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These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
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IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\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:"440",leadTitle:null,fullTitle:"Speech and Language Technologies",title:"Speech and Language Technologies",subtitle:null,reviewType:"peer-reviewed",abstract:"This book addresses state-of-the-art systems and achievements in various topics in the research field of speech and language technologies. 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\r\n\tThe ultimate goal of many fields of neuroscience research is to harness the ability of the mammalian brain to reorganize. The ability to control cortical reorganization in the adult cortex, either by controlling existing adult mechanisms for plasticity or by reactivating mechanisms of developmental plasticity, would be a tremendous advancement in the treatment of cortical damage and neurodegenerative diseases. Consequently, the specifics of the timing and types of reorganization possible in the mammalian visual cortex, in particular, have consistently generated tremendous interest in both the scientific community and the general public. Few sources, however, provide a combined look into the plasticity of the visual cortex in both juvenile and adult mammalian brains.
\r\n\r\n\tWhile it is clear that visual representations in the mammalian cortex can undergo significant reorganization during an early critical period of development, the extent of reorganization possible in the developing visual cortex is still an area of active investigation. This dynamic nature of cortical circuitry is important for learning, as well as for repair following nervous system injury. Similarly, several aspects of the visual cortex are thought to remain plastic into adulthood, allowing cortical sensorimotor maps to be modified continuously by experience. Because studies of the extent of cortical reorganization in the adult mammalian visual cortex have at times produced quite disparate results, many pioneering studies are now attempting to address these controversial measurements.
\r\n\r\n\tThis proposed book topic will examine our current understanding of the interplay of plasticity and stability in the developing and adult mammalian visual systems as well as our progress towards translating these fundamental research findings into updates for clinical practice.
\r\n\t
For the treatment of diabetes mellitus, dietary intervention is one of the most important basic approaches along with exercise therapy. Since dietary guidance for diabetes is often based on limiting caloric intake, it is important to understand the effects of fasting and caloric restriction on systemic metabolism. Furthermore, the effects of the Mediterranean diet and the pros and cons of carbohydrate-restricted diets have recently attracted attention, and it is now widely recognized that the proportion of certain nutrients in the diet and the order in which they are eaten can affect nutrient absorption and systemic metabolism. In countries where excessive food supply has caused obesity and the associated diseases, many people have adopted fasting and caloric restriction for weight control. Academic studies have shown that moderate caloric restriction has a positive effect on those diseases and contributes to longevity through anti-aging effects and prevention of age-related diseases. However, given that excessive fasting or caloric restriction can lead to malnutrition, it is important to accurately understand the effects on systemic metabolism.
During fasting, carbohydrates, fats, and proteins are utilized as energy sources in many organs. However, since the brain cannot directly utilize fatty acids derived from lipolysis, the insight into energy metabolism in the brain is essential to understand the systemic metabolism during fasting. In the early stages of fasting, glucose is provided to the brain by glycogenolysis (Figure 1A). In the case of prolonged fasting, gluconeogenesis is activated in the liver to produce glucose from pyruvate and lactate, as well as from glycerol produced by lipolysis and from amino acids produced by proteolysis (Figure 1B) [1]. When fasting is further prolonged, glucose is supplied by renal gluconeogenesis, and ketone bodies produced by fatty acid oxidation (or β-oxidation), and acetate are used as energy sources for the brain and skeletal muscles (Figure 1A) [2, 3]. Thus, brain activity is maintained by glucose and ketone bodies from the multiple sources. Of note, most of gluconeogenesis takes place in the liver and to a lesser extent in the proximal tubules of the kidney, and ketone bodies are mainly produced in the liver.
The brain energy sources under the fasting condition. A. Energy sources for the brain, B. Energy sources for gluconeogenesis.
It has long been known that fasting and caloric restriction are associated with an extended lifespan in many organisms. Longevity is regulated by several factors such as mechanistic target of rapamycin (mTOR), sirtuins (SIRTs), AMP-activated protein kinase (AMPK), forkhead box protein O (FOXO), and growth hormone (GH)/insulin-like growth factor-1 (IGF-1), but the mechanism by which these factors extend lifespan in humans is not yet fully understood. One possible hypothesis is that fasting and caloric restriction are memorized in the epigenome of cells. More specifically, metabolites produced during fasting serve as inhibitors or substrates of epigenetic enzymes. For example, ketone bodies mainly inhibit class I histone deacetylases (HDACs) to promote histone acetylation. In addition, acetyl-CoA, produced by fatty acid oxidation, and α-ketoglutarate (α-KG, also known as 2-oxoglutarate), an intermediate metabolite of the tricarboxylic acid (TCA) cycle (also known as the citric acid cycle or the Krebs cycle), are substrates for histone acetyltransferases and epigenetic demethylases, respectively. Thus, the states of energy metabolism, including fasting, are recorded in cells as epigenomic memories, which may cause the development of future diseases.
Under normal metabolic conditions, some of the excess glucose is stored as glycogen, mainly in the liver and muscles, and further excess energy is stored as fat mainly in the adipose tissue. Fat in the body consists of triglycerides (TGs), which are transported to the adipose tissue in the form of chylomicrons from the intestine, and also produced from excess glucose in the adipose tissue and the liver. Under the feeding conditions, glucose is metabolized mainly in adipocytes and hepatocytes via glycolysis to produce pyruvate, which is then converted to acetyl-CoA and combined with oxaloacetate to enter the TCA cycle as citrate in mitochondria. Excess citrate is transported to the cytoplasm and converted to acetyl-CoA, which is then used as a substrate for fatty acids synthesis via malonyl CoA produced by the rate-limiting enzyme, acetyl-CoA carboxylase. Fatty acids are esterified with glycerol to produce triglycerides and stored in the adipose tissue.
The liver, muscles, adipose tissues, and brain are all closely involved in energy metabolism and are important organs for understanding whole body metabolism in the fasting state. The brain cannot directly utilize fat because it is not capable of fatty acid oxidation unlike many other organs. Therefore, during prolonged fasting, glucose is supplied to the brain from multiple sources to maintain its functions. In addition, ketone bodies are produced as an energy source for the brain during extremely long fasting. The reason why the brain is unable to oxidize fatty acids remains controversial, but it is thought to be because fatty acids cannot cross the blood–brain barrier and the brain does not have the enzymes necessary for β-oxidation.
In the normal state of energy metabolism under feeding conditions, dietary sugar is commonly used as an energy source in all organs. Glucose is oxidized via glycolysis to eventually yield two molecules of pyruvate. In the presence of oxygen, pyruvate enters the TCA cycle, and it is completely oxidized to produce six molecules of carbon dioxide. At this step, NAD+ and FAD are reduced to produce NADH and FADH2, respectively, and are transported to the respiratory chain of mitochondria to produce energy in the form of ATP.
In the early stage of fasting, stored glycogen, a branched polymer of glucose, is degraded to provide glucose via glucose 6-phosphate (Figure 2). Glycogen-derived glucose is used for energy supply by the glycolytic pathway and the TCA cycle in most of organs except the liver, muscles, and adipose tissue. However, the amount of energy stored as glycogen is consumed in a day of fasting, and hepatic glycogen is almost completely depleted after two to three days of starvation. The degradation of glycogen proceeds as phosphorylase sequentially removes glucose monomers by cleaving the α-(1 → 4) bond in a phosphate-dependent manner. At the branched end of glycogen, when degradation proceeds to four glucose residues near the α-(1 → 6) bond, three glucose molecules at the branching end are transferred to the other chain end by a group of glycogen debranching enzymes. The remaining glucose molecules are then hydrolyzed to remove them, and further degradation by phosphorylases continues. The glucose 1-phosphate produced by phosphorylase is converted to glucose 6-phosphate by phosphoglucomutase and enters the glycolytic pathway (Figure 2). Glucose 6-phosphate is converted to glucose by the action of glucose 6-phosphatase (G6Pase) in the liver, and then released into the bloodstream via Glut2 to supply glucose to the brain and other organs. On the other hand, G6Pase is not expressed in the muscles, so stored glycogen is used only for local energy production.
Gluconeogenesis under the fasting condition.
