\r\n\tMany tried to define it, and its definition is always related to those who are in power, that being explained by the fact that this power and the abuse of it precisely, gives the access to being corrupted and practicing the acts that fall under corruption.
\r\n\r\n\tWe can find various types of corruption such as bribery, lobbying, extortion, cronyism, nepotism, parochialism, patronage, influence peddling, graft, and embezzlement. Also giving or accepting bribes or inappropriate gifts, double-dealing, under-the-table transactions, manipulating elections, diverting funds, laundering money, and defrauding investors.
\r\n\tNo government is immune to corruption. According to the World Bank, “the causes of corruption are always contextual, rooted in a country's policies, bureaucratic traditions, political development, and social history”.
\r\n\tThis indeed has consequences for increasing inequality, impacts government expenditure and services, shadow economy, and crime.
\r\n\tThis book will be a collection of chapters on Corruption. It welcomes contributions related to the nature of corruption its types and how corruption is undertaken in a certain context and the ways to deal with corruption will be part of this book. We value including materials on Corruption in organizations and ways to solve it. The origins of corruption and the way to deal with corruption, how to provide solutions, and any new insights on corruption will be part of this book.
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The neuronal network extends from the brain to all over the body and various neurotransmitters help transmit the message to target cells in different tissues. The part of the nervous system located in our gut is called the enteric nervous system (ENS). In all animals, gut brain axis is a lesser known nervous system so far. Our gut or “second brain” (ENS) chemically connects with the brain through neurons, secreted chemicals like hormones and neurotransmitters that send messages to the brain. The enteric nervous system’s network of neurons and neurotransmitters extends along the entire digestive tract – it starts from the esophagus to the stomach and intestines, and down to the anus. The “gut microbiome” comprises of microorganisms living in the gut (bacteria, viruses, and fungi) that can affect the chemical messages that pass between the gut and the brain. Microorganisms residing in the gut help regulate the body’s immune response. Since, the brain and the gastrointestinal (GI) system are intimately connected, therefore, they play key roles in certain diseases and to maintain our overall health to regulate cognitive and digestive behavior. The bidirectional communication between the brain and digestive system hence, are opening up avenues to think about diseases considering this angle.
Gut has recently become a subject of research in medical sciences wherein subjects with depressive symptoms, Parkinson’s and Alzheimer’s disease, autism, amyotrophic lateral sclerosis, multiple sclerosis, pain, anxiety and other neurodegenerative conditions are beginning to be looked to see what is going on in the gut. Effects of conditions like ulcers, constipation, and other GI problems have been a focus of research on aspects of brain functioning. The enteric microbiota impacts the gut brain axis (GBA), interacts locally with the intestinal cells and ENS as well as with the CNS through neuroendocrine and metabolic pathways. These studies suggest that GBA plays a vital role in maintaining mental health and can affect the feeding behavior when nutrient detection or absorption does not function properly as in case of metabolic conditions.
To ensure stability in the internal environment of body and drive adaptive changes, control mechanisms are key to animal’s survival. Recently GI has been recognized as a major source of signals modulating feeding behaviors, food intake, metabolism, insulin secretion and energy balance. Through its interaction with microbiota, it can shape our physiology and behavior in complex and sometimes unexpected ways. A growing scientific community has exploited the genetic amenability of
Easy genetic manipulation and effortless genetic tools make flies an insect of choice to study inter organ neuronal signaling including gut-brain axis neuronal connectivity. To understand human metabolic diseases and how a GI play a key role there is a recent focus of research. Some progressive studies also draw a link between neurodegenerative disorders and gut microbiota of humans and other insects.
Fruit flies have a simple and similar to humans- gut system (Figure 1). In mammals including humans, the esophagus (
Comparison between human and
The adult
Fly gut anatomy. (A) the
The fly midgut has been segmented into the anterior, middle and the posterior midgut (Figures 1,2A and B). It has been further subdivided morphologically and molecularly into 10–14 regions (Figure 2B) [11, 12, 13]. Midgut regionalization has been seen in the muscles, trachea and neurons that surround it [12, 13, 14, 15]. Physical properties (
The Malpighian tubules release at the junction between the midgut and hindgut (Figures 1,2A and B). The water/ion exchange occurs in the hindgut which consist of pylorus (a second valve-like structure), ileum, and rectum [7, 8]. The muscles that surround the epithelium in flies are striated, as opposed to the smooth muscles found in mammalian intestines [18]. An outer layer of longitudinal muscles found surrounding the midgut. Circular muscles are found to be present throughout the fly tract. Physiology of the intestine is maintained and regulated by autonomic innervation and by hormones. The tracheal system forms a branched structure surrounding the gut during development [15] and may influence epithelial regeneration in the adult. Owning to similarity of flies and human gut, we will be discussing further how gut of the flies is handled and controlled to understand about neural circuitry drawing it closer to the brain and diseases related to intestinal illnesses.
