Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
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We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\n
Throughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\n
We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
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However, simply taking a straight verbatim approach to catalog all proteins in all tissues of different organisms is not viable. Researchers may need to focus on the perspectives of proteomics that are essential to the functional outcome of the cells. In Integrative Proteomics, expert researchers contribute both historical perspectives, new developments in sample preparation, gel-based and non-gel-based protein separation and identification using mass spectrometry. Substantial chapters are describing studies of the sub-proteomes such as phosphoproteome or glycoproteomes which are directly related to functional outcomes of the cells. Structural proteomics related to pharmaceutics development is also a perspective of the essence. Bioinformatics tools that can mine proteomics data and lead to pathway analyses become an integral part of proteomics. Integrative proteomics covers both look-backs and look-outs of proteomics. 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He did his post-doctoral training in Baylor College of Medicine studying genomics and proteomics profiles of pediatrics medulloblastoma and osteosarcoma. Dr. Leung was a research scientists in Ciphergen Biosystems Inc. Briefly, and then was recruited to Genome Institute of Singapore to lead the clinical proteomics section. In 2006 he returned to USA. He was the director of the genomics and proteomics core laboratory of the Texas Children´s Hospital and director of genomics profiling of Baylor College of Medicine. At present, he is the director of the mass spectrometry-proteomics core facility of Baylor College of Medicine.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Baylor College of Medicine",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"35047",title:"Prof.",name:"Tsz Kwong",middleName:null,surname:"Man",slug:"tsz-kwong-man",fullName:"Tsz Kwong Man",profilePictureURL:"https://mts.intechopen.com/storage/users/35047/images/system/35047.jpg",biography:"Dr. Chris Man is an Associate Professor of Pediatrics at Baylor College of Medicine where he participates in the Bone Tumor Program and the Cancer Genetics and Genomics Program at Texas Children’s Cancer Center. 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1. Introduction
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Efficient seed germination is important for agriculture. Successful establishment of early seedling indeed requires a rapid and uniform emergence and root growth. Germination of orthodox seeds commonly implies three distinct phases (Figure 1) consisting in (1) Phase I: seed hydration process related to passive imbibition of dry tissues associated with water movement first occurring in the apoplastic spaces; (2) Phase II: activation phase associated with the re-establishment of metabolic activities and repairing processes at the cell level; and (3) Phase III: initiation of growing processes associated to cell elongation and leading to radicle protrusion. Phases I and III both involve an increase in the water content while hydration remains stable during Phase II. It is commonly considered that before the end of Phase II, germination remains a reversible process: the seeds may be dried again and remain alive during storage and able to subsequently re-initiate germination under favorable conditions.
Figure 1.
Seed hydration curves and germinating phases in unprimed and primed seeds.
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Water-based seed priming is defined as a pre-sowing treatment that partially hydrates seeds without allowing emergence [1]. Various treatments may indeed be applied during the reversible phase of germination (point 3). They widely differ according to the osmotic potential of the priming solution, the duration, the external temperature, and the presence of specific chemical compounds. The efficient treatments trigger metabolic processes activated during the phase II of germination, which are then temporally stopped before a loss of desiccation occurs (Figure 1) [2].
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The overall consequence of seed priming consists in an increased seed vigor defined as the whole set of properties conditioning seed lots performance in a wide range of environment [3]. Priming strategies may afford several economic and agronomic advantages to cultivated plants (point 4). Numerous data published in the literature indeed reported an improvement in the rate and uniformity of germination but also an obvious improvement in the behavior of the obtained seedlings in terms of plant growth and stress resistance.
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Although priming is used since decades by farmers and seed companies to improve germination, it can also occur under natural plant conditions. This is more especially the case in serotinous plants growing in deserts and able to retain their seeds for a long time. These seeds indeed undergo several hydration-dehydration cycles enhancing subsequent germination after final seed dispersion caused by heavy rain [4]. From a general point of view, the priming process not only concerns seeds but also the whole plant system itself and may be defined as an induced state whereby a plant reacts more rapidly and more efficiently to a stress [5]. In this acception, plants exposed to a primary constraint are triggering a set of temporary metabolic adaptation leading to a stress memory and allowing them to adapt more efficiently to subsequent episodes of stress [6, 7].
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Although the interest of seed priming has been demonstrated since a long time, the underlying physiological and biochemical basis of this fascinating process remain poorly understood. Holistic approaches related to omics tools now provide new opportunities to elucidate the molecular components of the priming phenomena. Similarly, nondestructive and noninvasive methods such as digital image technology may be used in a more precise way to study the kinetics of imbibition in relation to the modification of the seed ultrastructure. This chapter reviews the most recent progresses accomplished in the understanding of the seed priming-induced modifications.
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2. A brief history of seed priming
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Man established contact with seed physiology since the beginning of agriculture and quickly realized that many seeds do not germinate easily and uniformly. Ancient civilization was fascinated by the capacity of an apparently « dead seed » to resurrect and to produce a viable young and healthy seedling after germination. The Greek Theophrastus (ca. 372–287 BC) already focused on seed physiology and suggested that germination process may be temporarily interrupted [8]. Pre-hydration of legume seeds before sowing was performed by Roman farmers in order to increase the germination rate and synchronize germination as reported by the Roman naturalist Gaius Plinius Secundus. Several centuries later, these techniques were still used for a wide range of species according to the French agronomist Olivier de Serres (1539–1619) [8]. In 1664, Evelyn [9] mentioned that temperature prior sowing may have an impact on further germination while one century later, Ingenhousz [10] analyzed the impact of light on seedling emergence.
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During the nineteenth century, numerous botanists started to describe morphological processes associated with seed germination [11, 12]. Sachs [13] experimented the impact of various compounds (including tyrosine and asparagine) before and during germination. The discovery of plant hormones in the 1920s underlined the crucial role of these compounds in seed desiccation tolerance, reserve mobilization, as well as cell division and cell elongation occurring during germination. The possibility to influence final germination as a consequence of pre-sowing treatment has led to a wide range of empirical methods for numerous cultivated plant species during the year 1970s [14].
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3. Priming methods and priming agents
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Several methods of seed priming have been developed in order to invigorate seeds and alleviate the environmental stresses. A common feature of water-based priming techniques, which distinguishes them from other pre-sowing treatments, is partial seed pre-hydration and the activation of early germination events in seed. Priming efficiency is affected by many factors and strongly depends on treated plant species and chosen priming technique. Physical and chemical factors such as osmotica and water potential, priming agent, duration, temperature, presence or absence of light, aeration, and seed condition also influence priming success and determine germination rate and time, seedling vigor, and further plant development [15, 16].
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3.1. Hydropriming
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Hydropriming is the simplest method of seed priming, which relies on seed soaking in pure water and re-drying to original moisture content prior to sowing. No use of additional chemical substances as a priming agent makes this method a low-cost and environmentally friendly. The main disadvantage of hydropriming is uncontrolled water uptake by seeds. This is a consequence of free water availability to seeds during hydropriming, so that the rate of water uptake depends only on seed tissue affinity to water [17]. Moreover, this technique may result in unequal degree of seeds hydration thus leading to lack of simultaneous metabolic activation within seeds followed by unsynchronized emergence [18]. Considering these limiting factors, it is highly important to define accurate treatment duration, temperature, and water volume used in hydropriming to ensure desired level of seed hydration and to prevent radicle protrusion. Despite the aforementioned limitations, many reports indicated beneficial effect of hydropriming on seed germination and seedling growth under both optimal and stress conditions, in various crop plants such as chickpea, maize [19], wheat [20], Indian mustard [21], canola [22], sunflower [23], rice [24], mung bean [25], capsicum [26], and durum wheat [27].
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One of the commercially used types of hydropriming is the system named “drum priming”, patented in the early 1990s [28, 29]. In this technique, seeds are gently rotating in drum and gradually hydrated by addition of water in vapor form. Drum priming allows seed imbibition in a controlled manner and could be an attractive alternative to conventional hydropriming. Specially designed apparatus enables monitoring of the seed weight, precise regulation of time, and water amount during hydration process, what ultimately results in an appropriate and uniform moisture level of the seeds [30]. Drum priming with 24-epibrassinolide shows positive effect on germination time and seedling growth of bell pepper concomitant with improved superoxide dismutase (SOD), catalase (CAT), and peroxidase (POX) activities [31]. Another variant of hydropriming, so-called “on-farm priming”, consist of seed soaking in water followed by surface drying and subsequent sowing. The duration of treatment obligatorily cannot be longer than “safe limit” (maximum time of priming without risk of seed or seedling damage by premature germination) [32]. The positive impact of this method on crop emergence and yield was confirmed by Harris et al. [33]. On-farm priming is especially useful for resource-poor farmers in marginal tropical environment [34].
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3.2. Osmopriming
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Osmopriming involves soaking seeds in osmotic solution with low water potential instead of pure water. Due to low water potential of osmotic solutions, water enters seed slowly which allows gradual seed imbibition and activation of early phases of germination but prevents radicle protrusion [35]. Usually water potential of priming agent varies from −1.0 down to −2.0 MPa [36]. However, values of water potential together with duration of the priming treatment should be always adjusted to species, cultivar, and sometimes seed lot. Different compounds are used in osmopriming procedure including polyethylene glycol (PEG), mannitol, sorbitol, glycerol, and inorganic salts such as NaCl, KCl, KNO3, K3PO4, KH2PO4, MgSO4, and CaCl2 [37]. Priming with salt solutions is often referred as “halopriming”. Most common chemical employed in osmopriming treatment is PEG, mainly owing to its specific characteristic. Large molecular size of PEG prevents its penetration into the seed thus avoiding induction of potential cytotoxic effect and reduction of osmotic potential within seed [35]. Nevertheless, PEG exhibits some undesirable features including high viscosity, which restrict diffusion of oxygen in the solution so in PEG priming aeration system is preferred [2]. Seed priming with PEG has been shown as an effective method to improve seed germination, seedling emergence, and stress tolerance of several crop plants under unfavorable conditions such as salt, water, chilling, and nano-ZnO stresses [1, 3, 36–38].
