Journal of Food Microbiology

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Research Article - Journal of Food Microbiology (2022) Volume 6, Issue 5

REVIEW ON ANTIMICROBIAL MECHANISMS OF SPICES - ESSENTIAL OIL CONSTITUENTS

Mangamma Boya, Soni Komal Laxman, Yugesh Kannth N, Sundara Barathi K, Naveen Saji, Nethavath Akesh, Prateek Ekbote, Usha Amane, Jeepipalli Syam PK*

Department of Skill Development Cell (Food Processing), Central University of Karnataka, Kadaganchi, Aland Road, Kalaburagi District, Karnataka, India

*Corresponding Author:
Jeepipalli Syam PK
Department of Skill Development Cell (Food Processing)
Central University of Karnataka, Kadaganchi
Aland Road, Kalaburagi District, Karnataka, India
E-mail: syamsvu@gmail.com

Received: 04-Sep-2022, Manuscript No. AAFMY-22-73688; Editor assigned: 05-Sep-2022, PreQC No. AAFMY-22-73688(PQ); Reviewed: 19-Sep-2022, QC No AAFMY-22-73688; Revised: 21-Sep-2022, AAFMY-22-73688(R); Published: 27-Sep-2022, DOI:10.35841/aafmy-6.5.122

Citation: Jeepipalli SPK, Boya M, Laxman SK, et al. Review on antimicrobial mechanisms of spices- essential oil constituents. J Food Microbiol. 2022;6(5):122<

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Abstract

Spices have been employed as a flavoring and coloring agents. Essential oils of spices have wide antimicrobial functions. Specific constituents of the essential oils inhibit the synthesis of bacterial cell division proteins, cell membrane depolarization, decrease adenosine triphosphate and disturbing the ionic equilibrium. In the fungal species, the constituents of essential oils decrease the ergosterol synthesis interact with delta-14-sterol reductase, affecting mitochondrial enzymes and accelerating the telomere shortening. Present review discussed the antibacterial and antifungal mechanisms of spices ‘essential oil constituents’.

Keywords

Spices, Cinnamomum cassia, Ocimum basilicum, Antimicrobial, Essential oil.

Introduction

Plants contain numerous chemical components with different biological functions. Aromatically scented herbal products have been used since ancient times to flavor foods. The species of Cinnamomum cassia or Chinese cinnamon, C. verum or true cinnamon contain the spice ingredients in their inner bark. Cinnamon barks essential oils containing cinnamaldehyde as an antibiotic ingredient. The seeds of Thymus vulgaris or German thyme and Trachyspermum ammi or bishop’s weed contain essential oils that possess thymol as an antibiotic molecule. Bishop’s weeds are widely used in food products due to its pleasant flavor and preservative properties. Cumin or Cuminum cyminum contains β-pinene as an active antimicrobial monoterpene. Linalool is an acyclic monoterpene alcohol and antibiotic found in Ocimum basilicum plants. The essential oils of Anethum graveolens seeds containing carvone and limonene as antibiotic molecules. Trans-anethole is an antibiotic molecule found in the fruit essential oils of Pimpinella anisum L species. These different plant origin antibiotic molecules have potent inhibitory functions of bacterial species and fungal variants. The present review discusses the antimicrobial mechanisms alone from the selected research articles as part of our academic project, semester-V and subject code: BFP508S in B.Voc. Food processing programme.

Cinnamaldehyde

All bacterial species have a conserved cell division marker termed Filamentous temperature -sensitive protein Z (FtsZ) in the cytoplasm. Bacterial cytokinesis is mediated through the formation of a Z ring that contains the FtsZ of the cell wall component. The formed Z ring associates with other cell division proteins and contracts gradually for the closure of septum and formation of two daughter bacteria cells [1-3]. Cinnamaldehyde inhibits the bundling of FtsZ protofilaments in the Z ring and exerts antimicrobial response in the bacterial species [4,5]. Cinnamaldehyde interfere with the mechanisms of expression of cell wall construction genes which further lead to the damage of cell wall permeability and integrity Geotrichum citri-aurantii [6]. Cinnamaldehyde as a component is damaging the cell wall integrity by inhibiting the ergosterol content [7], membrane invaginations, elevating the levels of reactive oxygen species, destruction of organelles and disorganization and leakage of cytoplasm in the fungal spores of P. expansum or blue mold decay fungi [8]. Cinnamaldehyde inhibits the spore germination, mycelial growth and fungal biomass production in A. flavus by reducing the ergosterol synthesis, mitochondrial membrane potential, elevating Ca2+ levels, reactive oxygen species, release of cytochrome c, activation of metacaspase, phosphatidylserine externalization and DNA damage [9]. Trans form of cinnamaldehyde changes the cell membrane permeability in P. italicum causing the leakage of cell material [10]. Cinnamaldehyde influences the function of fungal mitochondria by inhibiting the activity of ATPase and SDHase [11].