Both humans and fly intestines share similar tissue, anatomy and physiological function [19, 20]. Their gut are of endothelial origin in nature [21, 22] and comprise of an epithelial monolayer of columnar or cuboidal ECs. A series of sequential depressions called the crypts of Lieberkühn, along the small and large intestine, and protruding villi along the internal surface of the small intestine in mammalian intestinal epithelium maximize its surface area [23]. Extensive folding has not been reported in the
In both flies and mammals, the epithelial monolayer is associated on its basal side on an extracellular collagenous matrix (known as basement membrane) [29]. A checkerboard of innervated and trachea-oxygenated longitudinal and circular muscles tissue underneath the basement membrane in flies drive the peristaltic movements [30] (Figure 2C). Mammalian intestine has a similar organization of intestinal external musculature in the outer layers where musculature is also innervated and oxygenated by a plexus of vasculature [31, 32]. Layers including, the submucosa, (a dense layer of connective tissue containing nerves and lymphatic and blood vessels); muscularis mucosae (an additional muscle layer); and the lamina propria underling the intestinal epithelium and contains connective tissue, lymph nodes (Peyer’s patches), immune cells (leukocytes, and dendritic and mast cells), vessels and myofibroblasts [33], fill the space between the outer musculature and the basement membrane in mammals.
About 65% of human-disease causing genes are shared as a functional homolog in fruit flies. This shows conservation of genes and function at an evolutionary level. Fundamental processes such as digestion is also conserved from flies to humans.
The lineage of fly posterior midgut with only one type of mature absorptive cell and one main type of secretory cell is very simple. Although asymmetric ISC divisions in the fly midgut produce transient cells (EBs), these cells do not undergo further cell division and remain close to the ISCs before maturation. Fly midgut ISCs are situated basally and are broadly dispersed in the intestinal epithelium. The cellular composition and regeneration in
Like the regional specialization of digestive functions, the expression of digestive enzymes has also been found to confined to specific segments of the digestive tract in flies [12, 46, 47]. In addition to its roles in nutrient extraction and utilization, the digestive tract responds to the food and bacteria in its lumen. Digestion takes place in fly midgut [48] which can be further modulated by various factors like temperature, redox potential, pH, and intestinal transit [8, 48]. It has been shown that the expression and activity of digestive enzymes are tightly regulated in many insects like enzymes involved in the breakdown of sugars in flies are enriched in anterior (R1/R3) portions of the adult midgut and Peptidase genes express more posteriorly [47].
The enzymatic activity of the intestine is a key factor determining availability of certain nutrients. A substantial reduction of intestinal digestive enzyme activities (trypsin, chymotrypsin, aminopeptidase, and acetate esterase) has been reported in flies lacking EE cells [49]. Though not extensively investigated in
Changes in the expression of p38 kinase or the Atf3 and Foxo transcription factors cause accumulation of neutral lipid in ECs [58, 84]. It has been shown that neutral lipid increase following depletion of the EE hormone Tk [85], or in sterile female flies after mating [86]. It has been suggested that activation of intestinal lipogenesis is key to survival in diet-restricted flies. Indeed, nutrient scarcity induces expression of the sugar sensor transcription factor
Many animals generate localized regions of low pH inside the intestinal lumen to facilitate protein breakdown, absorption of minerals and metals, and limit the survival of ingested microbes. While mammalian digestion takes place in acidic conditions, insect digestion occurs at neutral or basic pH including
The contribution of five ion transporters enriched in the acidic region have been studied [88]. These include: the potassium/chloride symporter Kazachoc (Kcc), a member the Slc12 family of electroneutral cation-chloride transporters (express in intestine) [91, 92]; the Slowpoke pore-forming subunit of a calcium-activated K+ channel (express in neurons, muscles, tracheal cells, and two types of midgut ECs in the copper and iron cell regions) [93]; the ligand-gated chloride channel pHCL-2 which, in addition to regulating fluid secretion in malpighian tubules (express in the copper cell, iron, and large flat cell regions of the midgut) [94, 95]; the carbonic anhydrase CAH1; and the bicarbonate/chloride exchanger CG8177, belonging to the Slc4a1–3 subfamily of anion exchangers (express in a specific midgut pattern similar to that of pHCl-2) [96]. Collectively, these findings suggest that the transport of H+, Cl−, K+, and HCO3− contributes to acid generation in the
Flies extract water from their diet to maintain hydration and ionic balance. This compensates for substantial water loss resulting from metabolic and physiological processes. Although malpighian tubules are important for this process, but intestine also contributes. Water absorption from the food occurs in the insect midgut and in rectal pads of rectum [8]. The rectal pads are also the crucial site for reabsorption of ions. Ions and water can cross the intestinal epithelium through or between cells and their transport play an important role in the maintenance of ion gradients that sustain active transport in the intestinal epithelium. The scanning ion-selective electrode technique (SIET) provides a way to probe intestinal gradients for ions such as K+, Na+, H+, or Cl− [24, 97]. K+ and Na+ absorption occur largely in the large flat cell and posterior regions of the midgut and, also in the anterior hindgut in the case of Na+ [97]. The two
Metal ions such as copper, iron and zinc are essential micronutrients required for the correct folding and activity of a broad range of enzymes. The contribution of the intestine to metal homeostasis has not been extensively investigated but midgut regions, the Cu cell and Fe regions, are the most proposed sites of metal ion absorption. The Cu cell region turns bright luminescent orange upon Cu ingestion due to the fixation of copper by metallothionein [101, 102], and appears to be an important site of accumulation of ingested radioactively labeled Cu [101, 103]. The Fe cell region in R4a stains by Prussian blue and also accumulates exogenously administered radioactive Fe [101, 104]. Many studies have confirmed the roles for the Cu/Fe regions by exploring the molecular machinery involved in the intestinal uptake, intracellular trafficking, and efflux of metal ions.
