\r\n\tNotably, the book encourages academic scholars and researchers to contribute to the modern concepts of CSR. Fundamentally, it speaks for well-developed literature for entrepreneurs and managers, thus assisting them in the decision-making process. \r\n\tFurthermore, this book is of great value to policymakers, practitioners, and corporations, thus contributing to various disciplines (e.g., social science and management). \r\n\tThese proposed themes encourage future researchers and professionals to share their ideas, concepts and work concerning these subject domains. All these suggested topics had recommended under the rubrics of CSR. Perhaps, all the professionals, researchers, and scholars are welcome to submit their piece of work, in particular to the suggested topics. \r\n\tIndeed, the recommended topics include the following but are not limited to these only. \r\n\t• Corporate Governance and Sustainability \r\n\t• Green Innovation and CSR \r\n\t• Social Entrepreneurship \r\n\t• Green Economy and Social and Environmental Sustainability \r\n\t• Sustainable Development and Industrialization
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1. Introduction
Luminous organisms, such as fireflies, Gaussia princeps, Oplophorus gracilirostris, and sea pansy Renilla reniformis, generate bioluminescence (BL), which is the light emission in the absence of external energy sources [1, 2]. In the core of BL, an enzymatic reaction occurs involving a bioluminescent substrate (luciferin) and enzyme (luciferase). In general, the enzymatic luminescence reaction proceeds between a specific luciferin-luciferase pair to allow for highly sensitive and specific detection/imaging of diverse molecular events in living subjects [2, 3, 4].
However, in some cases, bioluminescent or chemiluminescent substrates may induce enzymatic luminescence activity of non-bioluminescence enzymes. For example, CycLuc2, a synthetic analog of firefly luciferin, can be catalyzed to emit light by long-chain fatty acid acyl-CoA synthetase found in non-luminous insects [5, 6, 7]. In addition, the heme-containing enzyme myeloperoxidase, which is abundantly expressed in neutrophils and monocytes, can catalyze the luminescence reaction of xenobiotic luminol [8, 9]. These reports suggested that the introduction of appropriate exogenous luminescent substrates reveals luminous activity of non-bioluminescence enzymes, which can significantly differ from the conventional function of the enzyme and has potential for use in quantitative analysis of enzymes without any labeling procedures, including transgene introduction of luciferase from luminous organisms. Here, we describe the design and bioluminescence characterization of a luciferin analogue which was selectively catalyzed to exhibit bioluminescence by human serum albumin (HSA) [10]. Serum albumins perform various physiological functions; they maintain colloid osmotic blood pressure and transport several exogenous and endogenous molecules. However, they are not categorized in the list of EC number, indicating they are not considered typical enzymes. The bioluminescence system of HSA with the luciferin analogue synthesized by us is novel and different from the conventional luciferin-luciferase reaction systems.
2. Design of coelenterazine analogue
2.1 Coelenterazine analogue with HSA-specific bioluminescence
Most luciferases from luminous marine organisms use coelenterazine (CTZ) as their luciferin to form coelenteramide in an excited state, with emission ranging from blue to green at approximately 400–500 nm (Figure 1) [11, 12]. CTZ is oxidized by bovine serum albumin (BSA) in addition to luciferase, and this has been considered as nonspecific reaction mainly occurs because of a simple luminescence reaction that requires only an oxygen molecule [1] (Figure 1).
Figure 1.
Chemical reaction of coelenterazine (CTZ)-dependent bioluminescence. The imidazopyrazinone structure and modifiable substituent are highlighted in red and blue, respectively.
The emission ability of CTZ is derived from the imidazopyrazinone ring, and the chemical structure of sidechains at the C-2, C-6, and C-8 position of the imidazopyrazinone core significantly affect enzyme recognition. For example, Cypridina luciferase oxidizes only Cypridina luciferin, which contains a basic guanidine moiety at the C-8 position of the imidazopyrazinone ring, not CTZ (Figure 2) [13]. A mutant Oplophorus luciferase (NanoLuc) uses furimazine rather than CTZ, and is known as a versatile reporter of BL (Figure 2) [14]. Thus, each bioluminescence probe has been individually developed with an imidazopyrazinone analogue that is suitable for the geometry of the active site in the pocket of mutant luciferase. We also reported that RLuc8.6-535SG, a mutant R. reniformis luciferase, utilizes BottleBlue2.3 (BBlue2.3), a CTZA that can permeate the cell membrane and emits bright visible luminescence suitable for deep-tissue imaging of cancer cells in vivo (Figure 3a) [15].
Figure 2.
Chemical structures of imidazopyrazinone-based analogues.
Figure 3.
Chemical structures of coelenterazine analogues (CTZAs) upon (a) C-2 and/or C-6 substitution. (b) Luminescence intensities obtained with serum albumin (0.1 mg/mL).
To clarify the potential enzymatic luminescence activity of human proteins, we focused on HSA, which accounts for approximately 65% of serum proteins in the human body [16]. This abundant protein is involved in a wide variety of physiological functions, such as maintaining osmotic pressure, buffering blood pH levels, and carrying ligands including hormones, amino acids, and fatty acids [17, 18]. In addition, HSA and some ligand complexes often possess enzymatic activities, such as Kemp elimination and hydrolysis of esters because of their unique ability to bind small hydrophobic molecules in some cavities; however, the potential enzymatic activities remain unclear [17, 19].