During fasting, TGs in the adipose tissue are also degraded and used for fatty acid oxidation (Figures 2 and 3). TGs are broken down into fatty acids and glycerol by hormone-sensitive lipase (HSL) and a rate-limiting enzyme, adipose triglyceride lipase (ATGL). Fatty acids are bound to albumin and transported to the liver and muscles, where they are taken up by facilitated transport for fatty acid oxidation. Long-chain fatty acids taken up by the cells pass through the mitochondrial membrane to the matrix. Fatty acids are converted to acyl-CoA by acyl-CoA synthase and then conjugated with carnitine to form acyl-carnitine by carnitine palmitoyltransferase (CPT1) on mitochondrial outer membrane (CPT1a: mainly in the liver, CPT1b: mainly in the skeletal muscle and brown fat) and pass through mitochondrial inner membrane to the matrix via carnitine-acylcarnitine translocase (CACT). Fatty acids are then released from carnitine through the action of CPT2 on mitochondrial inner membrane (Figure 3). In mitochondrial matrix, fatty acids are continuously oxidized via FAD-dependent acyl-CoA dehydrogenase to produce FADH2, NADH+H+, and acetyl-CoA (Figure 3). Although fatty acid-derived acetyl-CoA enters the TCA cycle for energy production, it does not contribute to gluconeogenesis because two carbon atoms derived from the acetyl-CoA are removed in the TCA cycle. In contrast, the glycerol produced by lipolysis can be used as a substrate for gluconeogenesis (Figure 2).
Lipid metabolism and ketone body production during fasting.
When fasting persists, glucose is supplied to multiple organs via gluconeogenesis in the liver. Gluconeogenesis is particularly important to provide glucose as an energy source for the brain, which is unable to oxidize fatty acids. In the liver, gluconeogenesis is carried out from amino acids, pyruvate, lactate, glycerol, and ketone bodies (Figures 1B and 2). During several weeks of starvation, about 80 grams of glucose is produced daily via gluconeogenesis, of which 15–20 grams is derived from amino acids, mainly alanine, 35–40 grams from pyruvate and lactate, 20 grams from glycerol from fat, and 10 grams from ketone bodies [1]. Amino acids are supplied by degradation of proteins in the muscles during fasting. Alanine is transported to the liver via the bloodstream, and is then converted to pyruvate for gluconeogenesis (Figure 2). Pyruvate is metabolized to oxaloacetate by pyruvate carboxylase (PC) and then decarboxylated by phosphoenolpyruvate carboxykinase (PEPCK) to produce phosphoenolpyruvate (PEP) (Figure 2). PEP is an intermediate product of the glycolytic pathway, and the following gluconeogenic process utilizes the glycolytic enzymes except for the step of fructose-1,6-bisphosphate to fructose-6-phosphate which requires fructose-1,6-bisphosphatase [4] and the step of glucose-6-phosphate to glucose mediated by G6Pase. Lactic acid is converted to pyruvate by lactate dehydrogenase (LDH) for gluconeogenesis (Figure 2). Glycerol is phosphorylated by glycerol kinase in the liver to produce glycerol 3-phosphate, which is then oxidized by glycerol 3-phosphate dehydrogenase (G3PDH) to dihydroxyacetone phosphate, an intermediate of the glycolytic pathway. Dihydroxyacetone phosphate undergoes gluconeogenesis via glyceraldehyde 3-phosphate or fructose 1,6-diphosphate (Figure 2). Furthermore, under long-term starvation for several days or a week where water, vitamins, salt, and other minerals are supplied, glucose production occurs not only in the liver but also in the renal cortex, which is responsible for about 40% of total body glucose production [1].
Gluconeogenesis is tightly regulated by the products of fatty acid oxidation such as NADH+H+, acetyl-CoA, and ATP (Figure 4). In normal glucose metabolism, pyruvate enters the TCA cycle via acetyl-CoA by the action of pyruvate dehydrogenase (PDH). However, during fasting, pyruvate is converted to oxaloacetate by PC for gluconeogenesis as described above (Figure 4). The activity of PC is stimulated by acetyl-CoA. In addition, NADH+H+, acetyl-CoA, and ATP inhibit PDH activity (Figure 4). Furthermore, NADH+H+ inhibits isocitrate dehydrogenase (IDH), one of the enzymes responsible for the TCA cycle (Figure 4). Thus, NADH+H+, acetyl-CoA, and ATP, which are generated by fatty acid oxidation, regulate the activities of enzymes in the gluconeogenesis pathway, and these regulatory mechanisms ensure a consistent flow of metabolites for energy supply through gluconeogenesis and fatty acid oxidation during fasting. Since PEP produced by PEPCK is an intermediate product of the glycolytic pathway, it could theoretically be converted to pyruvate and re-enter the TCA cycle. However, because pyruvate kinase (PK) in the liver is inhibited by alanine and inactivated by protein kinase A (PKA), which is activated by glucagon, PEP produced during fasting is used for gluconeogenesis but not glycolysis. In other words, gluconeogenesis and amino acid metabolism are consistently regulated under fasting conditions. In addition, nitrogen sources stored in the muscles are used for gluconeogenesis in the renal cortex under prolonged fasting. Glutamine and alanine are metabolized from branched-chain amino acids such as leucine, isoleucine, and valine in the muscles, and released into the bloodstream. Glutamine is then primarily used for gluconeogenesis via the TCA cycle in the renal cortex. This indicates that diet therapies that focus primarily on fasting result not only in burning of stored fat but also loss of muscle mass.
Fatty acid oxidation and gluconeogenesis during fasting.
Under glucose-depleted conditions during fasting, the brain and muscles use ketone bodies and acetate as energy sources other than glucose (Figure 1B) [3, 5]. These energy sources are critical to sustain function of the brain because it cannot directly metabolize fatty acids. A human study investigated the energy sources of the brain under long-term starvation for 5–6 weeks. When only water, vitamins, and minerals such as salt are supplied, urinary nitrogen excretion, an indicator of amino acid-derived gluconeogenesis, dropped to about 4–5 grams per day, and two-thirds of the energy source of the brain comes from β-hydroxybutyrate and acetoacetate [1].
The metabolic systems that use ketone bodies as an energy source can be traced back to bacteria, archaea, and protozoa. In humans, most ketone bodies are produced in the liver. During fasting, the most part of acetyl-CoA produced by fatty acid oxidation is used for ketone body production, while only the limited amount enters the TCA cycle (Figure 3). At the first step of the TCA cycle, acetyl-CoA is conjugated to oxaloacetate through the action of citrate synthase to produce citrate. However, oxaloacetate is relatively scarce during fasting because it is consumed by glucose production. As a result, excess acetyl-CoA produced by fatty acid oxidation is used exclusively for ketone body production. In addition, NADH+H+, acetyl-CoA, and ATP, which are produced by fatty acid oxidation, regulate gluconeogenesis-related enzymes to stimulate gluconeogenesis. In addition, NADH+H+ suppresses the activity of IDH in the TCA cycle, which in turn suppresses the TCA cycle and directs fatty acid-derived acetyl-CoA toward ketone body production.
Ketone bodies are produced in mitochondria in the following reactions: two molecules of acetyl-CoA are combined by acetoacetyl-CoA thiolase to produce acetoacetyl-CoA, and an additional molecule of acetyl-CoA is conjugated by HMG-CoA synthase 2 (HMGCS2) to produce HMG-CoA, which is then cleaved by lyase to form acetoacetate (Figures 3 and 5). Acetoacetate can be converted to acetone through spontaneous non-enzymatic decarboxylation or to β-hydroxybutyrate (D-3-hydroxybutyrate) by 3-hydroxybutyrate dehydrogenase (BDH1) (Figure 3). β-Hydroxybutyrate is the most abundant ketone body in the blood. Here, the irreversible reaction by HMGCS2 is a key reaction for ketone body production, and the activity of BDH1 is increased by NADH+H+.
Production and utilization of ketone bodies.
The basal level of β-hydroxybutyrate in humans is at the level of a few μM under feeding conditions, and the blood concentration increases to 200–300 μM after 12–16 hours of fasting, 1–2 mM after 2 days of fasting, and as high as 6–8 mM after prolonged fasting [6]. Ketone bodies also reach more than 2 mM with a ketogenic diet that excludes most carbohydrates, and intense exercise for about 90 minutes also increases ketone bodies to 1–2 mM. In neonates, the production and utilization of ketone bodies are more efficient than adults. The serum concentration of ketone bodies is as high as 2–3 mM just after birth, and the neonatal brain uses ketone bodies as an important energy source.
