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1. Introduction
This review describes theories of human atherogenesis and experimental results evaluating gene or protein expression in the pigeon model for spontaneous atherosclerosis. The spontaneous disease in the pigeon differentiates from other animal models that require manipulation (genetic, nutritional, environmental) to induce the disease state. Both susceptible and resistant pigeons have been studied with susceptibility being inherited as an autosomal recessive trait. The aims are to present the pigeon data in comparison to current theories of the human disease.
Atherosclerotic cardiovascular disease is the leading cause of death in economically developed countries. The underlying cause(s) remains unclear despite a variety of hypotheses that have attempted to explain the initiation of atherosclerotic lesions. Many genetic factors that contribute to lesion progression and the probability of plaque rupture have been identified in the general population. All forms of heart disease have a strong familial component. However, little is known about the specific genes that determine disease predisposition or how such genes interact with each other and the environment to initiate foam cell formation in any one individual. Numerous, complex gene-environment interactions are believed to be involved in the disease [1] and “although there has been considerable success in identifying genes for the rare disorders associated with atherosclerosis, the understanding of genes involved in the more common forms is largely incomplete” [2]. New molecular markers need to be developed in order to identify susceptible individuals prior to the appearance of clinical symptoms. Until the heritable component of atherosclerosis susceptibility is understood, correlation of various risk factors with specific metabolic or pathological features will be difficult to assess, and prevention efforts will remain equivocal.
2. Theories of human atherogenesis
Many theories have been proposed to explain atherosclerotic lesion initiation in the aorta although there are model-specific differences in the order of events. The pathological steps common to all theories of atherogenesis are:
Site specific proliferation of intimal smooth muscle cells
Elaboration of excessive and/or abnormal extracellular components
Accumulation of lipids within and around cells
Entry of monocytes/macrophages into area of proliferation
The abnormal accumulation of lipid within smooth muscle and macrophage cells could arise from increased infiltration (influx), increased retention, decreased efflux, and/or increased lipid biosynthesis by the cells themselves [3-9].
2.1. Lipid infiltration theory
The lipid infiltration theory states that arterial wall cells will accumulate lipid if there is a high circulating blood lipid concentration, or a consistently elevated low-density lipoproteins (LDL). In the healthy human aorta, circulating LDL particles are incorporated into vascular smooth muscle cells (VSMC) by receptor-mediated endocytosis. In atherosclerosis, the rate of LDL influx could overwhelm these receptors, causing the excess lipid to be taken up by scavenger receptors. Modified lipoproteins such as oxidized [10], acetylated [11], or particularly small (<70 nm) [12], LDL are thought to slip through the loose junctions between endothelial cells and accumulate in the intima intact. In these cases, because of their altered conformation, it is hypothesized that the modified LDL molecules are readily incorporated into VSMC by uncharacterized scavenger receptors. As foam cells develop and burst, macrophage cells are recruited to the region. The precise mechanism of how cholesterol from circulating LDL enters the intima to be incorporated in the developing foam cell is not clear. In addition, the lipid infiltration theory does not, on its own, account for the SMC proliferation observed prior to lipid accretion.
If lipid infiltration of any type is coupled with decreased HDL levels, there will be reduced cholesterol clearance (efflux) from the cells, and the sterol will remain trapped. In addition, the innermost arterial cells are in a state of chronic hypoxia ]13]. If the fatty acids released by neutral cholesterol ester hydrolase (NCEH) are not completely oxidized, the metabolites will accumulate at an accelerated rate [14], and can potentially serve as substrate for endogenous cholesterol and/or triacylglycerol (TAG) synthesis. There is compelling evidence indicating that the increase of intracellular cholesterol is at least partly the result of biosynthesis, and not circulating lipoprotein [15] uptake. However, this mechanism is not explained by any of the current theories of atherogenesis, which are mainly focused on the infiltration and retention of plasma lipids and their subsequent inflammatory effects.
2.2. Response to retention theory
The response to retention theory [16] is a proposed explanation for increased circulating blood lipid retention. According to this theory, as proteoglycans (PG), especially versican [12, 17], accumulate in the extracellular matrix (ECM) of the proliferating smooth muscle and recruited macrophage cells, they bind to incoming LDL particles. Electrostatic interaction between the LDL apoB and the sulfated chains on the core PG protein binds the LDL to the cell surface [18] where its solubility is decreased [19]. PG-bound LDL is also more likely to become oxidized, and in either case, the trapped lipoprotein is incorporated into the developing foam cell. Presumably the lipid enters the individual cells by the action of scavenger receptors, but the proponents of this theory do not directly address this element. Despite this omission, the response to retention theory does provide a concrete mechanism for the adherence of circulating lipoproteins to the arterial intima. Therefore, advocates of this theory [16] claim that essentially all later progression can be traced to the initial attraction of circulating LDL to ECM proteoglycans.
The aforementioned lipid infiltration and retention theories provide mechanistic evidence of how lipoproteins can accumulate in the arterial intima, but key steps of atherogenesis are not addressed. Neither theory offers direct evidence for how cholesterol esters form within early foam cells, nor do they explain the initial VSMC proliferation prior to lipid accumulation. Neither theory explains the subsequent entry of monocytes and macrophages to the infiltration region, nor do they explain the predictable locations of lesion development along the arterial tree.
2.3. Response to injury theory
The observation that both smooth muscle and macrophage cell types were actively recruited to balloon catheterization sites led to the response to injury hypothesis [20]. According to this theory, the arterial endothelium is compromised by various perturbations such as environmental chemicals, high concentrations of blood lipids, certain types of bacteria and viruses, autoimmunity, and/or hemodynamic stress [21]. In response, the endothelial cells either slough off or become porous, allowing the subsequent lipoproteins and macrophages influx into the arterial intima. Once initial damage has occurred, the exposed intimal cells are increasingly vulnerable to additional hemodynamic and environmental aggravation, thus perpetuating the original injury and eliciting an immune response. Although endothelial denudation or injury is not necessary for foam cell formation, an obvious and observable inflammatory response seems to exacerbate the developing atherosclerotic plaque during the disease’s progressive stage.
2.4. Inflammation theory
Atherosclerosis is now considered a chronic inflammatory disease [22], largely because signs of inflammation occur concomitantly with hypercholesterolemia [23-26] in a variety of animal models. This inflammation theory proposes that the immune system is activated as a direct result of lipid infiltration [27, 28] and so readily explains the presence of monocytes and macrophages in the fatty streak. These cells express scavenger receptors that not only ingest lipid, especially oxidized LDL; they actively secrete cytokines and recruit adhesion molecules to the region. These actions are thought to be directly responsible for the increase in extracellular components observed during later stages of atherogenesis [29]. Increasing complexity of the matrix between cells advances opportunities for proteoglycans to bind and transform lipid molecules, thereby perpetuating the entire macrophage recruitment and cytokine signaling process.
In addition to macrophages, endothelial cells, VSMC, and platelets in the developing lesion are all capable of synthesizing and/or releasing chemoattractants and growth factors [9]. These cellular interactions work together to expand the initial fatty streak to a mature, fibrous plaque over time. The inflammatory response is well correlated with plaque stability, and there are already blood tests available that will assess the risk of thrombosis based on the levels of inflammatory markers [30]. However, as with other theories of atherogenesis, the inflammatory response does not account for the initial VSMC proliferation prior to lipid accumulation and macrophage recruitment. Nor does it explain that, in humans, early foam cells are primarily myogenic. For these reasons, the inflammatory theory explains the mechanisms of plaque progression and the likelihood of disease endpoint better than it explains atherogenesis itself.
2.5. Monoclonal origin theory
A fourth theory of atherogenesis, that has not gained wide acceptance, states that the VSMC that abnormally proliferate and accumulate lipid are transformed and of monoclonal origin [31, 32]. The VSMC which develop into foam cells are phenotypically different from their counterparts in the normal media [33, 34] in that they actively secrete ECM components such as proteoglycans and collagen [35]. Healthy, fully differentiated VSMC proliferate slowly and do not synthesize an extensive ECM [36]. Loss of cell cycle control and the ability to regulate cholesterol metabolism are early hallmarks of cancerous cells, pathological phenotypes that are seen in atherogenesis. However, technological advances in DNA sequence analyses have confirmed that although VSMC in general are largely heterogenic, subsets of cells involved in atherogenic events are derived from specific clones [37, 38] that seem to proliferate in patches [39]. A second observation that supports this controversial theory is existence of hypo-methylated DNA in atherosclerotic lesions [40]. Decreased methylation is significantly correlated with increases in transcriptional activity. During cancer development, normally silent oncogenes can be expressed because of under methylation [41]. The precise atherogenic role of hypo-methylated DNA and clonal VSMC cells is not determined.
Although the monoclonal origin theory explains the proliferation of an altered population of lipid-accumulating, ECM-producing SMC in the arterial intima, no specific transformation event or set of pathological conditions have been proposed that would account for the initial change in differentiation state, methylation status, and/or the increased mitotic rate in a specific VSMC subpopulation. In addition, animal and human examples in which atherosclerotic lesions appear to regress [42-44], are not readily explained by the monoclonal theory.
2.6. Smooth muscle cell phenotypic reversion theory
Smooth muscle cell differentiation is a complex process that requires multiple transcription factors to be successful [45]. The developing embryo’s VSMC are in the synthetic state as they are actively proliferating and synthesizing their contractile elements, myofilaments, and ECM to form the arterial intima [35, 46]. Once the blood vessels are fully formed, the VSMC further differentiate to the contractile state where they stop proliferating and function to facilitate muscle contraction in response to stimuli. A healthy vessel wall is able to maintain both contractility and the quiescent state [34, 47].
During atherogenesis, VSMC seem to revert to the synthetic state where they abnormally produce an extensive ECM [48]. This phenotypic modulation [35] is believed to occur before the cells begin to replicate and migrate to the arterial intima, but the stimulus for this change is unknown. An alternative explanation is that in individuals predisposed to atherosclerosis, the VSMC never fully differentiate. In either case, modified VSMC are characterized by a decrease in the alpha/beta actin isoform ratio [33, 34, 49, 50] and the loss of the intermediate filament proteins such as vinculin and desmin [34, 49, 50]. Ongoing efforts have focused on identifying more VSMC phenotypic markers [36, 45, 51] to clearly define the state of differentiation including elements driving its change [52, 53]. Despite the narrow focus on the VSMC role that does not address macrophage recruitment, this idea is a valid attempt to describe the earliest cellular atherogenic events [54].
2.7. Hemodynamic stress theory
Hemodynamic stress is a pervasive factor in all atherogenesis theories, because lesions typically develop at aortic regions of bi-directional flow. However, if it were simply a matter of arterial architecture, any organism with a branching aorta would spontaneously develop foam cells and initiate the atherosclerotic pathology. Because this is not the case, there must be some as yet unidentified factor intrinsic to the resistant individuals’ vessel wall that can withstand the low shear stress effects while maintaining the cells in a contractile phenotype.
Many theories explain lipid accumulation in the arterial wall, some describe the preferred site of fatty streak formation and the appearance of macrophage cells, but none completely describe the entire series of events that occurs in atherogenesis. Genetic factors clearly influence cholesterol metabolism [55], replication rates [56], the immune response [26, 57] and the mitochondrial oxidative capacity for cellular lipids [58, 59], thereby manifesting an underlying influence on all aspects of atherogenesis that warrants additional investigation.
3. Pigeon model of atherogenesis
The susceptible-resistant pigeon (Columba livia) model has been employed to understand genetic components of this disease [60]. White Carneau (WC-As) pigeons develop spontaneous atherosclerosis without known risk factors [61, 62]. The pigeon lesions [63, 64], have greater similarities to human atherosclerosis than any other animal model of heart disease. St. Clair [65] has reviewed multiple studies clearly demonstrating that WC-As susceptibility resides at the level of the arterial wall. The Show Racer (SR-Ar) pigeon is resistant to the development of atherosclerosis under identical diet and housing conditions, and with similar blood cholesterol levels [61]. Crossbreeding and backcross experiments demonstrated aortic atherosclerosis susceptibility to be inherited in a pattern consistent with an autosomal recessive Mendelian trait [66].
3.1. Differential gene expression
Representational Difference Analysis (RDA) was used in reciprocal experiments to identify genes expressed differentially between WC-As and SR-Ar aortic VSMC. Difference products were cloned, sequenced and identified by BLAST against the chicken genome. We found 134 genes with differential expression. An abridged list of the seventy-two transcripts upregulated in WC-As (Table 1) included caveolin (CAV1) and enolase (ENO1). CAV1, reported as WAG-65N20 Clone, was not yet annotated in the original analysis. Its subsequent identification was crucial data because CAV1 represented the biggest difference between breeds. Lumican (LUM) and cytochrome b (CYTB) were among the sixty-two genes upregulated in the SR-Ar. The abridged list is shown in Table 2.
We originally placed each individual transcript in 6 thematic metabolic pathways using the Kyoto Encyclopedia of Genes and Genomes (KEGG) [67] and Pathway Studio [68]. These included energy metabolism, VSMC phenotype, transcriptional regulation, translational regulation, cell signaling, and an immune response. Energy metabolism and contractility pathways exhibited the most striking disparity. Genes associated with glycolysis and a synthetic VSMC phenotype were expressed in WC-As cells whereas SR-Ar cells expressed genes indicative of oxidative phosphorylation and a contractile VSMC phenotype. In WC-As cells, the alternatives of insufficient ATP production limiting contractile function or the lack of functional contractile elements down-regulating ATP synthesis cannot be distinguished due to the compressed in-vitro versus in-vivo developmental time frame. However, the genetic potential for effectively coupling energy production to muscle contraction present in the resistant SR-Ar was lacking in the susceptible WC-As [69, 70].
For this review, we employed the Metacore database [71] from GeneGo (Carlsbad, CA) to automatically place genes into networks according to their biological function and known interactions. Monosaccharide catabolism, translation, and multicellular organism development were the most significant biological processes operating in the WC-As VSMC (Table 3). Monosaccharide catabolism was represented by ENO1, lactate dehydrogenase A (LDHA), transketolase (TKT1), and glucose-phosphate isomerase (GPI). Fourteen genes involved in translation were upregulated in our experiment including ribophorin (RPN1), Ligatin (LGTN), and a number of ribosomal proteins. Although many genes participate in multicellular organism development, 46 were upregulated in the WC-As including cyclin D (CCND2), annexin (ANXA2), collagen (COL5A2), beta actin (ACTB), vimentin (VIM), transmembrane protein 126a (TMEM126A), subunit 3 of the 26S Proteasome ATPase (PSMC3) and diacylglycerol O-acetyltransferase (DGAT2).