First, to obtain a rational luciferin with an imidazopyrazinone core for HSA-specific BL, we assayed CTZ and previously reported 18 CTZAs named as Bottle Blue (BBlue), where the p-hydroxy phenyl group at the C-6 position of CTZ was modified by alkylation (Figure 3), with serum albumins (fatty acid free HSA and BSA). In this chapter, except for in Section 2.2, luminescence measurements were performed using luminometers (GloMax20/20 Luminometer or GloMax Explorer Multimode Microplate Reader) manufactured by Promega (Madison, WI, USA). Next, BBlue2.3, a CTZA with a methoxy-terminated alkyl linker chain of three methylene units at the C-6 position, exhibited the brightest emission, which produced 16.6-fold higher luminescence when combined with HSA (i.e. BBlue2.3/HSA pair) compared to that of the CTZ/HSA pair (Figure 3).
Based on these results, we predicted that elimination of the benzyl group at the C-8 position of BBlue2.3 would relieve its steric hindrance with key amino acids in the substrate binding site of HSA and enhance the enzymatic luminescence reaction of HSA. We then designed and synthesized a novel CTZA, named as Human Luminophore 1 (HuLumino1) based on the synthetic procedures of BBlue2.3 [15] and an array of 5 CTZAs containing known analogues [20] to investigate the effect of substitution at the C-2, C-6, and C-8 positions of CTZ on serum albumin-dependent luminescence (Figure 4b–d). Moreover, the luminescence of commercially available CTZAs (DeepBlueC and MCLA) was compared with the synthesized CTZAs when fatty acid free HSA and BSA were added (Figure 4e). Although the autoluminescence levels in PB buffer of HuLumino1 was similar to that of CTZ, only HuLumino1 displayed significantly enhanced luminescence dependent on HSA (but not BSA containing fatty acid) concentrations, as indicated by the 14.1-fold higher emission compared with that of the BBlue2.3/HSA pair. Furthermore, the luminescence intensity of the HuLumino1/HSA pair was found to be 718-fold higher than that of the CTZ/BSA pair, which has been reported to produce luminescence [11, 12]. The HuLumino1/HSA pair exhibited flash-type luminescence with a peak wavelength of 432 nm. (Figure 4f). Unexpectedly, HuLumino1 selectively activated HSA by recognizing the subtle conformational difference in the substrate binding site, although the overall sequence homology between HSA and BSA is 75.6%.
Figure 4.
Chemical structures of coelenterazine analogues (CTZAs) upon (a) C-2, C-6, and C-8 substitutions, (b) HSA-specific substitution, (c) C-2 and C-6 substitution, and (d) C-2 or C-6 substitution. (e) Luminescence from serum albumins (0.1 or 1 mg/mL) treated with the indicated substrate (10 μM); error bars represent the standard deviations of three measurements. (f) Bioluminescence spectra of HuLumino1 in the presence or absence of HSA.
These results suggest “luciferase” activity of HSA catalyzes the enzymatic luminescence reaction of CTZAs to produce “bioluminescence”.
2.2 Quantitative evaluation of luminescence intensity
To characterize the enzymatic luminescence reaction with HSA, the bioluminescence intensity of CTZAs and HSA pairs was quantitatively evaluated. Bioluminescence intensity is generally determined by several reaction factors including the bioluminescence quantum yieldφBL of luciferin, turnover number (kcat), and active luciferase concentration. Kinetic parameters were determined using a custom-built luminometer with a photomultiplier tube (PMT) (H11890–01; Hamamatsu Photonics, Japan), and its absolute responsibility for total number of emitted photons in the instrument was calibrated for luminescence spectrum of each luciferin-luciferase pair [21, 22]. The absolute responsibility of the luminometer for the CTZ-utilizing bioluminescent system was determined as described previously [21]. The φBL values were calculated from the total number of emitted photons and total number of reacted luciferin molecules. To integrate all photons derived from the enzymatic reaction, the number of photons was monitored using the luminometer from before initiating the reaction to until the reaction was completed. The reaction was initiating by injection of fatty acid-free HSA PB solution (100 μg/mL or 10 mg/mL) into the preinstalled luciferin PB solution (20 nM) in the luminometer.
The Michaelis–Menten constant (Km) of luciferin was calculated from Lineweaver-Burk plots constructed using a standard method. The catalytic constant (kcat), which is the turnover number of the reaction for luciferin by a single luciferase molecule per second, was calculated from theφBL value and maximum velocity (Vmax) determined from the Lineweaver-Burk plots.
The apparent Km of the HuLumino1/HSA pair was 4.3 μM, which was comparable to that of the NanoLuc system [23]. In contrast, the kcat value of the NanoLuc system was 294-fold higher than that of the HuLumino1/HSA pair, and the catalytic efficiency of the luminescence reaction by HSA was lower than that of conventional luciferase [24]. However, in the luminescence system with HSA, HuLumino1 displayed a slightly higher Km value than CTZA-1, but its kcat value was approximately 3-fold higher (Table 1), resulting in 4.2-fold stronger light emission than that of CTZA-1 (Figure 4e). For luciferin with high enzyme affinity (e.g., CTZA −1), oxyluciferin, a product of the BL reaction, appears to competitively inhibit the luminescence reaction [25]. Moreover, HuLumino1 showed an enzyme affinity and bioluminescence quantum yield φBL of more than 5- and 100-fold higher than those of CTZ, respectively. The detailed luminescent profiles suggest that the structural properties of the alkyl linker chain modified at the C-6 position of the imidazopyrazinone core contribute to the efficient HSA-catalyzed emission reaction. Although the catalytic efficiency of HuLumino1/HSA is much lower than that of the NanoLuc system, HuLumino1 is a luciferin that is relatively more suitable for HSA than other existing luminescent substrates.
