\r\n\tHydroxyapatite (HA) is an important member of the calcium phosphate chemical family. It has been used in several medical applications for the past decades, due to its chemical similarity to the mineral phase of bone and high biocompatibility. Several studies demonstrated that bone mineral presents several ion substitutions, so in order to prepare a synthetic material with an even closer composition to bone mineral, HA has been prepared with the incorporation of several ions like, silicon or fluoride. These ions induced not only structural changes on HA lattice, but also on its biocompatibility. \r\n\tSignificant advances in nanotechnologies resulted in the preparation of HA in different forms, with a wider range of applications, from support to drug and gene delivery. \r\n\tThis book aims to collect the most relevant information regarding HA properties, modifications and its application in the biomedical field.
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1. Introduction
Invasive pituitary adenoma is a type of pituitary adenoma that locally invades contiguous anatomy structures surrounding pituitary gland [1, 2, 3, 4, 5, 6]. In fact, the rate of local invasion is about 40% of pituitary adenoma patients with macroscopic observation, and even up to 80% of pituitary adenoma patients with microscopic observation [1, 7, 8] although most pituitary adenomas are align. Magnetic resonance imaging (MRI) is commonly used method to measure the size of pituitary adenomas, and can classify pituitary adenomas into giant adenomas (>40 mm), macro-plus adenomas (20–30 mm), macroadenomas (10–20 mm), and microadenomas (<10 mm) [5, 7]. Furthermore, based on preoperative MRI and perioperative observation, pituitary adenomas are classified into grade I (enclosed microadenoma, <10 mm), grade II (enclosed macroadenoma, >10 mm), grade III (localized perforation of the sellar floor), and grade IV (diffuse destruction of the sellar floor) [9]. Grades III and IV are commonly looked as invasive pituitary adenomas. Invasiveness is very challenging clinical problem in pituitary adenoma patient, which reasons are that (1) invasiveness suppresses and/or damage surrounding structures because of the limited intracranial cavity and around important structure tissues, and (2) invasiveness causes incomplete removal of pituitary adenoma in neurosurgery to increase risks of complications including recurrence and poor outcome and need adjuvant therapy (radiotherapy or medications) [1]. However, the molecular mechanisms of pituitary adenoma invasiveness remain unclear, although some studies [10] found more vascular evidence in invasive pituitary adenomas compared to non-invasive tumors to indicate the role of angiogenesis [10], and some molecular and genetic changes in invasive pituitary adenomas including downregulation and methylation of CDH13 (H-cadherin) and CDH1 (E-cadherin) [11], loss of death-associated protein kinase and CpG island methylation [12], and loss of heterozygosity at 11q13 (MEN1 locus) and 13q (retinoblastoma gene RB locus) without mutation and overexpression of p53 and without homozygous deletions of p15 or p16 [13]. Multiomics analysis is an effective approach to investigate systematically molecular mechanisms of invasiveness of pituitary adenomas [14, 15, 16, 17, 18, 19]. Quantitative transcriptomics analysis [9, 20] identified differentially expressed gene (DEG) profiling (346 DEGs, including 233 upregulated and 113 downregulated) between invasive and non-invasive NFPAs. However, protein and its proteoforms are the functional performer of each gene, proteome is much more complex than transcriptome, and the coefficient of correlation is very low (about 0.4) in consistence analysis between proteome and transcriptome for the same tissue sample [21, 22]. Therefore, it is necessary to use proteomics for pituitary adenoma invasiveness [23, 24]. A comparative proteomics experiment revealed 30 differentially expressed proteins (DEPs) profiling between invasive and non-invasive pituitary adenoma tissues [25], however, this study did not distinguish the functional and non-functional pituitary adenomas (FPAs, and NFPAs). This chapter focused on the proteomic variations and molecular network changes in invasive relative to noninvasive NFPAs, investigated with two-dimensional gel electrophoresis (2DGE) coupled with mass spectrometry (MS) and pathway network analysis. The findings offer the scientific data to discover protein biomarkers for effective treatment of invasive NFPAs. An experimental flow-chart is shown to study proteomes between invasive and noninvasive NFPAs (Figure 1).
Figure 1.
Experimental flow-chart to comparatively study the proteomes between invasive and non-invasive NFPAs. Reproduced from Zhan et al. [5], with copyright permission from Wiley-VCH, copyright year 2014.
2. Materials and methods
2.1 2DGE analysis of pituitary adenoma specimen
The invasive (n = 4) and non-invasive (n = 4) NFPA tissues with pathological diagnosis were used in this study. Each tissue sample was used to individually extract proteins, and the protein content was quantified. Each tissue sample was analyzed with 2DGE for 3–4 times [5, 22]. For each 2DGE analysis, 150 μg proteins were used for isoelectric focusing (IEF) with IPG strips pH 3–10 NL (180 × 3 × 0.5 mm). After IEF, the proteins was reduced and alkalized, and then were separated with the 12% PAGE resolving gel (250 × 215 × 1.0 mm), followed by visualization with modified silver-staining [26]. The PDQuest 2D gel analysis software (version 7.1.0; Bio-Rad) was used to digitize and compare 2DGE gel images between invasive and non-invasive NFPAs. A total of 12 gel images for invasive NFPAs and 12 gel images for non-invasive NFPAs were used in this analysis to determine each DEPs with a 3-fold cutoff values and p < 0.05. In addition, four standard proteins, including myoglobin (17 kDa; p. 7.6), carbonic anhydrase (29 kDa; p. 7.0), ovalbumin (45 kDa; p. 5.1), and amyloglucosidase (89/70 kDa; p. 3.8), were applied to measure the observed pI and Mr on the 2D gel.
2.2 Mass spectrometry analysis of 2DGE-separated proteins
The protein that contains in gel spot was digested in-gel with trypsin, followed by ZipTipC18 purification [5, 26]. For LC-ESI-MS/MS analysis, the purified tryptic peptides were eluted in 6 μl of 85% acetonitrile plus 0.1% TFA, air-dried, and then resuspended in 6 μl of 85% acetonitrile plus 0.1% formic acid. The prepared peptide samples were analyzed by LC-ESI-qTOF mass spectrometer to obtain MS/MS spectrum. For MADI-TOF-MS analysis, the ZipTipC18 peptides were directly eluted on MALDI plate with 2 μl of а-cyano-4-hydroxycinnamic acid solution (seven cycles), and dried, and then were analyzed with Voyager DE STR MALDI-TOF mass spectrometer to obtain peptide mass fingerprint (PMF). The MS/MS data and PMF data were used to search SwissProt database with Mascot software for protein identification.
2.3 Bioinformatics
The software NIHDAVID (version 6.7, http://david.abcc.ncifcrf.gov/summary.jsp) was used to carry out gene-ontology (GO) analysis, including cellular components (CC), molecular functions (MF), and biological processes (BP), and furtherly were categorized into different functional clusters. Ingenuity pathway analysis (IPA) (www.ingenuity.com) [27] was applied to obtain statistically significant signaling pathways with identified DEP data between invasive and non-invasive NFPAs.