\n\t\t
\n\t\t
\n\t\t
\n\t\t
\n\t\t
\n\t\t\t
\n\t\t\t\tGene Product\n\t\t\t
\n\t\t\t
\n\t\t\t\tGene\n\t\t\t
\n\t\t\t
\n\t\t\t\tWC-As copies\n\t\t\t
\n\t\t\t
\n\t\t\t\tSR-Ar copies\n\t\t\t
\n\t\t
\n\t\t
\n\t\t\t
Caveolin-1
\n\t\t\t
CAV1
\n\t\t\t
39
\n\t\t\t
1
\n\t\t
\n\t\t
\n\t\t\t
Enolase, alpha
\n\t\t\t
ENO1
\n\t\t\t
30
\n\t\t\t
0
\n\t\t
\n\t\t
\n\t\t\t
Retinol binding protein 7
\n\t\t\t
RBP7
\n\t\t\t
19
\n\t\t\t
2
\n\t\t
\n\t\t
\n\t\t\t
Cleavage & polyadenylation specific factor 2
\n\t\t\t
CPSF2
\n\t\t\t
18
\n\t\t\t
0
\n\t\t
\n\t\t
\n\t\t\t
Mitochondrial ribosomal protein L27
\n\t\t\t
MRPL27
\n\t\t\t
18
\n\t\t\t
0
\n\t\t
\n\t\t
\n\t\t\t
N-acetyltransferase 13 (aka MAK3)
\n\t\t\t
NAT13
\n\t\t\t
18
\n\t\t\t
0
\n\t\t
\n\t\t
\n\t\t\t
Ribophorin I
\n\t\t\t
RPN1
\n\t\t\t
16
\n\t\t\t
0
\n\t\t
\n\t\t
\n\t\t\t
Stromal cell-derived factor 1 (aka SDF-1)
\n\t\t\t
CXCL12
\n\t\t\t
16
\n\t\t\t
2
\n\t\t
\n\t\t
\n\t\t\t
Diacylglycerol O-acetyltransferase 2
\n\t\t\t
DGAT2
\n\t\t\t
14
\n\t\t\t
0
\n\t\t
\n\t\t
\n\t\t\t
26S Proteasome ATPase Subunit 2
\n\t\t\t
PSMC2
\n\t\t\t
14
\n\t\t\t
0
\n\t\t
\n\t\t
\n\t\t\t
Ribosomal Protein Large Subunit 32
\n\t\t\t
RPL32
\n\t\t\t
9
\n\t\t\t
0
\n\t\t
\n\t\t
\n\t\t\t
Actin, beta
\n\t\t\t
ACTB
\n\t\t\t
9
\n\t\t\t
1
\n\t\t
\n\t\t
\n\t\t\t
Dachshund homolog-1c
\n\t\t\t
DACH1
\n\t\t\t
9
\n\t\t\t
1
\n\t\t
\n\t\t
\n\t\t\t
Annexin A2
\n\t\t\t
ANXA2
\n\t\t\t
8
\n\t\t\t
0
\n\t\t
\n\t\t
\n\t\t\t
Ligatin
\n\t\t\t
LGTN
\n\t\t\t
8
\n\t\t\t
0
\n\t\t
\n\t\t
\n\t\t\t
Sec61 alpha
\n\t\t\t
SEC61A
\n\t\t\t
8
\n\t\t\t
2
\n\t\t
\n\t\t
\n\t\t\t
Transketolase
\n\t\t\t
TKT1
\n\t\t\t
6
\n\t\t\t
0
\n\t\t
\n\t\t
\n\t\t\t
Collagen, alpha-2 type I
\n\t\t\t
COL1A2
\n\t\t\t
6
\n\t\t\t
1
\n\t\t
\n\t\t
\n\t\t\t
Aldehyde dehydrogenase E3
\n\t\t\t
ALDH9A1
\n\t\t\t
5
\n\t\t\t
1
\n\t\t
\n\t\t
\n\t\t\t
Solute carrier protein 25/A6 (ATP/ADP antiporter)
\n\t\t\t
SLC25A6
\n\t\t\t
5
\n\t\t\t
3
\n\t\t
\n\t\t
\n\t\t\t
Nucleoside diphosphate kinase
\n\t\t\t
CNDPK
\n\t\t\t
4
\n\t\t\t
0
\n\t\t
\n\t\t
\n\t\t\t
TNF-alpha induced protein 8
\n\t\t\t
TNFAIP8
\n\t\t\t
4
\n\t\t\t
0
\n\t\t
\n\t\t
\n\t\t\t
Lactate dehydrogenase subunit A
\n\t\t\t
LDHA
\n\t\t\t
3
\n\t\t\t
0
\n\t\t
\n\t\t
\n\t\t\t
Macrophage erythroblast attacher
\n\t\t\t
MAEA
\n\t\t\t
3
\n\t\t\t
0
\n\t\t
\n\t\t
\n\t\t\t
26S Proteasome ATPase Subunit 3
\n\t\t\t
PSMC3
\n\t\t\t
3
\n\t\t\t
0
\n\t\t
\n\t\t
\n\t\t\t
Spondin 1
\n\t\t\t
SPON1
\n\t\t\t
3
\n\t\t\t
0
\n\t\t
\n\t\t
\n\t\t\t
Transmembrane protein 167
\n\t\t\t
TMEM167
\n\t\t\t
3
\n\t\t\t
0
\n\t\t
\n\t\t
\n\t\t\t
Decorin (dermatan sulfate PG)
\n\t\t\t
DCN
\n\t\t\t
2
\n\t\t\t
0
\n\t\t
\n\t
Table 1.
Genes with the highest differential expression in White Carneau (WC-As) vascular smooth muscle cells (VSMC) in representational difference analysis abridged from [70].
\n\t\t
\n\t\t
\n\t\t
\n\t\t
\n\t\t
\n\t\t\t
\n\t\t\t\tGene Product\n\t\t\t
\n\t\t\t
\n\t\t\t\tGene\n\t\t\t
\n\t\t\t
\n\t\t\t\tWC-As copies\n\t\t\t
\n\t\t\t
\n\t\t\t\tSR-Ar copies\n\t\t\t
\n\t\t
\n\t\t
\n\t\t\t
Ribosomal Protein Large Subunit 3
\n\t\t\t
RPL3
\n\t\t\t
6
\n\t\t\t
73
\n\t\t
\n\t\t
\n\t\t\t
Lumican Precursor (keratan sulafate PG)
\n\t\t\t
LUM
\n\t\t\t
2
\n\t\t\t
47
\n\t\t
\n\t\t
\n\t\t\t
Cytochrome b
\n\t\t\t
CYTB
\n\t\t\t
0
\n\t\t\t
41
\n\t\t
\n\t\t
\n\t\t\t
Fibulin-5 precursor (aka DANCE)
\n\t\t\t
FBLN5
\n\t\t\t
0
\n\t\t\t
30
\n\t\t
\n\t\t
\n\t\t\t
Fbronectin type 1
\n\t\t\t
FN1
\n\t\t\t
0
\n\t\t\t
29
\n\t\t
\n\t\t
\n\t\t\t
Cytochrome Oxidase Subunit II
\n\t\t\t
CO II
\n\t\t\t
11
\n\t\t\t
28
\n\t\t
\n\t\t
\n\t\t\t
Lactate dehydrogenase subunit B
\n\t\t\t
LDHB
\n\t\t\t
21
\n\t\t\t
25
\n\t\t
\n\t\t
\n\t\t\t
Peroxiredoxin 1
\n\t\t\t
PRDX1
\n\t\t\t
8
\n\t\t\t
20
\n\t\t
\n\t\t
\n\t\t\t
NADH subunit 4
\n\t\t\t
ND4
\n\t\t\t
4
\n\t\t\t
19
\n\t\t
\n\t\t
\n\t\t\t
Eukaryotic translation initiation factor 4A2
\n\t\t\t
EIF4A2
\n\t\t\t
8
\n\t\t\t
19
\n\t\t
\n\t\t
\n\t\t\t
SMC Myosin Heavy Chain 11
\n\t\t\t
MYH11
\n\t\t\t
0
\n\t\t\t
12
\n\t\t
\n\t\t
\n\t\t\t
Proteosome maturation factor UMP1
\n\t\t\t
POMP
\n\t\t\t
6
\n\t\t\t
10
\n\t\t
\n\t\t
\n\t\t\t
Tropomyosin, alpha
\n\t\t\t
TPM1
\n\t\t\t
0
\n\t\t\t
9
\n\t\t
\n\t\t
\n\t\t\t
26S Proteasome Regulatory Lid (non ATPase)
\n\t\t\t
PSMD1
\n\t\t\t
0
\n\t\t\t
8
\n\t\t
\n\t\t
\n\t\t\t
Myosin light chain kinase; telokin
\n\t\t\t
MYLK
\n\t\t\t
0
\n\t\t\t
7
\n\t\t
\n\t\t
\n\t\t\t
Actin, alpha-2
\n\t\t\t
ACTA2
\n\t\t\t
0
\n\t\t\t
6
\n\t\t
\n\t\t
\n\t\t\t
Coactosin-like 1
\n\t\t\t
COTL1
\n\t\t\t
0
\n\t\t\t
5
\n\t\t
\n\t\t
\n\t\t\t
Cytochrome Oxidase Subunit I
\n\t\t\t
CO I
\n\t\t\t
0
\n\t\t\t
5
\n\t\t
\n\t\t
\n\t\t\t
Mariner 1 transposase gene (similar to)
\n\t\t\t
SETMAR
\n\t\t\t
0
\n\t\t\t
3
\n\t\t
\n\t\t
\n\t\t\t
RAS oncogene family (GTP binding)
\n\t\t\t
RAB1A
\n\t\t\t
0
\n\t\t\t
3
\n\t\t
\n\t\t
\n\t\t\t
Sec61 gamma
\n\t\t\t
SEC61G
\n\t\t\t
0
\n\t\t\t
3
\n\t\t
\n\t\t
\n\t\t\t
Squalene epoxidase
\n\t\t\t
SQLE
\n\t\t\t
0
\n\t\t\t
3
\n\t\t
\n\t\t
\n\t\t\t
Ribosomal Protein Small Subunit 8
\n\t\t\t
RPS8
\n\t\t\t
1
\n\t\t\t
3
\n\t\t
\n\t\t
\n\t\t\t
F0-ATP synthase subunits 6 & 8
\n\t\t\t
ATP6/8
\n\t\t\t
2
\n\t\t\t
3
\n\t\t
\n\t\t
\n\t\t\t
Fatty acid binding protein 4
\n\t\t\t
FABP4
\n\t\t\t
2
\n\t\t\t
3
\n\t\t
\n\t\t
\n\t\t\t
Prohibitin 2 (aka B-cell receptor protein 37)
\n\t\t\t
PHB2
\n\t\t\t
2
\n\t\t\t
3
\n\t\t
\n\t\t
\n\t\t\t
Activin A/TGFB Receptor 1
\n\t\t\t
ACVR1
\n\t\t\t
0
\n\t\t\t
2
\n\t\t
\n\t\t
\n\t\t\t
Fumarate hydratase/fumarase
\n\t\t\t
FH
\n\t\t\t
0
\n\t\t\t
2
\n\t\t
\n\t\t
\n\t\t\t
26S Proteasome ATPase Subunit 4
\n\t\t\t
PSMC1
\n\t\t\t
0
\n\t\t\t
2
\n\t\t
\n\t
Table 2.
Genes with the highest differential expression in Show Racer (SR-Ar) vascular smooth muscle cells (VSMC) in representational difference analysis abridged from [70].
\n\t\t
\n\t\t
\n\t\t
\n\t\t
\n\t\t\t
\n\t\t\t\tBiological Process\n\t\t\t
\n\t\t\t
\n\t\t\t\tRatio of significant expressed genes from total number of genes involved in process\n\t\t\t
\n\t\t\t
\n\t\t\t\tP-value\n\t\t\t
\n\t\t
\n\t\t
\n\t\t\t
monosaccharide catabolic process
\n\t\t\t
8/91
\n\t\t\t
4.737E-09
\n\t\t
\n\t\t
\n\t\t\t
Translation
\n\t\t\t
14/452
\n\t\t\t
6.498E-09
\n\t\t
\n\t\t
\n\t\t\t
multicellular organismal development
\n\t\t\t
46/4895
\n\t\t\t
6.897E-09
\n\t\t
\n\t\t
\n\t\t\t
glucose catabolic process
\n\t\t\t
7/69
\n\t\t\t
1.657E-08
\n\t\t
\n\t\t
\n\t\t\t
system development
\n\t\t\t
41/4195
\n\t\t\t
2.773E-08
\n\t\t
\n\t\t
\n\t\t\t
alcohol catabolic process
\n\t\t\t
8/114
\n\t\t\t
2.834E-08
\n\t\t
\n\t\t
\n\t\t\t
developmental process
\n\t\t\t
47/5334
\n\t\t\t
3.512E-08
\n\t\t
\n\t\t
\n\t\t\t
establishment of protein localization in endoplasmic reticulum
\n\t\t\t
8/119
\n\t\t\t
3.970E-08
\n\t\t
\n\t\t
\n\t\t\t
protein targeting to ER
\n\t\t\t
8/119
\n\t\t\t
3.970E-08
\n\t\t
\n\t\t
\n\t\t\t
anatomical structure development
\n\t\t\t
473/4620
\n\t\t\t
4.356E-08
\n\t\t
\n\t
Table 3.
Biological processes (GeneGo, Carlsbad, CA) upregulated in White Carneau (WC-As) vascular smooth muscle cells (VSMC) based on representational difference analysis.
The most relevant network from the dataset connects 8 identified genetic transcripts (Figure 1) including the extracellular signals decorin (DCN), and chemokine ligand 12 (CXCL12), the cytoskeletal components ezrin (VIL2), ACTB, and PSMC3, as well as the nuclear transcripts ENO1, CCND2, and daschund homoglog 1c (DACH1). The expression of ENO1, a glycolytic enzyme and a transcription factor, is promoted by three separate network factors. First, its expression is influenced by DACH1 directly. Second, ENO1 is activated indirectly by CXCL12, where it works through c-src (not in dataset) and ACTB. Finally, DCN, by way of talin (not in dataset) also activates ACTB. Once expressed, ENO1 participates generally in monosaccharide catabolism and specifically accelerates cell proliferation via CCND2.
Smooth muscle contraction and myofibril assembly were the most significant biological processes in the SR-Ar VSMC (Table 4). These pathways included alpha actin (ACTA2), myosin heavy chain (MYH11), tropomyosin (TPM1) and the telekin transcript from myosin light chain kinase (MYLK). There were also major differences in cellular component organization between the two breeds, with the SR-Ar expressing not only MYH11, but LUM, fibronectin (FN1), high mobility group transcription factor (HMG1), and activin 1, a receptor for transforming growth factor beta (TGF1), among many others.
The Figure 2 network depicts the critical nature of SP1, a transcription factor known to regulate VSMC differentiation by turning on the gene for myosin heavy chain [73]. Although SP1 was not found in our experiment, a required cofactor, CRSP2, was upregulated in the SR-Ar. SP1 also appears to influence alpha actin (ACTA2) activity. ACTA2, expressed in contractile VSMC of SR-Ar does not seem to influence transcription as does the beta isoform, which is associated with the synthetic phenotype found in Wc-As.
Figure 1.
Network analysis (GeneGo, Carlsbad, CA) incorporating genes upregulated in White Carneau (WC-As) vascular smooth muscle cells (VSMC) based on representational difference analysis. Abbreviations listed in [72].