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3.3. Solid matrix priming
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Solid matrix priming (SMP, matriconditioning), in which water uptake by seeds is controlled, has been developed as an alternative method to osmopriming because of high cost of osmotic agents and technical problems with aeration [2]. During solid matrix priming, seeds are mixed and incubated with wet solid water carrier for a certain period. Afterward, seeds are separated from matrix, rinsed, and back-dried. The use of solid medium allows seeds to hydrate slowly and simulates natural imbibition process occurring in the soil [18]. To successfully accomplish SMP, materials utilized as matrices should possess specific physical and chemical features such as low matrix potential, minimal water solubility, high water holding capacity and surface area, no toxicity to seeds, and ability to adhere to seed surface. In fact, vermiculite, peat moss, charcoal, sand, clay, and some commercially offered substrate such as Celie or Micro Cell are exemplary solid carries applied in solid matrix priming [2, 35]. In order to obtain the best priming performance, time of treatment and optimal water content must be determined separately for each matrix [39].
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Positive effects of SMP on crop seeds have been noted in many reports. Solid matrix priming enhanced field performance of carrot [40] as well as improved germination and seed vigor of soybean [41]. Study on onion showed that matriconditioning improved seed germination rate, seedling emergence, and growth under optimal and low temperature conditions [42]. Sand priming increased the activities of antioxidant enzymes such as catalase (CAT), peroxidase (POX), and soluble sugar content in waxy maize concomitant with improved rate of germination and seedling growth under high-salt stress conditions [43].
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It is well established that integration of SMP with biological and chemical factors may greatly enhance seed performance [18]. Adoreoli and de Adnrade [44] indicated that inclusion of gibberellins/fungicide/Bacillus subtilis to matriconditioning leads to improved stand establishment and productivity of some vegetable crops under tropical conditions. Similarly, matriconditioning with GA3 enhanced the quality of hot pepper seeds [45]. More recently published data demonstrated that solid matrix priming with Trichoderma viride improved seedling emergence and yield of okra under low temperatures [46].
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3.4. Hormopriming
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During hormopriming, seeds imbibition occurs in the presence of plant growth regulators, which can have direct impact on seed metabolism. The following regulators are commonly used for hormopriming: abscisic acid, auxins, gibberellins, kinetin, ethylene, polyamines, and salicylic acid (SA). Gibberellic acid (GA3) and PEG priming improved photosynthetic properties, antioxidant system, seedling emergence, and growth of white clover on heavy metal polluted soil [47]. Priming spring wheat seeds with GA3 increased grain yield and salt tolerance by modulating hormone homeostasis together with alterations of ion uptake and accumulation between shoots and roots [48]. Enhanced salt tolerance, growth, and grain yield of wheat were also observed after kinetin-priming [49]. Among the different techniques of seed priming (hydro-, osmo-, and halopriming), spermidine pretreatment appeared to be the most effective method for induction drought tolerance in rice [50]. High efficiency of polyamines-priming on the improvement of rice tolerance to drought has been demonstrated also by Farooq et al. [51]. Critical role of phytohormones exogenously supplied into seeds for plant response to salinity stress was stated in wheat seeds primed with ascorbic acid and salicylic acid, as this pretreatment method increases the ability of wheat to grow successfully under salt stress, whereas hormonal priming with ABA was not effective in this case [52].
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3.5. Biopriming
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Biopriming involves seed imbibition together with bacterial inoculation of seed [53]. As other priming method, this treatment increases rate and uniformity of germination, but additionally protects seeds against the soil and seed-borne pathogens. Hydration of seeds infected with pathogens during priming can result in a stronger microbial growth and consequently impairment of plant health. However, applying antagonistic microorganisms during priming is an ecological approach to overcome this problem [54]. Moreover, some bacteria used as biocontrol agents are able to colonize rhizosphere and support plant in both direct and indirect way after germination stage [55]. It was found that biopriming is a much more effective approach to disease management than other techniques such as pelleting and film coating [56]. Nowadays, the use of biopriming with plant growth-promoting bacteria (PGPB) as an integral component of agricultural practice shows great promise [57, 58]. In pearl millet, biopriming with Pseudomonas fluorescens isolates enhanced plant growth and resistance against downy mildew disease [59]. Biopriming with rhizobacteria improved germination parameters of radish seeds under saline conditions [60].
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3.6. Others
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Chemical priming refers to seed treatment with different chemical solutions used as priming agents. This approach includes priming with wide range of both natural and synthetic compounds such as antioxidants (ascorbic acid, glutathione, tocopherol, melatonin, and proline), hydrogen peroxide, sodium nitroprusside, urea, thiourea, mannose, selenium, chitosan, fungicide etc. Positive impact of chemical priming with various priming agents in a wide range of environmental conditions was indicated by numerous studies [26, 61–64]. Seed priming with β-amino butyric acid increased drought and salt tolerance of green gram [65]. Application of ascorbic acid as a seed priming agent induced drought and salt resistance of wheat [66, 67]. Analysis conducted by Fercha et al. [67] revealed that priming with ascorbate counteracts the negative effects of salinity stress by changes in abundance of proteins involved in metabolism, protein destination, and storage.
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Nutripriming is a technique in which seeds are soaked with solutions containing the limiting nutrient instead of pure water. The idea of this method is to obtain nutritional effect together with biochemical advantages of priming in order to improve seed quality, germination parameters, and seedling establishment [68]. Seed priming with Zn improved productivity of chickpea and wheat [69], germination and early seedling growth of rice [70], development and root growth of maize seedling exposed to low root zone temperatures [71], while K-priming brought favorable effect on growth and nutrient status of cotton seedling under saline conditions [72]. Some nutripriming techniques are commonly used by seed companies in the process of seed production and preparation for growers. One of this methods, broad spectrum nutrient seed priming (BSN), is based on imbibing seeds in mixture of minerals, such as zinc, copper, manganese, molybdenum, and phosphorus, which has been proved to fertilize the seed and provides the nutrients for early growth, which positively affects germination, seedling vigor, and root system development (http://seedprimer.com/).
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4. Seed priming and agriculture
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Pre-sowing priming induces a particular physiological status in seeds and has emerged as a promising strategy to improve plant behavior in the field. There is a strong interest for farmers and seed companies to find suitable cheap priming treatments but also to precisely identify the agronomical properties improved as a result of priming in cultivated species.
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4.1. Hastening and synchronization of germination
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Primed seeds often exhibit an increased germination rate and greater germination uniformity. An enhanced and uniform seedling emergence may contribute to regular crop establishment. Priming may enhance events taking place at the beginning of the germination, but the whole process is interrupted at a given state, which is the same for all concerned seeds. Priming may also induce structural and ultrastructural modifications that could facilitate subsequent water uptake and attenuate initial differences between the seeds in terms of imbibition, thus resulting in a more uniform germination [47].
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A faster emergence may help to improve competitivity of cultivated plants against weed species as recently demonstrated by Jalali and Salehi [73] for sugar beets. In mung bean plants, a faster seedling establishment resulting from priming may contribute to a total increase in yield up to 45% [74].
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Priming-induced increase in germination may be associated to a change in plant hormone biosynthesis and signaling. Priming has been reported to increase gibberellins (GA)/abscisic acid (ABA) ratio [75], and this may be a direct consequence of a priming impact in gene expression pattern [76]. A more uniform GA endogenous concentration in primed seeds may help to synchronize endosperm weakening, embryo cell elongation, and reserve mobilization [77]. Ethylene also directly influences germination speed and percentage. Increase in ethylene production during priming may promote endo-β-mannase activity facilitating endosperm weakening and post-priming germination [78]. Priming has been reported to initiate repair and reactivation of pre-existing mitochondria and to initiate the biogenesis of new ones [79]. It may thus afford a higher level of energy over a short time to sustain final germination [80].
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4.2. Plant growth
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Plants issued from primed seeds often exhibit a faster growth than those issued from unprimed ones. Determine whether such growth stimulation is the consequence of a more rapid seedling establishment or result from a long-term specific physiological status induced by priming still remains an unresolved question. In numerous cases, the beneficial impact of priming on plant growth is more obvious under nonoptimal than under optimal conditions, leading to the global concept that a major advantage of priming consists in an increase in stress resistance (point 4.10). Thus, in direct relation to memory events, the main question is related to the remanence of priming-induced modifications. Imram et al. [71] showed that such modifications remain intact several weeks after germination in maize.
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In rice, priming with 5-aminolevulinic acid improved shoot elongation [81] while priming with picomolar rutin augmented both root and shoot length in relation to an increase in photosynthetic pigments, phenolic and flavonoid contents [82]. In wheat, priming with sodium prusside stimulated plant growth as a consequence of improved capacity to scavenge free radicals by antioxidants [83], and a similar observation was reported for rice as a result of an increase in glutathione peroxidase (GPX) activity [24] and other antioxidant enzyme activities [84].
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The beneficial impact of priming on plant growth may be due to an improved nutrient use efficiency allowing a higher relative growth rate [85] and to an improved regulation of the plant water status [86]. Jisha and Puthur [65] confirmed that the priming effect of β-aminobutyric acid on seeds of Vigna radiata further get carried over the seedlings. A higher growth of seedlings issued from primed seeds may also be analyzed in relation to a direct impact of pretreatment on cell cycle regulation and cell elongation processes (point 7) [77, 78].