3. Results and discussion
3.1 2DE pattern and DEP profile between invasive and noninvasive NFPA proteomes
Each NFPA tissue sample (four invasive NFPAs and four non-invasive NFPAs) was analyzed by 2DGE for 3–5 times to guarantee at least three high-quality gel images. Thus, 24 high-quality 2DGE images (12 gel-images for invasive NFPAs; 12 gel images for non-invasive NFPAs) were obtained. About 1200 spots (an average of 1172 spots for invasive NFPAs and 1213 spots for non-invasive NFPAs) were present in each gel image (Figure 2), and most of spots were distributed within pH 4–9 and Mr 15–150 kDa [21]. The average between-gel matched percentage was 64% (61–67%) among invasive NFPA gels, and 67% (61–69%) among non-invasive NFPA gels. The positional deviation of the matched-spots was 2.05 ± 0.89 mm in the IEF direction and 1.41 ± 0.65 mm in the SDS-PAGE direction. For each sample, the average correlation coefficient (r) of the normalized volumes for between-gel matched-spots was 0.74 (range, 0.59–0.83), with a best-fit line of: y = 0.8685x + 0.0804 (r = 0.87; n = 811). The normalized spot volumes between 12 invasive NFPA gels and 12 non-invasive NFPA gels were compared to determine a differential protein spot with at least 3-fold change and p < 0.05. For example, Spot-2010 was identified as differential protein spots downregulated in invasive NFPAs compared to non-invasive NFPAs (Figure 3). With the same approach, 103 differential spots were identified, including 64 upregulated and 39 downregulated protein spots in invasive NFPAs relative to non-invasive NFPAs (Table 1 and Figure 1). It clearly demonstrated that the proteome was significantly different between invasive and non-invasive NFPAs.
Figure 2.
2DGE map with labeled 4 standard protein markers and 103 spots containing DEPs. IEF was carried out with 18-cm IPGStrip pH 3–10 NL. SDS-PAGE was carried out with 12% polyacrylamide gel. The red means downregulated protein spot in invasive NFPAs relative to noninvasive NFPAs. The black means upregulated spot in invasive NFPAs relative to noninvasive NFPAs. Reproduced from Zhan et al. [5], with copyright permission from Wiley-VCH, copyright year 2014.
Figure 3.
A presentative differential protein spots between invasive and non-invasive NFPAs (Spot-2010). IPT: Invasive pituitary tumor. NIPT: Non-invasive pituitary tumor. Reproduced from Zhan et al. [5], with copyright permission from Wiley-VCH, copyright year 2014.
SSP
Swiss-Prot No.
Protein name
Mr (kDa)
pI
Fold
Exp.
Theor.
Exp.
Theor.
0011
Q00535
Cyclin-dependent kinase 5
17.56
33.74
4.04
7.57
13.6
0045
P04434
Ig kappa chain V-III region VH (fragment)
14.35
12.86
4.04
5.63
10.2
0029
P00742/Q8N4Z0
Chain 1: factor X light chain/putative Ras-related protein Rab-42
Differentially expressed proteins between invasive and non-invasive NFPAs identified with 2DGE and mass spectrometry (fold > 3-fold or < −3-fold).
It was identified with LC-ESI-MS/MS, and the others with MALDI-TOF-PMF.
Fold (+) means that it is upregulated in invasive relative to noninvasive NFPAs. Fold (−) means that it is downregulated in invasive relative to noninvasive NFPAs. Exp. pI = −1.00 means that it was out of the pI range of standard markers. Reproduced from Zhan et al. [5], with copyright permission from Wiley-VCH, copyright year 2014.
Furthermore, each DEP in the differential spot was identified with MS [26]. For MALDI-TOF-MS PMF analysis, all interfering masses derived from contaminants including keratins, trypsin, matrix CHCA, and other unknown ones, were removed from MS spectrum of analyzed sample to obtain a corrected mass list for PMF data (Figure 4). Those nine masses labeled in Figure 4B were used with MASCOT PMF search tool to search Swiss-Prot database, and matched to the corresponding tryptic peptides from 78 kDa glucose-regulated protein (GRP78_HUMAN; P11021) (Figure 5), which was the DEP identified in the differential Spot-1809. With the same method, 43 DEPs was identified with PMF analysis (Figure 1 and Table 1). For LC-ESI-MS/MS analysis, the tryptic peptides were separated by LC and then sequenced by MS/MS on the qTOF MS instrument, followed by MASCOT MS/MS data search in the human Swiss-Prot database. For example, six tryptic peptides from Spot-7604 were sequenced and matched to ATP synthase subunit alpha (ATPA_HUMAN; P25705) (Figure 6). With the same method, 11 DEPs were identified with MS/MS data (Figure 1 and Table 1). A total of 57 DEPs, including 30 upregulated and 27 downregulated, were identified in invasive compared to non-invasive NFPAs (Table 1).
Figure 4.
All interfering masses from contaminants derived from the margin blank gel on a silver-stained 2D gel map (A) were removed from MALDI-TOF-MS spectrum derived from the proteins in Spot-1809 (B) to obtain a corrected mass list for PMF data that were labeled as the symbol *. Reproduced from Zhan et al. [5], with copyright permission from Wiley-VCH, copyright year 2014.
Figure 5.
Mascot search results from PMF data (Spot-1809). Modified from Zhan et al. [5], with copyright permission from Wiley-VCH, copyright year 2014.
Figure 6.
Mascot search results from a representative LC-ESI-MS/MS data from proteins in Spot-7604. Modified from Zhan et al. [5], with copyright permission from Wiley-VCH, copyright year 2014.
3.2 Functional characteristics of DEPs identified in invasive relative to noninvasive NFPAs
A total of 54 DEPs out of 57 DEPs were eligible for GO analysis to identify the significant BPs, CCs, and MFs, which are further grouped with hierarchical cluster into to functional clusters (Table 2). It clearly demonstrated those DEPs participated in multiple biological functions to associate with NFPA invasiveness, including peptidase and proteolysis, nucleotide metabolism, mitochondrial functions and oxidative stress, and protein kinase and cell signaling.
Category
Term
Count
P-value
Proteins (DEPs)
Annotation Cluster 1
GOTERM_BP_FAT
Regulation of protein kinase cascade
5
5.56E − 03
P29466, Q96BJ3, P00742, P01241, P04040
GOTERM_BP_FAT
Positive regulation of signal transduction
5
1.00E − 02
P29466, P00742, P01241, P04040, P78536
GOTERM_BP_FAT
Positive regulation of protein kinase cascade
4
1.22E − 02
P29466, P00742, P01241, P04040
GOTERM_BP_FAT
Positive regulation of cell communication
5
1.45E-02
P29466, P00742, P01241, P04040, P78536
Annotation Cluster 2
GOTERM_MF_FAT
Endopeptidase activity
6
3.99E − 03
P29466, P00742, Q99542, Q99797, P56817, P78536
GOTERM_MF_FAT
Peptidase activity, acting on L-amino acid peptides
The functional categories of 54 DEPs identified by GO analysis.
Modified from Zhan et al. [5], with copyright permission from Wiley-VCH, copyright year 2014.