Ketone bodies are produced by the liver and supplied to the brain, muscles, and kidneys during fasting, but the liver cannot utilize ketone bodies as an energy source because it does not express 3-keto acid CoA transferase (OXCT1/SCOT). β-Hydroxybutyrate is produced in the liver and released into the bloodstream via monocarboxylic acid transporter 7 (MCT7/SLC16A6) (Figure 5) [6]. During prolonged fasting, the high concentration of β-hydroxybutyrate in the blood is taken up by the brain through the blood–brain barrier via several monocarboxylic acid transporters, including MCT1 and MCT2 (Figure 5). Once taken up into neurons, β-hydroxybutyrate reverses the ketone body production pathway to produce acetoacetate by BDH1 and further converts to acetoacetyl-CoA by OXCT1/SCOT. The activity of BDH1 is promoted by NADH+H+ produced during fatty acid oxidation (Figures 3 and 5). In addition, the reaction of OXCT1/SCOT is the rate-limiting step to produce acetoacetyl-CoA, which is accompanied by the production of an intermediate metabolite of the TCA cycle, succinate, in a succinyl CoA-dependent manner (Figure 5).
In addition, acetate is also utilized as an energy source during prolonged fasting. In the liver, acetate is produced from acetyl-CoA by the action of acetyl-CoA hydroxylase during fasting, and is released from the liver to other organs. Acetate is utilized as an energy source for acetyl-CoA production via type 2 acetyl-CoA synthase (AceCS2), which is particularly abundant in mitochondria of the muscles [2].
HMGCS2 is a key enzyme for the regulation of ketone body production. The expression of HMGCS2 is strongly regulated by forkhead box protein A2 (FOXA2), peroxisome proliferators-activated receptor α (PPARα), fibroblast growth factor 21 (FGF21), and mTOR, and its activity is enhanced through deacetylation by sirtuin 3 (SIRT3) [6]. FOXA2 binds directly to the promoter region of HMGCS2 and activates its transcription. The expression of FOXA2 is regulated by insulin and glucagon. Insulin-mediated phosphorylation inactivates FOXA2 by translocating it out of the nucleus, while glucagon activates FOXA2 through p300-mediated acetylation, thereby contributing to ketone body production. FOXA2 deacetylation is also regulated by class I and class II HDACs and SIRT1, a class III HDAC. In addition, mTORC1 complex is known to suppress PPARα, and rapamycin promotes ketone body production by inhibiting mTORC1 complex.
PPARα is a nuclear receptor expressed in the liver, kidney, heart, and brown adipose tissue, which is activated by long-chain fatty acids and involved in fatty acid metabolism (Figure 6). PPARα forms a heterodimer with retinol X receptor (RXR) and regulates transcription by binding to the response sequence called PPAR response element (PPRE) in the gene regulatory regions. In the liver, PPARα promotes the expressions of a variety of genes related to β-oxidation, including FGF21, HMGCS2, CPT1a, and acyl-CoA oxidase (ACOX), which is the rate-limiting enzyme for peroxisomal β-oxidation (Figure 6).
Regulation of energy metabolism by FGF21.
FGF21, a target gene of PPARα, is a member of the FGF family, with 22 members in humans, and belongs to the same subfamily as FGF15/19 and FGF23 [7, 8]. FGFs in this subfamily characteristically function as hormones. FGF21 is expressed in the liver, adipose tissue, skeletal muscle, and pancreas, and the liver mainly secretes FGF21 as a hormone [9]. The expression of FGF21 is enhanced by fasting and ketogenic (or high-fat) diets [7, 10]. FGF21 levels in infants are higher than fasting FGF21 levels in adults, which is thought to be induced by milk-derived free fatty acids. In addition to PPARα, glucocorticoid receptors, activating transcription factor 4 (ATF4), cAMP response element binding protein H (CREBH), carbohydrate response element binding protein (ChREBP), PPARγ, farnesoid X receptor (FXR), and activin B induce the expression of FGF21 in the liver [11], while liver X receptor (LXR) inhibits the expression [12]. In the skeletal muscles, FGF21 is expressed through ATF4 under specific conditions such as metabolic stresses in mitochondria, and is also regulated by the phosphatidylinositol-3 kinase (PI3K) and Akt signals [12].
FGF21 plays an important role in the regulation of systemic energy metabolism during fasting. In the white adipose tissue, FGF21 induces lipolysis by enhancing the transcription of HSL and ATGL [7]. Free fatty acids produced by lipolysis promote fatty acid oxidation and the protein expression of HMGCS2, which induces the production of ketone bodies (Figure 6). FGF21 also enhances the expression of lipolytic enzymes in the liver, suppresses glycogenolysis, and promotes gluconeogenesis, but does not significantly affect glycolysis. FGF21 binds to the FGF receptor (FGFR) and its co-factor β-Klotho on the plasma membrane of target cells, and regulates transcription and translation of the target genes via phosphorylation cascades. FGF21 also regulates glucose metabolism in the liver partially via peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), which acts as a co-activator of transcriptional regulators and induces gene expression related to gluconeogenesis, fatty acid oxidation, and ketone body production during fasting [13]. In rodent models, pharmacological concentrations of FGF21 promote glucose uptake in adipocytes, increase insulin sensitivity, reduce blood triglyceride and hepatic fat, and suppress weight gain on a high-fat diet. In addition, it induces the expression of Glut1 in adipocytes [14], increases the number of pancreatic islets and the content of insulin per islet [15], and reduces blood glucagon levels by suppressing glucagon secretion [14]. In diabetic monkeys, FGF21 lowers blood glucose, serum insulin, triglyceride, and low density lipoprotein (LDL) cholesterol levels, increases high density lipoprotein (HDL) cholesterol levels in the blood, and induces weight loss without inducing hypoglycemia [16]. Human blood FGF21 levels were shown to be elevated in individuals with obesity, type 2 diabetes, and insulin resistance. It is also reported that blood FGF21 levels in hyperlipidemic patients are twice as high as in the normal group, and that administration of fibrate, a PPARα ligand, increases blood FGF21 levels. In addition, FGF21 levels in humans are increased by prolonged fasting for 7 days [17]. Thus, even under feeding conditions, FGF21 induces a fasting-like metabolic states, such as gluconeogenesis, fatty acid oxidation, and ketone body production (Figure 6) [12].
Living organisms suppress GH and reproductive signals to reduce unnecessary energy consumption during fasting. Mice with excess FGF21 show reduced response to GH and suppressed reproductive signals (Figure 6) [18, 19]. In detail, FGF21 transgenic mice show reduced phosphorylation of signal transducer and activator of transcription 5 (STAT5) downstream of Janus kinase (JAK) 2 in response to GH in the liver and reduced blood IGF-1 levels [18]. In addition, FGF21 transgenic female mice have a suppressed luteinizing hormone (LH) surge due to inhibition of vasopressin signals in the hypothalamus [19]. The latest statistical analysis, which excluded the contribution of insulin resistance and body fat percentage, showed elevated blood FGF21 levels in human anorexia [20], suggesting that FGF21 may be involved in impaired GH signaling in anorexic patients. In addition, FGF21 plays a role in energy conservation by inducing a hibernation-like state (torpor) in mice [7]. During mouse torpor and squirrel hibernation, in addition to hypothermia and hypoactivity, it is known that pancreatic lipase is ectopically induced outside the pancreas and FGF21 induces the ectopic expression in the liver [7, 21]. The pancreatic lipase is capable of hydrolyzing TGs into glycerol and fatty acids over a wide temperature range, and thus may provide fatty acids as an energy source during torpor and hibernation.