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4.3. Mineral nutrition
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Modification of nutrient uses efficiency by young seedlings may be a consequence of priming-induced overexpression of genes encoding for specific transporters, although only few transporters appear specifically induced by priming itself [36]. An efficient strategy to improve mineral nutrition of young seedling is to use nutrient-based seed priming strategy. Phosphorous seed priming supported crop development at early stages and may compensate for P deficiency in the soil [87, 88]. Jamil et al. [89] demonstrated that improvement of mineral status of P-primed cereals reduced strigolactone exudation and thus sensitivity to the parasite weed Striga hermonthica. Muhammad et al. [85] recently performed experiments using Zn, Mn, B, and P priming. These authors demonstrated that nutrient seed priming allowed maize plants to maintain Zn and Mn supply for at least 3 weeks in highly calcareous soils characterized by a low nutrient availability. Similarly, Pame et al. [90] showed that P accumulation in rice may be increased by using P-primed seeds, which is of special interest in Asia where about one-third of the area of rainfed rice is situated on P-deficient soils. Such a higher absorption could not be explained only by nutrient accumulation in the seeds during the primed phase since it is still observed in plants several weeks after sowing. It may therefore be hypothesized that priming interferes with regulation of acquisition mechanisms and further research is crucially needed to identify the molecular mechanisms involved in these processes. Priming with boron improves seedling emergence in rice and, on a long-term basis, increases panicle fertility in relation to an improvement in stigma receptivity [91]. Seed priming may also contribute to improve N nutrition, mainly through an enhanced nitrate reductase activity in plants [40]. Priming with nonessential beneficial elements, such as Si, leads to an increase in Si content of cultivated plants and has a protective impact on plant development [86].
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Beside the improvement of essential elements uptake, priming also helps to reduce accumulation of putatively toxic elements. Chromium (VI) accumulation is reduced in maize seedlings issued from salicylic acid primed seeds and cultivated in the presence of this toxic element [82]. Osmopriming with PEG and hormopriming with GA improved germination and early seedling growth of white clover maintained on a heavy metal-contaminated soil, but the impact on Cd accumulation by plants may differ according to the considered treatment since GA3 increased Cd accumulation while PEG reduced it [47]. Liu et al. [92] demonstrated that PEG increases Ca2+ cytosolic concentration through hyperpolarization-activated calcium permeable channels, which could explain a lower Cd accumulation as a consequence of an improved selectivity toward calcium.
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Numerous data are also available concerning the priming effect on the plant behavior exposed to salinity. It is frequently reported that priming-induced stress resistance may be a consequence of an improved discrimination for K+ over Na+ nutrition. Both osmo- and hydropriming were efficiently used to influence K+ selectivity of seedlings, but the underlying molecular basis of this improvement still needs to be identified, especially in terms of regulation of monovalent cation transporters.
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4.4. Yield-related parameters
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A huge amount of studies is devoted to the impact of seed priming on the seed germination phase and early seedling growth. Most of those studies are conducted under controlled environmental conditions in plant growth chambers or greenhouses. Data reporting a real improvement under field conditions remain rare. Yield effect may be linked to a faster plant establishment allowing a longer growth period. Khan et al. [93] reported that plant issued from primed seed benefits from a longer period of assimilates accumulation in sugar beet. Conversely, in some cases, phenological evolution of cultivated plants may be modified by priming: in chickpea, plants issued from priming encountered an earlier seed maturity allowing them to escape disease or heat terminal stress in the season [94]. Yield increase may also result from a higher plant density observed as a consequence of priming-induced increase in germination percentage [95].
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Since less than a decade, several data started to be available for priming-induced yield improvement in rice. Shah et al. [96] demonstrated that priming had a positive effect on the weight of 1000 grains in this species. Boron priming induced an obvious decrease in panicle sterility and consequently improved the number of grains per inflorescence [91]. Binang et al. [97] also demonstrated that priming had a significant effect on the number of tillers, number of fertile panicles, and consequently grain yield of new NERICA rice varieties. Promising yield improvement has also been reported for maize [85, 98], onion [99], okra [100], and sugar beet [73]. Beside its impact on quantitative parameters, priming may also improve the quality of harvested plants, as recently reported by Janecho et al. [101] for the vitamin content and nutritional value of legumes.
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4.5. Stress resistance
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Most of the studies performed on the seedlings issued from primed seeds demonstrated a clear improvement of resistance to environmental constraints. Table 1 is providing a nonexhaustive list of recent publications dealing with stress resistance improvement on cultivated plant species. Frequently, such improvement is obvious just after emergence at the seedling level, but progressively disappears at the adult stage. For example, some young plants issued from priming treatments displayed improvement of resistance to chilling [84], low temperature [75], salinity [43, 102], high temperature [80], drought [24, 65, 103], and UV exposure [82]. Some interesting studies also demonstrated that priming may afford resistance to biotic stresses such as Fusarium oxysporum in tomato [104], viral disease in Brassica rapa [105], and downy mildew in pearl millet [106]. Such a large set of data suggests that seed priming may elicit numerous pathways contributing to stress resistance. The molecular basis involved in this stress resistance remains intact during the dehydration phase following priming and may contribute to stress resistance during the final germination step. Moreover, some data suggest that a single priming treatment may induce resistance to various stresses.
Nonexhaustive list of recent studies devotes to priming-induced increase in the stress resistance of cultivated plant species.
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The priming procedure itself implies frequently the use of stressing agent, as it is the case for PEG and salt. In some cases, priming may be performed at low temperature to reduce the kinetics of seed hydration. A slow hydration may be considered as a stressing process since the water content is too low to allow radicle elongation (see point 5). It may thus induce defense responses within embryos. This is especially the case for biochemical processes involved in protection against reactive oxygen species (point 8). Several components of the ROS-mediated signaling pathways are activated during the first hydration phase of the priming process. The ultimate stress resistance in the seedlings may then be linked to the persistence of the antioxidative defenses after final germination. Since management of oxidative stress is an important component of resistance to a wide range of stress, this observation may, at least partly, explain the cross-resistance phenomena.
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The dehydration step that follows the partial hydration phase is also a major stressing phase. Numerous studies focus on late embryogenesis abundant proteins (LEA) normally involved in the acquisition of desiccation tolerance. Chen et al. [107] showed that the major dehydrins disappear during osmopriming while Maia et al. [108] conversely suggested that PEG may induce LEA synthesis. Water deprivation associated with the dehydration phase may also trigger accumulation of transcription factors, some of them being specifically involved in stress resistance [109, 110]. Molecular chaperones such as heat shock proteins (HSP) also explain a priming-induced improvement of stress resistance [78]. It may also be hypothesized that priming-induced modification of the seed hormonal status, mainly an increase in ABA, may somewhat influence the seed and young seedling response to environmental constraints in relation to a faster activation of ABA-responsive genes involved in stress acclimation [108, 109].
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The beneficial impact of priming treatments relies on numerous properties as indicated in Figure 2.
Figure 2.
General overview of biochemical and physiological basis of priming effects. Priming modifies seed ultrastructure, reserve mobilization, regulation of oxidative status and cell cycle, and seed water content. The obtained seedlings may be improved for growth, mineral nutrition, and stress resistance. The components of priming effect may be revealed through an integrated convergent proteomic, transcriptomic, and metabolomics holistic approach.
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5. Priming and seed water content
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Seed germination is characterized by triphasic kinetic of water uptake with a rapid initial uptake (imbibition), followed by an apparent lag phase. A further increase in water uptake occurs only after germination is completed, as the embryonic axis elongates [111] (Figures 1 and 2). Early imbibition of seeds involves the fastest and most drastic changes in tissue hydration observed during germination. The water content of seeds and tissues within seeds depends of the composition of stored reserves. Seed imbibition and subsequent embryo growth depend on water exchanges and water potential gradients represent the motive force for water flow and finally tissue expansion. Water transport across cell membranes is essential for the initiation of metabolism. This intracellular water transport is mediated by aquaporins.
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Aquaporins (AQPs) are transmembrane proteins, members of the major intrinsic protein (MIP) family that facilitate rapid and passive water transport across cell membranes and play a crucial role in plant water relations [112–114]. Plant aquaporins are remarkably diverse with several subfamilies of MIPs identified in dicots and monocots. Among them, the plasma membrane intrinsic proteins (PIPs) and the tonoplast intrinsic proteins (TIPs) subfamilies constitute the largest number of AQPs and correspond to AQPs that are abundantly expressed in the plasma and vacuolar membranes, respectively. Both PIP and TIP subfamilies are believed to play a key role in transcellular and intracellular plant water transport.
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To gain insight into the role of water channel in germination, the expression profiles of AQP genes were studied in Arabidopsis [115], Oryza sativa [116], and Brassica napus [117] during seed imbibition and early embryo growth. These results have demonstrated the possible role of several AQPs in seed germination also in response to abiotic stresses. Moreover, Liu et al. [116] have shown the reduced seed germination rate via OsPIP1;3 silencing and the promotion of seed germination via OsPIP1;3 over-expression under drought conditions demonstrating that OsPIP1;3 is required for normal seed germination.
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Seed priming involves imbibing seeds with restricted amounts of water to allow hydration sufficient to permit pre-germinative metabolic events to proceed while preventing radicle protrusion. This treatment can extend phase II of water uptake while preventing seeds from entering into phase III. The completion of radicle emergence is prevented by restricted amount of water provided to the seed (hydropriming, solid matrix priming) or decreased water potential (Ψw) of the imbibition medium by the use of osmotic solutes such as PEG or salts (osmopriming) [111]. In a study on Brassica napus osmopriming, Kubala et al. [36] revealed that at the beginning of the soaking period and at the end of drying phase, the seed water content was as low as 5%. The soaking treatment allowed seed imbibitions up to 50%, which should be enough to re-initiate metabolism.