\n\t\t
\n\t\t
\n\t\t
\n\t\t
\n\t\t\t
\n\t\t\t\tBiological Process\n\t\t\t
\n\t\t\t
\n\t\t\t\tRatio of signifcant expressed genes from total number of genes involved in process\n\t\t\t
\n\t\t\t
\n\t\t\t\tP-value\n\t\t\t
\n\t\t
\n\t\t
\n\t\t\t
smooth muscle contraction
\n\t\t\t
12/76
\n\t\t\t
2.981E-17
\n\t\t
\n\t\t
\n\t\t\t
muscle contraction
\n\t\t\t
14/258
\n\t\t\t
2.311E-13
\n\t\t
\n\t\t
\n\t\t\t
myofibril assembly
\n\t\t\t
9/64
\n\t\t\t
1.004E-12
\n\t\t
\n\t\t
\n\t\t\t
muscle system process
\n\t\t\t
14/305
\n\t\t\t
2.247E-12
\n\t\t
\n\t\t
\n\t\t\t
cellular component organization at cellular level
\n\t\t\t
38/3480
\n\t\t\t
3.841E-12
\n\t\t
\n\t\t
\n\t\t\t
skeletal myofibril assembly
\n\t\t\t
6/14
\n\t\t\t
4.050E-12
\n\t\t
\n\t\t
\n\t\t\t
actomyosin structure organization
\n\t\t\t
9/76
\n\t\t\t
5.025E-12
\n\t\t
\n\t\t
\n\t\t\t
cellular component organization or biogenesis at cellular level
\n\t\t\t
38/3604
\n\t\t\t
1.144E-11
\n\t\t
\n\t\t
\n\t\t\t
cellular catabolic process
\n\t\t\t
28/1908
\n\t\t\t
1.199E-11
\n\t\t
\n\t\t
\n\t\t\t
muscle tissue development
\n\t\t\t
14/347
\n\t\t\t
1.270E-11
\n\t\t
\n\t
Table 4.
Biological processes (GeneGo, Carlsbad, CA) upregulated in Show Racer (SR-Ar) vascular smooth muscle cells (VSMC) based on representational difference analysis.
3.2. Differential protein expression
DNA transcripts of a species do not directly reveal the protein complexity of that organism [74]. A more complete elucidation of gene expression can be achieved through characterization of the proteins, the biological determinants of phenotype. Towards that goal, soluble proteins in aortic smooth muscle cells cultured from WC-As and SR-Ar pigeons were extracted and separated on two-dimensional electrophoresis gels.
Proteins differentially-expressed were arrayed on a map, plotting molecular weight against isoelectric point (pI). Eight discrete zones were identified, five which included proteins unique to susceptible cells and three which included proteins unique to resistant cells. Of the 88 differentially-expressed proteins from WC-As cells, 41 were located in unique zones while 29 of 82 differentially-expressed proteins from Sr-Ar cells were in unique zones. Selected proteins from susceptibility and resistance zones were annotated by peptide mass fragments, molecular weights, pIs, and correspondence with genes differentially-expressed between cells from the two breeds. Eight proteins were unique to the WC-As, and eight proteins were exclusively expressed in the SR-Ar (Table 5). Some of the annotated proteins included smooth muscle myosin phosphatase (MYPT1), myosin heavy chain (MYH11) –and fatty acid binding protein (FABP) in the SR-Ar. Ribophorin (RPN1), heat shock protein (HSP70), cyclin (CCND2) and TNFα-inducing factor (TNF) were found in WC-As [75]. Ribophorin, cyclin, TNFα Induced Protein 8, FABP and MYH11 were also differentially expressed in the RDA experiments and are likely important to the atherosclerotic phenotype in pigeon VSMC.
Figure 2.
Network analysis (GeneGo, Carlsbad, CA) incorporating genes upregulated in Show Racer (SR-Ar) vascular smooth muscle cells (VSMC) based on representational difference analysis. Abbreviations listed in [72].
\n\t\t
\n\t\t
\n\t\t
\n\t\t
\n\t\t\t
\n\t\t\t\tProtein\n\t\t\t
\n\t\t\t
\n\t\t\t\tName\n\t\t\t
\n\t\t\t
\n\t\t\t\tBreed\n\t\t\t
\n\t\t
\n\t\t
\n\t\t\t
Heat shock protein
\n\t\t\t
HSP70
\n\t\t\t
WC-As
\n\t\t
\n\t\t
\n\t\t\t
Tumor necrosis factor alpha inducing factor
\n\t\t\t
TNF
\n\t\t\t
WC-As
\n\t\t
\n\t\t
\n\t\t\t
Mannosidase
\n\t\t\t
MAN2BA
\n\t\t\t
WC-As
\n\t\t
\n\t\t
\n\t\t\t
Tropomyosin
\n\t\t\t
TPM1
\n\t\t\t
WC-As
\n\t\t
\n\t\t
\n\t\t\t
Cyclin
\n\t\t\t
CCND2
\n\t\t\t
WC-As
\n\t\t
\n\t\t
\n\t\t\t
Lumican
\n\t\t\t
LUM
\n\t\t\t
WC-As
\n\t\t
\n\t\t
\n\t\t\t
Ribophorin
\n\t\t\t
RPN1
\n\t\t\t
WC-As
\n\t\t
\n\t\t
\n\t\t\t
Inhibitor of kappa light polypeptide enhancer in B cells
\n\t\t\t
IKBKAP
\n\t\t\t
WC-As
\n\t\t
\n\t\t
\n\t\t\t
Serine threonine kinase
\n\t\t\t
STK
\n\t\t\t
SR-Ar
\n\t\t
\n\t\t
\n\t\t\t
Smooth muscle myosin phosphatase
\n\t\t\t
MYPT1
\n\t\t\t
SR-Ar
\n\t\t
\n\t\t
\n\t\t\t
Activin binding protein
\n\t\t\t
FST
\n\t\t\t
SR-Ar
\n\t\t
\n\t\t
\n\t\t\t
Myosin heavy chain
\n\t\t\t
MHY11
\n\t\t\t
SR-Ar
\n\t\t
\n\t\t
\n\t\t\t
Serine threonine protein kinase
\n\t\t\t
STK24
\n\t\t\t
SR-Ar
\n\t\t
\n\t\t
\n\t\t\t
Phosphoglucomutase
\n\t\t\t
PGM
\n\t\t\t
SR-Ar
\n\t\t
\n\t\t
\n\t\t\t
Fatty acid binding protein
\n\t\t\t
FABP
\n\t\t\t
SR-Ar
\n\t\t
\n\t\t
\n\t\t\t
Peroxiredoxin
\n\t\t\t
PRDX1
\n\t\t\t
SR-Ar
\n\t\t
\n\t
Table 5.
Annotated differentially-expressed soluble proteins extracted from vascular smooth muscle cells (VSMC) of White Carneau (WC-As) and Show Racer (SR-Ar) pigeons abridged from [75].
All 16 annotated proteins were entered into GeneGo (Carlsbad, CA) to elucidate the metabolic networks operating in each breed. In the WC-As, regulation of molecular function, regulation of inclusion body assembly, and response to unfolded protein were the most significant biological processes (Table 6). Heat shock protein contributed to each of these processes, and was joined by CCND2, TPM1, TNF, and inhibitor of kappa light polypeptide enhancer in B cells (IKBKAP) in overall regulation of molecular function. In addition to those mentioned previously, TPM1 and IKBKAP were also differentially expressed in the RDA experiments. The major biological processes operating in the SR-Ar were myosin thick filament assembly and organization (Table 7), represented primarily by the proteins MHY11 and MYPT1. This was similar to the RDA experiment, where smooth muscle contraction and myofibril assembly were indicated by multiple genetic transcripts.
\n\t\t
\n\t\t
\n\t\t
\n\t\t
\n\t\t\t
\n\t\t\t\tBiological Process\n\t\t\t
\n\t\t\t
\n\t\t\t\tRatio of significant expressed genes from total number of genes involved in process\n\t\t\t
\n\t\t\t
\n\t\t\t\tP-value\n\t\t\t
\n\t\t
\n\t\t
\n\t\t\t
negative regulation of inclusion body assembly
\n\t\t\t
3/5
\n\t\t\t
1.604E-09
\n\t\t
\n\t\t
\n\t\t\t
regulation of molecular function
\n\t\t\t
11/2707
\n\t\t\t
5.827E-09
\n\t\t
\n\t\t
\n\t\t\t
regulation of inclusion body assembly
\n\t\t\t
3/8
\n\t\t\t
8.975E-09
\n\t\t
\n\t\t
\n\t\t\t
response to unfolded protein
\n\t\t\t
5/156
\n\t\t\t
2.053E-08
\n\t\t
\n\t\t
\n\t\t\t
response to topologically incorrect protein
\n\t\t\t
5/162
\n\t\t\t
2.481E-08
\n\t\t
\n\t\t
\n\t\t\t
regulation of catalytic activity
\n\t\t\t
10/2242
\n\t\t\t
2.507E-08
\n\t\t
\n\t\t
\n\t\t\t
regulation of cellular component biogenesis
\n\t\t\t
6/379
\n\t\t\t
3.864E-08
\n\t\t
\n\t\t
\n\t\t\t
negative regulation of myeloid cell apoptosis
\n\t\t\t
3/13
\n\t\t\t
4.576E-08
\n\t\t
\n\t\t
\n\t\t\t
negative regulation of vasoconstriction
\n\t\t\t
3/14
\n\t\t\t
5.822E-08
\n\t\t
\n\t\t
\n\t\t\t
protein refolding
\n\t\t\t
3-16
\n\t\t\t
8.951E-08
\n\t\t
\n\t
Table 6.
Biological processes (GeneGo, Carlsbad, CA) upregulated in proteomic analysis of White Carneau (WC-As) vascular smooth muscle cells (VSMC).
\n\t\t
\n\t\t
\n\t\t
\n\t\t
\n\t\t\t
\n\t\t\t\tBiological Process\n\t\t\t
\n\t\t\t
\n\t\t\t\tRatio of significant expressed genes from total number of genes involved in process\n\t\t\t
\n\t\t\t
\n\t\t\t\tP-value\n\t\t\t
\n\t\t
\n\t\t
\n\t\t\t
skeletal muscle myosin thick filament assembly
\n\t\t\t
4/8
\n\t\t\t
3.53E-12
\n\t\t
\n\t\t
\n\t\t\t
striated muscle myosin thick filament assembly
\n\t\t\t
4/8
\n\t\t\t
3.53E-12
\n\t\t
\n\t\t
\n\t\t\t
myosin filament assembly
\n\t\t\t
4/11
\n\t\t\t
1.66E-11
\n\t\t
\n\t\t
\n\t\t\t
cardiac muscle fiber development
\n\t\t\t
4/11
\n\t\t\t
1.66E-11
\n\t\t
\n\t\t
\n\t\t\t
elastic fiber assembly
\n\t\t\t
4/11
\n\t\t\t
1.66E-11
\n\t\t
\n\t\t
\n\t\t\t
myosin filament organization
\n\t\t\t
4/11
\n\t\t\t
1.66E-11
\n\t\t
\n\t\t
\n\t\t\t
skeletal myofibril assembly
\n\t\t\t
4/14
\n\t\t\t
5.04E-11
\n\t\t
\n\t\t
\n\t\t\t
extracellular matrix assembly
\n\t\t\t
4/14
\n\t\t\t
5.04E-11
\n\t\t
\n\t\t
\n\t\t\t
myofibril assembly
\n\t\t\t
4/64
\n\t\t\t
3.15E-08
\n\t\t
\n\t\t
\n\t\t\t
actomyosin structure organization
\n\t\t\t
4/76
\n\t\t\t
6.34E-08
\n\t\t
\n\t
Table 7.
Biological processes (GeneGo, Carlsbad, CA) upregulated in proteomic analysis of Show Racer (SR-Ar) vascular smooth muscle cells (VSMC).
The major network operating in the protein data set is depicted in Figure 3. This network shows the cellular signaling cascade initiated by the cytokine TNFα. Although TNFα itself was not found in either experiment, its activity is suggested by the induced factors expressed in the WC-As. The transcription factors c-Jun and Ap-1 activate TNFα, which then induces JAK1 gene expression via two receptors, TNFR1 and TNFR2. JAK1 turns on STAT1 and this pathway is known to regulate VSMC inflammatory processes [76]. TNFα also exerts its biological effect on apoptotic peptidase activating factor 1 (Apaf-1), which induces apoptosis via TRADD and the cellular caspases. This would be a simple story of inflammation and apoptosis, if it wasn’t for the concomitant HSP70 expression in the WC-As. This heat shock protein also works through JAK1, but has an inhibitory effect on Apaf-1 [77]. Therefore, although Apaf-1 expression is stimulated by c-Jun, both via TNFα and cytochrome c, HSP70 simultaneously blocks Apaf-1, possibly causing problematic cells to resist apoptosis and continue to proliferate. This pathway is not present in the SR-Ar.
4. Relevance to atherogenic theories
The idea that susceptible and resistant populations exhibit differences in VSMC differentiation is vigorously supported by our data. Both experiments showed SR-Ar VSMC to be in the contractile phase, while this was clearly not the case for WC-As. The WC-As did not express myosin-related genes or proteins, and the presence of beta actin correlates with a synthetic phenotype. Contractility was a major difference in our previous gene analysis [70], so finding related proteins strengthens this pathway’s relevance to the resistant phenotype. Contraction depends on the ATP produced by oxidative phosphorylation. Although mitochondrial respiration was a significant biological process in this analysis, monosaccharide catabolism was upregulated in the WC-As.
Glycolytic enzymes ENO1 and lactate dehydrogenase A (LDHA), both found in the WC-As, contain hypoxia response elements [78]. This may indicate that during oxygen deficit, VSMC shift their energy production from oxidative phosphorylation, which has an absolute oxygen requirement, to glycolysis, which is anaerobic. Glycolysis does not produce enough ATP to support a contractile phenotype, and the upregulation of ENO1 to support glycolysis would be problematic, given its dual role as a transcription factor (Figure 1). In the absence of oxygen, lipids cannot be fully oxidized which could have a two-fold effect. First, more substrate is available for cholesterol and TAG synthesis, an idea supported by DGAT2 expression in the WC-As. Second, the increased ROS generation from partially-oxidized lipids could be triggering the observed WC-As inflammatory pathway.
The theory that atherosclerosis is a chronic inflammatory disease is supported by the data sets, although the chemokines expressed in the WC-As are secondary indicators of inflammation, and the primary mediator remains unclear. In addition to the TNF alpha pathway uncovered in the WC-As proteomics experiment (Figure 3), CXCL12 was significantly upregulated in the RDA experiments. This is relevant to the human disease as it was recently identified as a CVD- susceptibility locus in a genome wide association study [79, 80]. Although newly implicated in atherosclerosis, CXCL12 is thought to exacerbate the probability of plaque rupture during the advanced stages of the disease [81]. The over-expression of CXCL12 in the earliest stages of atherogenesis is an important observation in the WC-As, especially given that it activates c-src (Figure 1). As described earlier in this review, c-src activates beta actin (synthetic phenotype) and enolase (glycolytic enzyme), and, like ENO1, CXCL12 has a hypoxia response element in its promoter [82]. CXCL12 has been implicated in the metastasis and angiogenesis of some cancers, and is an “independent predictor” of ovarian cancer survival rates [83]. In this capacity, it may contribute to the migration and proliferation of VSMC that occur early in atherogenesis.
Figure 3.
Network analysis (GeneGo, Carlsbad, CA) incorporating annotated differentially-expressed soluble proteins extracted from vascular smooth muscle cells (VSMC) of White Carneau (WC-As) and Show Racer (SR-Ar) pigeons. Abbreviations listed in [72].