Pair
φBLa×10−5
KmbμM
kcatcs−1
CTZ/HSA
0.32 ± 0.03
25.3 ± 5.2
2.75 ± 0.3
HuLumino1/HSA
30.9 ± 3.1
4.28 ± 1.24
0.30 ± 0.06
CTZA-4/HSA
42.2 ± 9.1
2.46 ± 0.40
0.11 ± 0.09
Table 1.
Luminescent profiles of CTZ and its analogues with HSA.
Errors represent standard error of the mean values for triplicate experiments.
Michaelis-Menten constant (Km) values were determined by Lineweaver-Burk plots via measurements of initial rates of light emission over a range 0.5 to 20 μM.
Turnover rate (kcat) values were calculated by dividing maximum velocity (Vmax) by the φBL. The Vmax were determined by Lineweaver-Burk plots.
2.3 Enzymatic reaction site of HSA
The crystal structure of HSA, with binding to a variety of drugs, clarified the two principal drug binding sites in different subdomains (site 1 in subdomain IIA and site 2 in subdomain IIIA) [26, 27]. To investigate the luminescent reaction site between HSA and HuLumino1, a competitive assay was conducted with two site-specific HSA drugs (warfarin-site1 and ibuprofen-site2) [27]. Fatty acid free HSA PB solution was pre-treated with the drugs (0–100 μM) to fill binding site 1 or 2 before adding HuLumino1. The luminescence of HuLumino1 was negligibly low in the presence of HSA-ibuprofen complex (Figure 5a). In contrast, HuLumino1 exhibited efficient luminescence with the HSA-warfarin complex, indicating that HuLumino1 selectivity binds to the site 2 cavity of HSA. In detailed analysis of the inhibitory kinetics, Lineweaver-Burk plots displayed that ibuprofen competitively inhibited the binding of HuLumino1 to HSA (Ki of ibuprofen was 6.3 nM) (Figure 5b). Therefore, the enzymatic reaction site of HuLumino1 was experimentally determined to be binding site 2. Next, docking simulation with the Molecular Operating Environment software package was carried out to predict the binding poses. The simulation displayed the specific binding of HuLumino1 to the hydrophobic cavity of site 2 by interacting with several amino acids including R410, K414, and L453 (Figure 5c–e). Particularly, R410, a key amino acid residue in the esterase activity of HSA [17], is also involved in the luminescence reaction (Figure 5e).
Figure 5.
(a) Luminescence response in the presence (I) vs. absence (I0) of the binding drug concentration (0–100μM). (b) Lineweaver-Burk plot indicating competitive inhibition by ibuprofen. V0 is defined as the luminescence intensity over the initial 30 s and [S] is the substrate concentration. The concentrations of ibuprofen were 1 nM (square) and 5 nM (triangle). Open circles indicate negative controls with no ibuprofen. (c) Ligand-binding site 2 of HSA with HuLumino1 as posed by the molecular operating environment software (d) magnified view of binding site 2. The ligand binding site in the blue region indicates the presence of the hydrophobic environment. (e) Predicted interaction between HuLumino1 and HSA.
Next, to investigate the effect of the steric structure of HSA on luminescence, HSA pretreated with 10 M guanidine hydrochloride, a reagent commonly used to induce denaturation of the α-helix structure of proteins [28], was prepared, and the luminescence of HuLumino1 was extremely low in the presence of denatured HSA (data not shown). Therefore, the enzymatic reaction of HuLumino 1 depends on the microenvironment and steric structure such as binding site 2 constructed by the folding structure of HSA. These results suggest that emission of HuLumino1/HSA is not a non-specific chemiluminescence commonly found in other imidazopyrazinone compounds.
2.4 Bioluminescent assay for HSA
Low levels of HSA in the serum (<35 mg/mL) are biomarkers of several diseases such as malnutrition, cirrhosis, and chronic hepatitis [29]. In hospitals, HSA is evaluated using the colorimetric bromocresol green assay or ELISA. Both can provide a reliable assessment of albumin but require sample preparation and processing time (e.g. 3 h for ELISA) [30]. Therefore, an assay for the simple, accurate and rapid detection of HSA in the serum should be developed for clinical diagnosis. We demonstrated that the BL assay can be used to evaluate HSA based on the enzymatic luminescence reaction of HuLumino1. Regarding the selectivity of the reaction of HuLumino1, no reactivity with other proteins (BSA, β-galactosidase,β-lactoglobulin, catalase, α-chymotrypsinogen, hemoglobin, human IgG, porcine lipase, papain, pepsin, trypsin, γ-globulin, carbonic anhydrase, concanavalin A, glucosidase, histone, myoglobin, and RNase, 0.1 mg/mL) was observed, and only HSA led to distinct luminescence enhancement (Figure 6a). Although the coexistence of most proteins did not affect the enzymatic reaction of the HSA/Hulumino1 pair, a slight decrease in luminescence was observed in the presence of some proteins (data not shown). This indicates that HuLumino1 nonspecifically binds to other proteins but does not exhibit BL. Hence, HuLumino1 can be used to detect HSA without interference from other proteins, as it exhibited excellent selectivity for HSA even in a complicated biological system. The luminescence of HuLumino1 was enhanced in an HSA concentration-dependent manner and exhibited a constant intensity at HSA concentrations above 10 mg/mL (Figure 6b). A linear increase in luminescence, within the spiked HSA concentration range of 0–0.1 mg/mL in PBS-diluted serum, resulted in a detection limit of 8.6 μg/mL for HSA, which was comparable to the standard detection limit of HSA in physiological systems (Figure 6c) [31].
Figure 6.