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As AQPs regulate water movement, it can be supposed that these proteins play an important role both in priming treatment (seed soaking) and post-priming germination under both favorable and unfavorable conditions. A role for aquaporin-controlled water transport across cell membranes in primed seeds of Brassica napus during germination was demonstrated by Gao et al. [118]. Seed priming with PEG or ABA resulted in an enhanced germination, particularly under salt and osmotic stresses at low temperature. Priming treatment induced expression of BnPIP1 but had no effect on transcript level of Bnγ-TIP2. However, transcripts of both BnPIP1 and Bnγ-TIP2 genes during germination were present earlier in primed seeds than nonprimed ones. Gao et al. [118] speculated that BnPIP1 was involved in water transport required for the activation of enzymatic metabolism of storage nutrients in the early stages of rapeseed germination, while Bnγ-TIP2 expression was correlated with cell growth during radicle emergence. Changes in the expression pattern of SoPIP1;1, SoPIP1;2, SoPIP2;1, and SoδTIP during Spinacia oleracea seeds osmopriming and post-priming germination under optimal conditions, chilling and drought have been reported by Chen et al. [119]. The authors have stated that all these genes were up-regulated within 2–4 d of priming (phase II-imbibition). Therefore, the high expression of those AQPs might contribute to water transport across plasma and vacuolar membranes to facilitate water supply to expanding tissues and to increase germination potential of primed seeds. The down-regulation of all AQPs genes expression was observed under chilling and drought. However, the expression of some AQPs genes was elevated in primed seeds that also exhibited greater chilling and drought tolerance [119]. Kubala et al. [36] revealed up-regulation of two genes encoding tonoplast AQPs (TIP4.1 and TIP1.2) in Brassica napus seeds in relation to osmopriming. In this study, expression of TIP1.2 increased approximately 20 fold during post-priming germination as compared to unprimed seeds. In addition, the same authors have also stated facilitated water uptake and higher stress tolerance of germinating primed Brassica napus seeds [26, 120]. The above-mentioned results have demonstrated that water transport and sufficient water supply for embryo during post-priming germination regulated by AQPs may be one of the crucial components modulated by pre-sowing seed priming that influences germination rate and stress resistance.
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As PIPs, but not TIP, are generally found at the plasma membrane, PIPs are thought to play a key role in seed water uptake. Nevertheless, both microarray [121] and macroarray experiments [115] with the complete set of genes encoding major intrinsic proteins revealed that out of 13 PIPs encoded by the Arabidopsis genome, transcripts for only three isoforms (PIP1;2, PIP1;4, and PIP1;5) were detectable in seeds. Mapping of TIPs in germinating Arabidopsis seeds has revealed that isoforms TIP3;1 and TIP3;2 detected in embryos, appear to localize to both the plasma membrane and tonoplast [122]. Vander Willigen et al. [115] have observed that during germination, very high level of TIP3 protein was coincident with decreased level of PIP1;2 and PIP2;1 polypeptides until phase III of water uptake. As stated by Vander Willigen et al. [115], it is intriguing how such low concentrations of PIP protein during the early phases of germination can achieve basic transcellular water transport in the seed. Gattolin et al. [122] have speculated that TIP3 may be the only AQP involved in seed water intake, and that the presence of TIP3 at the plasma membrane may compensate for the absence (or low concentration) of PIPs. In the light of these results, the enhanced germination potential of primed Brassica napus seeds could be partially explained by the up-regulation of TIPs during priming and post-priming germination [36]. However, the involvement of apoplastic water movement and simple diffusion of water across membranes during seed imbibition cannot be ruled out. The treatment of Arabidopsis seeds with mercury, a general blocker of aquaporins, reduced the speed of seed germination but did not affect its developmental sequence or basic aspects of seed water relations. Vander Willigen et al. [115] suggested that aquaporins functions are not involved in early seed imbibition but would rather be associated with water uptake accompanying expansion and growth of the embryo.
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The transmembrane water transport via the regulation of AQP quantity and activity endows seeds with a remarkable capacity to modulate water absorption, transport, and compartmentation within tissues. Nuclear magnetic resonance (NMR) spectroscopy has provided insights into changes in the physical states of seed water during germination [123–126]. In particular, magnetic resonance imaging (MRI) has revealed a precise spatial distribution of water within tissues of germinating seeds and different patterns between species [125, 127, 128] highlighting the tight control of water transport. Water status of primed seeds was characterized by Nagarajan et al. [129] in study on tomato halo-and osmopriming. Nagarajan et al. [129] pointed out that better performance of primed seeds may be attributed to the modifications of seed water-binding properties and reorganization of seed water during imbibition, so as to increase the macromolecular hydration water required for various metabolic activities related to the germination process. In the future, it will be crucial to see how the spatial pattern of aquaporin expression can fit the hydration pattern revealed by MRI during both priming and post-priming germination, therefore enabling a comprehensive understanding of water transport in seeds.
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Several studies have reported that water uptake is improved by priming treatment as primed seeds exhibited a faster imbibition in comparison with nonprimed ones, although pre-treated seeds were dried after priming to reach the same water content as nonprimed ones [36, 47, 107]. Although MRI studies revealed that water penetrates seeds through the hilum and micropyle [125, 130], Galhaut et al. [47] did not observe any particular modification of these structures after Trifolium repens priming, despite a faster seed hydration. However, scanning electron microscopy analysis showed that primed seeds of Trifolium repens exhibited seed coat tears and circular depressions that can favor seed imbibition. Moreover, X-ray photographs revealed tissue detachment in dry primed seeds that formed free space between the cotyledons and radicle, making water flow easier, thus contributing to tissue hydration [47]. Similarly, formation of free space surrounding the embryo in dry primed seeds of tomato was noticed by Liu et al. [131]. In brief, these observations suggest that structural modifications might contribute to rapid seed germination by improving water uptake.
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The maintenance of favorable water status is critical for survival of germinating seeds under environmental stresses leading to tissue dehydration. The accumulation of nontoxic, compatible solutes within seed tissues, that is, osmotic adjustment is a major trait associated with maintenance of high cell turgor pressure potential in response to stress conditions. Priming treatment itself may generate a moderate abiotic stress during soaking (e.g. osmotic stress, salt, and drought created by the priming agents) [36, 132]. The accumulation of osmotically active solutes such as amino acids (e.g. proline) ammonium compounds (e.g. glycine betaine), sugars (e.g. glucose, fructose, sucrose) during priming was noticed in several species and was shown to improve seed germination under subsequent water stress [3, 21, 133, 134].
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Seeds can also experience dehydration in the course of priming treatment, that is, during drying after soaking. Late embryogenesis abundant proteins (LEAs) can stabilize cell structure and macromolecules upon cell dehydration by preventing inactivation and aggregation of proteins and the loss of membranes integrity. This could be realized due to the ability of most LEA proteins to either coat intracellular macromolecules with a coherent layer of water or to interact with the surface of proteins and thus acting as water replacement [135]. As LEA proteins accumulate at a high level in response to cell/tissue dehydration, they may contribute to acquisition of tolerance to drought and related stresses such as osmotic, salt, and cold stress. In support of this, several studies revealed changes in the pattern of expression/accumulation of LEA transcript/protein in seeds caused by priming treatment and suggested their association with improved stress tolerance of primed seeds [36, 107, 136–138]. For example, the transcripts of two genes: Em6, encoding LEA group 1 protein and RAB18, encoding responsive to ABA 18 protein, belonging to LEA group 2, declined during osmopriming (soaking in PEG solution), reaccumulated after slow drying and again degraded during Brassica oleracea seeds germination [138]. The up-regulation of RAB18 and Em6 expression during slow seed drying suggests that they play a role in drought tolerance. Chen et al. [107] reported transient accumulation of four dehydrins-like proteins (32, 30, 26, 19-kD) in seeds of Spinacia oleracea during early stages of osmopriming followed by progressive degradation to a lower level in primed dry seeds compared to unprimed ones. A similar trend was confirmed to cold acclimation protein CAP85. In contrast to protein concentration, relative expression of CAP85 was greater in primed dry seeds than in unprimed ones. Recently, Kubala et al. [36] revealed accumulation of LEA transcripts (LEA4-1, LEA4-5) and LEA3 proteins during soaking in PEG solution. The authors proposed that soaking in PEG with a low osmotic potential should not be considered only as a rehydration phase: water uptake may be sufficient to reinitiate a physiological activity from a previous quiescent stage but water content of 50% remained low enough to represent a water stress situation, especially when it is maintained during several days [36].
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6. Priming and seed ultrastructure
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In general, the ability of seeds to germinate seems to be critically determined by a change in the balance between growth potential of the embryo and the mechanical resistance of the surrounding tissues. In many species, the endosperm tissue enclosing the embryo restrains the germination process acting as a physical barrier, which restricts radicle emergence.
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Weakening of tissues surrounding elongating radicle by cell separation due, for instance, to the activity of cell wall hydrolases may occur as a consequence of priming (Figure 2). It was determined that osmopriming induced hydrolysis of the endosperm tissue of Cucumis melo seeds [139] and increased the endo-β-mannanase activity in the endosperm cap and decreased its mechanical restraint on the elongating tomato embryo [140]. A strong correlation was observed between lowering of the mechanical restraint and the activity of endo-β-mannanase [141].
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Penetration of the structures surrounding the embryo is a consequence of radicle cells elongation. Up-regulation of the gene encoding xyloglucan endotransglucosylase/hydrolase (XTH) in response to osmopriming and accumulation of transcript for extensin-like protein (ELP) during post-priming germination was observed in rapeseed [36]. As XTHs have the ability to cleave xyloglucans and rejoin the cut ends with new partners, they are engaged in cell wall loosening during growth and in the restructuring of the cell walls after extension.
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Cytoskeleton reorganization is also necessary to achieve large rates of cells elongation that precedes radicle protrusion. The component of microtubules (β-tubulin) accumulated in tomato seeds during germination and priming and the expression preceded visible germination [142]. Higher level of β-tubulin protein accumulation was shown in rapeseed during PEG soaking, drying, and post-priming germination. The up-regulation of genes encoding γ- and β-tubulins was also noticed during post-priming germination [36].
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Ultrastructural observations performed during the 6-d period of solid matrix priming (SMP) of carrot (Daucus carrota) seeds indicated the breakdown of storage materials, specific to the catabolic phase of germination sensu stricto, both in the axis and in the micropylar endosperm covering the radicle tip [143]. It was found that complete degradation of storage protein and lipid bodies and subsequent starch accumulation occurred in the radicles of carrot seeds after 8-d SMP. In the endosperm, the catabolic changes were limited to the micropylar area, where extensive breakdown of storage cell walls, partial degradation of protein bodies, and no storage lipid hydrolysis were observed [144].