The response to retention theory is marginally supported by the data. Ribophorin and mannosidase expression in both experiments suggests increased glycosylation in the WC-As, a prerequisite of lipid retention. Lipid retention was further suggested by the expression of CAV1 in the WC-As. This finding is important because APOE knockout mice studies have shown that the loss of CAV1 is actually protective against atherosclerosis [84]. Therefore, its differential expression in the pigeon model may play an important role in the susceptible/ resistant phenotypes. Finally, the response to injury, monoclonal nature, and the effect of hemodynamic stress were not tested in either experiment, so their contribution to atherosclerosis in the pigeon model could not be determined.
Gene and protein expression in susceptible and resistant pigeon VSMC support current theories of human atherogenesis. Many genetic factors have been identified that contribute to plaque progression, but the gene or genes responsible for initiation of the disease remain unclear. The autosomal inheritance of spontaneous atherosclerosis in the White Carneau suggests that the affected gene is one having broad effects, such as a transcription factor. Because pigeon VSMC genes and proteins are differentially expressed prior to foam cell formation, the pigeon is a valuable model for studying the earliest events of atherogenesis.
Acknowledgements
Partial funding was provided by the New Hampshire Agricultural Experiment Station. This is Scientific Contribution Number 2490.
\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/42672.pdf",chapterXML:"https://mts.intechopen.com/source/xml/42672.xml",downloadPdfUrl:"/chapter/pdf-download/42672",previewPdfUrl:"/chapter/pdf-preview/42672",totalDownloads:1674,totalViews:127,totalCrossrefCites:0,totalDimensionsCites:1,totalAltmetricsMentions:0,impactScore:1,impactScorePercentile:68,impactScoreQuartile:3,hasAltmetrics:0,dateSubmitted:"May 22nd 2012",dateReviewed:"August 31st 2012",datePrePublished:null,datePublished:"February 27th 2013",dateFinished:"February 7th 2013",readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/42672",risUrl:"/chapter/ris/42672",book:{id:"3396",slug:"current-trends-in-atherogenesis"},signatures:"J. L. Anderson, S. C. Smith and R. L. Taylor Jr.",authors:[{id:"65600",title:"Dr.",name:"Robert",middleName:"Lawrence",surname:"Taylor Jr.",fullName:"Robert Taylor Jr.",slug:"robert-taylor-jr.",email:"bob.taylor@unh.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"118318",title:"Dr.",name:"Samuel",middleName:null,surname:"Smith",fullName:"Samuel Smith",slug:"samuel-smith",email:"samuels@cisunix.unh.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of New Hampshire",institutionURL:null,country:{name:"United States of America"}}},{id:"160990",title:"Dr.",name:"Janet",middleName:null,surname:"Anderson",fullName:"Janet Anderson",slug:"janet-anderson",email:"janderson@email.hesser.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Theories of human atherogenesis",level:"1"},{id:"sec_2_2",title:"2.1. Lipid infiltration theory",level:"2"},{id:"sec_3_2",title:"2.2. Response to retention theory",level:"2"},{id:"sec_4_2",title:"2.3. Response to injury theory",level:"2"},{id:"sec_5_2",title:"2.4. Inflammation theory",level:"2"},{id:"sec_6_2",title:"2.5. Monoclonal origin theory",level:"2"},{id:"sec_7_2",title:"2.6. Smooth muscle cell phenotypic reversion theory",level:"2"},{id:"sec_8_2",title:"2.7. Hemodynamic stress theory",level:"2"},{id:"sec_10",title:"3. Pigeon model of atherogenesis",level:"1"},{id:"sec_10_2",title:"3.1. Differential gene expression",level:"2"},{id:"sec_11_2",title:"3.2. Differential protein expression",level:"2"},{id:"sec_13",title:"4. Relevance to atherogenic theories",level:"1"},{id:"sec_14",title:"Acknowledgements",level:"1"}],chapterReferences:[{id:"B1",body:'Breslow JL. Genetic differences in endothelial cells may determine atherosclerosis susceptibility. 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Trends in Cardiovascular Medicine 2010; 20(6) 204-209.'},{id:"B82",body:'Martin SK, Diamond P, Williams SA, To LB, Peet DJ, Fujii N, Gronthos S, Harris AL, Zannettino A.C.W. Hypoxia-inducible factor-2 is a novel regulator of aberrant CXCL12 expression in multiple myeloma plasma cells. Haematologica 2010; 95(5) 776-784.'},{id:"B83",body:'Popple A, Durrant LG, Spendlove I, Rolland P, Scott IV, Deen S, Ramage JM. The chemokine, CXCL12, is an independent predictor of poor survival in ovarian cancer. British Journal of Cancer 2012; 106(7) 1306-1313.'},{id:"B84",body:'Frank PG, Lee H, Park DS, Tandon NN, Scherer PE, Lisanti MP. Genetic ablation of caveolin-1 confers protection against atherosclerosis. Arteriosclerosis Thrombosis and Vascular Biology 2004; 24(1) 98-105.'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"J. L. Anderson",address:null,affiliation:'
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1. Introduction
According to the U.S. Census Bureau [1], 62.1 million Americans identified as Hispanic, Latino, or Latinx (hereafter Latino) in 2020, comprising approximately 19% of the total population [2]. More than half (51.1%) of the total U.S. population growth during the last decade came from growth in the Latino population [3]. Latinos, people with a historical origin in Latin American countries where Spanish language is spoken, have become the largest ethnic minority group in the United States [1]. The Latino population in the United States is diverse in national origin and acculturation status. The U.S. Latino population is largely urban and has been concentrated in large metro areas, although the population of Latinos in smaller cities and rural areas is increasing as well [4]. In 2020, the poverty rate for Latinos was 17.0 percent accounting for 10.4 million individuals [3]. Latinos constitute a young population, with 40% under the age of 20 [5]. Two-thirds of U.S. Latinos are first- or second-generation immigrants [5].
Many of the risk factors for Latino substance use are associated with rejection from their environment and associated stressors. This may be construed as bias, discrimination, and/or racism in social, educational, and government institutions. There may be an indirect relationship between structural racism in the United States and Latino substance use. As such, we explore in this chapter, substance use patterns among individuals identified as Latino and how services and practices that consider the cultural and linguistic backgrounds of Latinos may combat the influence of structural racism on Latino substance use and access to needed treatment.
2. Prevalence of substance use and substance use disorders among Latinos
Among U.S. adults, the rate of illicit drug use during the prior month among persons aged 12 or older was 9.7% among Latinos compared to a national average of 11.7% [6]. Although Latinos have a lower drug use prevalence compared to other racial and ethnic groups in the United States, this level of drug use still has serious consequences for morbidity and mortality among Latinos. Particularly concerning is that the use of illicit drugs continues to increase among Latinos [7]. Regional patterns are also noticeable; in the Southwest, Latinos report more amphetamine use [8], whereas in the Midwest and East, Latinos report increased use of heroin [9].
U.S. Latinos are significantly less likely than Whites to have been diagnosed with a drug use disorder during their lifetime or the prior year [10]. However, during the last 40 years, reported substance use disorders (SUD) among Latinos have continued to increase in the United States [11, 12]. About 20.8 million people aged 12 or older had a SUD during the prior year [13]. SUD among U.S.-born Latinos (18.9%) are more prevalent than among all Latinos (11.3%, [14]). Among U.S. adolescents, Latinos have historically reported similar levels of substance use to those of Whites. In the last few years, however, Latinos have reported the highest rates of use of any illicit drug in 8th, 10th, and 12th grades, primarily due to their increase in marijuana use. Among 12th graders, Latinos have the highest prevalence of use of several substances, including marijuana, synthetic marijuana, inhalants, hallucinogens, LSD, cocaine, crack, methamphetamine, and crystal methamphetamine. Among 8th graders, Latinos report more use of nearly all classes of drugs compared to Whites and African Americans. However, Latino adolescents have a lower prevalence of misusing prescription drugs compared to Whites [15]. Experimenting with any use of substance during early adolescence has been related to a greater likelihood of SUD in adulthood [16, 17, 18].
3. Historical contexts
Throughout history, people of various cultures have used substances for reasons, such as altering or healing the mind [19, 20, 21]. Cultural beliefs have influenced SUD across many racial and ethnic minority groups, including Latinos living in the United States [19, 21]. Substance use behavior is defined as a human behavior motivated by sociocultural beliefs, peer and family influence, and environmental exposure [20]. The general notion is that culture shapes beliefs that lead to behavior and social norms, hence certain cultural beliefs may influence an individual’s motivation to engage in substance use [19]. Cultural beliefs are also embedded in the history of Latinos in North America.
The history of drug use among Latinos has been strongly influenced by the U.S. indigenous nations that have relied on substances to heal several ailments, including abuse of other substances [22]. For example, cannabis has had a long history as both a folk medicine and as an intoxicant. This complex history includes the system of legal control that has been instituted in both the U.S. and Latin American countries to regulate the substance. Another cogent example is a substance derived from peyote, a small spineless cactus, that has been used as a psychoactive drug in Northern Mexico to treat chronic alcohol addiction [23]. Native American churches have also used this substance for the spiritual treatment of chronic alcohol addiction [24]. Many indigenous cultures have used tobacco medicinally and spiritually for thousands of years, whereas in the mainstream U.S. culture, tobacco is considered a recreational and addictive substance [25]. These are important contextual conditions to consider when exploring substance use risk factors among Latino populations.
4. Risk and protective factors for substance use
Many of the risk and protective factors associated with substance use among Latinos are the same factors associated with substance use across multiple racial and ethnic groups, yet acculturation stress, in particular, plays a critical role in the risk of SUD among Latinos. Overall risk factors include substance use by friends or family members, perceived social norms about substance use, access to drugs, psychological comorbidities, impulsive or risk-taking personality traits, and coping skills [26]. Protective factors include antidrug social norms, parental monitoring, and bonding with prosocial mentors and institutions [27]. However, because of their ethnic minority status, immigration histories, and socioeconomic disparities, Latinos also might face additional risk factors for substance use [28]. Especially significant among Latinos is acculturation stress that stems from the circumstances of adapting to the dominant American culture. This persists and is compounded in stressors tied to tensions between the first and succeeding generations within Latino communities. Acculturation stress, which is related to immigrants’ perceptions of discrimination by mainstream Americans, increases the risk of SUD among Latinos [29].
The prevalence of SUD in the Latino population is affected by other psychosocial and emotional factors associated with unemployment, immigration, limited access to education, living in disadvantaged communities, family conflict, and racial and income discrimination [8, 11, 12]. Empirical evidence has revealed interesting relationships with substance use. For instance, Latinos are more likely to use illicit drugs and develop SUD if they do not have a strong connection with their ethnic and cultural background [12, 30, 31]. The importance of family connectedness and living in safe neighborhoods have been emphasized that may contribute to acculturation stress and play a role in Latinos’ substance use [30, 31].
5. Acculturation: U.S. orientation and Latino orientation
Because of the recognition of the centrality of acculturation stress as a risk factor for Latino SUD, a deeper understanding of acculturation is warranted. Most Latinos, even those born in the United States, have some degree of contact or identification with their Latino culture of origin, although this can vary widely across individuals. Latinos living in the United States also have some degree of contact and identification with U.S. culture. The extent to which their practices, values, and identification align with one or both cultures defines their acculturation status [32]. Early theories of acculturation assumed that immigrants replace their heritage culture with a new culture [33]. Later acculturation theories [32] propose that individuals can adopt aspects of the new culture but still identify strongly with the heritage culture. Several studies have concluded that acquisition of U.S. culture is associated with an increased risk of substance use among Latino adolescents [34, 35].
More recent research has drawn a more nuanced conclusion—that the loss of protective aspects of Latino culture, rather than the acquisition of U.S. culture, increase the risk of substance use. Latino adolescents who assimilate into U.S. culture without maintaining a connection to Latino culture are at greater risk of substance use [36] than Latino adolescents who maintain their Latino cultural orientation, especially those who simultaneously participate in U.S. culture and maintain ties with Latino culture [27, 37]. As emphasized above, the role of acculturation stress and rejection from mainstream society plays a central and significant role in Latinos’ higher risk of abusing alcohol and other substances. For example, higher acculturation is related to a higher risk of alcohol and illegal drug abuse as compared to less acculturated Latinos and Whites [38]. Acculturated Latinos reported a 7.2% increase in alcohol and illegal drug use during the previous month, compared to less than 1% of less acculturated Latinos and 6.4% of Whites [38]. Less acculturated Latinos had recently immigrated to the United States and therefore reported higher family values and lower rates of alcohol and drug use [29].
6. Acculturation discrepancies between parents and children
Acculturation occurs in a family system, with adolescents and their parents acculturating at different rates. Immigrant children typically learn and adopt a new culture more rapidly than their parents [33]. Children of immigrants grow up immersed in the receiving culture and are exposed to the heritage culture only secondhand. If families and communities do not maintain and support attributes of the heritage culture, adolescents might reject, forget, or never learn about their culture of origin, leading to acculturation discrepancies between adolescents and parents [33]. Acculturation discrepancies between parents and children can lead to family conflict, which can increase the likelihood that adolescents will experience emotional distress and turn to risky peer groups and risky behaviors in an attempt to cope with that stress [39, 40]. In addition, when parents are less acculturated to U.S. culture than their children, parents must rely on their children for help navigating U.S. culture [41]. This can undermine parental authority, place excessive stress on children, and boost youth’s risk of involvement in problem behaviors, such as substance use [27, 33, 41].
7. Ethnic identity
Ethnic identity includes knowing about one’s ethnic group, perceiving the value and emotional significance of that membership, and feeling a sense of belonging and commitment to the ethnic group [42]. Some studies have shown that a strong ethnic identity protects against substance use [43, 44]. However, this association has been inconsistent across studies, with some finding that a strong ethnic identity is a risk factor for substance use or that no association exists between ethnic identity and substance use [45, 46].
8. Cultural values
Cultural values are attitudes and priorities that are emphasized and encouraged by members of a culture. Endorsement of specific values varies widely across members of a culture, but cultural values are those generally viewed as positive in the culture. For example, individualist cultures encourage and reward outstanding achievements by individuals, whereas collectivist cultures encourage and reward the well-being and prosperity of the group. Certain cultural values might protect against substance use (e.g., obedience to parents, not ingesting intoxicating substances, and regarding one’s body as sacred), whereas other cultural values might increase the risk of substance use (e.g., glamorization of adolescent individualism and rebelliousness, expectations of intoxication in certain social contexts). The Latino cultural value of familism emphasizes the interdependence of family members [47]. This can involve a duty to take care of family members and serve as a resource and role model for family members—responsibilities that tend to be incompatible with substance use. However, familismo could be a risk factor for substance use if the family members are substance users and encourage other family members to use substances with them. Respeto emphasizes a child’s duty to respect and obey parents and other authority figures [48]. Previous studies have found that familism and respeto protect against adolescent substance use [49, 50].
9. Discrimination
Ethnic discrimination is differential treatment based on membership in a minority or lower-status group. It includes overt acts such as violence, harassment by police, discourteous treatment by store clerks, and subtler aggressions such as condescending speech [51]. Ethnic discrimination can be understood as one of the core mechanisms of structural racism. It is through the policies, arrangements, practices, designs, spaces, narrative, and other mechanisms that structural racism gives way to separate, exclude, and ultimately discriminate individuals and/or groups [52]. Perceived discrimination can cause emotional distress, and repeated experiences with discrimination can deplete coping resources and increase the attractiveness of avoidant coping strategies, such as substance use [53]. Perceived discrimination by the dominant culture also can signal to minority group members that they will be blocked from opportunities, which may lead them to identify with oppositional subcultures featuring antisocial norms [54]. Perceptions of discrimination have been associated with the use of tobacco, alcohol, and other substances [55] and with depression [56].