(a) Variation in luminescence of HuLumino1 (10 μM) in the presence of proteins (0.1 mg/mL); error bars represent the standard deviations of three measurements. (b) Luminescence intensity of HuLumino1 (20 μM) containing various concentrations of HSA (0–17 mg/mL) in PBS and (c) HSA (0–17 mg/mL) in PBS-diluted plasma (100-fold, pH 7.4).
Finally, two HSA assays, including our developed BL-based assay and ELISA, were performed to evaluate human serum from male AB plasma. The HSA levels calculated with HuLumino1 agreed well with those estimated by ELISA within 5% error. The spike and recovery tests also showed results within the margin of 7% error (Table 2). Therefore, the BL-based HSA assay showed analytical capability with high sensitivity and could detect HSA within 10 min including the sample preparation and measurement times. In addition, we detected the expression of recombinant HSA in living COS-1 cells (data not shown), indicating that HuLumino1 can be used in molecular biology studies and in biomedical applications.
Conditions: HuLumino1 (20μM) in PBS-diluted serum (1000-fold, 10 mM, pH 7.4).
ND: Not Determined.
We designed and synthesized the first luciferin (HuLumino1), an analogue with C-6 and C-8 modification of CTZ, which exhibited bioluminescence with HSA. HuLumino1 rapidly detected HSA with high sensitivity and specificity, even in real human plasma containing various interfering biomolecules. Detailed kinetic investigation of the enzymatic reaction clarified the enzyme recognition of HuLumino1 from HSA drug binding site 2, resulting a highly selective reaction and revealing a reaction with both native HSA and recombinant HSA expressed in COS-1 cells. Therefore, the BL-based assay with HuLumino1, either used alone or coupled with ELISA, can be used for the early diagnosis of HSA-related diseases, enabling accurate and rapid detection of HSA in serum samples without pre-treatment. The information obtained through detailed investigation of the HuLumino1/HSA pair may be extended to protein assays based on a luminescent reaction without genetically engineered luciferases.
Acknowledgments
We acknowledge funding from JST, PRESTO Grant Number JPMJPR20EB, JSPS KAKENHI Grant Number 20 K15421, AMED under Grant Number JP191m0203012, Shimazu Science Foundation, Research Foundation for Opto-Science and Technology, and Nakatani Foundation for Advancement of Measuring Technologies in Biomedical Engineering, and DAICENTER project grant from DBT (Govt. of India) to Renu Wadhwa and special strategic grant from AIST (Japan).
Conflict of interest
The authors declare no conflict of interest.
Notes/thanks/other declarations
We thank Dr. Tsukasa Ishihara (Biomedical Research Institute, National Institute of Advanced Industrial International Science and Technology) for his help with the docking simulation experiment.
\n',keywords:"Bioluminescence, Coelenterazine, Luciferin, Luciferase, Human serum albumin, Quantum yield, Enzyme-linked immunosorbent assay",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/76175.pdf",chapterXML:"https://mts.intechopen.com/source/xml/76175.xml",downloadPdfUrl:"/chapter/pdf-download/76175",previewPdfUrl:"/chapter/pdf-preview/76175",totalDownloads:196,totalViews:0,totalCrossrefCites:0,dateSubmitted:"February 24th 2021",dateReviewed:"March 15th 2021",datePrePublished:"April 19th 2021",datePublished:"December 15th 2021",dateFinished:"April 8th 2021",readingETA:"0",abstract:"This chapter describes the design of an imidazopyrazinone-type luciferin named as HuLumino1 by us and investigation of its luminescence properties. This luciferin was designed to generate bioluminescence by human serum albumin (HSA) rather than by luciferase derived from luminous organisms. HuLumino1 was developed by modifying a methoxy-terminated alkyl chain to the C-6 position and eliminating a benzyl group at the C-8 position of coelenterazine. To clarify the basis of light emission by HSA, the detailed kinetic properties of the HuLumino1/HSA pair were investigated using a calibrated luminometer. The enzymatic oxidation of HuLumino1 was observed only in the presence of HSA. Results of HSA quantification experiments using HuLumino1 agreed with less than 5% differences with those of enzyme-linked immunosorbent assays, suggesting HuLumino1 could be used for quantitative analysis of HSA levels in serum samples without any pretreatments. These results demonstrate the advantages of the coelenterazine analogue as a bioluminescence reagent to detect non-labeled proteins, which generally do not function as enzymes.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/76175",risUrl:"/chapter/ris/76175",signatures:"Ryo Nishihara, Kazuki Niwa, Tatsunosuke Tomita and Ryoji Kurita",book:{id:"9655",type:"book",title:"Bioluminescence",subtitle:"Technology and Biology",fullTitle:"Bioluminescence - Technology and Biology",slug:"bioluminescence-technology-and-biology",publishedDate:"December 15th 2021",bookSignature:"Hirobumi Suzuki and Katsunori Ogoh",coverURL:"https://cdn.intechopen.com/books/images_new/9655.