A total of 54 DEPs out of 57 DEPs were accepted for IPA pathway-network analysis to identify significant molecular networks and signaling pathways and molecular networks. Three molecular networks were identified (Figure 7). The hub molecules among those three molecular networks included ATPase, MAPK, ERK, ERK1/2, p38, Jnk, NFkB, AKT, PKA, PKC, EGFR, K-RAS, insulin, UBC, CCND1, IFNG, NFYB, ESR1, CDK5, calmodulin, and S100A1, which are obviously associated with cancer biological systems. About 19 statistically significant canonical pathways were minded from DEPs data (Figure 8), including superoxide radical degradation, mitochondrial dysfunction, eNOS signaling, inhibition of matrix metalloprotease, CDK5 signaling, endoplasmic reticulum stress pathway, ketolysis, ketogenesis, TR/RXR activation, amyloid processing, endothelin-1 signaling, semaphoring signaling in neurons, axonal guidance signaling, neuregulin signaling, and primary immunodeficiency signaling [5]. Also, 10 significant toxicological events were identified with those DEP data, including mitochondrial dysfunction, decreased permeability transition/transmembrane potential/depolarization of mitochondria and mitochondrial membrane, anti-oxidative response panel, and TR/RXR activation. Our previous studies also revealed that MAPK-signaling abnormality, oxidative stress, mitochondrial dysfunction, and TR/RXR activation are significantly associated with NFPAs and invasive NFPAs [27], and the changed molecule-pattern in each pathway-system was different between NFPA and invasive NFPA, which might contribute to the pathological processes of invasive NFPAs. Furthermore, ketogenesis and ketolysis, proteolysis abnormality, amyloid processing, and CDK5 signaling abnormality were also obviously related to invasive NAPFs. Therefore MAPK-signaling abnormality, mitochondrial dysfunction, TR/RXR activation, oxidative stress, proteolysis abnormality, CDK5 signaling abnormality, ketogenesis and ketolysis, and amyloid processing were significantly associated with invasive characteristics of invasive NFPAs, and pathway-network-based molecule patterns benefit to identify reliable biomarkers for invasive NFPAs.
Figure 7.
Significant molecular networks changed in invasive NFPAs. (A) Network 1 functioned in inflammatory disease and inflammatory response. (B) Network 2 functioned in tumor morphology, cancer, cell-to-cell signaling, and interaction. (C) Network 3 functioned in tissue morphology, nervous system development and function, and organismal development. A black solid edge means a direct relationship. A black unsolid edge means an indirect relationship. A red node means upregulated proteins. A green node means downregulated proteins. Reproduced from Zhan et al. [5], with copyright permission from Wiley-VCH, copyright year 2014.
Figure 8.
Statistically significant canonical pathways to involve DEPs in invasive NFPAs. Modified from Zhan et al. [5], with copyright permission from Wiley-VCH, copyright year 2014.
4. Conclusions
Invasiveness is serious clinical problem in human pituitary adenomas. It is necessary to clarify its molecular mechanisms and discover effective biomarkers to guide management of invasive NFPAs. This 2DGE-based comparative proteomics and bioinformatics successfully identified proteomic variation profiling and pathway-network changes in human invasive NFPAs compared to noninvasive NFPAs, found 103 differential protein spots (64 upregulated and 39 downregulated) in invasive versus noninvasive NFPA 2DE maps, and identified 57 DEPs (30 upregulated and 27 downregulated), which are significantly involved in pathogenetic process of invasive NFPAs, with altered pathway networks including MAPK-signaling abnormality, oxidative stress, mitochondrial dysfunction, ketogenesis and ketolysis, CDK5 signaling abnormality, TR/RXR activation, proteolysis abnormality, and amyloid processing. Moreover, some important hub-molecules were identified to associate with cancer biological processes, including ATPase, MAPK, ERK, ERK1/2, p38, Jnk, NFkB, AKT, PKA, PKC, EGFR, K-RAS, insulin, UBC, CCND1, IFNG, NFYB, ESR1, CDK5, calmodulin, and S100A1. Those DEPs, changed pathway networks, and hub-molecules provided new insights into molecular mechanisms of NFPA invasiveness, and important resource for discovery of effective biomarkers to guide the management of invasive NFPAs.
Acknowledgments
The authors acknowledge the financial supports from the Hunan Provincial “Hundred Talent Plan” program (to X.Z.), the Xiangya Hospital Funds for Talent Introduction (to X.Z.), the Hunan Provincial Natural Science Foundation of China (Grant No. 14JJ7008 to X.Z.), China “863” Plan Project (Grant No. 2014AA020610-1 to X.Z.), and the National Natural Science Foundation of China (Grant No. 81572278 and 81272798 to X.Z.). The scientific contributions of Dr. Dominic M. Desiderio from University of Tennessee Health Science Center were also acknowledged.
Conflict of interest
We declare that we have no financial and personal relationships with other people or organizations.
Author’s contributions
X.Z. conceived the concept, designed the book chapter, and wrote and critically revised the book chapter, coordinated and was responsible for the correspondence work and financial support. X.H.Z and X.W participated in experiments. X.H.Z edited the English language. All authors approved the final manuscript.
Acronyms and abbreviations
BP
biological processes
CC
cellular components
DEP
differentially expressed protein
ESI
electrospray ionization
FPA
functional pituitary adenomas
IEF
isoelectric focusing
IPA
ingenuity pathway analysis
IPG
immobilized pH gradient
LC
liquid chromatography
MALDI
matrix-assisted laser desorption/ionization
MF
molecular functions
Mr
relative mass
MRI
magnetic resonance imaging
MS
mass spectrometry
MS/MS
tandem mass spectrometry
NFPA
nonfunctional pituitary adenoma
pI
isoelectric point
PMF
peptide mass fingerprint
SDS-PAGE
sodium dodecyl sulfate-polyacrylamide gel electrophoresis
TOF
time-of-flight
2DGE
two-dimensional gel electrophoresis
\n',keywords:"invasive nonfunctional pituitary adenoma, two-dimensional gel electrophoresis, mass spectrometry, proteome, comparative proteomics, invasive biomarker",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/66459.pdf",chapterXML:"https://mts.intechopen.com/source/xml/66459.xml",downloadPdfUrl:"/chapter/pdf-download/66459",previewPdfUrl:"/chapter/pdf-preview/66459",totalDownloads:796,totalViews:0,totalCrossrefCites:0,dateSubmitted:"November 6th 2018",dateReviewed:"February 28th 2019",datePrePublished:"April 10th 2019",datePublished:"September 25th 2019",dateFinished:"March 29th 2019",readingETA:"0",abstract:"The invasive characteristic of nonfunctional pituitary adenoma (NFPA) is an important clinical problem without a clear molecular mechanism, which severely challenges its treatment strategy. Clarification of the proteomic alterations between invasive and non-invasive NFPAs is the key step for in-depth understanding of its mechanisms and discovering reliably invasive biomarkers. Two-dimensional gel electrophoresis (2DGE)-based comparative proteomics was carried out between four invasive and four non-invasive NFPAs. A total of 64 upregulated protein-spots and 39 downregulated protein-spots were identified among 24 (invasive n = 12; non-invasive n = 12) 2DGE maps (ca. 1200 spots/gel). Mass spectrometry identified 30 upregulated proteins and 27 downregulated proteins between invasive and non-invasive NFPAs. Those 57 differentially expressed proteins are involved in multiple biological functions, including oxidative stress, mitochondrial dysfunction, MAPK signaling alteration, proteolysis abnormality, CDK-C signaling, amyloid processing, and TR/RXR activation. These findings provide important clues to insights into molecular mechanisms of invasive NFPAs and to discovery of effective biomarkers for effective treatment of invasive NFPA patients.