Thymol

Thymol 2-isopropyl-5-methylphenol is a monoterpene plant compound. Different candida species are susceptible with mean diameter of inhibition zone between 15-21 mm [12]. Thymol and carvone compounds are toxic for the growth of 12 different fungal strains at its lowest concentrations [13]. Phenols located in the ring structure are the vital cause for antifungal activity [14]. Thymol accelerates telomere shortening in the yeast and increases the rate of cell senescence and apoptosis [15]. Intracellular Ca+2 ions homeostasis, glycan-mediated post-translational modifications and the levels of endogenous ergosterol content was significantly decreased in the thymol treated Cryptococcus neoformans [16]. Furthermore, thymol treatment reduced endogenous ergosterol content by decreasing the expression of ergosterol biosynthesis genes in a high-osmolarity glycerol (HOG) - mitogen-Activated Protein Kinase (MAPK) pathway-dependent manner. Thymol has the ability to integrate into the Lipid layer of the cell membrane, increasing the surface curvature and also affecting the activity of internal membrane enzymes and receptors [17].

Thymol is destroyed the integrity of cell membrane resulting in leakage of intracellular material and eventual death of zoonotic bacteria Aeromonas hydrophila [18]. It decreases the intracellular ATP pools of E. coli by disrupting the cytoplasmic membrane [19]. Thymol affects the cell membrane depolarization, decrease intracellular ATP concentrations and lowers pHi in the Enterobacter sakazakii [20]. Thymol promotes the leakage of proteins and nucleic acids in the vegetative and spore forms of Alicyclobacillus acidoterrestris [21].

Beta pinene

Beta-pinene (β-pinene) is a monoterpene, essential oil found in Cumin or Cuminum cyminum. Derivatives of β-pinene are antimicrobial to the bacterial strains of Klebsiella pneumoniae, Enterobacter aerogenes, Staphylococcus aureus, Staphylococcus epidermidis and fungus of Candida albicans. Change in substituent on the pyridine ring and benzene ring of 3-cyanopyridine derivatives is an important factor for inducing antimicrobial activity [22]. The bacterial strains of staphylococcus lost viability significantly 2-8 hours of β-pinene exposure [23]. (+)-β-pinene is an effective molecule in reducing the candida biofilm formation. The crucial antifungal activity is mediated through interference with the cell wall; through molecular interaction with Delta-14-sterol reductase and, to a lesser extent, with the 1,3-β- glucan synthase [24].

Linalool

Linalool also known as 3,7-dimethyl-1,6-octadien-3-ol is an acyclic monoterpene alcohol found in Ocimum basilicum with reported antimicrobial and antifungal properties [25]. Linalool affects the bacterial cells by losing the cell membrane polarization, wrinkling, glue together and broken conditions. Additionally, linalool is causing the intracellular nucleic acid leakage and decreasing the activity of bacterial respiratory dehydrogenases, ATPase’s, pyruvate kinase activities and disturbing the central carbon chain metabolism [26,27]. Linalool is affecting the biofilm formation in the fungal strain of C. albicans ATCC 14053. Linalool is affecting the expression of adhesin genes and the genes responsible for germ tube formation which potentially inhibits the growth of C. albicans fungal strain [28].