Furthermore, FGF21 transgenic mice exhibit a long lifespan (Figure 6) [22]. It is reported that the median lifespan of wild-type mice was 28 months, while that of FGF21 transgenic mice was 38 months. Interestingly, the longevity of the FGF21 transgenic mice did not require restriction of food intake, and insulin sensitivity was maintained even when food intake was increased. This suggests that FGF21 increases lifespan by shifting systemic metabolism to a fasting-like state regardless of changes in food intake. These phenotypes are attributed to the suppression of GH/IGF-1 signaling accompanied by decreased IGF-1 production, but do not involve mTOR signaling, AMPK signaling, and NAD+ metabolism. In the signaling of the endocrine FGF subfamily (FGF15/19, FGF21, and FGF23), β-Klotho on the plasma membrane is required for FGF15/19 and FGF21, and α-Klotho for FGF23. α-Klotho was originally reported as a longevity gene [23], and it inhibits insulin/IGF-1 signaling by its truncated extracellular region circulating in the bloodstream. Thus, it is possible that α-Klotho causes longevity through a similar mechanism to FGF21, but α-Klotho is different from FGF21 in that it causes insulin resistance [22]. FGF21 also decreases preference for sweetness and alcohol via the central nervous system [24, 25, 26, 27], which may contribute to the regulation of eating behavior in response to the energy states.
Low blood insulin levels play an important role in the regulation of energy metabolism during fasting. Insulin activates PI3K through phosphorylation of insulin receptor substrate (IRS), and subsequent activation of Akt leads to phosphorylation and translocation of FOXO1 out of the nucleus, resulting in the suppression of the expression of ATGL, the rate-limiting enzyme in lipolysis. In addition, insulin signaling phosphorylates FOXA2 and excludes it from the nucleus, thereby suppressing the expression of HMGCS2, the rate-limiting enzyme for ketone body production. Therefore, the decrease in insulin signaling during fasting is involved in the expression of ATGL, gluconeogenesis-related genes, and ketone body production-related genes. Fasting also regulates the expression of IRSs and the PI3K activity. The expression of IRS-2 and the PI3K activity are elevated during fasting and decrease immediately after food intake in the liver [28]. In this context, IRS-2 appears to act for a short time after food intake so that it can respond again to the next coming dietary stimuli, whereas the expression of IRS-1 is relatively constant regardless of feeding conditions [28]. Therefore, it is considered that while both IRS-1 and IRS-2 are involved in inhibition of gluconeogenesis immediately after food intake, IRS-1 is mainly involved in glycogen production that is initiated at an interval after that. IRS-1 and IRS-2 differ not only in their expression patterns but also in their functions. IRS-1 deficient mice do not show strong diabetic symptoms, because IRS-2 can compensate for glucose intolerance by promoting the proliferation of pancreatic β cells [29]. The increased transcription of the IRS-2 gene during fasting and its repression after refeeding are regulated by the glucagon receptor-PKA-CREB-regulated transcription coactivator 2 (CRTC2)-CREB pathway and the insulin receptor signaling in the liver, while the regulation mechanism in other tissues remains unclear [30]. Refeeding induces insulin binding to the insulin receptor and downstream PI3K activation, which represses IRS-2 transcription via FOXO1 phosphorylation by Akt.
During fasting, glucagon is secreted from pancreatic α cells in response to hypoglycemia and stimulates glucose production in the liver through gluconeogenesis and glycogenolysis. The glucagon receptor-cAMP-PKA pathway promotes gluconeogenesis by inducing the expression of the catalytic subunits of G6Pase and PEPCK in the liver. PKA-dependent phosphorylation of CREB and dephosphorylation of CRTC2 forms CREB-CRTC2 complex that recruits a histone acetyltransferase, CREB binding protein (CBP) and promotes transcription of the gene encoding PGC-1α. Furthermore, PGC-1α, which is activated by SIRT1-mediated deacetylation and inactivated by general control nonderepressible-5 (GCN5)-mediated acetylation, promotes gluconeogenesis together with FOXO1 and hepatocyte nuclear factor 4α (HNF4α) [30].
Fasting and caloric restriction have received so much attention because of their relationship to longevity. Fasting and caloric restriction to the extent that they do not lead to malnutrition are associated with longevity from nematodes to vertebrates, and are effective against aging and age-related diseases. For example, it has already been known for 80 years that restricting food intake prolongs lifespan in rats and mice [31]. Studies in monkeys showed that feeding a calorie-restricted diet from a young age inhibits the development of obesity, type 2 diabetes, cardiovascular disease, and cancer, and delays the onset of sarcopenia, senile deafness, and brain atrophy [31]. Although the molecular mechanisms by which caloric restriction maintains health and extends lifespan are not yet fully understood, various factors have been identified to be involved, including FGF21, insulin and IGF-1 signaling, mTOR, AMPK, SIRTs, NAD+, FOXO, heat shock factor (HSF), and nuclear factor-erythroid 2-related factor 2 (NRF2) [31].
FOXO is a DNA-binding transcriptional regulator, which promotes the expression of a group of genes involved in DNA repair, autophagy, antioxidant activity, stress tolerance, and cell proliferation [31]. NRF2 and HSF1 are thought to be involved in the maintenance of protein homeostasis and cell structure through induction of antioxidant and drug-metabolizing enzymes, thus extending lifespan [32].
mTOR, first found in bacteria collected from Easter Island soil, is a serine/threonine kinase that is activated by a variety of factors and regulates a wide range of biological processes. mTOR is activated by insulin and IGF-1 signaling, intracellular nutrients such as amino acids and glucose, and energy states as well as oxygen and stresses to regulate cell proliferation, metabolism, nutrition, and environmental stresses [33]. It was also shown that inhibition of mTOR signaling prolongs lifespan in yeast,
mTORC1 is activated by growth factors such as IGF-1, stresses, energy states, oxygen, and amino acids [33]. mTORC1 promotes ribosome biosynthesis and protein synthesis in the muscles, and inhibits ketone body production in the liver. In addition, it promotes adipocyte differentiation through activation of sterol regulatory element binding protein 1 (SREBP1) and PPARγ, and increases the number and the size of pancreatic β-cells. Furthermore, mTORC1 suppresses autophagy, enhances glycolytic gene expression, and regulates mitochondrial oxidative metabolism. Suppression of mTOR signaling by caloric restriction, methionine-restricted diet, and rapamycin is thought to be involved in longevity, presumably through the complex regulatory mechanisms described above [32].
mTORC2 is activated by insulin, IGF-1, and leptin through PI3K and other pathways, and then phosphorylates Akt, serum- and glucocorticoid-induced protein kinase 1 (SGK1), and protein kinase C (PKC) family members. Akt and SGK1 further phosphorylate FOXO1, which results in nuclear export of FOXO1 and repression of the expression of gluconeogenesis-related genes [32, 33]. Thus, mTORC2 is involved in the regulation of energy metabolism, but its role in longevity is still unclear.
SIRTs are known as “longevity genes,” and forced expression of SIRTs extends lifespan in yeast,
Insulin and IGF-1 signals function as a sensor of nutritional states, and are suppressed by fasting and caloric restriction. During fasting, IGF-1 signaling is repressed by FGF21 as described earlier. On the other hand, the mechanism of suppression of IGF-1 signaling by caloric restriction is complex and may differ among species. In humans, it was reported that protein intake is more important than total caloric intake for the suppression of IGF-1 signaling [31]. Insulin and IGF-1 signals have been shown to be involved in longevity, but its mechanism remains unclear. Genome-wide association studies (GWAS) showed an association between insulin and IGF-1 signaling and human lifespan, and also suggested that Akt, FOXO, PI3K, and SGK signaling pathways are involved in longevity [35]. Treatment of epithelial cells with serum from patients with Laron syndrome, which is characterized by refractoriness to GH, increases the expression of the superoxide dismutase 2 (SOD2) and decreases the expression of mTOR [36]. In addition, FOXO transcription factors are upregulated in the absence of IGF-1 signaling [36]. These studies suggest that insulin and IGF-1 signaling suppresses stress resistance responses. In
The energy states of organisms, such as fasting and caloric restriction, are memorized in cells, and can lead to the development of future diseases. Recently, epigenetic mechanisms have received much attention in the field of metabolism. The epigenome is a mechanism for regulation of gene expression without changing the genome sequence. Due to its high plasticity, epigenetic regulation is suitable for the memory of metabolic states. Such epigenetic regulations include covalent modifications of DNA, histone, and RNA. More than 100 modifications have been identified, among which methylation, phosphorylation, ubiquitination, and acetylation are well studied, while glycosylation, crotonylation, and succinylation, although functional, are poorly understood [37]. These modifications influence spatial chromatin structure and recruitment of transcription factors and enzymes that are involved in chromatin remodeling. A number of studies have revealed that fasting and obesity-associated diseases that induce a fasting-like metabolic state have a functional link to the epigenome.