Nutrient extraction and utilization may get affected by the passage of food along the alimentary canal and by its subsequent excretion. Transport of food to travel the entire length of the digestive tract takes less than 1 hour [105] in flies. As suggested, the amount of food retained in the crop is much larger in starved flies then refed flies than in flies fed
The ENS in humans, equivalent to GBA in flies is a part of the peripheral nervous system (PNS) that governs the running of the neurons which influence the GI. It is exploited nowadays in flies to understand more about how the two organs affect one another and lead to decisions regarding appetite, feeding mechanisms, taste preference and how to deal with hunger and satiety. How taste receptors detect different nutrients in the gut remains to be explored.
In humans, G-protein coupled receptors (GPCR) are involved in detection of five common tastes- sweet, salty, bitter, sour and umami. T1R family of taste receptors determine sweet and umami flavor. T2R family includes the bitter receptors [110]. Sweet taste receptors (T1R family) are found in intestinal tract as well as EE cells [111]. T1R1, T1R2, T1R3 and α-gustducin are expressed in the stomach, intestine and colon of humans and mice [112]. Cells of duodenal villi show co-localization of T1R1, T1R3 and α-gustuducin. Mammalian Gustducin protein is involved in bitter and sweet taste signaling and detection [113, 114]. α-subunit of gustducin is expressed in gastric cells and may play a role in nutrient detection [115, 116, 117] in rats and mice. Present in the mucosal lining of mammals and taste cells of the epithelium suggesting its possible role in taste uncovering on exposure to luminal contents [118]. Expression of T2R receptors in mouse GI tract including mT2R119 and mT2R108 has been looked into. mT2R119 expression is found in gastric and intestinal tissues, tongue and liver [115] like mT2R134 [118]. mT2R108, mT2R138 are present in the fundus, antrum, duodenum and tongue (not in liver) [119].
It has been found that sweet taste receptors stimulated in rat intestine influence and increase glucose absorption [120] through GLUT (glucose transporter) [121]. Presence of sugar in the diet galvanizes ECs into action to release hormones which in turn activate SGLT (Na+ / glucose cotransporter) [122, 123]. Similar results are shown in sheep where sugar receptor / sensor present on the luminal membrane stimulates SGLT1 via cAMP and G-protein dependent pathway [124]. Equine T1R2 (homologous to cows and pigs) is expressed on the luminal membrane of EE cells in the small intestine. In response to increased sugars, T1R2 along with T1R3, stimulates SGLT1 and enhances the ability of gut to absorb more glucose [125]. Analysis of in vitro line of ECs suggest that T1R2 and T1R3 detect sweet taste and exposure to sucralose increases release of hormones such as GIP (Gastric Inhibitory Polypeptide) and GLP (Glucagon like peptide) which further activate glucose activation and metabolism. An inhibitor of these receptors inhibits glucose metabolism suggesting these receptors present in the gut alter feeding mechanisms and post-ingestion decisions [120, 121].
Gustatory system in
Nutrient signaling and sensing are fundamental processes that animals including humans and flies undergo [131]. Proper coordination and communication between gut and brain is necessary to regulate metabolic homeostasis and physiology in all animals. In this regard, many research groups have shown the role of enteric neurons and endocrine signals as important mediators of these processes. The way the enteric nervous system communicates to the brain via neural circuits is a multifaceted question and poorly explored. In mammals such as humans, alterations in neuropeptides and brain – gut hormone levels can derail people otherwise on the path to a healthy life. These changes can also lead to diseases such as neurodegenerative diseases, metabolic syndrome and diabetes [132].
