type ATPases by ATP, exploring of allosteric sites of ATPases, and interaction of ATP with ATPases located in cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. Pakistan Institute of Nuclear Science & Technology (PINSTECH) Islamabad, Punjab Institute of Nuclear Medicine (PINM), Faisalabad and Institute of Nuclear Medicine and Radiology (INOR) Abbottabad are the main collaborating institutes.",institutionString:"Government College University",institution:{name:"Government College University, Faisalabad",country:{name:"Pakistan"}}},{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",country:{name:"Hungary"}}},{id:"277367",title:"M.Sc.",name:"Daniel",middleName:"Martin",surname:"Márquez López",slug:"daniel-marquez-lopez",fullName:"Daniel Márquez López",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/277367/images/7909_n.jpg",biography:"Msc Daniel Martin Márquez López has a bachelor degree in Industrial Chemical Engineering, a Master of science degree in the same área and he is a PhD candidate for the Instituto Politécnico Nacional. His Works are realted to the Green chemistry field, biolubricants, biodiesel, transesterification reactions for biodiesel production and the manipulation of oils for therapeutic purposes.",institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",country:{name:"Argentina"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",biography:"Francisco Javier Martín-Romero (Javier) is a Professor of Biochemistry and Molecular Biology at the University of Extremadura, Spain. He is also a group leader at the Biomarkers Institute of Molecular Pathology. Javier received his Ph.D. in 1998 in Biochemistry and Biophysics. At the National Cancer Institute (National Institute of Health, Bethesda, MD) he worked as a research associate on the molecular biology of selenium and its role in health and disease. After postdoctoral collaborations with Carlos Gutierrez-Merino (University of Extremadura, Spain) and Dario Alessi (University of Dundee, UK), he established his own laboratory in 2008. The interest of Javier's lab is the study of cell signaling with a special focus on Ca2+ signaling, and how Ca2+ transport modulates the cytoskeleton, migration, differentiation, cell death, etc. He is especially interested in the study of Ca2+ channels, and the role of STIM1 in the initiation of pathological events.",institutionString:null,institution:{name:"University of Extremadura",country:{name:"Spain"}}},{id:"217323",title:"Prof.",name:"Guang-Jer",middleName:null,surname:"Wu",slug:"guang-jer-wu",fullName:"Guang-Jer Wu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217323/images/8027_n.jpg",biography:null,institutionString:null,institution:null},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/148546/images/4640_n.jpg",biography:null,institutionString:null,institution:null},{id:"272889",title:"Dr.",name:"Narendra",middleName:null,surname:"Maddu",slug:"narendra-maddu",fullName:"Narendra Maddu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272889/images/10758_n.jpg",biography:null,institutionString:null,institution:null},{id:"242491",title:"Prof.",name:"Angelica",middleName:null,surname:"Rueda",slug:"angelica-rueda",fullName:"Angelica Rueda",position:"Investigador Cinvestav 3B",profilePictureURL:"https://mts.intechopen.com/storage/users/242491/images/6765_n.jpg",biography:null,institutionString:null,institution:null},{id:"88631",title:"Dr.",name:"Ivan",middleName:null,surname:"Petyaev",slug:"ivan-petyaev",fullName:"Ivan Petyaev",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Lycotec (United Kingdom)",country:{name:"United Kingdom"}}},{id:"423869",title:"Ms.",name:"Smita",middleName:null,surname:"Rai",slug:"smita-rai",fullName:"Smita Rai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424024",title:"Prof.",name:"Swati",middleName:null,surname:"Sharma",slug:"swati-sharma",fullName:"Swati Sharma",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"439112",title:"MSc.",name:"Touseef",middleName:null,surname:"Fatima",slug:"touseef-fatima",fullName:"Touseef Fatima",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424836",title:"Dr.",name:"Orsolya",middleName:null,surname:"Borsai",slug:"orsolya-borsai",fullName:"Orsolya Borsai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",country:{name:"Romania"}}},{id:"422262",title:"Ph.D.",name:"Paola Andrea",middleName:null,surname:"Palmeros-Suárez",slug:"paola-andrea-palmeros-suarez",fullName:"Paola Andrea Palmeros-Suárez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Guadalajara",country:{name:"Mexico"}}}]}},subseries:{item:{id:"12",type:"subseries",title:"Human Physiology",keywords:"Anatomy, Cells, Organs, Systems, Homeostasis, Functions",scope:"Human physiology is the scientific exploration of the various functions (physical, biochemical, and mechanical properties) of humans, their organs, and their constituent cells. The endocrine and nervous systems play important roles in maintaining homeostasis in the human body. Integration, which is the biological basis of physiology, is achieved through communication between the many overlapping functions of the human body's systems, which takes place through electrical and chemical means. Much of the basis of our knowledge of human physiology has been provided by animal experiments. Because of the close relationship between structure and function, studies in human physiology and anatomy seek to understand the mechanisms that help the human body function. The series on human physiology deals with the various mechanisms of interaction between the various organs, nerves, and cells in the human body.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11408,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. His interest later turned to the molecular mechanism and attenuating strategy of sarcopenia (age-related muscle atrophy). His opinion is to attenuate sarcopenia by improving autophagic defects using nutrient- and pharmaceutical-based treatments.",institutionString:null,institution:{name:"Tokyo Institute of Technology",institutionURL:null,country:{name:"Japan"}}},editorTwo:null,editorThree:{id:"331519",title:"Dr.",name:"Kotomi",middleName:null,surname:"Sakai",slug:"kotomi-sakai",fullName:"Kotomi Sakai",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000031QtFXQA0/Profile_Picture_1637053227318",biography:"Senior researcher Kotomi Sakai, Ph.D., MPH, works at the Research Organization of Science and Technology in Ritsumeikan University. She is a researcher in the geriatric rehabilitation and public health field. She received Ph.D. from Nihon University and MPH from St.Luke’s International University. Her main research interest is sarcopenia in older adults, especially its association with nutritional status. Additionally, to understand how to maintain and improve physical function in older adults, to conduct studies about the mechanism of sarcopenia and determine when possible interventions are needed.",institutionString:null,institution:{name:"Ritsumeikan University",institutionURL:null,country:{name:"Japan"}}},series:{id:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261"},editorialBoard:[{id:"213786",title:"Dr.",name:"Henrique P.",middleName:null,surname:"Neiva",slug:"henrique-p.-neiva",fullName:"Henrique P. 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