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83962-386-8",printIsbn:"978-1-83962-385-1",pdfIsbn:"978-1-83969-278-9",isAvailableForWebshopOrdering:!0,editors:[{id:"185746",title:"Dr.",name:"Hirobumi",middleName:null,surname:"Suzuki",slug:"hirobumi-suzuki",fullName:"Hirobumi Suzuki"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"232417",title:"Dr.",name:"Tatsunosuke",middleName:null,surname:"Tomita",fullName:"Tatsunosuke Tomita",slug:"tatsunosuke-tomita",email:"tatsunosuke-tomita@aist.go.jp",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"339928",title:"Dr.",name:"Ryo",middleName:null,surname:"Nishihara",fullName:"Ryo Nishihara",slug:"ryo-nishihara",email:"r.nishihara@aist.go.jp",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"340774",title:"Dr.",name:"Kazuki",middleName:null,surname:"Niwa",fullName:"Kazuki Niwa",slug:"kazuki-niwa",email:"niwa-k@aist.go.jp",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},{id:"340777",title:"Dr.",name:"Ryoji",middleName:null,surname:"Kurita",fullName:"Ryoji Kurita",slug:"ryoji-kurita",email:"r.kurita@aist.go.jp",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Design of coelenterazine analogue",level:"1"},{id:"sec_2_2",title:"2.1 Coelenterazine analogue with HSA-specific bioluminescence",level:"2"},{id:"sec_3_2",title:"2.2 Quantitative evaluation of luminescence intensity",level:"2"},{id:"sec_4_2",title:"2.3 Enzymatic reaction site of HSA",level:"2"},{id:"sec_5_2",title:"2.4 Bioluminescent assay for HSA",level:"2"},{id:"sec_7",title:"Acknowledgments",level:"1"},{id:"sec_10",title:"Conflict of interest",level:"1"},{id:"sec_7",title:"Notes/thanks/other declarations",level:"1"}],chapterReferences:[{id:"B1",body:'Shimomura O. Bioluminescence: Chemical Principles and Methods. Bioluminescence: Chemical Principles and Methods. Singapore: World Scientific Publishing Company; 2006. 471 p'},{id:"B2",body:'Badr C. Bioluminescent Imaging: Methods and Protocols. Bioluminescent Imaging: Methods and Protocols. New York: Springer; 2014. 1276 p'},{id:"B3",body:'Rowe L, Dikici E, Daunert S. 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Smart self-assembled organic nanoprobe for protein-specific detection: design, synthesis, application, and mechanism studies. Analytical Chemistry. 2017;89(18):10085–10093. DOI: 10.1021/acs.analchem.7b02923'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Ryo Nishihara",address:"r.nishihara@aist.go.jp",affiliation:'
National Institute of Advanced Industrial Science and Technology (AIST), Japan
National Institute of Advanced Industrial Science and Technology (AIST), Japan
University of Tsukuba, Japan
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Dairy farming being one of the agricultural production in Ethiopia, is practiced mainly as an extensive type of management system, which involves smallholder farmers in rural areas and semi-intensive and intensive managements in per urban and urban areas. Despite a large number of milking cows, there is low milk production because of many factors, including low genetic potential of indigenous breeds, extensive and poor husbandry practices, and widespread livestock diseases. Among the dairy cows’ diseases, mastitis is prevalent in the dairy production system incurring high economic losses and social burden. Several reports on mastitis in Ethiopia are present but are scattered. We focused on reviewing articles published in indexed journals reporting bovine mastitis to summarize its common etiologies, prevalence, and risk factors in Ethiopia. The common pathogens reported from different parts of Ethiopia are Staphylococcus aureus (Staph. aureus), non-aureus staphylococci, Streptococcus spp. (Strep. agalactiae, Strep. dysgalactiae, Strep. uberis), coliforms (E. coli, Klebsiella pneumonae), Trueperella pyogenes and Mannheimia haemolytica (M. haemolytica), Pseudomonas aeruginosa (P. aeroginosa), Enterobater aerogenes, Bacillus species, Micrococcus species. Staphylococcus aureus and E. coli are the most common isolates from clinical mastitis (CM). Staphylococcus aureus is also the most frequently isolated pathogen from sub-clinical mastitis (SCM). Sub-clinical mastitis which usually ranges from 25.4% to 73.3%, is highly prevalent than the clinical cases of mastitis which ranges from 3.2% to 26.5%. Several mastitis risk factors were reported. These were breed of animals, parity number, stage of lactation, presence of teat/udder lesion and hygiene measure of the farms. 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Cárdenas-Aguayo, M. del C. Silva-Lucero, M. Cortes-Ortiz,\nB. Jiménez-Ramos, L. Gómez-Virgilio, G. Ramírez-Rodríguez, E. Vera-\nArroyo, R. Fiorentino-Pérez, U. García, J. 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MRI is commonly used once treating brain, prostate cancers, ankle and foot. The Magnetic Resonance Imaging (MRI) images are usually liable to suffer from noises such as Gaussian noise, salt and pepper noise and speckle noise. So getting of brain image with accuracy is very extremely task. An accurate brain image is very necessary for further diagnosis process. During this chapter, a median filter algorithm will be modified. Gaussian noise and Salt and pepper noise will be added to MRI image. A proposed Median filter (MF), Adaptive Median filter (AMF) and Adaptive Wiener filter (AWF) will be implemented. The filters will be used to remove the additive noises present in the MRI images. The noise density will be added gradually to MRI image to compare performance of the filters evaluation. The performance of these filters will be compared exploitation the applied mathematics parameter Peak Signal-to-Noise Ratio (PSNR).",book:{id:"6144",slug:"high-resolution-neuroimaging-basic-physical-principles-and-clinical-applications",title:"High-Resolution Neuroimaging",fullTitle:"High-Resolution Neuroimaging - Basic Physical Principles and Clinical Applications"},signatures:"Hanafy M. Ali",authors:[{id:"213318",title:"Dr.",name:"Hanafy",middleName:"M.",surname:"Ali",slug:"hanafy-ali",fullName:"Hanafy Ali"}]},{id:"41589",doi:"10.5772/50323",title:"The Role of the Amygdala in Anxiety Disorders",slug:"the-role-of-the-amygdala-in-anxiety-disorders",totalDownloads:9671,totalCrossrefCites:4,totalDimensionsCites:28,abstract:null,book:{id:"2599",slug:"the-amygdala-a-discrete-multitasking-manager",title:"The Amygdala",fullTitle:"The Amygdala - A Discrete Multitasking Manager"},signatures:"Gina L. Forster, Andrew M. Novick, Jamie L. Scholl and Michael J. 