Accumulating evidence indicates that diet is one of the most important environmental factors that cause epigenetic changes in the growth process of organisms. One striking evidence of dietary effects on early development was found in honey bees [38]. Female honey bees have two distinct phenotypes, and female larvae that receive royal jelly exclusively develop into fertile queen bees while the other females develop into sterile workers. These phenotypic changes are accompanied by differential DNA methylation patterns and gene expressions between queens and workers through DNA methyltransferase 3 (DNMT3). Such epigenetic alterations during development in response to nutritional states are also found in mammals. A well-known example is the nutritional effect on coat color of the mouse by DNA methylation of the Agouti viable yellow (Avy) locus [38]. Insertion of an endogenous retrovirus (ERV) upstream of this gene locus causes constitutive expression of the Agouti gene as the ERV functions as an alternative promoter, resulting in yellow coat color and adult-onset of obesity. The DNA methylation level at the ERV locus increased in offspring but not in the mother in response to gestational intake of compounds related to the methionine cycle including folate. In rats, the locus-specific change in DNA methylation of the Ppara gene was also observed in offspring of the father or mother fed with a low protein diet [38]. It is also reported that feeding high-fat diet to pregnant Japanese macaques led to global hyperacetylation of histone H3 in their offspring [38]. In humans, epidemiological studies developed the important concept of ‘Developmental Origins of Health and Disease’ (DOHaD), which proposes that unfavorable adaptation to nutritional stress at the embryonic stage is a risk for abnormal growth and development and subsequent health disorders later in life [38]. Cohort studies on the Dutch Famine of 1944–1945 revealed that the severe maternal starvation during the peri-conceptional period induced mental and metabolic abnormalities such as obesity and type 2 diabetes along with changes in DNA methylation in the next generation.
Although epigenetic profiles are more prone to be altered by nutritional states during peri-conceptional, gestational, and early postnatal periods, dietary effects on the epigenetic state are also found in adult animals. Several lines of evidence have revealed that overnutrition induces epigenetic changes in adult organs. One study revealed 232 differentially methylated regions (DMRs) on the genomic DNA in the adipose tissue between mice fed a normal chow diet and those fed a high fat diet [39]. Importantly, the DMRs were also found in humans when comparing lean and obese subjects. Histone modifications are also influenced by diet. It is reported that mice fed a high-fat diet show the increased acetylation levels of histone H3K9 and H3K18 in the genomic regions encoding TNFα and CCL2 in the liver [40]. A mass spectrometry-based approach showed that high-fat diet increased the level of di-methylated histone H3K36 (H3K36me2) and other histone modifications in the mouse liver [41]. In human urine-derived podocyte-like cells, palmitate treatment induced sustained activation of FOXO1 even in the presence of insulin, which was accompanied by the increased H3K36me2 level in the promoter region of the FoxO1 gene [42]. The H3K27me3 in the FoxO1 promoter region decreased in the kidney of rat fed a high-fat diet. In addition to the DNA and histone modifications, RNA methylation is an emerging regulatory mechanism of epigenetics/epitranscriptomics. For example, there reported that a high-fat diet enhanced the expression of fat mass and obesity-associated protein (FTO)/alkB homolog 9 (ALKBH9), an RNA demethylase, and suppressed the N6-methyladenosine (m6A) levels in the mouse adipose tissue, which resulted in obesity [43]. The beneficial effects of fasting on health have also attracted attention in the field of epigenetics. Fasting is implicated in histone modifications via ketone body production as described below. In addition, a clinical human study showed that fasting stress increased methylated CpG sites of the Leptin and Adiponectin genes only in the group born with normal body weight but not in the group born with low body weight [44]. Collectively, epigenetic profiles reflect nutritional states not only in the fetus and infants but also in adults.
Although it is not well understood which component in the diets is responsible for epigenetic changes in organisms, it should be noted that the activity of epigenetic enzymes depends on metabolites and co-factors such as metals. These enzymes include acetyltransferases, deacetylases, methyltransferases, and demethylases for DNA, histone, and RNA. In reactions that add or remove epigenetic modifications, these enzymes utilize metabolites derived from metabolic pathways including glycolysis, fatty acid oxidation, the methionine cycle, and the TCA cycle. These metabolic pathways supply metabolites, such as acetyl-CoA, NAD+, S-adenosylmethionine (SAM), and α-KG as substrates to the enzymes (Figure 7). Ferrous iron is also an essential co-factor for epigenetic demethylases. Considering that the kinetic and thermodynamic properties of the interaction between an epigenetic enzyme and a metabolite are in a similar range as the physiological concentrations of metabolites [37], it is possible that dynamic changes in the availability of metabolites and co-factors may affect epigenetic outcomes. Here, we discuss the potential for regulation of epigenetic modifications through metabolites and co-factors.
Metabolite-mediated regulation of epigenetic enzymes. A. Production of substrates and co-factors of epigenetic enzymes in the metabolic process, B. Substrates, co-factors, and inhibitory metabolites of epigenetic enzymes.
HATs, such as CBP/p300, are enzymes that transfer an acetyl group from acetyl-CoA to lysine residues on histone proteins (Figure 7B). Acetyl-CoA is supplied from various nutrients through metabolic pathways such as glycolysis, the TCA cycle, and fatty acid oxidation (Figure 7A). In a study examining which nutrient-derived acetyl-CoA alters histone acetylation, only lipids, among various nutrients, induced direct acetylation of histones via fatty acid oxidation in mammalian cells [45]. Another study showed that the treatment of pancreatic β cells with palmitate increased HAT activity and histone acetylation [44]. However, a mass spectrometry-based study demonstrated that a high-fat diet rather decreased acetyl-CoA levels in the mouse white adipose tissue, which correlated with histone acetylation [45], suggesting that the regulation of histone acetylation by metabolites is more complex in obesity.
Acetyl groups on histones are removed by the action of HDACs. SIRTs (SIRT1–7), a class III HDACs, are NAD+-dependent deacetylases that sense the energy state in cells (Figure 7). They have been shown to be involved in longevity in a variety of species, including yeast,
DNMTs, histone methyltransferases (e.g., enhancer of zeste homolog 2 (EZH2), SET domain-containing methyltransferases (SETs), and mixed-lineage leukemias (MLLs)), and RNA methyltransferase (e.g., methyltransferase like 3 (METTL3) and METTL14) require SAM as a methyl donor for methylation of DNA, histone, and RNA, respectively (Figure 7B). SAM is provided by the methionine cycle from dietary components such as methionine and folate (Figure 7A). Decreased folate levels in the circulation was reported in patients with type 2 diabetes, and the folate levels were correlated with DNA methylation levels in the liver [44]. Additionally, administration of folate to mice fed a high-fat diet altered the DNA methylation patterns of genes in the adipose tissue and improved obesity-associated phenotype [44].