Gluconeogenesis is a biochemical pathway by which animals make sugars from non-carbohydrate precursors and sources [133]. It is used to regulate homeostasis and a stable internal state in post – fed state [134]. Studies in rats showed that stimulation of intestinal gluconeogenesis (IGN) sends a signal from sodium – glucose co- transporters present at the intestinal mucosa to the brain, initiating a neural gut – brain axis [135, 136, 137]. Diets rich in protein [138, 139, 140] and fiber [141] promote IGN stressing on the importance of nutrient sensing for initiating several gut – brain axis [137]. It has been found that μ – opoid receptors (MOR) regulate IGN. These receptors (present in the nerves in the portal vein wall) react to neuropeptides to stimulate a gut – brain neural circuit that affects IGN, hunger and satiety mechanisms [141]. Further analysis of MOR deficient mice shows the role of MORs in regulating food intake, referred as “reward” system [142, 143]. Analyses of MOR-knockouts (MOR-KO) demonstrate how they play a role in managing satiety effects of alimentary proteins, through a neural gut-brain circuit [140].
Vagus nerve (VN; pneumogastric nerve) is the longest cranial nerve [144] in humans which runs from the medulla oblongata in brain to colon in GI [145]. It innervates other structures as well such as larynx, pharynx, heart and lungs thus affects digestive, cardiovascular and respiratory system – all at one [146]. Vagal efferent send down signals from the brain to gut, which accounts for about 10% – 20% of all the nerve fibers. Remaining 80% is accounted for by the vagal afferents carrying information from the gut to the brain [147]. Vagal sensory neurons in the GI keep an eye on stomach volume and luminal contents through different neural circuits [148]. VN contains and branches into several sensory neurons (~2300 in mouse) that further innervate and render support and supply to other internal organs. A variety of sensory neurons, one side facing the brainstem and the terminal one facing the organ such as GI [149] have been revealed. Free terminals of vagal afferents are rooted within lamina propria of intestinal villi [148]. Some mammalian models like in cat and rat, it has been shown how these sensory neurons detect different nutrients in diets with the help of unambiguous and explicit fibers [150, 151, 152]. Vagal afferent endings in the intestine express several mechanosensitive as well as chemical receptors [153]. Glucagon- like peptide 1 (GLP1) is a gut hormone receptor that intercedes the nutrient sensing mechanism via VN [154]. GLP1R (GLP1 receptor) is present in many cells [155]. Agonists for GLP1R show how it affects brain further proving its presence in both, gut and brain [156]. Another receptor of vagal afferents, GPR65 near the intestinal villi, plays a role in nutrient detection drawing attention to how these sensory neurons are a part of the gut – brain axis [157, 158]. It detects serotonin and impact gut motility [147]. Such receptors detect several hormones present in the gut, like choleocystokinin (CKK), ghrelin and leptin which play a role in the regulation of hunger and satiety [159, 160, 161]. Because of its role in gut motility and mobility, VN and its afferent neurons present in the gut play a role in Intestinal Bowel Syndrome (IBS) [162] and new treatment plans around the same are being looked at in rat [162] and mice [158] models.
To take the findings in vagal nerves forward, nerves allowing communication of cNST (caudal nucleus of the solitary tract) with gut were focused on. Information about sugar detection to cNST via gut – brain axis is a topic of research nowadays. In live mice, it is noticed that glucose detection by cNST is robust and VN transaction silences that activation [163]. Nodose ganglion of vagus nerve when silenced prevents the sugar preference of cNST [163] suggesting the presence of a physical gut – brain axis. It has been shown that inactivation of sugar-activated cSNT prevents the mice to choose sugar from water or an artificial sweetener [163]. This study specifically calls attention to how organisms have paths for detecting nutrient signals, sensing them in the diet and also have circuitries to carry forward the signals and communicate with the rest of the body, purposely the brain.
With the help of several markers and reporter genes, it is found that
In the anterior portion of adult and larval midgut, serotonin positive neurites and various neuropeptides including Akh, Dh44, Myosuppressin, and possibly Allatostatin C and FMRFamide (or an FMRFamide-like peptide such as the NPY-like neuropeptide short neuropeptide F [sNPF]) [131, 168, 172, 180, 181, 182] have been described suggesting chemical diversity of enteric innervation. Four serotonergic neurons are found to innervate the enteric nervous system in fly larva. These neurons project from the antennal nerve (AN) near the SEZ and extend throughout the ENs [14]. These projections end at the anterior region of the midgut and are primarily around the proventriculus region and the foregut. These innervations are considered structurally analogous to the mammalian VN because of similar projections from the brain to the different structures of the foregut. It is yet to be seen if there are functional similarities as well [172].