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Particularly in the case of motor imagery BCIs, users may need several training sessions before they learn how to generate desired brain activity and reach an acceptable performance. A typical training protocol for such BCIs includes execution of a motor imagery task by the user, followed by presentation of an extending bar or a moving object on a computer screen. In this chapter, we discuss the importance of a visual feedback that resembles human actions, the effect of human factors such as confidence and motivation, and the role of embodiment in the learning process of a motor imagery task. Our results from a series of experiments in which users BCI-operated a humanlike android robot confirm that realistic visual feedback can induce a sense of embodiment, which promotes a significant learning of the motor imagery task in a short amount of time. We review the impact of humanlike visual feedback in optimized modulation of brain activity by the BCI users.",book:{id:"6610",slug:"evolving-bci-therapy-engaging-brain-state-dynamics",title:"Evolving BCI Therapy",fullTitle:"Evolving BCI Therapy - Engaging Brain State Dynamics"},signatures:"Maryam Alimardani, Shuichi Nishio and Hiroshi Ishiguro",authors:[{id:"11981",title:"Prof.",name:"Hiroshi",middleName:null,surname:"Ishiguro",slug:"hiroshi-ishiguro",fullName:"Hiroshi Ishiguro"},{id:"231131",title:"Dr.",name:"Maryam",middleName:null,surname:"Alimardani",slug:"maryam-alimardani",fullName:"Maryam Alimardani"},{id:"231134",title:"Dr.",name:"Shuichi",middleName:null,surname:"Nishio",slug:"shuichi-nishio",fullName:"Shuichi Nishio"}]}],mostDownloadedChaptersLast30Days:[{id:"29764",title:"Underlying Causes of Paresthesia",slug:"underlying-causes-of-paresthesia",totalDownloads:192666,totalCrossrefCites:3,totalDimensionsCites:7,abstract:null,book:{id:"1069",slug:"paresthesia",title:"Paresthesia",fullTitle:"Paresthesia"},signatures:"Mahdi Sharif-Alhoseini, Vafa Rahimi-Movaghar and Alexander R. 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Precise anatomical description along with a correct characterization of the component structures is essential for understanding its functions.",book:{id:"6331",slug:"hypothalamus-in-health-and-diseases",title:"Hypothalamus in Health and Diseases",fullTitle:"Hypothalamus in Health and Diseases"},signatures:"Miana Gabriela Pop, Carmen Crivii and Iulian Opincariu",authors:null},{id:"57103",title:"GABA and Glutamate: Their Transmitter Role in the CNS and Pancreatic Islets",slug:"gaba-and-glutamate-their-transmitter-role-in-the-cns-and-pancreatic-islets",totalDownloads:3478,totalCrossrefCites:3,totalDimensionsCites:9,abstract:"Glutamate and gamma-aminobutyric acid (GABA) are the major neurotransmitters in the mammalian brain. Inhibitory GABA and excitatory glutamate work together to control many processes, including the brain’s overall level of excitation. The contributions of GABA and glutamate in extra-neuronal signaling are by far less widely recognized. In this chapter, we first discuss the role of both neurotransmitters during development, emphasizing the importance of the shift from excitatory to inhibitory GABAergic neurotransmission. The second part summarizes the biosynthesis and role of GABA and glutamate in neurotransmission in the mature brain, and major neurological disorders associated with glutamate and GABA receptors and GABA release mechanisms. The final part focuses on extra-neuronal glutamatergic and GABAergic signaling in pancreatic islets of Langerhans, and possible associations with type 1 diabetes mellitus.",book:{id:"6237",slug:"gaba-and-glutamate-new-developments-in-neurotransmission-research",title:"GABA And Glutamate",fullTitle:"GABA And Glutamate - New Developments In Neurotransmission Research"},signatures:"Christiane S. Hampe, Hiroshi Mitoma and Mario Manto",authors:[{id:"210220",title:"Prof.",name:"Christiane",middleName:null,surname:"Hampe",slug:"christiane-hampe",fullName:"Christiane Hampe"},{id:"210485",title:"Prof.",name:"Mario",middleName:null,surname:"Manto",slug:"mario-manto",fullName:"Mario Manto"},{id:"210486",title:"Prof.",name:"Hiroshi",middleName:null,surname:"Mitoma",slug:"hiroshi-mitoma",fullName:"Hiroshi Mitoma"}]},{id:"35802",title:"Cross-Cultural/Linguistic Differences in the Prevalence of Developmental Dyslexia and the Hypothesis of Granularity and Transparency",slug:"cross-cultural-linguistic-differences-in-the-prevalence-of-developmental-dyslexia-and-the-hypothesis",totalDownloads:3601,totalCrossrefCites:2,totalDimensionsCites:7,abstract:null,book:{id:"673",slug:"dyslexia-a-comprehensive-and-international-approach",title:"Dyslexia",fullTitle:"Dyslexia - A Comprehensive and International Approach"},signatures:"Taeko N. Wydell",authors:[{id:"87489",title:"Prof.",name:"Taeko",middleName:"N.",surname:"Wydell",slug:"taeko-wydell",fullName:"Taeko Wydell"}]},{id:"58597",title:"Testosterone and Erectile Function: A Review of Evidence from Basic Research",slug:"testosterone-and-erectile-function-a-review-of-evidence-from-basic-research",totalDownloads:1331,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Androgens are essential for male physical activity and normal erectile function. Hence, age-related testosterone deficiency, known as late-onset hypogonadism (LOH), is considered a risk factor for erectile dysfunction (ED). This chapter summarizes relevant basic research reports examining the effects of testosterone on erectile function. Testosterone affects several organs and is especially active on the erectile tissue. The mechanism of testosterone deficiency effects on erectile function and the results of testosterone replacement therapy (TRT) have been well studied. Testosterone affects nitric oxide (NO) production and phosphodiesterase type 5 (PDE-5) expression in