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During seed germination, storage proteins, which provide a source of reduced nitrogen, and inorganic minerals need to be mobilized to support seedling growth. In addition, a lytic aqueous vacuolar compartment building up the turgescence necessary for cell expansion and to promote radicle protrusion and embryo elongation has to be formed (Figure 2). Bolte et al. [145] investigated the features and the dynamics of the vacuoles during the early stages of Arabidopsis seed germination and indicated the successive occurrence of two different lytic compartments in the protein storage vacuoles (PSV). The first one corresponds to globoids specialized in mineral storage and the second one is at the origin of the central lytic vacuole in these cells [145]. Different mechanisms for the transformation of PSV into lytic vacuole in the root tip cell of germinating tobacco (Nicotiana tabacum) seeds were proposed by Zheng and Staehelin [146]. Ultrastructural studies demonstrated that the radicle cells of tobacco contain only one type of vacuole at particular time of development. Upon rehydration, the radicle cells only contain PSVs, but during subsequent root development, the PSVs are systematically transformed into lytic vacuoles via cell type specific pathways.
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At present, we do not have a complete view of ultrastructural changes occurring during seed priming. One would expect that similar vacuole remodeling might occur during priming, especially in embryonic axis. The maintenance of metabolism over, for instance, several days of seed priming requires mobilization of embryo reserves. It is speculated that accumulation of endogenous osmotica, cell vacuolization, together with cell wall loosening initiated during priming, might determine the embryonic axis extension and radicle protrusion during post-priming germination. Deeper and more detailed studies should be continued in order to completely clarify this phenomenon.
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7. Seed priming and cell cycle regulation
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Some of the hypotheses proposing explanation for priming-induced improvement are based on its effect on DNA in relation to activation of DNA repair mechanisms, synchronization of the cell cycle in G2 and preparation to cell division (Figure 2). During seed maturation, most of the embryo cells are stopped at G1 or G0 phase of cell cycle and only some species have a small proportion of cells in the G2 phase [111]. During seed imbibition, meristematic activity is limited; however, some preparation to cell division occurs. In embryos of dry tomato seeds, most cells have 2C DNA level and are in G1 phase of nuclear division [147]. The authors observed that DNA synthesis preceded germination as during imbibition in water, 4C signal was found mostly in the embryonic root tip, which suggests that cell enters S phase. They also primed seeds for 14 d in PEG-6000, which enhanced the rate and uniformity of germination. The 4C DNA signal of root tip cells increased during priming starting from 3 d incubation in PEG and was constant after re-drying the seeds to the initial moisture content. This observation suggests that priming increased the ratio of cells in G2 phase to G1 phase and indicates that the beneficial effects of priming on seedling performance are associated with the replicative DNA synthesis prior to germination [147]. This is accompanied by increase in α- and δ-like DNA polymerase activities in primed seeds and during germination.
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The initiation of cell cycle and proceeding the cell to S phase may depend also on a G1 checkpoint control. Most, if not all, cell cycle proteins responsible for cell cycle control appear to be already present in dry mature seeds, although some of them should be synthesized de novo. However, not only protein synthesis but also their modification may play a regulatory function for cell cycle control [148]. Cell division starts just after radicle protrusion, thus, seed priming, which prolongs Phase II of seed germination and is finished just before Phase III, does not affect cell division in itself [16]. Seed priming extends Phase II, when DNA repair mechanisms and expression of genes encoding proteins needed in cell cycle control and commencement are activated and overreach the level observed in unprimed seeds. Pre-activation of cell cycle by priming could be through regulation of the activity of cell cycle proteins such as cyclin-dependent protein kinases and proliferating-cell nuclear antigens [16]. It was found that osmopriming of Brassica napus seeds induced expression of cell division control protein 48 homolog C, cyclin P4;1, cyclin like protein and topoisomerase II in dry seeds, as well as proliferating-cell nuclear antigen 2 and cyclin dependent kinase 3;2 during imbibition [36]. Accumulation of proliferating-cell nuclear antigen during maize seed imbibition was associated with transition of the cells from G1 to G2 [149]. Moreover, microtubules, apart from cytoskeleton formation, cytoplasmic streaming, organellar movement, and cell wall formation, function in mitotic spindle formation during mitosis. Microtubules in dry seeds are depolymerized and form discrete granular bodies, which become organized into the cytoskeleton during imbibition [111, 142]. Higher expression of genes encoding microtubule-associated protein 65-1 and 70-2 as well as tubulin subunits γ-1, β-1, β-3 and microtubule motor activity proteins belonging to kinesin family was also observed during PEG soaking and in dry osmoprimed Brassica napus seeds [36]. Enhanced expression of tubulin genes was associated with accumulation of β-tubulin protein during osmopriming and subsequent germination [36]. Also in pre-hydrated seeds of Arabidopsis thaliana and Solanum lycopersicum accumulation of tubulins (mainly β-tubulin) was stated during germination as compared to unprimed seeds [136, 142].
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During Phase II of seed germination, when water uptake is severely limited, major metabolic processes are activated [111]. One of the most important events undergoing during Phase II is DNA repair, which precedes cell cycle activation [142, 150]. The process of DNA replication is preceded by repair of DNA damage caused mainly by reactive oxygen species, which are accumulated during seed storage and aging [151]. DNA repair covers first period of DNA synthesis, while the second period of DNA synthesis (replication) is observed before cell division. DNA synthesis in Phase II of germination and also during seed priming corresponds rather to DNA repair, mainly in organelle such as plastids and mitochondria [152]. Increased number of mitochondria in leek embryo cell of osmoprimed seeds was observed by Ashraf and Bray [153]. Mitochondria biogenesis before mitochondria division involved the transition of promitochondria to mature mitochondria. This process is accompanied by the expression of genes of nucleotide biosynthesis, transport, and organelle RNA- and DNA-related functions [154, 155]. Pre-sowing seed osmopriming induced higher expression of genes corresponding to mitochondria biogenesis such as translocases of the inner membrane (TIM) complex TIM10 and TIM23-1, mitochondrial ribosomal protein and translational elongation factor EF2, which is targeted into mitochondria [36].
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There are still some gaps in comprehensive understanding of pre-sowing seed priming impact on DNA repair and cell cycle regulation. Activation of different DNA repair mechanism has been observed during seed imbibition preceding germination and they are believed to be essential for successful reactivation of cell cycle [111]. They include α and β tyrosyl-DNA phosphodiesterase 1, α and β DNA topoisomerase I [156], 8-oxoguanine DNA glycosylase/lyase and formamidopyrimidine-DNA glycosylase [157], transcription elongation factor II-S [158], DNA ligase VI and IV [159]. Varier et al. [16] have suggested that in primed seeds DNA damage is repaired before replication, primarily through DNA synthesis. However, in a study on Cicer arietinum primed seeds, the role of DNA repair genes in enhancing the physiological quality of seeds was postulated [160]. The authors tested the expression level of genes encoding proteins with already proved function on DNA repair mechanisms in relation to priming methods and seed size. Moreover, enhanced accumulation of transcripts was found in dry and imbibed osmoprimed Brassica napus seeds [36] for genes involved in DNA repair according to function description in databases, such as DUTP-pyrophosphatase-like 1, endonuclease V family protein, ribonucleoside-diphosphate reductase subunit M2 (TSO), casein kinase II, replicon protein A2, DNA glycosylase DEMETER (DME), BARD1, RECQ helicase L4B, and MUTS homolog 2. Thus, activation of DNA repair mechanisms in seeds occurs prior to their germination and contributes to enhanced germination rate and better quality of seeds undergoing pre-sowing seed priming.
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8. Management of oxidative status
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Management of oxidative status is also considered as an important part of primed seeds physiology [18, 36, 161, 162] (Figure 2). Beginning with the seed development through maturation and germination, the seed moisture content as well as seed metabolic activity is subjected to dramatic changes. The biochemical and cellular events triggered by water uptake and subsequent loss are accompanied by a generation of reactive oxygen species (ROS) [151, 163]. During seed imbibition and early stages of germination, ROS production occurs mainly through respiratory activities of mitochondria, activities of β-oxidation pathways and enzymes such as NADPH oxidases, extracellular peroxidases, and oxalate oxidases [163]. ROS accumulation and associated oxidative damage can be regarded as a source of stress that may affect the successful completion of germination. As ROS, particularly H2O2 can act as signaling molecules, seeds must be endowed with a ROS removing system that tightly regulates their concentration. Scavenging of ROS is carried out by antioxidant system, a multifunctional machine, which includes enzymes (i.e. catalase (CAT), superoxide dismutase (SOD), and ascorbate peroxidase (APX), monodehydroascorbate reductase (DHAR), and glutathione reductase (GR)) as well as nonenzymatic compounds (i.e. ascorbic acid (AsA) or reduced glutathione (GSH) [1, 151]. Metabolism of ROS, mainly H2O2, which is believed to play a central role in oxidative status signaling, is strictly associated to other reactive species and signaling molecules such as nitric oxide and hydrogen sulfide, which contribute and regulate the transition from dormant to germination phase [151, 163, 164].