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/66459",risUrl:"/chapter/ris/66459",signatures:"Xianquan Zhan, Xiaohan Zhan and Xiaowei Wang",book:{id:"6914",type:"book",title:"Proteomics Technologies and Applications",subtitle:null,fullTitle:"Proteomics Technologies and Applications",slug:"proteomics-technologies-and-applications",publishedDate:"September 25th 2019",bookSignature:"Ibrokhim Y. Abdurakhmonov",coverURL:"https://cdn.intechopen.com/books/images_new/6914.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-78984-611-9",printIsbn:"978-1-78984-610-2",pdfIsbn:"978-1-83962-221-2",isAvailableForWebshopOrdering:!0,editors:[{id:"213344",title:"Prof.",name:"Ibrokhim Y.",middleName:null,surname:"Abdurakhmonov",slug:"ibrokhim-y.-abdurakhmonov",fullName:"Ibrokhim Y. 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Conclusions",level:"1"},{id:"sec_10",title:"Acknowledgments",level:"1"},{id:"sec_10",title:"Conflict of interest",level:"1"},{id:"sec_11",title:"Author’s contributions",level:"1"},{id:"sec_12",title:"Acronyms and abbreviations",level:"1"}],chapterReferences:[{id:"B1",body:'Hussaini IM, Trotter C, Zhao Y, Abdel-Fattah R, Amos S, Xiao A, et al. Matrix metalloproteinase-9 is differentially expressed in nonfunctioning invasive and noninvasive pituitary adenomas and increases invasion in human pituitary adenoma cell line. The American Journal of Pathology. 2007;170:356-365. DOI: 10.2353/ajpath.2007.060736'},{id:"B2",body:'Martins AN, Hayes GJ, Kempe LG. Invasive pituitary adenomas. Journal of Neurosurgery. 1965;22:268-276. DOI: 10.3171/jns.1965.22.3.0268'},{id:"B3",body:'Zhang X, Fei Z, Zhang W, Zhang JN, Liu WP, Fu LA, et al. Endoscopic endonasal transsphenoidal surgery for invasive pituitary adenoma. Journal of Clinical Neuroscience. 2008;15:241-245. DOI: 10.1016/j.jocn.2007.03.008'},{id:"B4",body:'Hashimoto N, Handa H, Yamashita J, Yamagami T. Long-term follow-up of large or invasive pituitary adenomas. Surgical Neurology. 1986;25:49-54. DOI: 10.1016/0090-3019(86)90114-X'},{id:"B5",body:'Zhan X, Desiderio DM, Wang X, Zhan X, Guo T, Li M, et al. Identification of the proteomic variations of invasive relative to non-invasive non-functional pituitary adenomas. Electrophoresis. 2014;35:2184-2194. DOI: 10.1002/elps.201300590'},{id:"B6",body:'Zhan X, Wang X, Cheng T. Human pituitary adenoma proteomics: New progresses and perspectives. Frontiers in Endocrinology. 2016;7:54. DOI: 10.3389/fendo.2016.00054'},{id:"B7",body:'Meij BP, Lopes MB, Ellegala DB, Alden TD, Laws ER Jr. The long-term significance of microscopic dural invasion in 354 patients with pituitary adenomas treated with transsphenoidal surgery. Journal of Neurosurgery. 2002;96:195-208. DOI: 10.3171/jns.2002.96.2.0195'},{id:"B8",body:'Selman WR, Laws ER Jr, Scheithauer BW, Carpenter SM. The occurrence of dural invasion in pituitary adenomas. Journal of Neurosurgery. 1986;64:402-407. DOI: 10.3171/jns.1986.64.3.0402'},{id:"B9",body:'Galland F, Lacroix L, Saulnier P, Dessen P, Meduri G, Bernier M, et al. Differential gene expression profiles of invasive and non-invasive non-functioning pituitary adenomas based on microarray analysis. Endocrine-Related Cancer. 2010;17:361-371. DOI: 10.1677/ERC-10-0018'},{id:"B10",body:'Turner HE, Nagy Z, Gatter KC, Esiri MM, Harris AL, Wass JA. Angiogenesis in pituitary adenomas—Relationship to endocrine function, treatment and outcome. Journal of Endocrinology. 2000;165:475-481'},{id:"B11",body:'Qian ZR, Sano T, Yoshimoto K, Asa SL, Yamada S, Mizusawa N, et al. Tumor-specific downregulation and methylation of the CDH13 (H-cadherin) and CDH1 (E-cadherin) genes correlate with aggressiveness of human pituitary adenomas. Modern Pathology. 2007;20:1269-1277. DOI: 10.1038/modpathol.3800965'},{id:"B12",body:'Simpson DJ, Clayton RN, Farrell WE. Preferential loss of death associated protein kinase expression in invasive pituitary tumours is associated with either CpG island methylation or homozygous deletion. Oncogene. 2002;21:1217-1224. DOI: 10.1038/sj.onc.1205195'},{id:"B13",body:'Nam DH, Song SY, Park K, Kim MH, Suh YL, Lee JI, et al. Clinical significance of molecular genetic changes in sporadic invasive pituitary adenomas. Experimental & Molecular Medicine. 2001;33:111-116. DOI: 10.1038/emm.2001.20'},{id:"B14",body:'Farrell WE. Pituitary tumours: Findings from whole genome analyses. Endocrine-Related Cancer. 2006;13:707-716. DOI: 10.1677/erc.1.01131'},{id:"B15",body:'Zhan X, Desiderio DM. Editorial: Systems biological aspects of pituitary Tumors. Frontiers in Endocrinology. 2016;7:86. DOI: 10.3389/fendo.2016.00086'},{id:"B16",body:'Zhan X, Long Y. Exploration of molecular network variations in different subtypes of human non-functional pituitary adenomas. Frontiers in Endocrinology. 2016;7:13. DOI: 10.3389/fendo.2016.00013'},{id:"B17",body:'Hu R, Wang X, Zhan X. Multi-parameter systematic strategies for predictive, preventive and personalised medicine in cancer. The EPMA Journal. 2013;4:2. DOI: 10.1186/1878-5085-4-2'},{id:"B18",body:'Cheng T, Zhan X. Pattern recognition for predictive, preventive, and personalized medicine in cancer. The EPMA Journal. 2017;8:51-60. DOI: 10.1007/s13167-017-0083-9'},{id:"B19",body:'Lu M, Zhan X. The crucial role of multiomic approach in cancer research and clinically relevant outcomes. The EPMA Journal. 2018;9:77-102. DOI: 10.1007/s13167-018-0128-8'},{id:"B20",body:'Wierinckx A, Auger C, Devauchelle P, Reynaud A, Chevallier P, Jan M, et al. A diagnostic marker set for invasion, proliferation, and aggressiveness of prolactin pituitary tumors. Endocrine-Related Cancer. 2007;14:887-900. DOI: 10.1677/ERC-07-0062'},{id:"B21",body:'Zhan X, Desiderio DM. Comparative proteomics analysis of human pituitary adenomas: Current status and future perspectives. Mass Spectrometry Reviews. 2005;24:783-813. DOI: 10.1002/mas.20039'},{id:"B22",body:'Moreno CS, Evans CO, Zhan X, Okor M, Desiderio DM, Oyesiku NM. Novel molecular signaling and classification of human clinically nonfunctional pituitary adenomas identified by gene expression profiling and proteomic analyses. Cancer Research. 2005;65:10214-10222. DOI: 10.1158/0008-5472.CAN-05-0884'},{id:"B23",body:'Zhan X, Huang Y, Long Y. Two-dimensional gel electrophoresis coupled with mass spectrometry methods for an analysis of human pituitary adenoma tissue proteome. Journal of Visualized Experiments. 2018;134:1. DOI: 10.3791/56739'},{id:"B24",body:'Zhan X, Desiderio DM. The use of variations in proteomes to predict, prevent, and personalize treatment for clinically nonfunctional pituitary adenomas. The EPMA Journal. 2010;1:439-459. DOI: 10.1007/s13167-010-0028-z'},{id:"B25",body:'Liu Z, Liu Y, Fang W, Chen W, Li C, Xiao Z. Establishment of differential expression profiles from invasive and non-invasive pituitary adenomas. Journal of central south university (medical sciences). 2009;34:569-575. DOI: 1672-7347(2009)07-0569-07'},{id:"B26",body:'Zhan X, Desiderio DM. A reference map of a human pituitary adenoma proteome. Proteomics. 2003;3:699-713. DOI: 10.1002/pmic.200300408'},{id:"B27",body:'Zhan X, Desiderio DM. Signaling pathway networks mined from human pituitary adenoma proteomics data. BMC Medical Genomics. 2010;3:13. DOI: 10.1186/1755-8794-3-13'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Xianquan Zhan",address:"yjzhan2011@gmail.com",affiliation:'
Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, P.R. China
State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, P.R. China
Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, P.R. China
State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, P.R. China
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Saleh and Amal I. Hassan",coverURL:"https://cdn.intechopen.com/books/images_new/11120.jpg",editedByType:"Edited by",publishedDate:"June 23rd 2022",editors:[{id:"144691",title:"Prof.",name:"Hosam M.",middleName:null,surname:"Saleh",slug:"hosam-m.-saleh",fullName:"Hosam M. Saleh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10696",title:"Applications of Calorimetry",subtitle:null,isOpenForSubmission:!1,hash:"8c87f7e2199db33b5dd7181f56973a97",slug:"applications-of-calorimetry",bookSignature:"José Luis Rivera Armenta and Cynthia Graciela Flores Hernández",coverURL:"https://cdn.intechopen.com/books/images_new/10696.jpg",editedByType:"Edited by",publishedDate:"June 23rd 2022",editors:[{id:"107855",title:"Dr.",name:"Jose Luis",middleName:null,surname:"Rivera Armenta",slug:"jose-luis-rivera-armenta",fullName:"Jose Luis Rivera Armenta"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"372",title:"Phytology",slug:"phytology",parent:{id:"41",title:"Plant Biology",slug:"agricultural-and-biological-sciences-plant-biology"},numberOfBooks:4,numberOfSeries:0,numberOfAuthorsAndEditors:81,numberOfWosCitations:135,numberOfCrossrefCitations:18,numberOfDimensionsCitations:35,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicId:"372",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"9704",title:"Cucumber Economic Values and Its Cultivation and Breeding",subtitle:null,isOpenForSubmission:!1,hash:"779dad6540f8023acf09657acf0b5da8",slug:"cucumber-economic-values-and-its-cultivation-and-breeding",bookSignature:"Haiping Wang",coverURL:"https://cdn.intechopen.com/books/images_new/9704.jpg",editedByType:"Edited by",editors:[{id:"280406",title:"Dr.",name:"Haiping",middleName:null,surname:"Wang",slug:"haiping-wang",fullName:"Haiping Wang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8044",title:"Root Biology",subtitle:"Growth, Physiology, and Functions",isOpenForSubmission:!1,hash:"e29d230e2fb39fddbf72452c91fe411d",slug:"root-biology-growth-physiology-and-functions",bookSignature:"Takuji Ohyama",coverURL:"https://cdn.intechopen.com/books/images_new/8044.jpg",editedByType:"Edited by",editors:[{id:"30061",title:"Prof.",name:"Takuji",middleName:null,surname:"Ohyama",slug:"takuji-ohyama",fullName:"Takuji Ohyama"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7491",title:"Forage Groups",subtitle:null,isOpenForSubmission:!1,hash:"0f0fb28490411c41af2c39eaf6412aec",slug:"forage-groups",bookSignature:"Ricardo Loiola Edvan and Edson Mauro Santos",coverURL:"https://cdn.intechopen.com/books/images_new/7491.jpg",editedByType:"Edited by",editors:[{id:"283266",title:"Dr.",name:"Ricardo",middleName:null,surname:"Loiola Edvan",slug:"ricardo-loiola-edvan",fullName:"Ricardo Loiola Edvan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1814",title:"Botany",subtitle:null,isOpenForSubmission:!1,hash:"c692bbecba40bcdc059399e3ddb10de2",slug:"botany",bookSignature:"John Kiogora Mworia",coverURL:"https://cdn.intechopen.com/books/images_new/1814.jpg",editedByType:"Edited by",editors:[{id:"26063",title:"Dr.",name:"John",middleName:"Kiogora",surname:"Mworia",slug:"john-mworia",fullName:"John Mworia"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:4,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"67771",doi:"10.5772/intechopen.87083",title:"The Role of Plant Growth-Promoting Bacteria in the Growth of Cereals under Abiotic Stresses",slug:"the-role-of-plant-growth-promoting-bacteria-in-the-growth-of-cereals-under-abiotic-stresses",totalDownloads:1607,totalCrossrefCites:7,totalDimensionsCites:13,abstract:"Plant growth-promoting rhizobacteria (PGPR) are known to improve plant performance by multiple mechanisms, such as the production of beneficial hormones, the enhancement of plant nutritional status, and the reduction of the stress-related damage. The interaction between plants and PGPR becomes of particular interest in environments that are characterized by suboptimal growing conditions, e.g., high or low temperatures, drought, soil salinity, and nutrient scarcity. The positive role of PGPR will become even more appealing in the future, as world agriculture is facing issues as climate change and soil degradation. This chapter aims to discuss the main mechanisms of the interaction between PGPR and plants and will focus of how PGPR can decrease abiotic stress damage in cereals, which are critical crops for human diet.",book:{id:"8044",slug:"root-biology-growth-physiology-and-functions",title:"Root Biology",fullTitle:"Root Biology - Growth, Physiology, and Functions"},signatures:"Martino Schillaci, Sneha Gupta, Robert Walker and Ute Roessner",authors:null},{id:"64176",doi:"10.5772/intechopen.81186",title:"Tropical Forage Legumes in India: Status and Scope for Sustaining Livestock Production",slug:"tropical-forage-legumes-in-india-status-and-scope-for-sustaining-livestock-production",totalDownloads:2010,totalCrossrefCites:3,totalDimensionsCites:6,abstract:"Livestock contributes enormously in food and nutritional security apart from livelihood security to rural population all over the world. India has the largest number of livestock, representing over 17% of world population. Availability of forage legumes is essential for better animal health, production and increasing the nutritive value of forage-based rations, besides providing a source of biological nitrogen fixation for enriching soil, reducing land degradation and mitigating climate change. However, supply of quality green fodder in India is extremely precarious, and the gap is huge against demand. The major fodder legume crops cultivated in India are Medicago sativa, Trifolium alexandrinum, Vigna unguiculata, Vigna umbellate and range legumes are Stylosanthes spp., Desmanthus virgatus, and Clitoria ternatea. Indian subcontinent represents wide spectrum of eco-climates and reported diversity of 21 forage legumes genera viz., Desmodium, Lablab, Stylosanthes, Vigna, Macroptelium, Centrosema and browse plants Leucaena, Sesbania, Albizia, Bauhinia, Cassia, Grewia, etc. Diversity of forage legumes were collected (>3200 accessions), evaluated and sources for different biotic and abiotic stress tolerance were identified, apart from >50 cultivars developed. Considering these aspects, tropical legumes for livestock production, soil health and ecosystem services, diversity, evaluation and breeding for improved varieties are discussed in this chapter.",book:{id:"7491",slug:"forage-groups",title:"Forage Groups",fullTitle:"Forage Groups"},signatures:"Tejveer Singh, Srinivasan Ramakrishnan, Sanat Kumar Mahanta,\nVikas C. Tyagi and Ajoy Kumar Roy",authors:[{id:"254954",title:"Dr.",name:"Srinivasan",middleName:null,surname:"Ramakrishnan",slug:"srinivasan-ramakrishnan",fullName:"Srinivasan Ramakrishnan"},{id:"254958",title:"Dr.",name:"Tejveer",middleName:null,surname:"Singh",slug:"tejveer-singh",fullName:"Tejveer Singh"},{id:"254959",title:"Dr.",name:"Sanath Kumar",middleName:null,surname:"Mahanta",slug:"sanath-kumar-mahanta",fullName:"Sanath Kumar Mahanta"},{id:"254960",title:"Dr.",name:"Vikas",middleName:null,surname:"Tyagi",slug:"vikas-tyagi",fullName:"Vikas Tyagi"},{id:"254961",title:"Dr.",name:"A.K.",middleName:null,surname:"Roy",slug:"a.k.