Carvone and Limonene

Anethum graveolens (Dill) seeds containing essential oils of carvone and limonene possessing antimicrobial activity. Essential oils increase relative electric conductivity, extracellular ATP concentration and cell constituent of Campylobacter species [29]. Dill compounds inhibiting the bacterial strains of Staphylococcus aureus ATCC25923, clinical Vibrio cholerae, E. coli ATCC 25922 and Pseudomonas aeruginosa 8821M [30]. E. coli and S. aureus strains facing alterations in hydrophobicity, surface charge and membrane integrity that subsequently promote the K+ ions leakage [31]. Dill seed oils also cause morphological changes in the cells of Aspergillus flavus and a reduction in the ergosterol quantity. Fungal cells losing the mitochondrial membrane potential, decreasing ATPase and dehydrogenase activity which indicates dill seed essential oils inhibiting fungi through induction of reactive oxygen species [32]. Derivatives of carvone effective against E. coli and weak antifungal over C. tropicalis and C. parapsilosis [33]. The essential oils containing 78.76% of carvone and 11.50% of limonene are effectively inhibiting the growth of gram positive bacteria [34]. Carvone of Anethum sowa is inhibiting the growth of human pathogenic bacteria and fungi [35]. The components of carvone and limonene significantly inhibit the growth of the Colletotrichum gloeosporioides, Lasiodiplodia theobromae and Alternaria fungal isolates [36]. Carvone is a versatile antifungal compound promoting the cell surface roughness, formation of pores and leakage of cellular content in the candida species [37]. Carvone is an effective inhibitor for the formation of germ tubes in the Candida albicans [38]. Thymol and carvone compounds are toxic for the growth of 12 different fungal strains at the lowest concentrations of 0.017% to 0.051% [13].

Trans-anethole

Pimpinella anisum L fruits containing trans-anethole as the major essential oil component [39,40]. Aqueous decoction of aniseed is 18.1% effective against 176 oral bacteria isolated from 200 individuals [41]. Aromatic compounds could potentially inhibit bacterial growth by precipitating cell wall proteins of Staphylococcus aureus NCTC6571 and Escherichia coli NCTC 5933 [42]. Seed aqueous extracts inhibiting the strains of Bacillus cereus, Staphylococcus aureus, Salmonella typhimurium, and Escherichia coli [43]. Additionally, anise seed oil extracts inhibiting the fungal mycelial growth of Alternaria alternata, Aspergillus niger and Aspergillus parasiticus [40]. Anethole is exhibiting the strong synergism as bacteriostatic with polygodia, an aldehyde phytocompound [44]. The fungal strains of Candida albicans, C. parapsilosis, C. tropicalis, C. pseudotropicalis and C. krusei are effectively inhibiting by anise seed components [45]. Anethole is blocking the recovery of S. cerevisiae and C. albicans from fungistatic effects of dodecanol [46]. Plant pathogenic fungal strains significantly inhibited by the trans-anethole contained essential oil [47]. Trans-anethole disrupts the cell wall integrity of Bacillus cereus and promotes the leakage of nucleic acid components [48]. Anethole, an antivirulence compound- inhibiting the in vitro expression of cholera toxin and toxin coregulated pilus through by over expressing crp genes of cyclic AMP receptor signaling system [49,50].

Conclusion

Essential oil extracts of spices effectively inhibiting or killing the microbial flora of bacterial and fungal species. Hence, food industry is more beneficial to use spices as condiments and its essential components as controlling agents for bacteria and fungi. Active components of spices-essential oils significantly disrupting the biological systems of bacteria and fungi, hence suggested as preservatives in the food industry. Further studies about the antimicrobial mechanisms and their molecular events of spices-essential oil active components were needful.

Acknowledgement

All the authors of this article were most thankful to the B. Voc. Programme coordinator and The Central University of Karnataka, India.

References

  1. Li X, Ma S. Advances in the discovery of novel antimicrobials targeting the assembly of bacterial cell division protein FtsZ. EJMECH. 2015;95:1-5.

    2. Indexed at, Google Scholar, Cross Ref

  2. Panda D, Bhattacharya D, Gao QH, et al. Identification of agents targeting FtsZ assembly. Future Med Chem. 2016;8(10):1111-32.

    3. Indexed at, Google Scholar, Cross Ref

  3. Haranahalli K, Tong S, Ojima I. Recent advances in the discovery and development of antibacterial agents targeting the cell-division protein FtsZ. Bioorg Med Chem. 2016;24(24):6354-69.