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Kubala et al. [36] have considered the priming as a process, which consists of two main phases: controlled hydration of the seeds and drying back to the initial moisture content. Seed pre-hydration followed by re-drying during priming treatment, similarly to seed maturation and germination, exerts changes in moisture content, which leads to ROS production and activation of the antioxidant system. The activation of APX and the accumulation of AsA and GSH during osmopriming of spinach seeds (Spinacia oleracea) were accompanied by the repression of SOD and CAT activity [1]. These results indicated that activation of AsA-GSH cycle during osmopriming of spinach seeds can decrease the level of lipid peroxidation products in primed seeds. Moreover, the same authors have suggested that the renewal of antioxidant defense system, possibly required by seedling establishment, occurred during the late stages of germination as a result of up-regulation of CAT activity after initial reduction and overall antioxidant activation [1]. Kubala et al. [36] have indicated through an integrated transcriptomic and proteomic approach that the priming-induced germination can be linked with the activation of antioxidant system. The authors showed that during osmopriming of Brassica napus seeds CAT2 and PER21 encoding peroxidase 21 were up-regulated and GR protein was accumulated. Moreover, the same authors have observed up-regulation of PER13 gene and accumulation of peroxidase 12, DHAR and peroxiredoxin proteins during post-priming germination. Furthermore, Kubala et al. [162] have postulated a correlation between activation of antioxidant metabolism in osmoprimed Brassica napus seeds and increased tolerance to salt stress during germination. The enhanced activity of APX, SOD, and CAT corresponded with increased expression rate of APX, SOD, and CAT genes. Similar result has been obtained by Nouman et al. [165], who showed that priming of Moringa oleifera seeds with Moringa leaf extract (MLE) improves growth under saline condition mainly by activation of antioxidant system (SOD, CAT, and POD). Priming of mung bean seeds (Vigna radiata L. Wilczek) with β-amino butyric acid (BABA) enhanced the activities of SOD and POX leading to improved tolerance to NaCl and PEG 6000 stresses [65]. Enhanced chilling stress tolerance in two tobacco varieties (MSk326 and HHDJY) was due to increased activity of antioxidant enzymes (SOD, POD, CAT, and APX) as a result of priming seeds with putrescine [165]. Results obtained by Islam et al. [167] showed that in haloprimed wheat (Triticum aestivum) seeds, increased activity of CAT, POD, and APX enhanced tolerance to salinity stress. Osmopriming with PEG has improved sorghum (Sorghum bicolor) seed germination and seedling establishment under adverse soil moisture conditions and has been correlated with antioxidant system activation (APX, CAT, POD, and SOD) [3]. Rice (Oryza sativa) seeds primed with polyethylene glycol (PEG) showed increased activity of APX in parallel with decreased activity of SOD, POD, and CAT under ZnO nanoparticles stress [38]. The same authors have also observed down-regulation of genes encoding the antioxidant enzymes (APXa, APXb, CATa, CATb, CATc, SOD2, and SOD3) in PEG primed seeds under nano-ZnO stress. They have concluded that priming with PEG significantly alleviates the toxic effects of nano-ZnO through improved cell structures of leaf and roots.
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Seed aging during storage is associated with ROS production. Appearance of oxidative stress results in a decrease of seed quality. Kibinza et al. [161] showed that priming plays an important role in seed recovery from aging through CAT activation. Their results revealed accumulation of hydrogen peroxide (H2O2) and reduction of CAT at the gene expression level and protein content during sunflower (Helianthus annuus L) seed aging. Interestingly, the adverse results of aging were recovered by seed osmopriming, which led to induction of CAT synthesis by activating gene expression and translation of the enzyme.
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Summing up, the management of oxidative status in primed seeds plays a very important role as a machinery, which leads to protection against oxidative stress, recovery from aging, and regulation of ROS production/accumulation. Alleviation in ROS level exerts a signal, which could be perceived, transduced, and crosstalk with other signaling pathways, thus executing physiological response by activation or repression of molecular processes.
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9. Reserve mobilization
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Recent transcriptome and proteome study of cabbage (Brassica oleracea) and Arabidopsis seeds as well as integrated transcriptomic and proteomic approach in study of rapeseeds (Brassica napus) osmopriming revealed that germination and priming altered similar processes [36, 136, 138]. Indeed, it is proposed that germination-related processes such as respiration, energy metabolism, and early reserve mobilization can also occur during priming [16] (Figure 2). Faster and uniform rice (Oryza sativa) seed germination due to priming was related to improved activity of α-amylase, resulting in increased level of soluble sugars in primed kernels [168]. Sung and Chang [169] have shown that priming of maize (Zea mays) seeds leads to increased activity of enzymes for carbohydrates (α and β amylases) and lipids (isocitrate lyase, ICL) mobilization. Priming of chickpea (Cicer arietinum L. Cv PBG-1) seeds with mannitol led to increased activity of amylase, invertases (acid and alkaline), sucrose synthase (SS), and sucrose phosphate synthase (SPS) in shoots of primed seedlings. The higher amylase activity in shoots suggests a rapid hydrolysis of transitory starch formed in the shoots of primed seedlings leading to more availability of glucose for seedling growth. [170]. Higher content of soluble protein, aldolase, and ICL activity has been observed in haloprimed pepper (Capsicum annum L) seeds than in control seeds [171]. Moreover, the α-glucosidase accumulation and increased level of globulin degradation products were observed during the priming process of sugar beet (Beta vulgaris L.) seed [172]. Similar observation on primed sugar beet seed has been done by Capron et al. [173] who showed increased solubilization of 11S-globulin-β-subunit in response to hydro- and osmopriming. Gallardo et al. [136] have also observed higher polypeptides content in both hydro- and osmoprimed Arabidopsis seeds. They were identified as products of 12S-cruciferin-β-subunit degradation.
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Kubala et al. [36] have shown that during Brassica napus seeds osmopriming and post-priming germination accumulation of transcript and proteins for seed storage proteins occurred. The authors have observed up-accumulation of cruciferin CRU1. The group of six genes encoding GDSL-like lipases, playing a role in triacylglycerols (major storage lipids in rape seeds) catabolism, were strongly up-regulated during post-priming germination while the other three genes for GDSL-like lipases as well as extracellular lipase 6 were up-regulated in osmoprimed seeds [36]. The activation of lipid catabolism-related genes was correlated with the activation of genes involved in lipid transport such as genes encoding bifunctional inhibitor/lipid-transfer protein/seed storage 2S albumin superfamily protein [36]. Priming can also reduce a level of oleosins-proteins, which surround oil bodies. In osmoprimed Brassica napus seeds as well as during post-priming germination, down accumulation of oleosin S4-3 protein and down-regulation of OLEOSIN2 gene were observed, respectively [36].
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Activation of respiration and rapid ATP production is primary metabolic events occurring during priming [18], and higher respiratory activity is required to cover energy pool for speed up germination. The increased ATP level/energy charge after priming was observed in tomato (Solanum lycopersicum), eggplant (Solanum melongena), araucaria (Araucaria columnaris), spinach, oat (Avena sativa), and cabbage (Brassica oleracea) [174, 175]. Primed seed needs a large amount of fuel, which supplies energy required for higher reserve mobilization rate. All together lead to improved energy turnover and increased metabolism rate of primed seed and contribute to better germination and stress tolerance.
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10. Holistic “omic” approaches of seed priming
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The identification of biomarkers of seed priming effect is a relevant goal for plant physiologists. The sequence of events associated with water-based priming involves a limited hydration step during the soaking period followed by a more or less rapid dehydration phase (Figure 1). It may be considered that each phase has its own profile of activation/deactivation. Transcription is not necessarily coordinately associated with translation, resulting in some cases in a limited correspondence between mRNA levels and protein abundance. Some proteins synthesized during incubation may also be degraded during dehydration, although the rate of degradation might somewhat be influenced by the rate of drying. Finally, protein synthesis may also occur as a result of the translation of long-lived mRNA previously synthesized during seed maturation [17, 37, 103, 110].
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The advantage of these complementary holistic approaches is that they provide a large set of data allowing physiologist to obtain a global view of all parameters of the metabolism associated with priming. The major disadvantage, however, is that these techniques are rather expensive. As a consequence, samples are frequently analyzed after a given duration of treatment and the time-dependent evolution of parameters are rarely considered. It is still difficult to reconstitute a kinetic approach, but published studies rather provide a large set of information at a given moment while the priming procedure is a dynamic process.
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10.1. Transcriptomics
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Transcriptomics is the study of the transcriptome—the complete set of RNA transcripts that are produced by the genome under specific circumstances—using high-throughput methods. Several techniques are available for transcriptomic approaches, including microarray, c-DNA amplified fragment length polymorphism (cDNA-AFLP), expressed sequence tag sequencing, serial analysis of gene expression, RNAseq, and massive parallel signature sequencing [176]. According to Buitink et al. [109], more than 1300 genes may be differentially regulated during priming with PEG at -1.7 MPa in Medicago truncatula. Genes whose expression are regulated during the priming process are commonly categorized according to the function of the corresponding protein (metabolism and regulation of metabolism, cell cycle regulation, DNA processing, transcription regulation, cellular transport and communications, stress responses, etc.). However, a consistent part of the identified genes is still not annotated.
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In Brassica napus, numerous priming-regulated genes are involved in gluconeogenesis, which is essential for triacylglycerol breakdown into small molecules. Another important category of genes involved in water-based priming of rapeseed encodes for transcription factors, and this is especially the case after hormopriming with ABA [138]. In the same species, it was demonstrated that germination of primed seeds involves a specific set of genes comparatively to germination of unprimed ones [36]. In young seedlings obtained from primed seeds, the expression of stress-related genes is often more rapid than in plants from unprimed ones, as recently exemplified for cold tolerance [26]. Not only genes related to protein synthesis but also genes involved in protein degradation may be induced by priming. Some transcription factors may be down-regulated during soaking and up-regulated during drying [36]. Genes involved in the synthesis of osmoprotectant, such as proline, may also be regulated at various steps of priming [120].
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In Brassica oleracea, transcripts that are abundant in dry seeds rapidly decline during osmopriming and germination expression programs are initiated during osmopriming [138]. For these authors, genes expressed during slow drying following the soaking period are correlated with the stress resistance properties of primed-material. This may especially concern cell-cycle-regulated genes, enzymes involved in C metabolism, and components of the translation machinery. Acquisition of the desiccation tolerance after the soaking period is a crucial trait for priming. Transcriptomic data demonstrated that the molecular determinism associated with such trait may be, at least partly, similar to those involved during a « normal » seed dehydration process during maturation. In Medicago truncatula, several regulatory genes expressed during drought stress are also up-regulated during seed maturation. During priming, these genes are involved in post-soaking dehydration while genes conditioning cell cycle, cell wall biogenesis, and energy metabolism are repressed [109]. Transcripts accumulated after PEG-priming treatment comprise those encoding for LEA and seed storage proteins, or genes controlling seed dormancy while genes involved in photosynthesis and cell wall modifications are commonly repressed [108].