10. Immigration and substance use
Substance abuse has been regarded as a complex phenomenon due to the biological, sociocultural, and historical concepts involved. Therefore, as highlighted above, understanding substance abuse in a target population requires considering its history and context that includes the experience of immigration. This critical factor contributes to substance abuse in Latinos’ complex history that encompasses immigration, migration, or changes of state, such as among Mexicans living in territory acquired by the United States in the early 20th century. These individuals faced new sociocultural values in their host country or new national context. This is most pertinent to Mexicans, who represent more than 65% of the total population of Latinos in the United States [19, 21]. Migration status and experiences are a proxy for the stress, trauma, and potential destitution or disenfranchisement associated with immigrants. Again, this stress has been associated with a higher risk of SUD behaviors.
Previous research indicated that Latinos who move to the United States are more likely to be at risk of illicit substance use compared to those who stay in their home country [38, 57, 58, 59]. Mexican migrants residing in the United States are more likely to experience deficient health care and treatment compared to their U.S.-born Mexican counterparts, specifically women relative to access to treatment [60]. Mexico is one of the largest countries to experience return migration from 2009 to 2012 [61]. Mexicans who migrate to the United States and then return either voluntarily or by deportation for criminal activities to Mexico (i.e., transnational Mexicans) have reported an increased rate of substance use [30, 57, 58, 62, 63].
In addition, transnational Mexicans’ family members (i.e., including relatives who did not migrate) are more likely to use substances (e.g., alcohol, marijuana, and other illicit substances) as compared to other Mexicans [62]. This population often does not seek treatment as readily as Mexicans who did not migrate to the United States [57, 58]. Furthermore, the high risk of substance abuse among transnational Mexicans has negative effects on the quality of life of residents in both countries [58, 64]. Although this may be the case, increasing concern is centered on alcohol and tobacco use among Mexicans living in Mexico [57, 58]. Similarly, compared to men, women reported particular increases in the use of marijuana and cocaine from 2008 to 2011 in Mexico [65].
Marijuana consumption is increasing among adolescents and adults living in Mexico [66]. In Mexico, frequent alcohol use and drinking in large quantities are most common [67]. It appears that this drinking behavior is passed on to adolescents, a substantial number of whom report becoming problem drinkers [68, 69]. Mexico’s National Addictions Survey has shown an increasing proportion of the population needs to seek SUD treatment and learn how to moderate alcohol intake and avoid reoccurring patterns of binge drinking [67].
In Mexico, approximately 13 million Mexicans have reported using at least 100 cigarettes during their lifetime and more than 53,000 deaths occur each year due to tobacco-related diseases [67, 68, 70]. Older adults with higher education are more likely to use tobacco than older adults with a lower education level [71]. Youth are also affected by tobacco use in Mexico because initiation occurs at 13.7 years old on average [67]. This further contributes to the increase in public and social health concerns in Mexico, which have not started to shift away from cigarette use, potentially contributing to an increase in substance use among adolescents [71].
Increasing understanding of how migration affects SUD would help inform epidemiological efforts to reduce substance use behaviors and lead to better treatment outcomes [72]. It is also important to connect translational migrants with their networks and communities to bring about SUD behavior change in the Mexican population [62, 72]. Research has suggested that ecological factors are associated with substance use (e.g., marijuana, other illicit substances; [73]); however, these relationships need to be studied further, specifically in the context of migration [74], family networks, and substance use. Previous studies have recognized that Mexican migrants typically have additional risk factors for substance use, such as low socioeconomic status, immigration status, and social isolation [75, 76]. Therefore, it is still unclear whether substance use is a consequence of the stress of being a Mexican migrant or a manifestation of these other risk factors. This emerging evidence suggests the importance of continuing to explore substance use factors among Mexican transnationals [58] to inform public health efforts to reduce SUD in broad populations, including those in Mexico and the United States. Increasing efforts to understand SUD in other countries will help identify ecological factors and risk factors that affect multiple populations, informing the development and implementation of SUD treatment programs that help alleviate symptoms across a spectrum of populations and communities.
11. Cultural competence in SUD treatment
Latinos have become the fastest-growing population entering SUD treatment, reaching 12% of the total treatment population in the past 10 years [8, 77]. It is important to highlight the need for culturally competent practices and for providers to understand and use clients’ cultural backgrounds, including immigration and acculturation experiences, to support their recovery from SUD. For instance, studies have suggested that among Mexican Americans in the United States, an extended period of residence contributes to a higher prevalence of SUD [78, 79]. Cultural competence may play a critical role in reducing the impact of structural racism in enhancing access to and engagement in the prevention and treatment of Latino substance use [19, 80, 81]. For instance, Latino clients are influenced by individual, program, and community characteristics when facing decisions about substance use and seeking help [7]. As is common with other cultural groups, it is important to establish trust and effective communication to foster positive health outcomes for Latino clients [7]. Engagement occurs through understanding and accepting cultural distinctions, speaking the client’s language, and addressing sociocultural and economic issues related to the problem. In turn, structural racism creates policies, systems, structures, and norms to deny and/or minimize cultural strengths and disempower culturally diverse groups and their attempts to invest in their wellness.
Increasing cultural competence in prevention or treatment improves SUD problems among individuals from various cultural backgrounds [19]. Sociocultural beliefs can influence an individual’s approach to substance use and abuse and further shape treatment options. For Latinos and other racial and ethnic minorities, language barriers and unavailability of bilingual interpreters can also add to long waiting periods to receive treatment [80, 81, 82]. Even further, Latinos and other racial and ethnic minorities experience more difficulties in navigating the health care system as compared to Whites [80]. These findings suggest that it is vital for SUD treatment programs to address the cultural and linguistic needs of their Latino and other minority clients by tailoring services and practices to help achieve better treatment outcomes. Specifically, with diverse populations continuing to increase in the United States, it becomes vital to assess an individual’s substance use and abuse based on his or her racial and ethnic background.
12. Organizational cultural competence
Culturally responsive policies, institutions, communities, and programs can become an intervention to address, decrease and eliminate the creation and use of structural racism. The Office of Minority Health helped in developing standards for healthcare providers to abide by 14 standards (practices) to respond to the cultural and linguistic service needs of diverse populations [83]. Many of the culturally responsive practices have been associated with positive SUD prevention and treatment [80, 84, 85]. For instance, structural, policies, and practices that discriminate against certain groups may be a significant risk of dropout. For culturally and linguistically relevant service outcomes to improve, it is important to identify the methodological flaws of the practices [86]. Cultural competence has been correlated with improved communication, positive therapeutic alliance (e.g., provider-client trust), and higher client satisfaction [80, 87, 88, 89]. In particular, Latinos as well as other racial and ethnic minority clients are more likely to remain in treatment when the services they receive are responsive to their cultural and linguistic needs. Considering the initial evidence suggesting cultural competence can increase the quality of care in SUD prevention and intervention, it is critical to developing nuanced, cost-effective interventions.
13. Training SUD treatment providers in cultural competence
Training staff members to practice cultural competence in SUD treatment is vital to dismantle mechanisms from structural racism that limit clients seeking treatment and improve outcomes. As recently noted in the Diagnostic and Statistical Manual of Mental Disorders, it is important for clinicians and staff members to be aware of the cultural differences of each client [90]. Staff composition is crucial to the implementation of treatment programs, specifically concerning access and retention [91]. In fact, appointing qualified staff members who share similar racial and ethnic backgrounds as clients dramatically increases the likelihood of patients entering treatment [91]. The central goal of the staff should be focused on making patients feel welcomed to help improve treatment outcomes [90]. Staff members can learn about the history of vulnerable groups that may be connected with stress and other factors associated with substance use, such as immigration and acculturation experiences. This is a clear outcome for training staff members that can increase the success of treatment programs and organizations by not only fostering an environment of acceptance but also making the patient feel capable of completing treatment [91].
It is equally important to instill cultural competence in the organization because this will influence policies and programs and integrate cultural empowerment values and beliefs in the system [92]. A culturally competent organization thrives on bringing diverse individuals together to alter their practices and make them more acceptable across various groups [93]. The organizational outcomes and benefits associated with increasing cultural competence in the organization include improving respect, increasing participation, improving trust and collaboration, and promoting equality [92, 93]. Organizations can become culturally competent by seeking collaboration with individuals from various racial and ethnic backgrounds and further identifying the needs of these groups [94]. Identifying those needs provides a space to better adapt and learn how organizations can meet the demands of their diverse clients.
14. Cultural competence applied to different treatment modalities
The importance of applying cultural competence to various settings and organizations is increasing. It is becoming the norm to request that professionals be culturally competent in the health care system [95]. Culturally competent environments are rapidly growing in organizations. For instance, culturally competent models are being applied to cognitive behavioral therapy as a means of improving outcomes in treatment among minority groups, such as Latinos [96]. This is achieved by providing bilingual translators and programs to Latino clients and training staff members to be respectful of their cultural backgrounds. This has led to the development of mutually respectful and cooperative relationships between clients and their providers.
Cultural competence has been applied to interventions that focus on individuals with depression to improve treatment outcomes among racial and ethnic minority groups [97]. In fact, culturally competent adaptations to psychotherapy have been found to be more effective in reducing symptoms of mental conditions (e.g., depression) as compared to a wait-list control group [97, 98]. Professions that have focused on including cultural competence in their work environment include business, social work, psychology, public relations, education, and health care [99, 100, 101, 102].
15. Cultural competence in the community
Aside from improving cultural competence in organizations, it is equally important to focus these efforts on refining communities. With minority populations migrating to different communities in the United States, there is an urgent need to make communities more inclusive (e.g., increase awareness of implicit bias and understanding of groups’ needs through CLAS and other culturally responsive practices) toward diverse populations [103]. This diversity and inclusion may help mitigate some of the psychosocial stresses related to SUD among minority populations. Access to treatment for clients is usually available in their own neighborhoods and communities, and therefore it is critical for SUD treatment programs to adopt a community approach to cultural competence. Mounting evidence suggests that programs with greater knowledge and investment in minority communities are more likely to increase access to care [104]. Programs investing in communities of color may also benefit some of the most vulnerable members of society, such as homeless individuals [105].
Clients with SUD issues should feel comfortable accessing providers in their own communities that offer a safe and acceptable space for them to seek health care options. Efforts should be made to culturally integrate communities to develop programs and policies that are meaningful for diverse populations and to ensure cultural values are shared across the population [103, 106]. Cultural competence in the community setting could lead to the inclusion of community members and even increased participation and involvement in community issues [103]. Cultural competence could lead to numerous benefits from the individual to the communal level and lead to improved health outcomes by increasing understanding, acceptance, and respect for diverse clients and their communities [107].
16. Conclusion and future directions
The evidence provided in this chapter suggests that Latinos, as the largest ethnic minority group in the U.S., have a distinctive history of substance use and help-seeking behaviors. The socialization of substance use in their lives and the role of substances in their history of immigration, for instance, are important issues that may be impacted by structural racism. The prevalence of SUD in Latinos is affected by factors, such as unemployment, acculturation stress, and discrimination. Discrimination, in terms of exclusive prevention and treatment policies and practices by funders, regulators, and service providers, maybe one of the most critical factors contributing to SUD. A clear example is the bifurcated opioid treatment system, where low income and publicly insured Latinos are more likely to receive methadone, while mid- and high-income non-Latino Whites are more likely to receive buprenorphine, a medication with significant advantages to obtain, impact, and side effects.
Latinos have also distinctive prevalence rates regarding the use of specific substances. Some of these substances are more accessible in some regions of the United States. Latino adolescents also have unique primary substances of choice (e.g., marijuana and methamphetamine) compared to adults, and the prevalence of use among these youth reflects their developmental stage, with much higher use during thrill-seeking ages that decreases as adolescents age. Overall, ecological factors, such as family, employment, migration, and discrimination, play an important role in Latino substance use and need to be studied further.
Cultural competence has become a critical approach to understand and respond to the substance use disorder issues experienced by groups vulnerable to discrimination and/or racism. In the past 30 years, research in the definition, operationalization, and assessment of this concept has slowly gained attention because of its potential to improve prevention and interventions to address SUD. But significant challenges remain to implement culturally responsive practices in social, educational, and government institutions to reduce acculturation stress related to Latino substance use and access to SUD treatment. Additional research is needed to establish the impact of key components of culturally responsive practices (e.g., inclusive policies, matching provider and clients based on language and cultural background) with different areas that support minorities achieving sobriety.
Future research is needed to understand the risk and protective factors for problematic substance use and treatment access among Latino migrants and future generations of Latinos living in the United States and intervene with structural factors, such as immigration and inclusive policies and responsive organizational practices to improve Latino health. If resilience factors can be identified and encouraged, addiction and its adverse medical and social consequences can be reduced. Latinos have become the fastest-growing population entering SUD treatment. The distinctive nature of Latinos’ patterns of substance use, substance of choice, co-occurring mental and primary care issues, and barriers to access care highlights the importance of developing and implementing culturally informed interventions that consider clients’ background, immigration experience, and linguistic service needs to help reduce substance abuse among Latinos. Policies and practices that are culturally responsive also referred to as antiracist may have the foundation and drive to have a significant impact on eliminating disparities and promoting the health equity that Latinos have long deserved.