Among epigenetic demethylases, DNA demethylases (ten-eleven translocation methylcytosine dioxygenases (TETs)), histone lysine demethylases with a JmjC domain (e.g., KDMs), and RNA demethylases (ALKBH5 and FTO/ALKBH9 require oxygen and α-KG as substrates and ferrous iron as a cofactor (Figure 7B). α-KG is an intermediate metabolite of the TCA cycle and is also supplied by a flux of amino acids such as glutamate (Figure 7A), while ferrous iron is taken up from outside the cell via transferrin receptors or supplied internally by ferritin-selective autophagy [47]. Interestingly, these demethylases are classified into the 2-oxoglutarate-dependent dioxygenase (2OGD) family, and the structure of their catalytic domain is highly conserved among all the enzymes [48]. Notably, the iron-binding site of the enzymes is composed of a highly conserved amino acid sequence, that is, histidine, and aspartate or glutamate located two amino acids away from the histidine, followed by histidine located around a hundred amino acids away from the two amino acids (HXD/G…H). A ferrous iron molecule bound to these amino acids serve as a catalytic center of the demethylase, which oxidizes the methyl group of the substrates and removes the methyl group from DNA, histone, and RNA. Several studies suggested that both α-KG and iron are critical regulators of 2OGDs. α-KG has been shown to increase during adipocyte differentiation and to promote differentiation through demethylation of H3K9 at the Pparg locus [49]. Similarly, adipocyte differentiation in 3T3-L1 cells, which involves dynamic changes in the epigenome, is inhibited by iron depletion, although how the ferrous iron level is altered during differentiation has not been explored [50, 51]. It is also noteworthy that some types of cancer cells harboring mutations on IDH1 and IDH2 produce an inhibitor of 2OGDs, (R)-2-hydroxyglutarate (R-2HG) (Figure 7) and show characteristic DNA and histone hypermethylation [37]. Additionally, fumarate and succinate can inhibit 2OGDs (Figure 7), and deletion of fumarate dehydrogenase and succinate dehydrogenase induced histone and DNA hypermethylation [37]. Considering the recent findings that KDM5A/JARID1A and KDM6A/UTX function as oxygen sensors whose demethylase activity is inhibited under hypoxia [52, 53], it is possible that change in the concentrations of metabolites and cofactors may also affect the demethylase activity of 2OGDs, and thus control epigenetic consequences of cellular processes.
Therefore, it is conceivable that energy states could regulate epigenetic mechanisms and be memorized, subsequently influencing the onset of a variety of diseases. Thus, understanding the relationship between energy states and the epigenome is essential for establishment of an appropriate diet-based therapy. As future challenges, it is necessary to elucidate how concentrations of metabolites and cofactors change during biological processes, and which epigenetic enzymes are responsible for the metabolite- and/or cofactor-mediated epigenetic alterations. However, measuring local concentrations of metabolites and cofactors, especially in the nucleus, has been difficult due to technical barriers. We have recently developed a fluorescence resonance energy transfer (FRET)-based biosensor to measure nuclear α-KG concentrations and have found that nuclear α-KG concentrations increase with adipocyte differentiation [54]. The development of such tools will shed light on the regulatory mechanisms of the epigenome by biomolecules in the future.
Now that the development of the internet and other factors have made it easy for non-medical professionals to obtain medical knowledge, the effects of caloric restriction, fasting, the order in which foods are eaten, and the nutritional composition of diets have become familiar topics of interest in the treatment of diabetes and obesity. Therefore, it is more and more important than ever for researchers to understand whole body metabolism based on accurate evidence. There is no doubt that diet plays an important role in the maintenance of health, and new molecular mechanisms including epigenetics have recently emerged in addition to the widely accepted concepts on metabolism. In addition, the involvement of unknown regulatory factors has been implicated. Extensive research will lead to a better understanding of energy metabolism in the body and contribute to the extension of healthy life.
None.
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F. Kaiser, H.A. Aboulela, H. A. El-Serehy and H. Ezz El-Din",authors:[{id:"3900",title:"Dr.",name:"Mona",middleName:null,surname:"Kaiser",slug:"mona-kaiser",fullName:"Mona Kaiser"},{id:"126516",title:"Dr.",name:"Hamdy",middleName:null,surname:"Aboulela",slug:"hamdy-aboulela",fullName:"Hamdy Aboulela"},{id:"150469",title:"Dr.",name:"H.",middleName:null,surname:"El-Serehy",slug:"h.-el-serehy",fullName:"H. El-Serehy"}]},{id:"55867",doi:"10.5772/intechopen.69214",title:"The Marine Biodiversity of the Mediterranean Sea in a Changing Climate: The Impact of Biological Invasions",slug:"the-marine-biodiversity-of-the-mediterranean-sea-in-a-changing-climate-the-impact-of-biological-inva",totalDownloads:2332,totalCrossrefCites:8,totalDimensionsCites:18,abstract:"The Mediterranean Sea, one of the most complex marine ecosystems, is inhabited by a rich and diverse biota which is disproportionate to its dimensions. It is currently affected by different pressures, mainly driven by human activities such as climate change and bioinvasions. This Sea, also due to its geographic position (wedged between the temperate climate of central Europe and the arid climate of northern Africa), seems to be one of the regions most susceptible to global climate change. The increased rates of introduction and spread of marine alien species may represent a supplementary stress factor to Mediterranean marine native biota already challenged by climatic abnormalities. The Suez Canal is considered to be the main vector of introduction of non‐indigenous marine species into the Mediterranean Sea. Due to the dramatically accelerating rate of such introductions and due to the sheer magnitude of shipping traffic, the Mediterranean Sea may be considered as a true hotspot of marine bioinvasions. The complexity of interactions between native and invasive species and the associated resulting impacts make environmental management of such an issue particularly difficult. A collaboration between researchers, resource management agencies and policy makers is called for to bolster the effectiveness of invasive species management procedures.",book:{id:"5995",slug:"mediterranean-identities-environment-society-culture",title:"Mediterranean Identities",fullTitle:"Mediterranean Identities - Environment, Society, Culture"},signatures:"Anna M. Mannino, Paolo Balistreri and Alan Deidun",authors:[{id:"202075",title:"Prof.",name:"Alan",middleName:null,surname:"Deidun",slug:"alan-deidun",fullName:"Alan Deidun"},{id:"203773",title:"Dr.",name:"Anna Maria",middleName:null,surname:"Mannino",slug:"anna-maria-mannino",fullName:"Anna Maria Mannino"},{id:"203777",title:"Dr.",name:"Paolo",middleName:null,surname:"Balistreri",slug:"paolo-balistreri",fullName:"Paolo Balistreri"}]}],mostDownloadedChaptersLast30Days:[{id:"77362",title:"Role of Eco-Village Initiatives in Mitigating Desertification in Semi-Arid Areas of Tanzania",slug:"role-of-eco-village-initiatives-in-mitigating-desertification-in-semi-arid-areas-of-tanzania",totalDownloads:105,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Climate change adaptation actions for mitigating desertification and improving community livelihood in developing countries have attracted numerous scholarly works. However, there have been insufficient findings on the adaptation regarding the eco-village practices in semi-arid areas in particular. This inspired a study to assess the role of eco-village practices in strengthening climate change adaptive capacity and mitigating desertification in semi-arid areas of Chololo village, Dodoma region in central Tanzania. Data were collected using mixed methods, that is, household survey (92), focus group discussions (21), key informants interviews (6), field observation and documentary review. Statistical Package for Social Sciences (SPSS) and content analysis were used in analyzing quantitative and qualitative data respectively. The study found a relatively high level of community awareness on the eco-village initiative; the initiative rehabilitated village forest reserve; improved land productivity for sorghum and pearl millet; increased number of planted trees; and strengthening communities’ adaptation to climate change through improved households’ nutrition, income and reduced water stress.",book:{id:"8969",slug:"deserts-and-desertification",title:"Deserts and Desertification",fullTitle:"Deserts and Desertification"},signatures:"Fredy S. Mswima and Abiud L. Kaswamila",authors:[{id:"115390",title:"Prof.",name:"Abiud L.",middleName:"Lucas",surname:"Kaswamila",slug:"abiud-l.-kaswamila",fullName:"Abiud L. Kaswamila"},{id:"415117",title:"Dr.",name:"Fredy S.",middleName:null,surname:"Mswima",slug:"fredy-s.