the corpus cavernosum through molecular pathways, preserves smooth muscle contractility by regulating both contraction and relaxation, and maintains the structure of the corpus cavernosum. Interestingly, testosterone deficiency has relationship to neurological diseases, which leads to ED. Testosterone replacement therapy is widely used to treat patients with testosterone deficiency; however, this treatment might also induce some problems. Basic research suggests that PDE-5 inhibitors, L-citrulline, and/or resveratrol therapy might be effective therapeutic options for testosterone deficiency-induced ED. Future research should confirm these findings through more specific experiments using molecular tools and may shed more light on endocrine-related ED and its possible treatments.",book:{id:"5994",slug:"sex-hormones-in-neurodegenerative-processes-and-diseases",title:"Sex Hormones in Neurodegenerative Processes and Diseases",fullTitle:"Sex Hormones in Neurodegenerative Processes and Diseases"},signatures:"Tomoya Kataoka and Kazunori Kimura",authors:[{id:"219042",title:"Ph.D.",name:"Tomoya",middleName:null,surname:"Kataoka",slug:"tomoya-kataoka",fullName:"Tomoya Kataoka"},{id:"229066",title:"Prof.",name:"Kazunori",middleName:null,surname:"Kimura",slug:"kazunori-kimura",fullName:"Kazunori Kimura"}]}],onlineFirstChaptersFilter:{topicId:"18",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81646",title:"Cortical Plasticity under Ketamine: From Synapse to Map",slug:"cortical-plasticity-under-ketamine-from-synapse-to-map",totalDownloads:14,totalDimensionsCites:0,doi:"10.5772/intechopen.104787",abstract:"Sensory systems need to process signals in a highly dynamic way to efficiently respond to variations in the animal’s environment. For instance, several studies showed that the visual system is subject to neuroplasticity since the neurons’ firing changes according to stimulus properties. This dynamic information processing might be supported by a network reorganization. Since antidepressants influence neurotransmission, they can be used to explore synaptic plasticity sustaining cortical map reorganization. To this goal, we investigated in the primary visual cortex (V1 of mouse and cat), the impact of ketamine on neuroplasticity through changes in neuronal orientation selectivity and the functional connectivity between V1 cells, using cross correlation analyses. We found that ketamine affects cortical orientation selectivity and alters the functional connectivity within an assembly. These data clearly highlight the role of the antidepressant drugs in inducing or modeling short-term plasticity in V1 which suggests that cortical processing is optimized and adapted to the properties of the stimulus.",book:{id:"11374",title:"Sensory Nervous System - Computational Neuroimaging Investigations of Topographical Organization in Human Sensory Cortex",coverURL:"https://cdn.intechopen.com/books/images_new/11374.jpg"},signatures:"Ouelhazi Afef, Rudy Lussiez and Molotchnikoff Stephane"},{id:"81582",title:"The Role of Cognitive Reserve in Executive Functioning and Its Relationship to Cognitive Decline and Dementia",slug:"the-role-of-cognitive-reserve-in-executive-functioning-and-its-relationship-to-cognitive-decline-and",totalDownloads:22,totalDimensionsCites:0,doi:"10.5772/intechopen.104646",abstract:"In this chapter, we explore how cognitive reserve is implicated in coping with the negative consequences of brain pathology and age-related cognitive decline. Individual differences in cognitive performance are based on different brain mechanisms (neural reserve and neural compensation), and reflect, among others, the effect of education, occupational attainment, leisure activities, and social involvement. These cognitive reserve proxies have been extensively associated with efficient executive functioning. We discuss and focus particularly on the compensation mechanisms related to the frontal lobe and its protective role, in maintaining cognitive performance in old age or even mitigating the clinical expression of dementia.",book:{id:"11742",title:"Neurophysiology",coverURL:"https://cdn.intechopen.com/books/images_new/11742.jpg"},signatures:"Gabriela Álvares-Pereira, Carolina Maruta and Maria Vânia Silva-Nunes"},{id:"81488",title:"Aggression and Sexual Behavior: Overlapping or Distinct Roles of 5-HT1A and 5-HT1B Receptors",slug:"aggression-and-sexual-behavior-overlapping-or-distinct-roles-of-5-ht1a-and-5-ht1b-receptors",totalDownloads:19,totalDimensionsCites:0,doi:"10.5772/intechopen.104872",abstract:"Distinct brain mechanisms for male aggressive and sexual behavior are present in mammalian species, including man. However, recent evidence suggests a strong connection and even overlap in the central nervous system (CNS) circuitry involved in aggressive and sexual behavior. The serotonergic system in the CNS is strongly involved in male aggressive and sexual behavior. In particular, 5-HT1A and 5-HT1B receptors seem to play a critical role in the modulation of these behaviors. The present chapter focuses on the effects of 5-HT1A- and 5-HT1B-receptor ligands in male rodent aggression and sexual behavior. Results indicate that 5-HT1B-heteroreceptors play a critical role in the modulation of male offensive behavior, although a definite role of 5-HT1A-auto- or heteroreceptors cannot be ruled out. 5-HT1A receptors are clearly involved in male sexual behavior, although it has to be yet unraveled whether 5-HT1A-auto- or heteroreceptors are important. Although several key nodes in the complex circuitry of aggression and sexual behavior are known, in particular in the medial hypothalamus, a clear link or connection to these critical structures and the serotonergic key receptors is yet to be determined. This information is urgently needed to