\n',keywords:"structural racism, cultural competence, substance use, Latino, disparities",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/81201.pdf",chapterXML:"https://mts.intechopen.com/source/xml/81201.xml",downloadPdfUrl:"/chapter/pdf-download/81201",previewPdfUrl:"/chapter/pdf-preview/81201",totalDownloads:22,totalViews:0,totalCrossrefCites:0,dateSubmitted:"December 1st 2021",dateReviewed:"February 14th 2022",datePrePublished:"April 10th 2022",datePublished:"May 25th 2022",dateFinished:"April 10th 2022",readingETA:"0",abstract:"Disparities in substance use disorders (SUD) and access to treatment among individuals identified as Latino/Hispanic have become a significant public health issue in the United States. National efforts to identify, understand, and eliminate such disparities have highlighted the role of structural racism in Latino health. In this chapter, we offer a critical review of how Latino substance use and access to care may be impacted by discrimination, acculturation stress, and other mechanisms of structural racism. As structural racism is represented by policies, systems, structures, and norms that deny and/or minimize cultural strengths and disempower culturally diverse groups and their attempts to invest in their wellness, we highlight how cultural competence may reduce the risk of SUD and may enhance access to treatment among Latinos. We conclude by highlighting policies and responsive organizational practices that may improve Latino health.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/81201",risUrl:"/chapter/ris/81201",signatures:"Erick Guerrero, Tenie Khachikian, Richard C. Cervantes, Charles Kaplan, Rene D. Olate and Jennifer B. Unger",book:{id:"10914",type:"book",title:"Effective Elimination of Structural Racism",subtitle:null,fullTitle:"Effective Elimination of Structural Racism",slug:"effective-elimination-of-structural-racism",publishedDate:"May 25th 2022",bookSignature:"Erick Guerrero",coverURL:"https://cdn.intechopen.com/books/images_new/10914.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83969-283-3",printIsbn:"978-1-83969-282-6",pdfIsbn:"978-1-83969-284-0",isAvailableForWebshopOrdering:!0,editors:[{id:"294761",title:"Dr.",name:"Erick",middleName:null,surname:"Guerrero",slug:"erick-guerrero",fullName:"Erick Guerrero"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"294761",title:"Dr.",name:"Erick",middleName:null,surname:"Guerrero",fullName:"Erick Guerrero",slug:"erick-guerrero",email:"erickguerrero454@gmail.com",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294761/images/system/294761.jpg",institution:null},{id:"473117",title:"Dr.",name:"Tenie",middleName:null,surname:"Khachikian",fullName:"Tenie Khachikian",slug:"tenie-khachikian",email:"dummy+11352334531342255241342342346983@intechopen.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"473118",title:"Dr.",name:"Richard C.",middleName:null,surname:"Cervantes",fullName:"Richard C. Cervantes",slug:"richard-c.-cervantes",email:"dummy+11533451322555241364237423486983@intechopen.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"473119",title:"Dr.",name:"Charles",middleName:null,surname:"Kaplan",fullName:"Charles Kaplan",slug:"charles-kaplan",email:"dummy+11352334531342255241777342342346983@intechopen.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"473120",title:"Dr.",name:"Rene D.",middleName:null,surname:"Olate",fullName:"Rene D. Olate",slug:"rene-d.-olate",email:"dummy+113523345313422552413462379842346983@intechopen.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"473121",title:"Dr.",name:"Jennifer B.",middleName:null,surname:"Unger",fullName:"Jennifer B. Unger",slug:"jennifer-b.-unger",email:"dummy+114444354513252416342342346983@intechopen.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Prevalence of substance use and substance use disorders among Latinos",level:"1"},{id:"sec_3",title:"3. Historical contexts",level:"1"},{id:"sec_4",title:"4. Risk and protective factors for substance use",level:"1"},{id:"sec_5",title:"5. Acculturation: U.S. orientation and Latino orientation",level:"1"},{id:"sec_6",title:"6. Acculturation discrepancies between parents and children",level:"1"},{id:"sec_7",title:"7. Ethnic identity",level:"1"},{id:"sec_8",title:"8. Cultural values",level:"1"},{id:"sec_9",title:"9. Discrimination",level:"1"},{id:"sec_10",title:"10. Immigration and substance use",level:"1"},{id:"sec_11",title:"11. Cultural competence in SUD treatment",level:"1"},{id:"sec_12",title:"12. Organizational cultural competence",level:"1"},{id:"sec_13",title:"13. Training SUD treatment providers in cultural competence",level:"1"},{id:"sec_14",title:"14. Cultural competence applied to different treatment modalities",level:"1"},{id:"sec_15",title:"15. Cultural competence in the community",level:"1"},{id:"sec_16",title:"16. Conclusion and future directions",level:"1"}],chapterReferences:[{id:"B1",body:'U.S. Census Bureau. Latino Heritage Month. 2014. Available from: https://www.census.gov/eeo/special_emphasis_programs/Latino_heritage.html'},{id:"B2",body:'U.S. Census Bureau. Census Redistricting Data. 2020. Available from: from https://www.census.gov/library/visualizations/interactive/racial-and-ethnic-diversity-in-the-united-states-2010-and-2020-census.html'},{id:"B3",body:'U.S. Census Bureau. Income and Poverty in the United States: 2020. Washington, DC: U.S. Government Publishing Office; 2021'},{id:"B4",body:'Pew Latino Center. (2013). 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Education and practice: Dynamic partners for improving cultural competence in public health. Family and Community Health. 2004;27:298-307. DOI: 10.1097/00003727-200410000-00006'},{id:"B101",body:'Johnston ME, Herzig RM. The interpretation of “culture”: Diverging perspectives on medical provision in rural Montana. Social Science & Medicine. 2006;63:2500-2511. DOI: 10.1016/j.socscimed.2006.06.013'},{id:"B102",body:'National Association of Social Workers. NASW Standards for Cultural Competence in Social Work Practice. Washington, DC: Author; 2001'},{id:"B103",body:'Bennett WL. News: The Politics of Illusion. 6th ed. Boston, MA: Pearson Education; 2005'},{id:"B104",body:'Guerrero EG, Fenwick K, Kong Y, Grella C, D’Aunno T. Paths to improving engagement among racial and ethnic minorities in addiction health services. Substance Abuse Treatment, Prevention, and Policy. 2015;10:40. DOI: 10.1186/s13011-015-0036-z'},{id:"B105",body:'Guerrero EG, Song A, Henwood B, Kong Y, Kim T. Response to culturally competent drug treatment among homeless persons with different living arrangements. Evaluation and Program Planning. 2018;66:63-69'},{id:"B106",body:'Wells MI. Beyond cultural competence: A model for individual and institutional cultural development. Journal of Community Health Nursing. 2000;17:189-199. DOI: 10.1207/S15327655JCHN1704_1'},{id:"B107",body:'Wilson-Stronks A, Mutha S. From the perspective of CEOs: What motivates hospitals to embrace cultural competence? Journal of Healthcare Management. 2010;55:339-352'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Erick Guerrero",address:"erickguerrero454@gmail.com",affiliation:'
I-Lead Institute, Research to End Healthcare Disparities Corp, USA
'},{corresp:null,contributorFullName:"Rene D. Olate",address:null,affiliation:'
ALBAS Consulting Group, USA
'},{corresp:null,contributorFullName:"Jennifer B. Unger",address:null,affiliation:'
University of Southern California, USA
'}],corrections:null},book:{id:"10914",type:"book",title:"Effective Elimination of Structural Racism",subtitle:null,fullTitle:"Effective Elimination of Structural Racism",slug:"effective-elimination-of-structural-racism",publishedDate:"May 25th 2022",bookSignature:"Erick Guerrero",coverURL:"https://cdn.intechopen.com/books/images_new/10914.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83969-283-3",printIsbn:"978-1-83969-282-6",pdfIsbn:"978-1-83969-284-0",isAvailableForWebshopOrdering:!0,editors:[{id:"294761",title:"Dr.",name:"Erick",middleName:null,surname:"Guerrero",slug:"erick-guerrero",fullName:"Erick Guerrero"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"445896",title:"Dr.",name:"Hardip Singh",middleName:null,surname:"Gendeh",email:"hardip88@gmail.com",fullName:"Hardip Singh Gendeh",slug:"hardip-singh-gendeh",position:null,biography:null,institutionString:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"1",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:null},booksEdited:[],chaptersAuthored:[{id:"81023",title:"Paranasal Sinuses Anatomy and Anatomical Variations",slug:"paranasal-sinuses-anatomy-and-anatomical-variations",abstract:"Anatomical variations of the sinuses are common and may lead to obstruction to the ventilation and drainage of the sinuses. This may lead to osteomeatal complex disease refractory to medications. A preoperative CT of the paranasal sinuses acts as road map guide to identify vital anatomical variations and its relationship to the orbit, skull base, neurological and vascular structures, to prevent iatrogenic injuries. To control intraoperative bleeding, it is critical to identify the anterior and posterior ethmoidal artery indentations and sphenopalatine artery in the anterior and lateral nasal walls. It is essential for the surgeon to familiarize with the anatomy of the ethmoid region, lateral nasal wall, sphenoid sinus, sella and parasellar region and pterygopalatine/infratemporal fossa before embarking on these approaches. The advent of CT scans and state-of-the-art FESS instrumentation has made surgery of the paranasal sinuses less of a mystery for the surgeon. Therefore, identifying and addressing these anatomical variations during FESS is crucial in restoring ventilation and drainage.",signatures:"Hardip Singh Gendeh and Balwant Singh Gendeh",authors:[{id:"67669",title:null,name:"Balwant Singh",surname:"Gendeh",fullName:"Balwant Singh Gendeh",slug:"balwant-singh-gendeh",email:"bsgendeh@gmail.com"},{id:"445896",title:"Dr.",name:"Hardip Singh",surname:"Gendeh",fullName:"Hardip Singh Gendeh",slug:"hardip-singh-gendeh",email:"hardip88@gmail.com"}],book:{id:"10725",title:"Paranasal Sinuses Anatomy and Conditions",slug:"paranasal-sinuses-anatomy-and-conditions",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"67669",title:null,name:"Balwant Singh",surname:"Gendeh",slug:"balwant-singh-gendeh",fullName:"Balwant Singh Gendeh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/67669/images/system/67669.png",biography:"Dr. Balwant Singh Gendeh is a senior consultant ENT surgeon with a sub-specialty interest in rhinology (allergy, sino-nasal diseases, endoscopic sinus, anterior and ventral skull base surgery, and functional and cosmetic nasal surgery). 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UK Research and Innovation (former Research Councils UK (RCUK) - including AHRC, BBSRC, ESRC, EPSRC, MRC, NERC, STFC.) Processing charges for books/book chapters can be covered through RCUK block grants which are allocated to most universities in the UK, which then handle the OA publication funding requests. It is at the discretion of the university whether it will approve the request.)
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Chls are located in the membrane of thylakoids where they constitute the two photosystems (PSII and PSI) of terrestrial plants, responsible for both light absorption and transduction of chemical energy via photosynthesis. The high efficiency of photosystems in terms of light absorption correlates with the need to protect themselves against absorption of excess light, a process that leads to the so-called photoinhibition. Dynamic photoinhibition consists of the downregulation of photosynthesis quantum yield and a series of photo-protective mechanisms aimed to reduce the amount of light reaching the chloroplast and/or to counteract the production of reactive oxygen species (ROS) that can be grouped in: (i) the first line of chloroplast defence: non-photochemical quenching (NPQ), that is, the dissipation of excess excitation light as heat, a process that takes place in the external antennae of PSII and in which other pigments, that is carotenoids, are directly involved; (ii) the second line of defence: enzymatic antioxidant and antioxidant molecules that scavenge the generated ROS; alternative electron transport (cyclic electron transport, pseudo-cyclic electron flow, chlororespiration and water-water cycle) can efficiently prevent the over-reduction of electron flow, and reduced ferredoxin (Fd) plays a key role in this context.",book:{id:"5841",slug:"chlorophyll",title:"Chlorophyll",fullTitle:"Chlorophyll"},signatures:"Lucia Guidi, Massimiliano Tattini and Marco Landi",authors:[{id:"198635",title:"Prof.",name:"Lucia",middleName:null,surname:"Guidi",slug:"lucia-guidi",fullName:"Lucia Guidi"},{id:"199774",title:"Dr.",name:"Massimiliano",middleName:null,surname:"Tattini",slug:"massimiliano-tattini",fullName:"Massimiliano Tattini"},{id:"199775",title:"Dr.",name:"Marco",middleName:null,surname:"Landi",slug:"marco-landi",fullName:"Marco Landi"}]},{id:"54601",doi:"10.5772/67955",title:"Chlorophyll as Photosensitizer in Dye-Sensitized Solar Cells",slug:"chlorophyll-as-photosensitizer-in-dye-sensitized-solar-cells",totalDownloads:2918,totalCrossrefCites:8,totalDimensionsCites:15,abstract:"Chlorophyll, being the most abundant pigment that commonly found in plants, bacteria, bryophytes and algae, plays a vital role in photosynthesis. Chlorophylls are natural pigments and therefore safe, environmental friendly, easily available and cheap. Chlorophyll has been experimented to function as a photosensitizer in dye-sensitized solar cells (DSSCs) as DSSCs mimic the photosynthesis process in green plants. DSSC was first developed by Gratzel in 1991 and since then has gained tremendous attention as its fabrication is cheap and easy. A DSSC basically comprises a semiconductor that has been soaked in sensitizing dye (chlorophyll), a counter electrode, and an electrolyte containing a redox mediator. The dye absorbs light, which is transformed into electricity. Chlorophyll can be extracted from the leaves of pomegranate, bougainvillea, papaya, Pandanus amaryllifolius, spinach, green grasses, seaweeds, algae and bryophytes. Chlorophyll from these sources has been studied as possible photosensitizers for DSSCs. Most researches done in chlorophyll DSSC use the extracted natural pigments. The type of solvent and pH of the dye solution will also affect the stability of chlorophyll and subsequently the performance of the DSSCs. This chapter will present an inexhaustive overview on DSSCs using chlorophyll as dye.",book:{id:"5841",slug:"chlorophyll",title:"Chlorophyll",fullTitle:"Chlorophyll"},signatures:"Abdul Kariem Arof and Teo Li Ping",authors:[{id:"186084",title:"Dr.",name:"Abdul Kariem",middleName:null,surname:"Arof",slug:"abdul-kariem-arof",fullName:"Abdul Kariem Arof"},{id:"199862",title:"Dr.",name:"L.P.",middleName:null,surname:"Teo",slug:"l.p.