-mswima",fullName:"Fredy S. Mswima"}]},{id:"77741",title:"Characteristic on the Stability of Haloxylon ammodendron Plantation in the Southern Fringe of Gurbantunggut Desert, Northwest China",slug:"characteristic-on-the-stability-of-em-haloxylon-ammodendron-em-plantation-in-the-southern-fringe-of-",totalDownloads:150,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Using chronosequence theory and method, the characteristics of vegetation-soil coupling and structure stability of Haloxylon ammodendron plantations in the southern fringe of Gurbantunggut Desert were analyzed. The results showed, the canopy storey of H. ammodendron plantation experienced three stages, rapid growth (the age of 7 to 20), then slow growth (the age of 20 to 28) and last decline (over the age of 28). The best natural regeneration started from 17-yr-old plantation. Vegetation-soil system coupling degree (C) and coupling coordinative degree (D) of plantations with different age were not one-to-one correspondence. The system of H. ammodendron plantations always stayed in disorder recession, vegetation and soil were prone to loss type during the process of sand-fixation. Five principal components evaluated that the first rank was 42-yr-old plantation. It was inferred that the trend of the vegetation and soil system was from senescence to harmonious development. So the trend of coordinated development between vegetation and soil would be promoted, if the artificial tending and management measures strengthened.",book:{id:"8969",slug:"deserts-and-desertification",title:"Deserts and Desertification",fullTitle:"Deserts and Desertification"},signatures:"Qinghong Luo, Qimin Chen, Miao He and Na Li",authors:[{id:"340564",title:"Dr.",name:"Qinghong",middleName:null,surname:"Luo",slug:"qinghong-luo",fullName:"Qinghong Luo"},{id:"347848",title:"Mr.",name:"Qimin",middleName:null,surname:"Chen",slug:"qimin-chen",fullName:"Qimin Chen"},{id:"348214",title:"Associate Prof.",name:"Miao",middleName:null,surname:"He",slug:"miao-he",fullName:"Miao He"},{id:"348215",title:"Associate Prof.",name:"Na",middleName:null,surname:"Li",slug:"na-li",fullName:"Na Li"}]},{id:"77086",title:"Bowing Sand, Dust, and Dunes, Then and Now–A North American Perspective",slug:"bowing-sand-dust-and-dunes-then-and-now-a-north-american-perspective",totalDownloads:83,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Dune fields of the present day, the Dust Bowl disaster of the 1930s U.S. Great Plains, and contemporary efforts to forecast, simulate, and understand dust storms have a striking, uniform commonality. What these apparently diverse phenomena have in common is that they all result from blowing sand and dust. This review paper unifies these three disparate but related phenomena. Its over-arching goal is to clearly explain these manifestations of windblown sand and dust. First, for contemporary dune fields, we offer reviews of two technical papers that explain the eolian formation and the continuing development of two major dune fields in southeastern California and northwestern Sonora, Mexico: the Algodones Dunes and the Gran Desierto de Altar. Second, historical, geological, meteorological, and socioeconomic aspects of the 1930s Great Plains Dust Bowl are discussed. Third, and last, we return to the present day to summarize two lengthy reports on dust storms and to review two technical papers that concern their forecasting and simulation. The intent of this review is to acquaint the interested reader with how eolian transport of sand and dust affects the formation of present-day dune fields, human agricultural enterprises, and efforts to better forecast and simulate dust storms. Implications: Blowing sand and dust have drastically affected the geological landscape and continue to shape the formation of dune fields today. Nearly a century ago the U.S. Great Plains suffered through the Dust Bowl, yet another consequence of blowing sand and dust brought on by drought and mismanagement of agricultural lands. Today, this phenomenon adversely affects landscapes, transportation, and human respiratory health. A more complete understanding of this phenomenon could (and has) led to more effective mitigation of dust sources, as well as to a more accurate predictive system by which the public can be forewarned.",book:{id:"8969",slug:"deserts-and-desertification",title:"Deserts and Desertification",fullTitle:"Deserts and Desertification"},signatures:"Peter Hyde and Alex Mahalov",authors:[{id:"348247",title:"Dr.",name:"Peter",middleName:null,surname:"Hyde",slug:"peter-hyde",fullName:"Peter Hyde"},{id:"419631",title:"Dr.",name:"Alex",middleName:null,surname:"Mahalov",slug:"alex-mahalov",fullName:"Alex Mahalov"}]},{id:"61738",title:"Assessment of the Riparian Vegetation Changes Downstream of Selected Dams in Vhembe District, Limpopo Province on Based on Historical Aerial Photography",slug:"assessment-of-the-riparian-vegetation-changes-downstream-of-selected-dams-in-vhembe-district-limpopo",totalDownloads:1533,totalCrossrefCites:0,totalDimensionsCites:2,abstract:"Dams have been associated with various impacts on downstream river ecosystems, including a decrease in stream flow, species biodiversity, water quality, altered hydrology and colonisation of the area by invasive alien plant species. The impacts normally interfere with the ecosystem functioning of riparian and aquatic environments, thereby leading to decreased biodiversity. This study aims to assess the impacts of dams on downstream river ecosystems, using data from aerial photographs and orthophotos, supplemented by field work. Five dams in Limpopo Province, South Africa, were selected (Albasini, Damani, Mambedi, Nandoni and Vondo), and photographs from different years were used. The area devoid of trees of certain species both downstream and upstream of the dams was calculated using grids of predetermined square sizes on each available photograph. Aerial photographs and orthophoto data were supplemented by field work. The nearest-individual method was used in the field to determine tree density of particular tree species. The environments downstream of the dams show a loss of obligate riparian vegetation and an increase of obligate terrestrial vegetation (Acacia Karroo, Acacia Ataxacantha and Bauhinia galpinii). Treeless area increased in all cases, especially in the case of Mambedi and Vondo dams, indicating lower resilience and higher fragility there.",book:{id:"6706",slug:"environmental-risks",title:"Environmental Risks",fullTitle:"Environmental Risks"},signatures:"John M. Mokgoebo, Tibangayuka A. Kabanda and Jabulani R.\nGumbo",authors:[{id:"224099",title:"Prof.",name:"Jabulani",middleName:null,surname:"Gumbo",slug:"jabulani-gumbo",fullName:"Jabulani Gumbo"},{id:"250766",title:"Mr.",name:"M.J.",middleName:null,surname:"Mokgoebo",slug:"m.j.-mokgoebo",fullName:"M.J. Mokgoebo"},{id:"250767",title:"Prof.",name:"T.A.",middleName:null,surname:"Kabanda",slug:"t.a.-kabanda",fullName:"T.A. Kabanda"}]},{id:"78428",title:"Jojoba - The Gold of Desert",slug:"jojoba-the-gold-of-desert",totalDownloads:218,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Jojoba [Simmondsia chinensis (Link) Schneider] is evergreen, perennial and drought resistant shrub belongs to the family of Simmondsiaceae. It is a multipurpose oil seed crop mainly grown in desert regions of world. This plant has unique oil among plant kingdom which is chemically a liquid-wax. The liquid-wax is made up of an ester of long chain fatty acids and alcohols. The liquid-wax is unique in nature because have no traces of glycerine and easily modified via hydrolysis, hydrogenation, halogenation, sulfurization, phosphosulfurization and ozonization techniques. The main uses of liquid-wax in various industries like cosmetics, pharmaceuticals, petrochemicals and lubricants. It is a potential seed oil crop for desert region so it is well known as the gold of desert. The main purpose of this chapter is to review the complete information about this plant so that it can produce and utilized maximally. Moreover, the review focuses on biology, biogeography, physico-chemical properties of jojoba oil and propagation techniques of the plant of desert regions.",book:{id:"8969",slug:"deserts-and-desertification",title:"Deserts and Desertification",fullTitle:"Deserts and Desertification"},signatures:"Raman Bala",authors:[{id:"347678",title:"Dr.",name:"Raman",middleName:null,surname:"Bala",slug:"raman-bala",fullName:"Raman Bala"}]}],onlineFirstChaptersFilter:{topicId:"135",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[],lsSeriesList:[],hsSeriesList:[],sshSeriesList:[],testimonialsList:[]},series:{item:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343",scope:"Biomedical Engineering is one of the fastest-growing interdisciplinary branches of science and industry. The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. This series is intended for doctors, engineers, and scientists involved in biomedical engineering or those wanting to start working in this field.",coverUrl:"https://cdn.intechopen.com/series/covers/7.jpg",latestPublicationDate:"May 13th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:12,editor:{id:"50150",title:"Prof.",name:"Robert",middleName:null,surname:"Koprowski",slug:"robert-koprowski",fullName:"Robert Koprowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTYNQA4/Profile_Picture_1630478535317",biography:"Robert Koprowski, MD (1997), PhD (2003), Habilitation (2015), is an employee of the University of Silesia, Poland, Institute of Computer