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Beside involvement of transcription factors, it could be of primary importance in the future to analyze the priming-induced epigenetic changes. Indeed, DNA methylation may be directly involved in « stress memory » and some changes, such as cytosine methylation or overexpression of histone deacetylase was reported to occur during germination [78].
\n
\n
10.2. Proteomics
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Proteome is the entire set of proteins present at a given moment in a given biological sample and proteomic is the large-scale study allowing identification and quantification of these proteins. Proteomics has now been practiced in different plant systems through the separation of proteins by two-dimensional gel electrophoresis followed by peptide mass fingerprinting. Tandem mass spectrometry can get sequence information from individual isolated peptides. Quantitative proteomics represent an important extension enabling the comparison of changes in protein levels across different samples [177]. Gel-free shotgun proteomic is an alternative for identification and quantification of protein in large-scale studies. This method was recently used to reveal potential biomarkers of priming-induced salt tolerance in durum wheat with a concomitant use of protein fractionation and hydrogel nanoparticles enrichment technique [27]. According to these authors, hydropriming was accompanied by a significant change in 72 proteins. Most of them are involved in proteolysis, protein synthesis, metabolism regulation, and disease or defense response. Priming with ascorbic acid changed the pattern of proteome signature and most of identified proteins are involved in metabolism regulation, antioxidant protection, repair processes, and methionine-related metabolism.
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Cycloheximide, a potent inhibitor of protein synthesis, may be added to priming or to germination solution to analyze the precise requirement of protein synthesis during these steps. It appears that protein synthesis is not necessarily required for normal germination process, which could be related to the fact that in some cases, germination relies only on translation of pre-stored long-lived mRNA produced during seed maturation [14, 178]. Cycloheximide may drastically affect osmopriming-induced improvement of Cd resistance in Poa pratensis and Trifolium repens in relation to a decrease in α and β-amylase [179]. Protein concentration in primed seeds is the result of two contrasting pathways: the first implies specific protein synthesis while the second involves the breakdown of storage proteins through protease activation. It was demonstrated that priming may act on protease activities and also influence the expression of protease encoding-gene [180].
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Some strategies are also used to separately identify proteins in embryos and in embryo-surrounding tissues. In monocots, a special attention is often paid to aleurone layers involved in hydrolytic enzyme synthesis [181]. Aleurone layer is easily separated in some plant material such as wheat or barley but is more difficult with other monocot such as turfgrasses with very small seeds. In wheat, it was demonstrated that the set of proteins regulated by priming is quite different in embryos and in surrounding tissues and the number of proteins affected by priming was by far higher in the embryos than in the other parts of the seed. Proteins regulated in embryos involve those directly linked to metabolism regulation (especially methionine biosynthesis, glutamate/glutamine metabolism, amino acids synthesis, etc.), energy supply, cell growth and maintenance of cell structure while proteins up-regulated in surrounding tissues are mainly involved in reserves mobilization or in the management of the oxidative stress [67]. In barley, however, ascorbate peroxidase was observed only in the embryo while several other redox-related proteins differed in spatio-temporal patterns at the onset of radicle elongation [181].
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Priming is considered as an invigoration treatment and several proteomic approaches were performed to unravel the biomarker of seed vigor. Catusse et al. [182] found that 18 proteins are accumulated during hydropriming of sugarbeet seeds and that the same proteins appear directly reduced during aging. Seed vigor appears directly related to lipid and starch mobilization, protein synthesis and methionine cycle. In poplar, more than 81 proteins showed a significant change in abundance when comparing the proteomes among seed with different vigor [183]. According to these data, the decrease in seed vigor is an energy-dependent process, which requires protein synthesis and degradation as well as cellular defense and rescue. Salicylic acid (SA) was proposed as an invigorating elicitor promoting seed germination under saline conditions: SA re-induced the late maturation program during early stages of germination, induced the synthesis of antioxidant enzymes, and improved the quality of protein translation [184]. Similarly, the “prime-ome” approach performed by Tanou et al. [185] confirmed the importance of redox proteomic and processes such as N-nitrosilation, tyrosine nitration, and mitogen-activated protein kinase MPK3 signaling in priming effects.
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Osmotic priming was reported to trigger desiccation tolerance in Medicago truncatula [110]. Proteomic analysis demonstrated that such trait is directly linked to the synthesis of late-embryogenesis abundant proteins from different groups. Secondary structure of some proteins was compared in the hydrated and dry state after fast or slow drying using Fourier transform infrared spectroscopy, which confirms that these proteins adopted α helices and β-sheets conformation during drying process.
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Some proteomic approaches are conducted on plant species whose genomes are not sequenced. A recent 2DE-MS/MS-based proteomic study was conducted on pearl millet seeds primed by β-aminobutyric acid and showed an over-representation of proteins belonging to glucose metabolism, and a majority of induced proteins are directly related to energy [106]. Seedlings issued from those seeds are more resistant to downy mildew (Sclerospora graminicola). It is interesting to note that several of the elicited proteins are present in the extracellular space and in organelles (mainly mitochondrion and chloroplast).
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10.3. Metabolomics
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Metabolome refers to the complete set of small-molecule metabolites present within a plant tissue or organ at a moment. Metabolomic should thus be considered as the quantitative measurements of the whole set of compounds involved in the metabolism of a given biological sample. Plant metabolomics has become an essential part of functional genomics. It often appears difficult to analyze the entire range of metabolites by a single analytical method, and several tools are thus commonly combined for this purpose: high performance liquid chromatography (HPLC), gas chromatography (GC), electrospray ionization coupled with mass spectrometry, capillary electrophoresis, atmospheric pressure chemical ionization (APCI), and secondary ion mass spectrometry (SIMS). Metabolomic approach, however, still remains difficult to perform on seed material considering the high proportion of molecule issued from reserve mobilization. An excess of soluble sugar in graminaea and an excess of small lipids issued from oil digestion in oleaginous plant material may greatly hamper isolation of other compounds involved in hastening the germination of primed seeds. Similarly, some important compounds might be present only in specific tissues or cell compartments and react with sugars during extraction processes; this is especially the case of gibberellins which play a crucial role in germination but are believed to conjugate with sugar or phenol compounds, which greatly compromise isolation of and identification procedures of numerous metabolites [186].
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Priming process may drastically modify the synthesis and accumulation of endogenous antioxidant such as glutathione, ascorbic acid, and even α-tocopherol. A modification in reducing sugars concentration, such as glucose resulting from partial starch digestion during priming, may influence protein glycation, a nonenzymatic reaction between reducing sugars and amino groups in protein [150]. The amount of proline was reported to be modified in osmoprimed seeds [120]. Some other data reported modifications in aspartate, leucine, threonate, glutamate, fumarate, or pinitol content in primed seeds from different species [1, 2, 35, 104, 152]. Methionine may also play a key role in priming process, mainly as a precursor of both ethylene and polyamine synthesis. Polyamines are small aliphatic molecules influencing all aspects of plant metabolism and development, including the germination processes. Ethylene is also involved in various aspects of seed germination, and priming was reported to modify the kinetics of ethylene synthesis from its precursor 1-aminocyclopropane-1-carboxylic acid (ACC) [186]. Other phytohormones are expected to assume important functions in priming effect (ABA, gibberellins, cytokinins, auxin, etc.) [50, 52], but the quantitative impact of priming procedure on these compounds is still not well established.
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\n
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11. Main limitations of priming techniques
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Seed priming has emerged as an effective approach for increasing seed vigor. The optimal treatment differs between species, cultivar, and seed lots. Such variability is a major limitation of the priming method since numerous trials are required to identify the most appropriate strategy for each situation. There is no “general rule” concerning modalities of seed priming and there is no clear trend of priming response according to the taxonomic position of the species [188]. This, undoubtedly, limits the commercial implementation of priming treatments.
\n
Some priming treatments may imply a risk of medium contamination by fungi and bacteria, which may heavily impair subsequent seed germination [189]. This may especially be the case for PEG and sometimes requires the simultaneous use of pesticide, although the impact of these compounds on the priming efficiency remains unknown. After priming treatment, seeds are dried back to their initial moisture content, but this dehydration phase is usually performed rapidly and occurs faster than classical dehydration of maturing seeds. It has been hypothesized that this brutal desiccation procedure alters the beneficial effect of priming [2].
\n
The major drawback of priming is that it reduces the longevity of primed seeds as compared with the nonprimed seeds [190–192]. Storability of primed seed material is consequently reduced, and this results in higher costs for material maintenance for farmers and seed companies. The loss of viability, however, appears quite variable depending on the species, cultivars, and seed lots. In extreme cases, priming-induced advantages may even disappear after only 14 d of storage and the obtained seedling may then perform worse than those issued from unprimed seeds [193]. One of the limitations of these studies, however, is that experiments are commonly performed on artificially aged seeds using short-term exposure to high temperature in a moist environment, which is not necessarily fulling relevant from a real aging process. Some studies, using classical long-term strategies, reported that longevity is not necessarily affected or may even be increased by priming treatments [194]. Hussain et al. [195] recently demonstrated that post-priming temperature plays a key role in maintenance of seed longevity, which is indeed rapidly compromised in rice seeds maintained at room temperature while it remains intact when the material is stored at 4°C. According to these authors, the deleterious effect observed at 25°C storage was related to hampered starch metabolism in primed seeds. It was also suggested that maintenance of the seed longevity at 4°C may be due to a high viscosity that strongly reduces molecular mobility in the cytoplasm and thus limits the impact of deteriorative process even in seeds exhibiting low water content [196]. Oxygen during storage may trigger metabolic processes in primed seeds, which did not re-establish a true quiescent stage after dehydration when stored at room temperature while oxygen had no influence at low temperatures [195].