Pigment- dispersing factor (Pdf), Ion transport peptide, and Proctolin positive neurites have been reported in the larval and adult hindgut [169, 183, 184, 185, 186]. All three innervated regions receive insulinergic innervation from the CNS; the
Innervation of adult
Functional studies of insect innervation have primarily focused on the control of peristalsis and peptide hormone secretion so far. Studies of peristaltic regulation in flies have primarily concerned the effects of neuropeptides (Allatostatins, Myosuppressin, or Drosulfakinins) on
Recently epithelial roles for gut-innervating neurons e.g. role in the control of fluid balance have been revealed by a semi-automated analysis of defecation behavior in adult flies, providing quantitative readouts for food intake, fluid/ion balance, and intestinal transit [14, 193]. The HGN1 neurons (2–5 CNS neurons located in the posterior segments of the abdominal ganglion) innervate the hindgut and the rectum (Figure 3), with a subset of their neurites projecting through the visceral muscles to reach the underlying epithelium [14]. HGN1 neuronal silencing experiments resulted in increased defecation rate. These neurons are shown to be required for the post-mating changes in intestinal fluid retention due to their epithelial innervation. It has been established that HGN1 neurons and the Pdf hindgut-innervating neurons have their direct action on the hindgut and anal sphincter muscles [192]. A role for gut-innervating neurons in the maintenance of epithelial turnover has also been suggested by the finding of anatomical proximity between enteric neurites in the posterior midgut and adult somatic intestinal progenitors, and the reduced ISC to EC differentiation resulting from downregulating Hedgehog (Hh) signaling (albeit pan-neuronally) [194]. The more anterior innervation of the proventriculus may also play a role in maintaining gut permeability. This is inferred from the finding that inactivation of a relatively broad subset of neurons, including a subset of anterior midgut-innervating neurons results in an abnormal proventricular structure, increased permeability of the epithelial barrier, and increased susceptibility to oral bacterial infection: all suggestive of defects in the production of peritrophic matrix [175].
In adult flies, inactivation of insulin-producing neurons results in contrasting effects on the hyperphagic response triggered by nutrient scarcity. Silencing of the insulin-producing cells of the brain PI that innervates the anterior midgut lowered this response, whereas silencing of the hindgut-innervating Ilp7 neurons increased it, and also resulted in higher circulating glucose [14, 195]. Not much is known about the importance of sparse sensory innervation of the intestine. One remarkable exception are the pharyngeal taste neurons.
Post-ingestive sensory feedback from the gut has been assumed to inhibit feeding based on work in other insects for example severing the recurrent nerve or the medial abdominal nerve, which transmit information from the gut to the brain, results in overconsumption in blowflies [199]. Work done in flies lends support to this idea; whereas severing the medial abdominal nerve did not disturb food consumption, severing the recurrent nerve elevated consumption of sucrose but not water or bitter tasting solutions [200]. The existence of neuronal stretch receptors on the gut that monitor the volume of ingested food is supported by both neurophysiological and anatomical data in numerous other insects [4, 80, 199, 201]. However, the existence and molecular nature of these receptors in
The gut–brain transmission systems involve both circulation-based endocrine-like and neuronal communication routes [205]. Neuropeptides (transmitters or neurosecretory) act as messenger molecules of enteric, sensory, autonomic and central neurons. Several peptide families have been found in both brain and gut. They act as neuropeptides and/or gut hormones and have significantly contributed to the understanding of gut brain interaction. Central and peripheral neurons together with EE cells in the GI tract and other endocrinologically active cells produce variety of peptides [206, 207, 208, 209, 210, 211] including hormones peptide YY (PYY) and pancreatic polypeptide (PP); neuropeptide Y (NPY), on the other hand [212]. These and other peptide families represented by glucagon-like peptide (GLP), ghrelin, cholecystokinin (CCK), corticotropin-releasing factor (CRF), leptin, osteocalcin and insulin (the last three are extra intestinal endocrine peptides) act on specific and genetically related groups of receptors that are expressed by distinct cells in the periphery and CNS. For their functional roles, endocrine peptides and neuropeptides are relevant for the regulation of digestion, control of food intake, metabolic homeostasis, and the impact of GI signals on sensation, emotion, affect, and cognition. Disturbances of the gut microbiota–brain axis result in changes of the expression and activity of many neuropeptides and their receptors in the CNS. Neuropeptides are therefore important secondary messengers of gut microbes in cerebral neuro circuitries that mediate the alterations in brain function and behavior that take place in response to changes in the GI microbial community [212]. Together it is emerging that neuropeptide systems such as NPY, CRF, ghrelin, and brain-derived neurotrophic factor (BDNF) play a particular role in the cerebral manifestations of gut microbiota perturbations.