Science, Department of Biomedical Computer Systems. For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:5,paginationItems:[{id:"91",title:"Sustainable Economy and Fair Society",coverUrl:"https://cdn.intechopen.com/series_topics/covers/91.jpg",isOpenForSubmission:!0,editor:{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo",profilePictureURL:"https://mts.intechopen.com/storage/users/181603/images/system/181603.jpg",biography:"Antonella Petrillo is a Professor at the Department of Engineering of the University of Naples “Parthenope”, Italy. She received her Ph.D. in Mechanical Engineering from the University of Cassino. Her research interests include multi-criteria decision analysis, industrial plant, logistics, manufacturing and safety. She serves as an Associate Editor for the International Journal of the Analytic Hierarchy Process. She is a member of AHP Academy and a member of several editorial boards. She has over 160 Scientific Publications in International Journals and Conferences and she is the author of 5 books on Innovation and Decision Making in Industrial Applications and Engineering.",institutionString:null,institution:{name:"Parthenope University of Naples",institutionURL:null,country:{name:"Italy"}}},editorTwo:null,editorThree:null},{id:"92",title:"Health and Wellbeing",coverUrl:"https://cdn.intechopen.com/series_topics/covers/92.jpg",isOpenForSubmission:!0,editor:{id:"348225",title:"Prof.",name:"Ann",middleName:null,surname:"Hemingway",slug:"ann-hemingway",fullName:"Ann Hemingway",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035LZFoQAO/Profile_Picture_2022-04-11T14:55:40.jpg",biography:"Professor Hemingway is a public health researcher, Bournemouth University, undertaking international and UK research focused on reducing inequalities in health outcomes for marginalised and excluded populations and more recently focused on equine assisted interventions.",institutionString:null,institution:{name:"Bournemouth University",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null},{id:"93",title:"Inclusivity and Social Equity",coverUrl:"https://cdn.intechopen.com/series_topics/covers/93.jpg",isOpenForSubmission:!0,editor:{id:"210060",title:"Prof. Dr.",name:"Ebba",middleName:null,surname:"Ossiannilsson",slug:"ebba-ossiannilsson",fullName:"Ebba Ossiannilsson",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6LkBQAU/Profile_Picture_2022-02-28T13:31:48.png",biography:'Professor Dr. Ebba Ossiannilsson is an independent researcher, expert, consultant, quality auditor and influencer in the fields of open, flexible online and distance learning (OFDL) and the "new normal". Her focus is on quality, innovation, leadership, and personalised learning. She works primarily at the strategic and policy levels, both nationally and internationally, and with key international organisations. She is committed to promoting and improving OFDL in the context of SDG4 and the future of education. Ossiannilsson has more than 20 years of experience in her current field, but more than 40 years in the education sector. She works as a reviewer and expert for the European Commission and collaborates with the Joint Research Centre for Quality in Open Education. Ossiannilsson also collaborates with ITCILO and ICoBC (International Council on Badges and Credentials). She is a member of the ICDE Board of Directors and has previously served on the boards of EDEN and EUCEN. Ossiannilsson is a quality expert and reviewer for ICDE, EDEN and the EADTU. She chairs the ICDE OER Advocacy Committee and is a member of the ICDE Quality Network. She is regularly invited as a keynote speaker at conferences. She is a guest editor for several special issues and a member of the editorial board of several scientific journals. She has published more than 200 articles and is currently working on book projects in the field of OFDL. Ossiannilsson is a visiting professor at several international universities and was recently appointed Professor and Research Fellow at Victoria University of Wellington, NZ. Ossiannilsson has been awarded the following fellowships: EDEN Fellows, EDEN Council of Fellows, and Open Education Europe. She is a ICDE OER Ambassador, Open Education Europe Ambassador, GIZ Ambassador for Quality in Digital Learning, and part of the Globe-Community of Digital Learning and Champion of SPARC Europe. On a national level, she is a quality developer at the Swedish Institute for Standards (SIS) and for ISO. She is a member of the Digital Skills and Jobs Coalition Sweden and Vice President of the Swedish Association for Distance Education. She is currently working on a government initiative on quality in distance education at the National Council for Higher Education. She holds a Ph.D. from the University of Oulu, Finland.',institutionString:"Swedish Association for Distance Education, Sweden",institution:null},editorTwo:null,editorThree:null},{id:"94",title:"Climate Change and Environmental Sustainability",coverUrl:"https://cdn.intechopen.com/series_topics/covers/94.jpg",isOpenForSubmission:!1,editor:null,editorTwo:null,editorThree:null},{id:"95",title:"Urban Planning and Environmental Management",coverUrl:"https://cdn.intechopen.com/series_topics/covers/95.jpg",isOpenForSubmission:!0,editor:{id:"181079",title:"Dr.",name:"Christoph",middleName:null,surname:"Lüthi",slug:"christoph-luthi",fullName:"Christoph Lüthi",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRHSqQAO/Profile_Picture_2022-04-12T15:51:33.png",biography:"Dr. Christoph Lüthi is an urban infrastructure planner with over 25 years of experience in planning and design of urban infrastructure in middle and low-income countries. He holds a Master’s Degree in Urban Development Planning from the University College of London (UCL), and a Ph.D. in Urban Planning & Engineering from TU Berlin. He has conducted applied research on urban planning and infrastructure issues in over 20 countries in Africa and Asia. In 2005 he joined Eawag-Sandec as Leader of the Strategic Environmental Sanitation Planning Group. 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He collaborates with the Environmental Resources Analysis Research Group (ARAM), University of Extremadura (UEx), Spain; VALORIZA - Research Center for the Enhancement of Endogenous Resources, Polytechnic Institute of Portalegre (IPP), Portugal; Centre for Tourism Research, Development and Innovation (CITUR), Madeira, Portugal; and AQUAGEO Research Group, University of Campinas (UNICAMP), Brazil.",institutionString:"University of Johannesburg, South Africa and WSB University, Poland",institution:{name:"University of Johannesburg",institutionURL:null,country:{name:"South Africa"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:11,paginationItems:[{id:"81920",title:"Rethinking an Approach for Sustainable Globalization",doi:"10.5772/intechopen.105141",signatures:"Parakram Pyakurel",slug:"rethinking-an-approach-for-sustainable-globalization",totalDownloads:0,totalCrossrefCites:null,totalDimensionsCites:null,authors:null,book:{title:"Globalization and Sustainability - Recent Advances, New Perspectives and Emerging Issues",coverURL:"https://cdn.intechopen.com/books/images_new/11476.jpg",subseries:{id:"91",title:"Sustainable Economy and Fair Society"}}},{id:"81297",title:"Legumes Cropping and Nitrogen Fixation under Mediterranean Climate",doi:"10.5772/intechopen.104473",signatures:"Fernando Teixeira",slug:"legumes-cropping-and-nitrogen-fixation-under-mediterranean-climate",totalDownloads:3,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Food Systems Resilience",coverURL:"https://cdn.intechopen.com/books/images_new/10897.jpg",subseries:{id:"91",title:"Sustainable Economy and Fair Society"}}},{id:"81493",title:"Rust Disease Classification Using Deep Learning Based Algorithm: The Case of Wheat",doi:"10.5772/intechopen.104426",signatures:"Shivani Sood, Harjeet Singh and Suruchi Jindal",slug:"rust-disease-classification-using-deep-learning-based-algorithm-the-case-of-wheat",totalDownloads:40,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Food Systems Resilience",coverURL:"https://cdn.intechopen.com/books/images_new/10897.jpg",subseries:{id:"91",title:"Sustainable Economy and Fair Society"}}},{id:"81428",title:"Observatory of Sustainable Development in Postgraduate Study Programs in Baja California",doi:"10.5772/intechopen.104641",signatures:"Rodolfo Martinez-Gutierrez, Maria Marcela Solis-Quinteros, Maria Esther Ibarra-Estrada and Angel Ernesto Jimenez-Bernardino",slug:"observatory-of-sustainable-development-in-postgraduate-study-programs-in-baja-california",totalDownloads:9,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Globalization and Sustainability - 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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University, Kuwait. 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He is also an editor and editor in chief for various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:"Beijing University of Technology",institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Lakhno Igor Victorovich was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZkkQAG/Profile_Picture_2022-05-09T12:55:18.jpg",biography:null,institutionString:null,institution:null},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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