-roy",fullName:"A.K. Roy"}]},{id:"65365",doi:"10.5772/intechopen.83402",title:"Mob Grazing Results in High Forage Utilization and Reduced Western Snowberry Size",slug:"mob-grazing-results-in-high-forage-utilization-and-reduced-western-snowberry-size",totalDownloads:966,totalCrossrefCites:0,totalDimensionsCites:3,abstract:"Mob-grazing strives to maximize forage utilization and minimize selective grazing by using high stocking densities in small paddocks for short durations (12–24 hr). Rotational-grazing uses low stocking densities for a longer time period, retaining about half of the original available forage; although selective grazing can occur. Three cattle (Bos taurus × Bos indicus) grazing intensities: mob- (stocking densities from 32,000 to 67,000 kg ha−1; duration—24 hr); rotation (stocking density—2500 kg ha−1; duration—35 d); and non-grazed systems were compared based on forage utilization and changes to western snowberry (Symphoricarpos occidentalis) (WS) patch volume in a 2-year South Dakota study. Pre- and post-grazing forage height was measured every 2.5 m along multiple 50-m transects with WS patch volume measured every 5 m. Forage utilization (consumed and trampled) ranged from 42 to 90% in mob-grazed areas, and harvest efficiency (forage consumed) ranged from 15 to 64%. WS patch volumes decreased by ≥45% in mob-grazed treatments compared with no change in rotational-grazing and increased cover in non-grazed areas. WS pre-graze patch size influenced mob-grazing impact; patches >6500 cm3 were browsed or trampled to a greater extent than smaller patches.",book:{id:"7491",slug:"forage-groups",title:"Forage Groups",fullTitle:"Forage Groups"},signatures:"Heidi Reed, Sharon Clay, Alexander Smart, David Clay and Michelle\nOhrtman",authors:[{id:"37140",title:"Prof.",name:"David",middleName:null,surname:"Clay",slug:"david-clay",fullName:"David Clay"},{id:"87430",title:"Prof.",name:"Sharon",middleName:null,surname:"Clay",slug:"sharon-clay",fullName:"Sharon Clay"},{id:"255998",title:"Dr.",name:"Heidi",middleName:null,surname:"Reed",slug:"heidi-reed",fullName:"Heidi Reed"},{id:"256000",title:"Dr.",name:"Alexander",middleName:null,surname:"Smart",slug:"alexander-smart",fullName:"Alexander Smart"},{id:"285225",title:"Dr.",name:"Michelle",middleName:null,surname:"Ohrtman",slug:"michelle-ohrtman",fullName:"Michelle Ohrtman"}]},{id:"68685",doi:"10.5772/intechopen.87099",title:"Morphological and Physiological Root Plasticity and Its Relationships with Shoot Growth of Rice with Water Regimes and Microbial Densities",slug:"morphological-and-physiological-root-plasticity-and-its-relationships-with-shoot-growth-of-rice-with",totalDownloads:847,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"There is renewed interest in root research for undergirding a second Green Revolution. The modular nature of root systems makes them amenable to both morphological and/or physiological plasticity when encountering heterogeneous environments. Such plasticity, the ability to change and adapt in response to variations in the underground environment, is linked to a shoot response and to consequent dry matter production, which is an important subject of research. This exploration is relevant in paddy production, especially in the context of climate change where rice production needs to be intensified with reduced water application and with reduced methane emission. This chapter reviews the plastic response of roots and illustrates some preliminary findings on the effects of biotic (soil microbes) and abiotic (water regimes) stimuli on root growth and activity and their relationships with shoot growth and its implications for mitigation of methane production without compromising grain yield.",book:{id:"8044",slug:"root-biology-growth-physiology-and-functions",title:"Root Biology",fullTitle:"Root Biology - Growth, Physiology, and Functions"},signatures:"Abha Mishra",authors:null},{id:"64055",doi:"10.5772/intechopen.81509",title:"Ensiling Alfalfa (Medicago sativa L.) and Orchard Grass (Dactylis glomerata L.) Forage Harvested at 08:00 or 14:00, without Wilting or 1 or 2 h Wilting and with or without Use of Bacterial Inoculant",slug:"ensiling-alfalfa-medicago-sativa-l-and-orchard-grass-dactylis-glomerata-l-forage-harvested-at-08-00-",totalDownloads:1084,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Alfalfa forage is difficult to ensile due to low water-soluble carbohydrate content and high buffering capacity. The objective was to assess at Chapingo, Mexico, during the rainy season effects of combinations of harvest hours (08:00, 14:00), wilting time (0, 1, 2 h) and bacterial inoculants on the quality of silage made of alfalfa and orchard grass forage, made in 200-L containers. The experiment was conducted in three phases with two replicates per phase. Variables measured in freshly cut forage and silages were dry matter content (DM), buffer capacity, pH, and alcohol soluble carbohydrates (ASC). Silos remained sealed during 60 d, and additional variables measured in silage were aerobic stability, NH3 -N and in vitro disappearance of DM. In forage harvested at 14:00 h, DM and ASC contents were higher; pH and buffering capacity were not affected by harvest hour; in silages made of that forage, NH3-N levels were lower, while ASC contents and in vitro disappearance of MS were unaffected by harvest hour. Treatments with inoculants were less aerobic stable for 5 days when made of forage harvested at 08:00 h but more stable when made of forage harvested at 14:00 h. Harvesting at 14:00 h was advantageous as silage presented higher DM and ASC contents.",book:{id:"7491",slug:"forage-groups",title:"Forage Groups",fullTitle:"Forage Groups"},signatures:"Ricardo D. Améndola-Massiotti, Renato González-Ortiz, Luis A.\nMiranda-Romero, Juan A. Burgueño-Ferreira and Pedro Topete-\nPelayo",authors:[{id:"253852",title:"Dr.",name:"Ricardo D.",middleName:null,surname:"Améndola-Massiotti",slug:"ricardo-d.-amendola-massiotti",fullName:"Ricardo D. Améndola-Massiotti"},{id:"264572",title:"MSc.",name:"Renato",middleName:null,surname:"González-Ortiz",slug:"renato-gonzalez-ortiz",fullName:"Renato González-Ortiz"},{id:"264573",title:"Dr.",name:"Luis Alberto",middleName:null,surname:"Miranda-Romero",slug:"luis-alberto-miranda-romero",fullName:"Luis Alberto Miranda-Romero"},{id:"265415",title:"Dr.",name:"Juan",middleName:null,surname:"A. Burgueño-Ferreira",slug:"juan-a.-burgueno-ferreira",fullName:"Juan A. Burgueño-Ferreira"},{id:"265416",title:"Dr.",name:"Pedro",middleName:null,surname:"Topete-Pelayo",slug:"pedro-topete-pelayo",fullName:"Pedro Topete-Pelayo"}]}],mostDownloadedChaptersLast30Days:[{id:"63148",title:"Domestic Livestock and Its Alleged Role in Climate Change",slug:"domestic-livestock-and-its-alleged-role-in-climate-change",totalDownloads:15897,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"It is very old wisdom that climate dictates farm management strategies. In recent years, however, we are increasingly confronted with claims that agriculture, livestock husbandry, and even food consumption habits are forcing the climate to change. We subjected this worrisome concern expressed by public institutions, the media, policy makers, and even scientists to a rigorous review, cross-checking critical coherence and (in)compatibilities within and between published scientific papers. Our key conclusion is there is no need for anthropogenic emissions of greenhouse gases (GHGs), and even less so for livestock-born emissions, to explain climate change. Climate has always been changing, and even the present warming is most likely driven by natural factors. The warming potential of anthropogenic GHG emissions has been exaggerated, and the beneficial impacts of manmade CO2 emissions