detect and develop new selective anti-aggressive (serenic) and pro-sexual drugs for human applications.",book:{id:"10195",title:"Serotonin and the CNS - New Developments in Pharmacology and Therapeutics",coverURL:"https://cdn.intechopen.com/books/images_new/10195.jpg"},signatures:"Berend Olivier and Jocelien D.A. Olivier"},{id:"81093",title:"Prehospital and Emergency Room Airway Management in Traumatic Brain Injury",slug:"prehospital-and-emergency-room-airway-management-in-traumatic-brain-injury",totalDownloads:49,totalDimensionsCites:0,doi:"10.5772/intechopen.104173",abstract:"Airway management in trauma is critical and may impact patient outcomes. Particularly in traumatic brain injury (TBI), depressed level of consciousness may be associated with compromised protective airway reflexes or apnea, which can increase the risk of aspiration or result in hypoxemia and worsen the secondary brain damage. Therefore, patients with TBI and Glasgow Coma Scale (GCS) ≤ 8 have been traditionally managed by prehospital or emergency room (ER) endotracheal intubation. However, recent evidence challenged this practice and even suggested that routine intubation may be harmful. This chapter will address the indications and optimal method of securing the airway, prehospital and in the ER, in patients with traumatic brain injury.",book:{id:"11367",title:"Traumatic Brain Injury",coverURL:"https://cdn.intechopen.com/books/images_new/11367.jpg"},signatures:"Dominik A. Jakob, Jean-Cyrille Pitteloud and Demetrios Demetriades"},{id:"81011",title:"Amino Acids as Neurotransmitters. The Balance between Excitation and Inhibition as a Background for Future Clinical Applications",slug:"amino-acids-as-neurotransmitters-the-balance-between-excitation-and-inhibition-as-a-background-for-f",totalDownloads:19,totalDimensionsCites:0,doi:"10.5772/intechopen.103760",abstract:"For more than 30 years, amino acids have been well-known (and essential) participants in neurotransmission. They act as both neuromediators and metabolites in nervous tissue. Glycine and glutamic acid (glutamate) are prominent examples. These amino acids are agonists of inhibitory and excitatory membrane receptors, respectively. Moreover, they play essential roles in metabolic pathways and energy transformation in neurons and astrocytes. Despite their obvious effects on the brain, their potential role in therapeutic methods remains uncertain in clinical practice. In the current chapter, a comparison of the crosstalk between these two systems, which are responsible for excitation and inhibition in neurons, is presented. The interactions are discussed at the metabolic, receptor, and transport levels. Reaction-diffusion and a convectional flow into the interstitial fluid create a balanced distribution of glycine and glutamate. Indeed, the neurons’ final physiological state is a result of a balance between the excitatory and inhibitory influences. However, changes to the glycine and/or glutamate pools under pathological conditions can alter the state of nervous tissue. Thus, new therapies for various diseases may be developed on the basis of amino acid medication.",book:{id:"10890",title:"Recent Advances in Neurochemistry",coverURL:"https://cdn.intechopen.com/books/images_new/10890.jpg"},signatures:"Yaroslav R. Nartsissov"},{id:"80821",title:"Neuroimmunology and Neurological Manifestations of COVID-19",slug:"neuroimmunology-and-neurological-manifestations-of-covid-19",totalDownloads:41,totalDimensionsCites:0,doi:"10.5772/intechopen.103026",abstract:"Infection with SARS-CoV-2 is causing coronavirus disease in 2019 (COVID-19). Besides respiratory symptoms due to an attack on the broncho-alveolar system, COVID-19, among others, can be accompanied by neurological symptoms because of the affection of the nervous system. These can be caused by intrusion by SARS-CoV-2 of the central nervous system (CNS) and peripheral nervous system (PNS) and direct infection of local cells. In addition, neurological deterioration mediated by molecular mimicry to virus antigens or bystander activation in the context of immunological anti-virus defense can lead to tissue damage in the CNS and PNS. In addition, cytokine storm caused by SARS-CoV-2 infection in COVID-19 can lead to nervous system related symptoms. Endotheliitis of CNS vessels can lead to vessel occlusion and stroke. COVID-19 can also result in cerebral hemorrhage and sinus thrombosis possibly related to changes in clotting behavior. Vaccination is most important to prevent COVID-19 in the nervous system. There are symptomatic or/and curative therapeutic approaches to combat COVID-19 related nervous system damage that are partly still under study.",book:{id:"10890",title:"Recent Advances in Neurochemistry",coverURL:"https://cdn.intechopen.com/books/images_new/10890.jpg"},signatures:"Robert Weissert"}],onlineFirstChaptersTotal:17},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:{},subseries:{paginationCount:0,paginationItems:[]},overviewPageOFChapters:{paginationCount:0,paginationItems:[]},overviewPagePublishedBooks:{paginationCount:0,paginationItems:[]},openForSubmissionBooks:{},onlineFirstChapters:{},subseriesFiltersForOFChapters:[],publishedBooks:{},subseriesFiltersForPublishedBooks:[],publicationYearFilters:[],authors:{}},subseries:{item:{},onlineFirstChapters:{},publishedBooks:{},testimonialsList:[]},submityourwork:{pteSeriesList:[],lsSeriesList:[],hsSeriesList:[],sshSeriesList:[],subseriesList:[],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"May 24th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:288,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:"profile.detail",path:"/profiles/335066",hash:"",query:{},params:{id:"335066"},fullPath:"/profiles/335066",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)}()