In rats, choleocystokinin and glutamate neuro-epithelial circuit makes the communication between the brain and intestinal lumen possible stressing on the importance of a physical gut – brain axis [213]. It has been proposed that the physical connection between vagal nodose neurons and EE cells is present in rats which leads to regulation of gastrointestinal functions [213]. Intragastric nutrient infusion and optical readings of AgRP (Agouti-related protein) neurons in live and awake mice [214] suggest AgRP neurons affect long term homesostasis and energy balance of the body and do not get altered by minute changes in nutrient levels [215]. AgRP neurons get inhibited by high levels of satiation signals such as CCK and PYY (peptide YY). Receptors for both CCK and PYY are expressed by vagal afferent neurons’ terminals that innervate GI [159] suggesting a possibility of a physical connection between the gut and brain carrying the message from one point to another [216].
Apart from using neurons, fly intestine can also communicate with other organs through systemic signals. Intestinal physiology is modulated by both extrinsic hormonal signals (emanating from endocrine glands, neuroendocrine structures, or organs such as the fat body) and by its own peptide hormones, produced by EE cells. In turn, gut-derived signals such as EE cell-derived peptide hormones can have long-range effects on other internal organs. EE cells accounts for 5–10% of midgut epithelial cells in flies compared to 0.4–0.6% in the mammalian small intestine [217, 218, 219]. Majority of them express peptide hormones, often more than one and with regional stereotypy [219, 220, 221, 222]. The developmental program of EE cells shares similarities with that of neurons, probably reflecting a common phylogenetic origin [223, 224, 225]. Consistent with this idea, all known EE peptide hormones (exception insect CCHamides) [226] are also produced by the brain. Acting through these hormones, EE cells may play “neural-like” roles in regulating intestinal physiology and conveying intestinal as well as nutritional state to other cell types or organs. These roles are particularly prominent in the midgut given the relatively sparse innervation of midgut region.
A role for EE cells on muscle peristalsis has been suggested by the finding that ablation of Diuretic hormone 31 (Dh31)-expressing EE cells or Dh31 downregulation both reduce muscle peristalsis in the larval anterior midgut, which may function as a valve to minimize mixing of acidified and non-acidified food in the acidic region of the midgut [227]. Adult EE cells produce Bursicon. Signaling through the Bursicon/DLGR2 receptor in visceral muscle, represses the production of the visceral muscle-derived mitogen Vein and, consequently, ISC proliferation. Another study found in
A high-sugar diet leads to increased midgut EE cell number and enhanced production of EE-derived Activin ligand (Activin-β not Daw) [230] suggesting systemic roles for EE-derived peptide hormones. Mirroring the activin-mediated fat-to-gut signaling involved in sucrose repression, midgut-derived Activin-β binds to the TGF-β receptor Baboon in fat cells which, in turn, leads to enhancement of Akh signaling it the fat body and consequent hyperglycemia [230]. CCHamides are insect hormones [231, 232] and their expression is promoted by nutrient availability and sites of expression include the gut EE cells, a subset of central neurons and, possibly, the fat body [226, 233, 234]. Their receptors are expressed in the nervous system including the insulin-producing neurons, and are absent from the gut [226, 234]. Although not strictly gut-derived, a new peptide hormone produced not by EE cells, but by an adjacent secretory gland may have provided the most compelling example to date of gut-to-brain communication. Indeed, Limostatin (Lst) peptide is produced by the
In animals with a vascular system, peptides secreted from EE cells can enter the bloodstream and reach tissues at a considerable distance, ranging from other cells in the digestive tract to brain centers regulating appetite [236]. Nutrient availability can also affect the number of EE cells; signaling through the nuclear hormone receptor Hr96, dietary lipids control EE differentiation during the first few days of adult life, providing another way to couple nutrient availability with tissue architecture and physiology [237]. Modulation of intestinal physiology by systemic signals has also been looked into [220, 221]. Control of epithelial turnover by insulin-like peptides or JH (juvenile hormone), and the coupling of dietary availability of sugars with EC digestive enzyme production via the fat body-derived Activin ligand Daw are some examples. The actions of the diuretic peptide Leucokinin (Lk), secreted into the circulation from CNS-derived nerves that terminate at the abdominal wall [14, 238, 239] is an another example. Downregulation of either this peptide or its receptor leads to abnormal excreta and extreme fluid retention that can rupture the abdominal wall [14]. Finally, a link between energy balance, intestinal permeability, and immunity has been suggested by the finding that sNPF is a target of the Crtc/CREB energy sensing pathway, and functions to maintain epithelial barrier integrity acting through its receptor in ECs [240]. Although the precise source of sNPF remains to be established, tissue-specific genetic and expression data points to roles in neurosecretory cells [240], consistent with roles as a neuroendocrine hormone or in gut-innervating neurons. Gut can also produce long-range signals to affect the physiology of other organs, for example by production of the signaling protein Hh by larval EC. Circulating Hh regulates developmental timing by controlling ecdysteroid production in the prothoracic gland, and is required for mobilization of fat body TAG stores during starvation [241].