for nature, agriculture, and global food security have been systematically suppressed, ignored, or at least downplayed by the IPCC (Intergovernmental Panel on Climate Change) and other UN (United Nations) agencies. Furthermore, we expose important methodological deficiencies in IPCC and FAO (Food Agriculture Organization) instructions and applications for the quantification of the manmade part of non-CO2-GHG emissions from agro-ecosystems. However, so far, these fatal errors inexorably propagated through scientific literature. Finally, we could not find a clear domestic livestock fingerprint, neither in the geographical methane distribution nor in the historical evolution of mean atmospheric methane concentration. In conclusion, everybody is free to choose a vegetarian or vegan lifestyle, but there is no scientific basis, whatsoever, for claiming this decision could contribute to save the planet’s climate.",book:{id:"7491",slug:"forage-groups",title:"Forage Groups",fullTitle:"Forage Groups"},signatures:"Albrecht Glatzle",authors:[{id:"252990",title:"Dr.",name:"Albrecht",middleName:null,surname:"Glatzle",slug:"albrecht-glatzle",fullName:"Albrecht Glatzle"}]},{id:"32711",title:"Flooding Stress on Plants: Anatomical, Morphological and Physiological Responses",slug:"flooding-stress-on-plants-anatomical-morphological-and-physiological-responses",totalDownloads:7796,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"1814",slug:"botany",title:"Botany",fullTitle:"Botany"},signatures:"Gustavo Gabriel Striker",authors:[{id:"93232",title:"Prof.",name:"Gustavo",middleName:"Gabriel",surname:"Striker",slug:"gustavo-striker",fullName:"Gustavo Striker"}]},{id:"65604",title:"Evaluation and Prediction of the Nutritive Value of Underutilised Forages as Potential Feeds for Ruminants",slug:"evaluation-and-prediction-of-the-nutritive-value-of-underutilised-forages-as-potential-feeds-for-rum",totalDownloads:1570,totalCrossrefCites:0,totalDimensionsCites:2,abstract:"The aim of the chapter was to evaluate and predict the nutritive and feeding value of unknown and underutilised forages. Underutilised forages were collected from various regions. Chemical composition and degradability of forages in the rumen were determined. A dataset was created bearing degradability parameters of feeds from 40 studies. Using the dataset, a step-wise regression procedure was used to develop regression equations to predict rumen degradability. Of the underutilised forages, crude protein content tended to be double for Brassica oleracea var. acephala compared to Colophospermum mopane leaves and pods. Forage grasses tended to have very low crude protein contents compared to legumes and concentrates. Underutilised Brassica oleracea var. acephala tended to have higher crude protein levels compared to commonly used protein sources. The regression model for predicting the soluble fraction accounted for 59% (development) and 71% (validation) of the variation. The regression model for predicting the potential degradability accounted for 65% (development) and 24% (validation) of the variation. In conclusion, the nutritive value of underutilised forages was good, high in crude protein and high potential degradability. After correcting for factors that significantly affected degradability parameters, predicted solubility and effective degradability lay near the ideal prediction line, giving good predictions.",book:{id:"7491",slug:"forage-groups",title:"Forage Groups",fullTitle:"Forage Groups"},signatures:"Mehluli Moyo, Siyabonga T. Bhiya, Masande Katamzi and Ignatius\nV. Nsahlai",authors:[{id:"201527",title:"Prof.",name:"Ignatius V.",middleName:null,surname:"Nsahlai",slug:"ignatius-v.-nsahlai",fullName:"Ignatius V. Nsahlai"},{id:"203798",title:"Mr.",name:"Mehluli",middleName:null,surname:"Moyo",slug:"mehluli-moyo",fullName:"Mehluli Moyo"},{id:"260135",title:"Mr.",name:"Katamzi",middleName:null,surname:"Masande",slug:"katamzi-masande",fullName:"Katamzi Masande"},{id:"283732",title:"Mr.",name:"Siyabonga",middleName:null,surname:"Bhiya",slug:"siyabonga-bhiya",fullName:"Siyabonga Bhiya"}]},{id:"76675",title:"Introductory Chapter: Studies on Cucumber",slug:"introductory-chapter-studies-on-cucumber",totalDownloads:447,totalCrossrefCites:0,totalDimensionsCites:1,abstract:null,book:{id:"9704",slug:"cucumber-economic-values-and-its-cultivation-and-breeding",title:"Cucumber Economic Values and Its Cultivation and Breeding",fullTitle:"Cucumber Economic Values and Its Cultivation and Breeding"},signatures:"Huixia Jia and Haiping Wang",authors:[{id:"280406",title:"Dr.",name:"Haiping",middleName:null,surname:"Wang",slug:"haiping-wang",fullName:"Haiping Wang"},{id:"417904",title:"Dr.",name:"Huixia",middleName:null,surname:"Jia",slug:"huixia-jia",fullName:"Huixia Jia"}]},{id:"64176",title:"Tropical Forage Legumes in India: Status and Scope for Sustaining Livestock Production",slug:"tropical-forage-legumes-in-india-status-and-scope-for-sustaining-livestock-production",totalDownloads:2010,totalCrossrefCites:3,totalDimensionsCites:6,abstract:"Livestock contributes enormously in food and nutritional security apart from livelihood security to rural population all over the world. India has the largest number of livestock, representing over 17% of world population. Availability of forage legumes is essential for better animal health, production and increasing the nutritive value of forage-based rations, besides providing a source of biological nitrogen fixation for enriching soil, reducing land degradation and mitigating climate change. However, supply of quality green fodder in India is extremely precarious, and the gap is huge against demand. The major fodder legume crops cultivated in India are Medicago sativa, Trifolium alexandrinum, Vigna unguiculata, Vigna umbellate and range legumes are Stylosanthes spp., Desmanthus virgatus, and Clitoria ternatea. Indian subcontinent represents wide spectrum of eco-climates and reported diversity of 21 forage legumes genera viz., Desmodium, Lablab, Stylosanthes, Vigna, Macroptelium, Centrosema and browse plants Leucaena, Sesbania, Albizia, Bauhinia, Cassia, Grewia, etc. Diversity of forage legumes were collected (>3200 accessions), evaluated and sources for different biotic and abiotic stress tolerance were identified, apart from >50 cultivars developed. Considering these aspects, tropical legumes for livestock production, soil health and ecosystem services, diversity, evaluation and breeding for improved varieties are discussed in this chapter.",book:{id:"7491",slug:"forage-groups",title:"Forage Groups",fullTitle:"Forage Groups"},signatures:"Tejveer Singh, Srinivasan Ramakrishnan, Sanat Kumar Mahanta,\nVikas C. Tyagi and Ajoy Kumar Roy",authors:[{id:"254954",title:"Dr.",name:"Srinivasan",middleName:null,surname:"Ramakrishnan",slug:"srinivasan-ramakrishnan",fullName:"Srinivasan Ramakrishnan"},{id:"254958",title:"Dr.",name:"Tejveer",middleName:null,surname:"Singh",slug:"tejveer-singh",fullName:"Tejveer Singh"},{id:"254959",title:"Dr.",name:"Sanath Kumar",middleName:null,surname:"Mahanta",slug:"sanath-kumar-mahanta",fullName:"Sanath Kumar Mahanta"},{id:"254960",title:"Dr.",name:"Vikas",middleName:null,surname:"Tyagi",slug:"vikas-tyagi",fullName:"Vikas Tyagi"},{id:"254961",title:"Dr.",name:"A.K.",middleName:null,surname:"Roy",slug:"a.k.-roy",fullName:"A.K. 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He has published research in Research Policy, Applied Economics, Review of Economic Philosophy, Strategic Change, International Journal of Logistics, Sustainability, Journal of Environmental Management, Journal of Global Information Management, Journal of Cleaner Production, M@N@GEMENT, and more. He is a member of CEDIMES Institut (France), Academy of International Business (AIB), Strategic Management Society (SMS), Academy of Management (AOM), Administrative Science Association of Canada (ASAC), and Canadian council of small business and entrepreneurship (CCSBE). He is currently the director of the Research Group on Contemporary Asia (GERAC) at Laval University. 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\r\n\tIn general, the harsher the environmental conditions in an ecosystem, the lower the biodiversity. Changes in the environment caused by human activity accelerate the impoverishment of biodiversity.