    4. Indexed at, Google Scholar, Cross Ref

  4. Domadia P, Swarup S, Bhunia A, et al. Inhibition of bacterial cell division protein FtsZ by cinnamaldehyde. Biochem Pharmacol. 2007;74(6):831-40. `

    5. Indexed at, Google Scholar, Cross Ref

  5. Doyle AA, Stephens JC. A review of cinnamaldehyde and its derivatives as antibacterial agents. Fitoterapia. 2019;139:104405.

    6. Indexed at, Google Scholar, Cross Ref

  6. OuYang Q, Duan X, Li L, et al. Cinnamaldehyde exerts its antifungal activity by disrupting the cell wall integrity of Geotrichum citri-aurantii. Front. Microbiol. 2019;10:55.

    7. Indexed at, Google Scholar, Cross Ref

  7. Wei J, Bi Y, Xue H, et al. Antifungal activity of cinnamaldehyde against Fusarium sambucinum involves inhibition of ergosterol biosynthesis. J Appl Microbiol. 2020;129(2):256-65.

    8. Indexed at, Google Scholar, Cross Ref

  8. Wang Y, Feng K, Yang H, et al. Antifungal mechanism of cinnamaldehyde and citral combination against Penicillium expansum based on FT-IR fingerprint, plasma membrane, oxidative stress and volatile profile. RSC advances. 2018;8(11):5806-15.

    9. Indexed at, Google Scholar, Cross Ref

  9. Qu S, Yang K, Chen L,  et al. Cinnamaldehyde, a promising natural preservative against Aspergillus flavus. Front Microbiol. 2019;10:2895.

    10. Indexed at, Google Scholar, Cross Ref

  10. Huang F, Kong J, Ju J, et al. Membrane damage mechanism contributes to inhibition of trans-cinnamaldehyde on Penicillium italicum using Surface-Enhanced Raman Spectroscopy (SERS). Sci Rep. 2019;9(1):1-0.

    11. Indexed at, Google Scholar, Cross Ref

  11. Niu A, Wu H, Ma F, et al. The antifungal activity of cinnamaldehyde in vapor phase against Aspergillus niger isolated from spoiled paddy. LWT. 2022;159:113181.

    12. Indexed at, Google Scholar, Cross Ref

  12. Sharifzadeh A, Shokri H, Katiraee F. Anti-adherence and anti-fungal abilities of Thymol and Carvacrol against Candida species isolated from patients with Oral candidiasis in comparison with fluconazole and Voriconazole. JJNPP. 2021;16(1).

    13. Google Scholar, Cross Ref

  13. Morcia C, Malnati M, Terzi V. In vitro antifungal activity of terpinen-4-ol, eugenol, carvone, 1, 8-cineole (eucalyptol) and thymol against mycotoxigenic plant pathogens. Food Addit Contam: Part A. 2012;29(3):415-22.

    14. Indexed at, Google Scholar, Cross Ref

  14. Ahmad A, Khan A, Akhtar F, et al. Fungicidal activity of thymol and carvacrol by disrupting ergosterol biosynthesis and membrane integrity against Candida. EJCMID. 2011;30(1):41-50.

    15. Indexed at, Google Scholar, Cross Ref

  15. Darvishi E, Omidi M, Bushehri AA, et al. Thymol antifungal mode of action involves telomerase inhibition. Med Mycol. 2013;51(8):826-34.

    16. Indexed at, Google Scholar, Cross Ref

  16. Jung KW, Chung MS, Bai HW, et al. Investigation of Antifungal Mechanisms of Thymol in the Human Fungal Pathogen, Cryptococcus Neoformans. Molecules. 2021;26(11):3476.

    17. Indexed at, Google Scholar, Cross Ref

  17. Kowalczyk A, Przychodna M, Sopata S, et al. Thymol and thyme essential oil—new insights into selected therapeutic applications. Molecules. 2020;25(18):4125.

    18. Indexed at, Google Scholar, Cross Ref

  18. Liang C, Huang S, Geng Y, et al. A Study on the antibacterial mechanism of thymol against Aeromonas hydrophila in vitro. Aquac Int. 2022;30(1):115-29.

    19. Google Scholar, Cross Ref

  19. Helander IM, Alakomi HL, Latva-Kala K, et al. Characterization of the action of selected essential oil components on Gram-negative bacteria. J Agric Food Chem. 1998;46(9):3590-5.