-teo",fullName:"L.P. Teo"}]},{id:"54681",doi:"10.5772/67991",title:"Effects on the Photosynthetic Activity of Algae after Exposure to Various Organic and Inorganic Pollutants: Review",slug:"effects-on-the-photosynthetic-activity-of-algae-after-exposure-to-various-organic-and-inorganic-poll",totalDownloads:2649,totalCrossrefCites:6,totalDimensionsCites:13,abstract:"Algal studies remain necessary for risk assessment and their utility in ecotoxicology is the evaluation of lethal and sub-lethal toxic effects of potential toxicants on inhabitants of several ecosystems. Effects on algal photosynthetic apparatus caused by various chemical species have been extensively studied. The present chapter summarizes the published data concerning the toxicity of various organic and inorganic pollutants such as oils, pesticides, antifoulants and metals on photosynthesis of aquatic primary producers. Biochemical mode of action resulting in the disruption of photosynthesis depends on the chemical’s nature and the characteristics of the exposed microorganism. Observed differences in response and sensitivity by different species to the same toxicant were attributed to several algal characteristics including photosynthetic capacity, pigment type, cellular lipid and protein content, and cell size. Single species bioassays either for one chemical alone or in mixture have been well reported and tolerance of both marine and freshwater water-column phytoplaktonic species has been examined. Adequate published information on multispecies tests (communities) in laboratory and field studies exists. However, risk assessment on photosynthesis of microbenthic periphyton is inadequate, though it is essential especially for hydrophobic organic molecules. Further studies are required to evaluate the adverse effects of metabolites on aquatic microalgae.",book:{id:"5841",slug:"chlorophyll",title:"Chlorophyll",fullTitle:"Chlorophyll"},signatures:"Andreas S. Petsas and Maria C. Vagi",authors:[{id:"200196",title:"Dr.",name:"Andreas",middleName:null,surname:"Petsas",slug:"andreas-petsas",fullName:"Andreas Petsas"},{id:"200198",title:"Dr.",name:"Maria",middleName:null,surname:"Vagi",slug:"maria-vagi",fullName:"Maria Vagi"}]},{id:"54510",doi:"10.5772/67913",title:"Light‐Emitting Diodes: Progress in Plant Micropropagation",slug:"light-emitting-diodes-progress-in-plant-micropropagation",totalDownloads:2153,totalCrossrefCites:2,totalDimensionsCites:12,abstract:"In commercial micropropagation laboratories, the light source is one of the most important factors controlling plant morphogenesis and metabolism of plant cells and tissue and organ cultures. Lamp manufacturers have begun to rate lamps specifically for plant needs. The traditional light source used for in vitro propagation is fluorescent lamps (FLs). However, power consumption in FL use is expensive and produces a wide range of wavelengths (350–750 nm) unnecessary for plant development. Light‐emitting diodes (LEDs) have recently emerged as an alternative for commercial micropropagation. The flexibility of matching LED wavelengths to plant photoreceptors may provide more optimal production, influencing plant morphology and chlorophyll content. Although previous reports have confirmed physiological effects of LED light quality on morphogenesis and growth of several plantlets in vitro, these study results showed that LED light is more suitable for plant morphogenesis and growth than FLs. However, the responses vary according to plant species. This chapter describes the applications and benefits of LED lamps on chlorophyll in plant micropropagation. Two study cases are exposed, Anthurium (Anthurium andreanum) and moth orchids (Phalaenopsisis sp.), both species with economic importance as ornamental plants, where LEDs have a positive effect on in vitro development and chlorophyll content.",book:{id:"5841",slug:"chlorophyll",title:"Chlorophyll",fullTitle:"Chlorophyll"},signatures:"Jericó J. Bello‐Bello, Juan A. Pérez‐Sato, Carlos A. Cruz‐Cruz and\nEduardo Martínez‐Estrada",authors:[{id:"197218",title:"Dr.",name:"Jericó Jabín",middleName:null,surname:"Bello Bello",slug:"jerico-jabin-bello-bello",fullName:"Jericó Jabín Bello Bello"},{id:"197368",title:"MSc.",name:"Eduardo",middleName:null,surname:"Martínez Estrada",slug:"eduardo-martinez-estrada",fullName:"Eduardo Martínez Estrada"},{id:"197369",title:"Dr.",name:"Carlos Alberto",middleName:null,surname:"Cruz Cruz",slug:"carlos-alberto-cruz-cruz",fullName:"Carlos Alberto Cruz Cruz"},{id:"205358",title:"Dr.",name:"Juan Antonio",middleName:null,surname:"Pérez-Sato",slug:"juan-antonio-perez-sato",fullName:"Juan Antonio Pérez-Sato"}]},{id:"54702",doi:"10.5772/67610",title:"Effects of pH and Phosphorus Concentrations on the Chlorophyll Responses of Salvia chamelaeagnea (Lamiaceae) Grown in Hydroponics",slug:"effects-of-ph-and-phosphorus-concentrations-on-the-chlorophyll-responses-of-salvia-chamelaeagnea-lam",totalDownloads:1481,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Salvia chamelaeagnea (Lamiaceae) is a slow growing water‐wise evergreen shrub originating from the western province of South Africa. It is an attractive landscape, and S. chamelaeagnea is a medicinal plant. It is important to develop enhanced cultivation protocols that could result in high yield and high‐quality medicinal materials. Chlorophyll is a fundamental part of the light‐dependent reactions of the photosynthesis process. This chapter investigates the effects of four phosphorus concentrations and three pH levels of supplied irrigated water on the production of chlorophyll A, chlorophyll B, total chlorophyll, leaf colour and the nutrient uptake of S. chamelaeagnea grown in hydroponics over an 8‐week period at the Cape Peninsula University of Technology. The treatments of pH 4, pH 6 and pH 8 at 31, 90, 150 and 210 ppm of phosphorus were received by 12 groups of plants and were replicated 10 times. The results indicated that at pH 4, P fertilization significantly (P < 0.05) induced a higher chlorophyll production of S. chamelaeagnea grown in hydroponics compared to other pH treatments (pH 8 and pH 6).",book:{id:"5841",slug:"chlorophyll",title:"Chlorophyll",fullTitle:"Chlorophyll"},signatures:"Kerwin Lefever, Charles P. Laubscher, Patrick A. Ndakidemi and Felix\nNchu",authors:[{id:"200292",title:"Dr.",name:"Felix",middleName:null,surname:"Nchu",slug:"felix-nchu",fullName:"Felix Nchu"},{id:"200819",title:"Prof.",name:"Charles",middleName:"Petrus",surname:"Petrus Laubscher",slug:"charles-petrus-laubscher",fullName:"Charles Petrus Laubscher"},{id:"201292",title:"Mr.",name:"Kerwin",middleName:null,surname:"Lefever",slug:"kerwin-lefever",fullName:"Kerwin Lefever"},{id:"201293",title:"Prof.",name:"Patrick A.",middleName:null,surname:"Ndakedemi",slug:"patrick-a.-ndakedemi",fullName:"Patrick A. Ndakedemi"}]}],mostDownloadedChaptersLast30Days:[{id:"54681",title:"Effects on the Photosynthetic Activity of Algae after Exposure to Various Organic and Inorganic Pollutants: Review",slug:"effects-on-the-photosynthetic-activity-of-algae-after-exposure-to-various-organic-and-inorganic-poll",totalDownloads:2649,totalCrossrefCites:6,totalDimensionsCites:13,abstract:"Algal studies remain necessary for risk assessment and their utility in ecotoxicology is the evaluation of lethal and sub-lethal toxic effects of potential toxicants on inhabitants of several ecosystems. Effects on algal photosynthetic apparatus caused by various chemical species have been extensively studied. The present chapter summarizes the published data concerning the toxicity of various organic and inorganic pollutants such as oils, pesticides, antifoulants and metals on photosynthesis of aquatic primary producers. Biochemical mode of action resulting in the disruption of photosynthesis depends on the chemical’s nature and the characteristics of the exposed microorganism. Observed differences in response and sensitivity by different species to the same toxicant were attributed to several algal characteristics including photosynthetic capacity, pigment type, cellular lipid and protein content, and cell size. Single species bioassays either for one chemical alone or in mixture have been well reported and tolerance of both marine and freshwater water-column phytoplaktonic species has been examined. Adequate published information on multispecies tests (communities) in laboratory and field studies exists. However, risk assessment on photosynthesis of microbenthic periphyton is inadequate, though it is essential especially for hydrophobic organic molecules. Further studies are required to evaluate the adverse effects of metabolites on aquatic microalgae.",book:{id:"5841",slug:"chlorophyll",title:"Chlorophyll",fullTitle:"Chlorophyll"},signatures:"Andreas S. Petsas and Maria C. Vagi",authors:[{id:"200196",title:"Dr.",name:"Andreas",middleName:null,surname:"Petsas",slug:"andreas-petsas",fullName:"Andreas Petsas"},{id:"200198",title:"Dr.",name:"Maria",middleName:null,surname:"Vagi",slug:"maria-vagi",fullName:"Maria Vagi"}]},{id:"54510",title:"Light‐Emitting Diodes: Progress in Plant Micropropagation",slug:"light-emitting-diodes-progress-in-plant-micropropagation",totalDownloads:2153,totalCrossrefCites:2,totalDimensionsCites:12,abstract:"In commercial micropropagation laboratories, the light source is one of the most important factors controlling plant morphogenesis and metabolism of plant cells and tissue and organ cultures. Lamp manufacturers have begun to rate lamps specifically for plant needs. The traditional light source used for in vitro propagation is fluorescent lamps (FLs). However, power consumption in FL use is expensive and produces a wide range of wavelengths (350–750 nm) unnecessary for plant development. Light‐emitting diodes (LEDs) have recently emerged as an alternative for commercial micropropagation. The flexibility of matching LED wavelengths to plant photoreceptors may provide more optimal production, influencing plant morphology and chlorophyll content. Although previous reports have confirmed physiological effects of LED light quality on morphogenesis and growth of several plantlets in vitro, these study results showed that LED light is more suitable for plant morphogenesis and growth than FLs. However, the responses vary according to plant species. This chapter describes the applications and benefits of LED lamps on chlorophyll in plant micropropagation. Two study cases are exposed, Anthurium (Anthurium andreanum) and moth orchids (Phalaenopsisis sp.), both species with economic importance as ornamental plants, where LEDs have a positive effect on in vitro development and chlorophyll content.",book:{id:"5841",slug:"chlorophyll",title:"Chlorophyll",fullTitle:"Chlorophyll"},signatures:"Jericó J. Bello‐Bello, Juan A. Pérez‐Sato, Carlos A. Cruz‐Cruz and\nEduardo Martínez‐Estrada",authors:[{id:"197218",title:"Dr.",name:"Jericó Jabín",middleName:null,surname:"Bello Bello",slug:"jerico-jabin-bello-bello",fullName:"Jericó Jabín Bello Bello"},{id:"197368",title:"MSc.",name:"Eduardo",middleName:null,surname:"Martínez Estrada",slug:"eduardo-martinez-estrada",fullName:"Eduardo Martínez Estrada"},{id:"197369",title:"Dr.",name:"Carlos Alberto",middleName:null,surname:"Cruz Cruz",slug:"carlos-alberto-cruz-cruz",fullName:"Carlos Alberto Cruz Cruz"},{id:"205358",title:"Dr.",name:"Juan Antonio",middleName:null,surname:"Pérez-Sato",slug:"juan-antonio-perez-sato",fullName:"Juan Antonio Pérez-Sato"}]},{id:"54559",title:"Introductory Chapter: Chlorophyll Molecules and Their Technological Relevance",slug:"introductory-chapter-chlorophyll-molecules-and-their-technological-relevance",totalDownloads:1630,totalCrossrefCites:1,totalDimensionsCites:2,abstract:null,book:{id:"5841",slug:"chlorophyll",title:"Chlorophyll",fullTitle:"Chlorophyll"},signatures:"Maria Isabel Queiroz, Andrêssa Silva Fernandes, Mariany Costa\nDeprá, Eduardo Jacob-Lopes and Leila Queiroz Zepka",authors:[{id:"171980",title:"Dr.",name:"Eduardo",middleName:null,surname:"Jacob-Lopes",slug:"eduardo-jacob-lopes",fullName:"Eduardo Jacob-Lopes"},{id:"200454",title:"Dr.",name:"Andrêssa",middleName:null,surname:"Fernandes",slug:"andressa-fernandes",fullName:"Andrêssa Fernandes"},{id:"200455",title:"Dr.",name:"Mariany",middleName:null,surname:"Deprá",slug:"mariany-depra",fullName:"Mariany Deprá"},{id:"200457",title:"Prof.",name:"Maria Isabel",middleName:null,surname:"Queiroz",slug:"maria-isabel-queiroz",fullName:"Maria Isabel Queiroz"},{id:"261969",title:"Dr.",name:"Leila",middleName:null,surname:"Queiroz Zepka",slug:"leila-queiroz-zepka",fullName:"Leila Queiroz Zepka"}]},{id:"54601",title:"Chlorophyll as Photosensitizer in Dye-Sensitized Solar Cells",slug:"chlorophyll-as-photosensitizer-in-dye-sensitized-solar-cells",totalDownloads:2918,totalCrossrefCites:8,totalDimensionsCites:15,abstract:"Chlorophyll, being the most abundant pigment that commonly found in plants, bacteria, bryophytes and algae, plays a vital role in photosynthesis. Chlorophylls are natural pigments and therefore safe, environmental friendly, easily available and cheap. Chlorophyll has been experimented to function as a photosensitizer in dye-sensitized solar cells (DSSCs) as DSSCs mimic the photosynthesis process in green plants. DSSC was first developed by Gratzel in 1991 and since then has gained tremendous attention as its fabrication is cheap and easy. A DSSC basically comprises a semiconductor that has been soaked in sensitizing dye (chlorophyll), a counter electrode, and an electrolyte containing a redox mediator. The dye absorbs light, which is transformed into electricity. Chlorophyll can be extracted from the leaves of pomegranate, bougainvillea, papaya, Pandanus amaryllifolius, spinach, green grasses, seaweeds, algae and bryophytes. Chlorophyll from these sources has been studied as possible photosensitizers for DSSCs. Most researches done in chlorophyll DSSC use the extracted natural pigments. The type of solvent and pH of the dye solution will also affect the stability of chlorophyll and subsequently the performance of the DSSCs. This chapter will present an inexhaustive overview on DSSCs using chlorophyll as dye.",book:{id:"5841",slug:"chlorophyll",title:"Chlorophyll",fullTitle:"Chlorophyll"},signatures:"Abdul Kariem Arof and Teo Li Ping",authors:[{id:"186084",title:"Dr.",name:"Abdul Kariem",middleName:null,surname:"Arof",slug:"abdul-kariem-arof",fullName:"Abdul Kariem Arof"},{id:"199862",title:"Dr.",name:"L.P.",middleName:null,surname:"Teo",slug:"l.p.-teo",fullName:"L.P. Teo"}]},{id:"54702",title:"Effects of pH and Phosphorus Concentrations on the Chlorophyll Responses of Salvia chamelaeagnea (Lamiaceae) Grown in Hydroponics",slug:"effects-of-ph-and-phosphorus-concentrations-on-the-chlorophyll-responses-of-salvia-chamelaeagnea-lam",totalDownloads:1482,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Salvia chamelaeagnea (Lamiaceae) is a slow growing water‐wise evergreen shrub originating from the western province of South Africa. It is an attractive landscape, and S. chamelaeagnea is a medicinal plant. It is important to develop enhanced cultivation protocols that could result in high yield and high‐quality medicinal materials. Chlorophyll is a fundamental part of the light‐dependent reactions of the photosynthesis process. This chapter investigates the effects of four phosphorus concentrations and three pH levels of supplied irrigated water on the production of chlorophyll A, chlorophyll B, total chlorophyll, leaf colour and the nutrient uptake of S. chamelaeagnea grown in hydroponics over an 8‐week period at the Cape Peninsula University of Technology. The treatments of pH 4, pH 6 and pH 8 at 31, 90, 150 and 210 ppm of phosphorus were received by 12 groups of plants and were replicated 10 times. The results indicated that at pH 4, P fertilization significantly (P < 0.05) induced a higher chlorophyll production of S. chamelaeagnea grown in hydroponics compared to other pH treatments (pH 8 and pH 6).",book:{id:"5841",slug:"chlorophyll",title:"Chlorophyll",fullTitle:"Chlorophyll"},signatures:"Kerwin Lefever, Charles P. Laubscher, Patrick A. Ndakidemi and Felix\nNchu",authors:[{id:"200292",title:"Dr.",name:"Felix",middleName:null,surname:"Nchu",slug:"felix-nchu",fullName:"Felix Nchu"},{id:"200819",title:"Prof.",name:"Charles",middleName:"Petrus",surname:"Petrus Laubscher",slug:"charles-petrus-laubscher",fullName:"Charles Petrus Laubscher"},{id:"201292",title:"Mr.",name:"Kerwin",middleName:null,surname:"Lefever",slug:"kerwin-lefever",fullName:"Kerwin Lefever"},{id:"201293",title:"Prof.",name:"Patrick A.",middleName:null,surname:"Ndakedemi",slug:"patrick-a.-ndakedemi",fullName:"Patrick A. Ndakedemi"}]}],onlineFirstChaptersFilter:{topicId:"353",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:99,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:288,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{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,numberOfPublishedBooks:27,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-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"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:9,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",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",slug:"ana-isabel-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",slug:"christian-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",slug:"francisco-javier-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",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",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",slug:"azhar-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",slug:"sergey-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",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",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",slug:"anca-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",slug:"attilio-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",slug:"yanfei-(jacob)-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",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. 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She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. 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He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNVJQA4/Profile_Picture_2022-03-07T13:23:04.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Associate Prof.