\r\n
\r\n\tBiodiversity refers to “the variability of living organisms from any source, including terrestrial, marine and other aquatic ecosystems and the ecological complexes of which they are part; it includes diversity within each species, between species, and that of ecosystems”.
\r\n
\r\n\tBiodiversity provides food security and constitutes a gene pool for biotechnology, especially in the field of agriculture and medicine, and promotes the development of ecotourism.
\r\n
\r\n\tCurrently, biologists admit that we are witnessing the first phases of the seventh mass extinction caused by human intervention. It is estimated that the current rate of extinction is between a hundred and a thousand times faster than it was when man first appeared. The disappearance of species is caused not only by an accelerated rate of extinction, but also by a decrease in the rate of emergence of new species as human activities degrade the natural environment. The conservation of biological diversity is "a common concern of humanity" and an integral part of the development process. Its objectives are “the conservation of biological diversity, the sustainable use of its components, and the fair and equitable sharing of the benefits resulting from the use of genetic resources”.
\r\n
\r\n\tThe following are the main causes of biodiversity loss:
\r\n
\r\n\t• The destruction of natural habitats to expand urban and agricultural areas and to obtain timber, minerals and other natural resources.
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\r\n\t• The introduction of alien species into a habitat, whether intentionally or unintentionally which has an impact on the fauna and flora of the area, and as a result, they are reduced or become extinct.
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\r\n\t• Pollution from industrial and agricultural products, which devastate the fauna and flora, especially those in fresh water.
\r\n
\r\n\t• Global warming, which is seen as a threat to biological diversity, and will become increasingly important in the future.
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\r\n\tThe environment is subject to severe anthropic effects. Among them are those associated with pollution, resource extraction and overexploitation, loss of biodiversity, soil degradation, disorderly land occupation and planning, and many others. These anthropic effects could potentially be caused by any inadequate management of the environment. However, ecosystems have a resilience that makes them react to disturbances which mitigate the negative effects. It is critical to understand how ecosystems, natural and anthropized, including urban environments, respond to actions that have a negative influence and how they are managed. It is also important to establish when the limits marked by the resilience and the breaking point are achieved and when no return is possible. The main focus for the chapters is to cover the subjects such as understanding how the environment resilience works, the mechanisms involved, and how to manage them in order to improve our interactions with the environment and promote the use of adequate management practices such as those outlined in the United Nations’ Sustainable Development Goals.
\r\n\tPollution is caused by a wide variety of human activities and occurs in diverse forms, for example biological, chemical, et cetera. In recent years, significant efforts have been made to ensure that the environment is clean, that rigorous rules are implemented, and old laws are updated to reduce the risks towards humans and ecosystems. However, rapid industrialization and the need for more cultivable sources or habitable lands, for an increasing population, as well as fewer alternatives for waste disposal, make the pollution control tasks more challenging. Therefore, this topic will focus on assessing and managing environmental pollution. It will cover various subjects, including risk assessment due to the pollution of ecosystems, transport and fate of pollutants, restoration or remediation of polluted matrices, and efforts towards sustainable solutions to minimize environmental pollution.
\r\n\tWater is not only a crucial substance needed for biological life on Earth, but it is also a basic requirement for the existence and development of the human society. Owing to the importance of water to life on Earth, early researchers conducted numerous studies and analyses on the liquid form of water from the perspectives of chemistry, physics, earth science, and biology, and concluded that Earth is a "water polo". Water covers approximately 71% of Earth's surface. However, 97.2% of this water is seawater, 21.5% is icebergs and glaciers, and only 0.65% is freshwater that can be used directly by humans. As a result, the amount of water reserves available for human consumption is limited. The development, utilization, and protection of freshwater resources has become the focus of water science research for the continued improvement of human livelihoods and society.
\r\n
\r\n\tWater exists as solid, liquid, and gas within Earth’s atmosphere, lithosphere, and biosphere. Liquid water is used for a variety of purposes besides drinking, including power generation, ecology, landscaping, and shipping. Because water is involved in various environmental hydrological processes as well as numerous aspects of the economy and human society, the study of various phenomena in the hydrosphere, the laws governing their occurrence and development, the relationship between the hydrosphere and other spheres of Earth, and the relationship between water and social development, are all part of water science. Knowledge systems for water science are improving continuously. Water science has become a specialized field concerned with the identification of its physical, chemical, and biological properties. In addition, it reveals the laws of water distribution, movement, and circulation, and proposes methods and tools for water development, utilization, planning, management, and protection. Currently, the field of water science covers research related to topics such as hydrology, water resources and water environment. It also includes research on water related issues such as safety, engineering, economy, law, culture, information, and education.
",coverUrl:"https://cdn.intechopen.com/series_topics/covers/41.jpg",keywords:"Water, Water resources, Freshwater, Hydrological processes, Utilization, Protection"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:{title:"Environmental Sciences",id:"25"},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:"June 24th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:314,numberOfPublishedBooks:31,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://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/63828",hash:"",query:{},params:{id:"63828"},fullPath:"/profiles/63828",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)}()