    20. Indexed at, Google Scholar, Cross Ref

  20. Tian L, Wang X, Liu R, et al. Antibacterial mechanism of thymol against Enterobacter sakazakii. Food Control. 2021;123:107716.

    21. Indexed at, Google Scholar, Cross Ref

  21. Cai R, Zhang M, Cui L, et al. Antibacterial activity and mechanism of thymol against Alicyclobacillus acidoterrestris vegetative cells and spores. LWT. 2019;105:377-84.

    22. Indexed at, Google Scholar, Cross Ref

  22. Liao S, Shang S, Shen M, et al. One-pot synthesis and antimicrobial evaluation of novel 3-cyanopyridine derivatives of (−)-β-pinene. Bioorg Med Chem Lett. 2016;26(6):1512-5.

    23. Indexed at, Google Scholar, Cross Ref

  23. Leite AM, Lima ED, Souza EL, et al. Inhibitory effect of beta-pinene, alpha-pinene and eugenol on the growth of potential infectious endocarditis causing Gram-positive bacteria. Revista Brasileira de Ciências Farmacêuticas. 2007;43:121-6.

    24. Indexed at, Google Scholar

  24. de Macedo Andrade AC, Rosalen PL, et al. Antifungal activity, mode of action, docking prediction and anti-biofilm effects of (+)-β-pinene enantiomers against Candida spp. Curr Top Med Chem. 2018;18(29):2481-90.

    25. Indexed at, Google Scholar, Cross Ref

  25. Duman AD, Telci I, Dayisoylu KS, et al. Evaluation of bioactivity of linalool-rich essential oils from Ocimum basilucum and Coriandrum sativum varieties. Nat Prod Commun. 2010;5(6):1934578X1000500634.

    26. Indexed at, Google Scholar, Cross Ref

  26. Guo F, Chen Q, Liang Q, et al, Chen W. Antimicrobial activity and proposed action mechanism of linalool against Pseudomonas fluorescens. Front Microbiol. 2021;12:562094.

    27. Indexed at, Google Scholar, Cross Ref

  27. He R, Chen W, Chen H, et al. Antibacterial mechanism of linalool against L. monocytogenes, a metabolomic study. Food Control. 2022;132:108533.

    28. Indexed at, Google Scholar, Cross Ref

  28. Hsu CC, Lai WL, Chuang KC, et al. The inhibitory activity of linalool against the filamentous growth and biofilm formation in Candida albicans. Med Mycol. 2013;51(5):473-82.

    29. Indexed at, Google Scholar, Cross Ref

  29. Mutlu-Ingok A, Karbancioglu-Guler F. Cardamom, cumin, and dill weed essential oils: Chemical compositions, antimicrobial activities, and mechanisms of action against Campylobacter spp. Molecules. 2017;22(7):1191.

    30. Indexed at, Google Scholar, Cross Ref

  30. Derakhshan S, Navidinia M, Ahmadi A. Antibacterial activity of Dill (Anethum graveolens) essential oil and antibiofilm activity of Cumin (Cuminum cyminum) alcoholic extract. Infect epidemiol microbiol. 2017;3(4):122-6.

    31. Google Scholar, Cross Ref

  31. Lopez-Romero JC, Gonzalez-Rios H, Borges A, et al. Antibacterial effects and mode of action of selected essential oils components against Escherichia coli and Staphylococcus aureus. eCAM. 2015;2015.

    32. Indexed at, Google Scholar, Cross Ref

  32. Tian J, Ban X, Zeng H, et al. The mechanism of antifungal action of essential oil from dill (Anethum graveolens L.) on Aspergillus flavus. PloS one. 2012;7(1):e30147.

    33. Indexed at, Google Scholar, Cross Ref

  33. Moro IJ, Gondo GD, Pierri EG, et al. Evaluation of antimicrobial, cytotoxic and chemopreventive activities of carvone and its derivatives. Brazilian J Pharm Sci. 2018;53.

    34. Indexed at, Google Scholar, Cross Ref

  34. Shahbazi Y. Chemical composition and in vitro antibacterial activity of Mentha spicata essential oil against common food-borne pathogenic bacteria. J Pathog. 2015;2015.