Other functions of brain-gut peptides and hormones include detection and utilization of nutrients during hunger, stress or normal conditions. Diuretic hormone 44 (Dh44), a homolog of the mammalian corticotropin –releasing -hormone (CRH) activate by nutritive sugars. Disturbed activity of Dh44 neurons leads to fail to select nutritive sugars [131]. These neurons localized to PI in adult brain, counterpart of mammalian hypothalamus [242] are filled with neurosecretory cells [131]. Dh44 conveys information from Dh44 neurons to Dh44 receptor R1 neurons in the brain and R2 cells in the gut suggesting requirement for nutrient selection. Artificial activation of these neurons causes rapid PER and it has been suggested that Dh44 is necessary and sufficient for gut motility and excretion in flies [131]. Both Dh44 neurons and the gut-innervating insulin-producing neurons of the PI are innervated by Hugin-producing neurons that suppress food intake and induce locomotion, providing a possible link between food-related behaviors and intestinal physiology [243]. It is seen later that Dh44+ neurons rapidly activate during amino acid feeding and are a direct sensor of dietary amino acids [244].
Fly gut peptide Dromyosuppressin [181] expresses in the number of cells in central nervous system (CNS) in adult stage, extending into the rectum, near the anus; part of the adult gut. Their immunoreactive fibers also project into the crop and show expression of Dromyosuppressin [172] and crop abundantly expresses Dromyosuppressin receptors (Dromyosuppressin receptor I) [220]. The effects of neuropeptide on neural regulation of crop motility and contractions have been shown [245]. Serotonergic neurons have also been shown to regulate insulin producing cells (IPC) located in the PI of the adult brain of the fly [246]. DILP2, 3 and 5 express particularly in midgut [187, 220, 247] and extend their axons to proventriculus, crop and corpora cardiaca [248]. DILP2 is particularly involved in carbohydrate metabolism [249]. Decreased levels of DILP2 affects stored trehalose as well [248]. IPC knockdown flies show increased glycogen storage, high levels of circulating triglycerides and extended lifespan [248].
Mammalian neuropeptide NPY (Neuropeptide – Y- precursor) has an invertebrate homologous peptide called NPF due to characteristic C- terminal F residue [250]. NPF has been shown to co- localize within midgut cells in
Other neuropeptides include Allatostatin characterized into three kinds namely Allatostatin A/B/C [258, 259, 260]. The endocrine cells producing Allatostatin are found in the posterior midgut and is innervated by axons from thoracico-abdominal ganglion [220]. Its receptors, DAR1 and DAR2 are predominantly located in the central nervous system and gastrointestinal tract (including crop, midgut and hindgut) respectively [261, 262]. Allatostain is also present throughout midgut. Another major peptide is PDF. It is expressed in central nervous system [263] and its neurons are also found in thoracico-abdominal ganglion [184]. Axons from these neurons innervate midgut and hindgut and in the crop. These neuropeptides are closely associated to circadian rhythm [264] and locomotor activity as well.
Various studies have suggested that intestinal health has a significant impact on neurodegeneration. Specifically, dysregulation of GBA cross talk has been associated with metabolic syndrome [265, 266] and psychiatric disorders. GBA is largely mediated by CNS, ENS and intestinal microbiota. With its much simpler gut microbiota (1–30 taxa) as opposed to vertebrates intestine (1–500 taxa) [267],
Most genes and pathways that play crucial roles in metabolic diseases are conserved between flies and humans [268]. Diet-induced obesity in flies is associated with many of the pathophysiological consequences found in humans, including hyperglycemia, insulin resistance, cardiac arrhythmia and fibrosis, reduced longevity [269, 270] and nephrosis [271]. The gut is crucial for peripheral body fat storage and serves as a major site of dietary lipid absorption and absorbs other dietary macronutrients (sugars, proteins and fats). It also metabolizes both glucose and lipids into metabolic intermediates, which after loading into hemolymph get used in other tissues and organs. In flies, lipoprotein complexes containing apolipophorins carry sterols and diacylglycerols from the gut to other tissues [81]. Fly lipoproteins also contain Hh, a cholesterol-linked, gut-derived ligand that binds the transmembrane receptor Patched on fat body target cells to promote lipolysis during larval starvation [241, 272]. The human anti-obesity drug orlistat, a gastric lipase inhibitor, has been shown to reduce body fat accumulation in adult flies [56]. Supporting a crucial role for lipolysis, midgut lipid accumulation and global fat storage are reduced by the insulin signaling pathway inhibitor Foxo in enterocytes, via reducing the expression of
The gut microbiota and its metabolism plays an important role in modulation of fat storage in the fly. As seen in humans, fly gut is enriched in
Recently
In the recent past, data from the intestinal mechanisms found in flies have been shown to be active in mammals, and may therefore become relevant in the context of human pathologies including diabetes, obesity, neurodegenerative diseases, gastrointestinal cancers, or aging. Parallel findings of communication between gut and brain via neuropeptides in
Developing new techniques and behavioral assays can help us explore physiological drives: what is the gut function to maintain the overall health of the animal. It would be interesting to find out the key intestinal sensors. How the physical association between gut and brain via neural micro circuits regulate decisions regarding nutrition, hunger and satiety is under question. Better “holistic” and quantitative methods, integration of spatial and temporal information about genetic events more comprehensively are required, so that cause and effect can be uncoupled in a physiological context [306]. We anticipate and hope that fly models of intestinal pathology, in addition to uncovering newly identified genes (chemosensory and others) and basic biology mechanisms will emphasize the most conserved aspects of human intestinal biology. As a result, fly will contribute to translational research investigating drug effects, and microbial and host genetic component analyses, leading to biological findings that are broadly applicable to human health and disease.