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/15648_n.jpg",biography:"Dr. Mohd Aftab Siddiqui is currently working as Assistant Professor in the Faculty of Pharmacy, Integral University, Lucknow for the last 6 years. He has completed his Doctor in Philosophy (Pharmacology) in 2020 from Integral University, Lucknow. He completed his Bachelor in Pharmacy in 2013 and Master in Pharmacy (Pharmacology) in 2015 from Integral University, Lucknow. He is the gold medalist in Bachelor and Master degree. He qualified GPAT -2013, GPAT -2014, and GPAT 2015. His area of research is Pharmacological screening of herbal drugs/ natural products in liver and cardiac diseases. He has guided many M. Pharm. research projects. He has many national and international publications.",institutionString:"Integral University",institution:null},{id:"255360",title:"Dr.",name:"Usama",middleName:null,surname:"Ahmad",slug:"usama-ahmad",fullName:"Usama Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255360/images/system/255360.png",biography:"Dr. Usama Ahmad holds a specialization in Pharmaceutics from Amity University, Lucknow, India. He received his Ph.D. degree from Integral University. Currently, he’s working as an Assistant Professor of Pharmaceutics in the Faculty of Pharmacy, Integral University. From 2013 to 2014 he worked on a research project funded by SERB-DST, Government of India. He has a rich publication record with more than 32 original articles published in reputed journals, 3 edited books, 5 book chapters, and a number of scientific articles published in ‘Ingredients South Asia Magazine’ and ‘QualPharma Magazine’. He is a member of the American Association for Cancer Research, International Association for the Study of Lung Cancer, and the British Society for Nanomedicine. Dr. Ahmad’s research focus is on the development of nanoformulations to facilitate the delivery of drugs that aim to provide practical solutions to current healthcare problems.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. Dr. Khullar has a keen research interest in genetics of hypertension, and is currently studying pharmacogenetics of hypertension.",institutionString:"Post Graduate Institute of Medical Education and Research",institution:{name:"Post Graduate Institute of Medical Education and Research",country:{name:"India"}}},{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",biography:"Xianquan Zhan received his MD and Ph.D. in Preventive Medicine at West China University of Medical Sciences. He received his post-doctoral training in oncology and cancer proteomics at the Central South University, China, and the University of Tennessee Health Science Center (UTHSC), USA. He worked at UTHSC and the Cleveland Clinic in 2001–2012 and achieved the rank of associate professor at UTHSC. Currently, he is a full professor at Central South University and Shandong First Medical University, and an advisor to MS/PhD students and postdoctoral fellows. He is also a fellow of the Royal Society of Medicine and European Association for Predictive Preventive Personalized Medicine (EPMA), a national representative of EPMA, and a member of the American Society of Clinical Oncology (ASCO) and the American Association for the Advancement of Sciences (AAAS). He is also the editor in chief of International Journal of Chronic Diseases & Therapy, an associate editor of EPMA Journal, Frontiers in Endocrinology, and BMC Medical Genomics, and a guest editor of Mass Spectrometry Reviews, Frontiers in Endocrinology, EPMA Journal, and Oxidative Medicine and Cellular Longevity. He has published more than 148 articles, 28 book chapters, 6 books, and 2 US patents in the field of clinical proteomics and biomarkers.",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",country:{name:"China"}}},{id:"297507",title:"Dr.",name:"Charles",middleName:"Elias",surname:"Assmann",slug:"charles-assmann",fullName:"Charles Assmann",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/297507/images/system/297507.jpg",biography:"Charles Elias Assmann is a biologist from Federal University of Santa Maria (UFSM, Brazil), who spent some time abroad at the Ludwig-Maximilians-Universität München (LMU, Germany). He has Masters Degree in Biochemistry (UFSM), and is currently a PhD student at Biochemistry at the Department of Biochemistry and Molecular Biology of the UFSM. His areas of expertise include: Biochemistry, Molecular Biology, Enzymology, Genetics and Toxicology. He is currently working on the following subjects: Aluminium toxicity, Neuroinflammation, Oxidative stress and Purinergic system. Since 2011 he has presented more than 80 abstracts in scientific proceedings of national and international meetings. Since 2014, he has published more than 20 peer reviewed papers (including 4 reviews, 3 in Portuguese) and 2 book chapters. He has also been a reviewer of international journals and ad hoc reviewer of scientific committees from Brazilian Universities.",institutionString:"Universidade Federal de Santa Maria",institution:{name:"Universidade Federal de Santa Maria",country:{name:"Brazil"}}},{id:"217850",title:"Dr.",name:"Margarete Dulce",middleName:null,surname:"Bagatini",slug:"margarete-dulce-bagatini",fullName:"Margarete Dulce Bagatini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217850/images/system/217850.jpeg",biography:"Dr. Margarete Dulce Bagatini is an associate professor at the Federal University of Fronteira Sul/Brazil. She has a degree in Pharmacy and a PhD in Biological Sciences: Toxicological Biochemistry. She is a member of the UFFS Research Advisory Committee\nand a member of the Biovitta Research Institute. She is currently:\nthe leader of the research group: Biological and Clinical Studies\nin Human Pathologies, professor of postgraduate program in\nBiochemistry at UFSC and postgraduate program in Science and Food Technology at\nUFFS. She has experience in the area of pharmacy and clinical analysis, acting mainly\non the following topics: oxidative stress, the purinergic system and human pathologies, being a reviewer of several international journals and books.",institutionString:"Universidade Federal da Fronteira Sul",institution:{name:"Universidade Federal da Fronteira Sul",country:{name:"Brazil"}}},{id:"226275",title:"Ph.D.",name:"Metin",middleName:null,surname:"Budak",slug:"metin-budak",fullName:"Metin Budak",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226275/images/system/226275.jfif",biography:"Metin Budak, MSc, PhD is an Assistant Professor at Trakya University, Faculty of Medicine. He has been Head of the Molecular Research Lab at Prof. Mirko Tos Ear and Hearing Research Center since 2018. His specializations are biophysics, epigenetics, genetics, and methylation mechanisms. He has published around 25 peer-reviewed papers, 2 book chapters, and 28 abstracts. He is a member of the Clinical Research Ethics Committee and Quantification and Consideration Committee of Medicine Faculty. His research area is the role of methylation during gene transcription, chromatin packages DNA within the cell and DNA repair, replication, recombination, and gene transcription. His research focuses on how the cell overcomes chromatin structure and methylation to allow access to the underlying DNA and enable normal cellular function.",institutionString:"Trakya University",institution:{name:"Trakya University",country:{name:"Turkey"}}},{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",slug:"anca-pantea-stoian",fullName:"Anca Pantea Stoian",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",biography:"Anca Pantea Stoian is a specialist in diabetes, nutrition, and metabolic diseases as well as health food hygiene. She also has competency in general ultrasonography.\n\nShe is an associate professor in the Diabetes, Nutrition and Metabolic Diseases Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. She has been chief of the Hygiene Department, Faculty of Dentistry, at the same university since 2019. Her interests include micro and macrovascular complications in diabetes and new therapies. Her research activities focus on nutritional intervention in chronic pathology, as well as cardio-renal-metabolic risk assessment, and diabetes in cancer. She is currently engaged in developing new therapies and technological tools for screening, prevention, and patient education in diabetes. \n\nShe is a member of the European Association for the Study of Diabetes, Cardiometabolic Academy, CEDA, Romanian Society of Diabetes, Nutrition and Metabolic Diseases, Romanian Diabetes Federation, and Association for Renal Metabolic and Nutrition studies. She has authored or co-authored 160 papers in national and international peer-reviewed journals.",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",country:{name:"Romania"}}},{id:"279792",title:"Dr.",name:"João",middleName:null,surname:"Cotas",slug:"joao-cotas",fullName:"João Cotas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/279792/images/system/279792.jpg",biography:"Graduate and master in Biology from the University of Coimbra.\n\nI am a research fellow at the Macroalgae Laboratory Unit, in the MARE-UC – Marine and Environmental Sciences Centre of the University of Coimbra. My principal function is the collection, extraction and purification of macroalgae compounds, chemical and bioactive characterization of the compounds and algae extracts and development of new methodologies in marine biotechnology area. \nI am associated in two projects: one consists on discovery of natural compounds for oncobiology. The other project is the about the natural compounds/products for agricultural area.\n\nPublications:\nCotas, J.; Figueirinha, A.; Pereira, L.; Batista, T. 2018. An analysis of the effects of salinity on Fucus ceranoides (Ochrophyta, Phaeophyceae), in the Mondego River (Portugal). Journal of Oceanology and Limnology. in press. DOI: 10.1007/s00343-019-8111-3",institutionString:"Faculty of Sciences and Technology of University of Coimbra",institution:null},{id:"279788",title:"Dr.",name:"Leonel",middleName:null,surname:"Pereira",slug:"leonel-pereira",fullName:"Leonel Pereira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/279788/images/system/279788.jpg",biography:"Leonel Pereira has an undergraduate degree in Biology, a Ph.D. in Biology (specialty in Cell Biology), and a Habilitation degree in Biosciences (specialization in Biotechnology) from the Faculty of Science and Technology, University of Coimbra, Portugal, where he is currently a professor. In addition to teaching at this university, he is an integrated researcher at the Marine and Environmental Sciences Center (MARE), Portugal. His interests include marine biodiversity (algae), marine biotechnology (algae bioactive compounds), and marine ecology (environmental assessment). Since 2008, he has been the author and editor of the electronic publication MACOI – Portuguese Seaweeds Website (www.seaweeds.uc.pt). He is also a member of the editorial boards of several scientific journals. Dr. Pereira has edited or authored more than 20 books, 100 journal articles, and 45 book chapters. He has given more than 100 lectures and oral communications at various national and international scientific events. He is the coordinator of several national and international research projects. In 1998, he received the Francisco de Holanda Award (Honorable Mention) and, more recently, the Mar Rei D. Carlos award (18th edition). He is also a winner of the 2016 CHOICE Award for an outstanding academic title for his book Edible Seaweeds of the World. In 2020, Dr. Pereira received an Honorable Mention for the Impact of International Publications from the Web of Science",institutionString:"University of Coimbra",institution:{name:"University of Coimbra",country:{name:"Portugal"}}},{id:"61946",title:"Dr.",name:"Carol",middleName:null,surname:"Bernstein",slug:"carol-bernstein",fullName:"Carol Bernstein",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61946/images/system/61946.jpg",biography:"Carol Bernstein received her PhD in Genetics from the University of California (Davis). She was a faculty member at the University of Arizona College of Medicine for 43 years, retiring in 2011. Her research interests focus on DNA damage and its underlying role in sex, aging and in the early steps of initiation and progression to cancer. In her research, she had used organisms including bacteriophage T4, Neurospora crassa, Schizosaccharomyces pombe and mice, as well as human cells and tissues. She authored or co-authored more than 140 scientific publications, including articles in major peer reviewed journals, book chapters, invited reviews and one book.",institutionString:"University of Arizona",institution:{name:"University of Arizona",country:{name:"United States of America"}}},{id:"182258",title:"Dr.",name:"Ademar",middleName:"Pereira",surname:"Serra",slug:"ademar-serra",fullName:"Ademar Serra",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/182258/images/system/182258.jpeg",biography:"Dr. Serra studied Agronomy on Universidade Federal de Mato Grosso do Sul (UFMS) (2005). He received master degree in Agronomy, Crop Science (Soil fertility and plant nutrition) (2007) by Universidade Federal da Grande Dourados (UFGD), and PhD in agronomy (Soil fertility and plant nutrition) (2011) from Universidade Federal da Grande Dourados / Escola Superior de Agricultura Luiz de Queiroz (UFGD/ESALQ-USP). Dr. Serra is currently working at Brazilian Agricultural Research Corporation (EMBRAPA). His research focus is on mineral nutrition of plants, crop science and soil science. Dr. Serra\\'s current projects are soil organic matter, soil phosphorus fractions, compositional nutrient diagnosis (CND) and isometric log ratio (ilr) transformation in compositional data analysis.",institutionString:"Brazilian Agricultural Research Corporation",institution:{name:"Brazilian Agricultural Research Corporation",country:{name:"Brazil"}}}]}},subseries:{item:{id:"8",type:"subseries",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",hasOnlineFirst:!1,hasPublishedBooks:!0,annualVolume:11404,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. He received his MSc and PhD in Biomedical Engineering respectively from the Federal University of Uberlândia (UFU, Brazil) in 2000 and from the University of Reading (UK) in 2005. He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). He was the head of the undergraduate program in Biomedical Engineering of the Federal University of Uberlândia (2015 - June/2019) and the head of the Centre for Innovation and Technology Assessment in Health (NIATS/UFU) since 2010. He is the head of the Postgraduate Program in Biomedical Engineering (UFU, July/2019 - to date). He was the secretary of the Parkinson's Disease Association of Uberlândia (2018-2019). Dr. Andrade's primary area of research is focused towards getting information from the neuromuscular system to understand its strategies of organization, adaptation and controlling in the context of motor neuron diseases. His research interests include Biomedical Signal Processing and Modelling, Assistive Technology, Rehabilitation Engineering, Neuroengineering and Parkinson's Disease.",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,series:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343"},editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",slug:"hitoshi-tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",slug:"marcus-vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",slug:"ramana-vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},onlineFirstChapters:{paginationCount:1,paginationItems:[{id:"81644",title:"Perspective Chapter: Ethics of Using Placebo Controlled Trials for Covid-19 Vaccine Development in Vulnerable Populations",doi:"10.5772/intechopen.104776",signatures:"Lesley Burgess, Jurie Jordaan and Matthew Wilson",slug:"perspective-chapter-ethics-of-using-placebo-controlled-trials-for-covid-19-vaccine-development-in-vu",totalDownloads:9,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"SARS-CoV-2 Variants - Two Years After",coverURL:"https://cdn.intechopen.com/books/images_new/11573.jpg",subseries:{id:"6",title:"Viral Infectious Diseases"}}}]},publishedBooks:{paginationCount:0,paginationItems:[]},testimonialsList:[{id:"8",text:"I work with IntechOpen for a number of reasons: their professionalism, their mission in support of Open Access publishing, and the quality of their peer-reviewed publications, but also because they believe in equality.",author:{id:"202192",name:"Catrin",surname:"Rutland",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",slug:"catrin-rutland",institution:{id:"134",name:"University of Nottingham",country:{id:null,name:"United Kingdom"}}}},{id:"27",text:"The opportunity to work with a prestigious publisher allows for the possibility to collaborate with more research groups interested in animal nutrition, leading to the development of new feeding strategies and food valuation while being more sustainable with the environment, allowing more readers to learn about the subject.",author:{id:"175967",name:"Manuel",surname:"Gonzalez Ronquillo",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",slug:"manuel-gonzalez-ronquillo",institution:{id:"6221",name:"Universidad Autónoma del Estado de México",country:{id:null,name:"Mexico"}}}},{id:"18",text:"It was great publishing with IntechOpen, the process was straightforward and I had support all along.",author:{id:"71579",name:"Berend",surname:"Olivier",institutionString:"Utrecht University",profilePictureURL:"https://mts.intechopen.com/storage/users/71579/images/system/71579.png",slug:"berend-olivier",institution:{id:"253",name:"Utrecht University",country:{id:null,name:"Netherlands"}}}}]},submityourwork:{pteSeriesList:[],lsSeriesList:[],hsSeriesList:[],sshSeriesList:[],subseriesList:[],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:null},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/445896",hash:"",query:{},params:{id:"445896"},fullPath:"/profiles/445896",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)}()