    35. Indexed at, Google Scholar, Cross Ref

  35. Aggarwal KK, Khanuja SP, Ahmad A, et al. Antimicrobial activity profiles of the two enantiomers of limonene and carvone isolated from the oils of Mentha spicata and Anethum sowa. Flavour Fragr J. 2002;17(1):59-63.

    36. Google Scholar, Cross Ref

  36. Regnier T, Combrinck S, Du Plooy W, et al. Evaluation of Lippia scaberrima essential oil and some pure terpenoid constituents as postharvest mycobiocides for avocado fruit. Postharvest Biol Technol. 2010;57(3):176-82.

    37. Google Scholar, Cross Ref

  37. Giovana CB, Simone NB, Priscilla DL, et al. Antifungal and cytotoxic activity of purified biocomponents as carvone, menthone, menthofuran and pulegone from Mentha spp. Afr J  Plant Sci. 2016;10(10):203-10.

    38. Google Scholar, Cross Ref

  38. Piras A, Porcedda S, Falconieri D, et al. Antifungal activity of essential oil from Mentha spicata L. and Mentha pulegium L. growing wild in Sardinia island (Italy). Nat Prod Res. 2021;35(6):993-9.

    39. Indexed at, Google Scholar, Cross Ref

  39. Özcan MM, Chalchat JC. Chemical composition and antifungal effect of anise (Pimpinella anisum L.) fruit oil at ripening stage. Ann. Microbiol. 2006;56(4):353-8.

    40. Indexed at, Google Scholar, Cross Ref

  40. Orav A, Raal A, Arak E. Essential oil composition of Pimpinella anisum L. fruits from various European countries. Nat Prod Res. 2008;22(3):227-32.

    41. Indexed at, Google Scholar, Cross Ref

  41. Chaudhry NM, Tariq P. Bactericidal activity of black pepper, bay leaf, aniseed and coriander against oral isolates. Pak J Pharm Sci. 2006;19(3):214-8.

    42. Indexed at, Google Scholar

  42. Fatima SS, Bushra AM, Zainab SA. Extraction and identification of oil extract from anise (Pimpinellaanisum L.) seeds and study of its antimicrobial activity. GJPACR. 2015;3:1-6.

    43. Google Scholar

  43. Amer AM, Aly UI. Antioxidant and antibacterial properties of anise (Pimpinella anisum L.). Egypt Pharm J. 2019;18(1):68.

    44. Indexed at, Google Scholar, Cross Ref

  44. Kubo I, Fujita KI. Naturally occurring anti-Salmonella agents. J Agric Food Chem. 2001;49(12):5750-4.

    45. Indexed at, Google Scholar, Cross Ref

  45. Kosalec I, Pepeljnjak S, KUŠTRAK D. Antifungal activity of fluid extract and essential oil from anise fruits (Pimpinella anisum L., Apiaceae). Acta Pharm. 2005;55(4):377-85.

    46. Indexed at, Google Scholar

  46. Fujita KI, Fujita T, Kubo I. Anethole, a potential antimicrobial synergist, converts a fungistatic dodecanol to a fungicidal agent. Phytother Res: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives. 2007;21(1):47-51.

    47. Indexed at, Google Scholar, Cross Ref

  47. Huang Y, Zhao J, Zhou L, et al. Antifungal activity of the essential oil of Illicium verum fruit and its main component trans-anethole. Molecules. 2010;15(11):7558-69.

    48. Indexed at, Google Scholar, Cross Ref

  48. Naksang P, Tongchitpakdee S, Thumanu K, et al. Assessment of antimicrobial activity, mode of action and volatile compounds of Etlingera pavieana essential oil. Molecules. 2020;25(14):3245.

    49. Indexed at, Google Scholar, Cross Ref

  49. Zahid MS, Awasthi SP, Asakura M, et al. Suppression of virulence of toxigenic Vibrio cholerae by anethole through the cyclic AMP (cAMP)-cAMP receptor protein signaling system. PloS one. 2015;10(9):e0137529.

    50. Indexed at, Google Scholar, Cross Ref

  50. Zahid MS, Awasthi SP, Hinenoya A, et al. Anethole inhibits growth of recently emerged multidrug resistant toxigenic Vibrio cholerae O1 El Tor variant strains in vitro. J Vet Sci. 2015:14-0664.

    51. Indexed at, Google Scholar, Cross Ref

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