The authors declare no conflict of interest.
This work is supported by Wellcome Trust/DBT India Alliance Fellowship (grant number IA/I/15/2/502074) awarded to PK.
ZS, SK and PK all substantially contributed to the conception and design of the work. Everybody participated in drafting and revising the work, made the figures, wrote the chapter and approved the final version for publication.
ENS | Enteric nervous system |
GI | Gastrointestinal |
GBA | Gut brain axis |
CNS | Central nervous system |
ISCs | Intestinal stem cells |
ECs | Enterocytes |
EE | Enteroendocrine |
EBs | Enteroblasts |
TA | Transient amplifying |
AMP-5′ | Adenosine monophosphate |
AMPK- 5’ | AMP activated kinase |
TAG | Triacylglyceride |
Sug | Sugarbabe |
CD36 | Cluster of differentiation 36 |
Npc1 | Niemann-Pick C1 |
SREBPs | Sterol regulatory element-binding proteins |
Akh | Adipokinetic hormone |
RNAi | RNA interference |
Kcc | Kazachoc |
SIET | Scanning ion-selective electrode technique |
Dh44 | Diuretic hormone 44 |
GPCR | G-protein coupled receptors |
PNS | Peripheral nervous system |
GLUT | Glucose transporter |
SGLT | Na+/glucose cotransporter |
GIP | Gastric inhibitory polypeptide |
GLP | Glucagon like peptide |
TK | Tachykinin |
MOR | μ – opoid receptors |
IGN | Intestinal gluconeogenesis |
MOR-KO | MOR-knockouts |
cNST | Caudal nucleus of the solitary tract |
GLP1 | Glucagon- like peptide 1 |
sNPF | Short neuropeptide F |
AN | Antennal nerve |
Ilp7 | Insulin-like peptide 7 |
VN | Vagus nerve |
IBS | Intestinal bowel syndrome |
HGN1 | Hindgut neuron1 |
Hh | Hedgehog |
Poxn | Pox-neuro |
Dh31 | Diuretic hormone 31 |
Lst | Limostatin |
Lk | Leucokinin |
JH | Juvenile hormone |
Crtc/CREB | cAMP-regulated transcriptional co-activator/ cyclic AMP-responsive element-binding protein |
SEZ | Suboesophageal zone |
CRH | Corticotropin –releasing -hormone |
PI | Pars intercerebralis |
IPC | Insulin producing cells |
DILP | Drosophila insulin- like- peptide |
5-HT1A-5 | Hydroxy tryptamine /serotonin |
AKH | Adipokinetic hormone |
PYY | Peptide YY |
AgRP | Agouti-related protein |
CCK | Choleocystokinin |
PP | Pancreatic polypeptide |
NPY | Neuropeptide Y |
Pigment- dispersing factor | |
CRF | Corticotropin-releasing factor |
BDNF | Brain-derived neurotrophic factor |
SCFAs | Short-chain fatty acid |
AMP | Anti-microbial peptide |
ROS | Reactive oxygen species |
DUOX | Dual oxidase |
IMD | Immune deficiency |
APC | Adenomatous polyposis coli gene |
CRC | Colorectal cancer |
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Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"May 26th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:289,numberOfPublishedBooks:27,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRqB9QAK/Profile_Picture_1626163237970",institutionString:null,institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"chapter.detail",path:"/chapters/33112",hash:"",query:{},params:{id:"33112"},fullPath:"/chapters/33112",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()