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In some cases, repeat priming treatment after storage may partly remove the damaging effect on seed viability [193] while, in other cases, such a loss is permanent and not reversible [194]. Whatever, the fact that an additional treatment may be required to restore full germination potential represents an additional cost and source of variability.
\n
\n
12. Conclusions
\n
Seed priming is an old empirical strategy used since centuries by farmers, and since decades by seed companies, to improve germination processes in cultivated plant species. The underlying mechanisms involved in this positive impact of pre-sowing treatments remained obscure for a long time. The present review aimed to summarize recent information provided by various tools allowing the identification of molecular cues conditioning priming efficiency.
\n
Data obtained from molecular approaches applied to some well-known plant species (rice, rapeseed, tomato, etc.) are now available. The role of genes associated to metabolic and cell cycle events now starts to be deciphered, mainly those encoding for translational components such as ribosomal subunits, translational initiation factor, enzyme involved in carbon metabolism, histones, and transcription factors. A putative epigenetic basis of priming effects should also be considered. Some authors identified enzyme activity changes in relation to priming while others also reported numerous changes in the seed storage protein. Priming has also been reported to increase proteins related to the cell cycle activities such as α- and δ-DNA polymerase. Protecting proteins like dehydrins or HSP is expected to assume protective functions during the dehydration step. Similarly, proteins involved in water transport, cell wall modification, cytoskeletal organization, and cell divisions, may be to some extent regulated during priming. Gene expression and enzyme activities involved in osmocompatible solute synthesis may be of primary importance to regulate tissue protection during the dehydration step and water fluxes during the final germination phase. Measurements of water uptake by primed seeds suggest a reduction in the lag time of imbibition. Water uptake and its subsequent cell-to-cell movement during germination might be controlled by aquaporins and expression of the corresponding genes constitutes a specific target of the priming treatment.
\n
Among the different hypothesis proposed to explain the biochemical basis for germination improvement, DNA replication and cell cycle advancement during priming treatment as well as synchronization of the cell cycle at the G2 phase are supported by some experimental evidences. DNA synthesis is involved during priming treatment itself but also during post-germinative events. Changes are also observed with the modification of the membrane structure and reorganization of mitochondrial integrity. Activation of antioxidative properties by priming treatment may also explain the improved behavior of plant material, especially when final germination and/or growth occur under stress condition.
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The priming-induced decrease of the storage capacity is a major limitation for the application of the priming technique by seed companies. Partial vacuum storage may be useful for extending the longevity of primed seeds. Improved longevity may be related to enhanced anti-oxidative activity that minimizes the accumulation of total peroxide during long-term storage. Another challenge for private seeds company is to identify appropriate treatments able to restore vigor of old dry seed lots in order to increase their mean percentage of germination to values compatible with commercial purposes.
\n
If priming may undoubtedly be considered as a valuable strategy to improve stand establishment, its impact on final yield and crop production has not be always confirmed. Most studies devoted to “omics” approaches of seed priming are performed on young seedling cultivated under fully controlled environmental conditions. The link between seedling behavior in plant growth chambers and the adult plant performance in field conditions is far from being clear. As a consequence, there is an urgent need to focus on transcriptomic, proteomic, and metabolomics of adult plants issued from primed seeds, especially at the reproductive stage, in order to assess the long-term impact of priming on cultivated plants throughout the plant cycle.
\n
In cultivated plant species, a given priming treatment also has contrasting effects on various cultivars. It may be hypothesized that the ability to respond to priming treatment might be genetically controlled but, to the best of our knowledge, no data are available concerning this important aspect. Thus, further progresses are needed not only to identify the set of genes that are regulated by priming, but also the set of genes that putatively regulate priming response and efficiency themselves.
\n
\n\n',keywords:"germination, omics approaches, priming, seedling growth, stress resistance",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/51934.pdf",chapterXML:"https://mts.intechopen.com/source/xml/51934.xml",downloadPdfUrl:"/chapter/pdf-download/51934",previewPdfUrl:"/chapter/pdf-preview/51934",totalDownloads:8067,totalViews:4044,totalCrossrefCites:58,totalDimensionsCites:127,totalAltmetricsMentions:0,introChapter:null,impactScore:37,impactScorePercentile:100,impactScoreQuartile:4,hasAltmetrics:0,dateSubmitted:"November 5th 2015",dateReviewed:"May 30th 2016",datePrePublished:null,datePublished:"October 12th 2016",dateFinished:"August 6th 2016",readingETA:"0",abstract:'Seed priming is a pre-sowing treatment which leads to a physiological state that enables seed to germinate more efficiently. The majority of seed treatments are based on seed imbibition allowing the seeds to go through the first reversible stage of germination but do not allow radical protrusion through the seed coat. Seeds keeping their desiccation tolerance are then dehydrated and can be stored until final sowing. During subsequent germination, primed seeds exhibit a faster and more synchronized germination and young seedlings are often more vigorous and resistant to abiotic stresses than seedlings obtained from unprimed seeds. Priming often involves soaking seed in predetermined amounts of water or limitation of the imbibition time. The imbibition rate could be somehow controlled by osmotic agents such as PEG and referred as osmopriming. Halopriming implies the use of specific salts while "hormopriming" relies on the use of plant growth regulators. Some physical treatments (UV, cold or heat,..) also provide germination improvement thus suggesting that priming effects are not necessarily related to seed imbibition. A better understanding of the metabolic events taking place during the priming treatment and the subsequent germination should help to use this simple and cheap technology in a more efficient way.',reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/51934",risUrl:"/chapter/ris/51934",book:{id:"5218",slug:"new-challenges-in-seed-biology-basic-and-translational-research-driving-seed-technology"},signatures:"Stanley Lutts, Paolo Benincasa, Lukasz Wojtyla, Szymon Kubala S,\nRoberta Pace, Katzarina Lechowska, Muriel Quinet and Malgorzata\nGarnczarska",authors:[{id:"94090",title:"Prof.",name:"Stanley",middleName:null,surname:"Lutts",fullName:"Stanley Lutts",slug:"stanley-lutts",email:"stanley.lutts@uclouvain.be",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Université Catholique de Louvain",institutionURL:null,country:{name:"Belgium"}}},{id:"181730",title:"Prof.",name:"Paolo",middleName:null,surname:"Benincasa",fullName:"Paolo Benincasa",slug:"paolo-benincasa",email:"paolo.benincasa@unipg.it",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Perugia",institutionURL:null,country:{name:"Italy"}}},{id:"181732",title:"Dr.",name:"Lukasz",middleName:null,surname:"Wojtyla",fullName:"Lukasz Wojtyla",slug:"lukasz-wojtyla",email:"lukasz.wojtyla@amu.edu.pl",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Université Catholique de Louvain",institutionURL:null,country:{name:"Belgium"}}},{id:"181733",title:"Dr.",name:"Szymon",middleName:null,surname:"Kubala",fullName:"Szymon Kubala",slug:"szymon-kubala",email:"szymon.globus@ibb.waw.pl",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Université Catholique de Louvain",institutionURL:null,country:{name:"Belgium"}}},{id:"181734",title:"Mrs.",name:"Katzzarina",middleName:null,surname:"Lechowska",fullName:"Katzzarina Lechowska",slug:"katzzarina-lechowska",email:"k.lechowska88@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Université Catholique de Louvain",institutionURL:null,country:{name:"Belgium"}}},{id:"181735",title:"Dr.",name:"Muriel",middleName:null,surname:"Quinet",fullName:"Muriel Quinet",slug:"muriel-quinet",email:"muriel.quinet@uclouvain.be",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Université Catholique de Louvain",institutionURL:null,country:{name:"Belgium"}}},{id:"181736",title:"Prof.",name:"Malgorzata",middleName:null,surname:"Garnczarska",fullName:"Malgorzata Garnczarska",slug:"malgorzata-garnczarska",email:"garnczar@amu.edu.pl",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Adam Mickiewicz University in Poznań",institutionURL:null,country:{name:"Poland"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. A brief history of seed priming",level:"1"},{id:"sec_3",title:"3. Priming methods and priming agents",level:"1"},{id:"sec_3_2",title:"3.1. Hydropriming",level:"2"},{id:"sec_4_2",title:"3.2. Osmopriming",level:"2"},{id:"sec_5_2",title:"3.3. Solid matrix priming",level:"2"},{id:"sec_6_2",title:"3.4. Hormopriming",level:"2"},{id:"sec_7_2",title:"3.5. Biopriming",level:"2"},{id:"sec_8_2",title:"3.6. Others",level:"2"},{id:"sec_10",title:"4. Seed priming and agriculture",level:"1"},{id:"sec_10_2",title:"4.1. Hastening and synchronization of germination",level:"2"},{id:"sec_11_2",title:"4.2. Plant growth",level:"2"},{id:"sec_12_2",title:"4.3. Mineral nutrition",level:"2"},{id:"sec_13_2",title:"4.4. Yield-related parameters",level:"2"},{id:"sec_14_2",title:"4.5. Stress resistance",level:"2"},{id:"sec_16",title:"5. Priming and seed water content",level:"1"},{id:"sec_17",title:"6. Priming and seed ultrastructure",level:"1"},{id:"sec_18",title:"7. Seed priming and cell cycle regulation",level:"1"},{id:"sec_19",title:"8. Management of oxidative status",level:"1"},{id:"sec_20",title:"9. Reserve mobilization",level:"1"},{id:"sec_21",title:"10. Holistic “omic” approaches of seed priming",level:"1"},{id:"sec_21_2",title:"10.1. Transcriptomics",level:"2"},{id:"sec_22_2",title:"10.2. Proteomics",level:"2"},{id:"sec_23_2",title:"10.3. Metabolomics",level:"2"},{id:"sec_25",title:"11. Main limitations of priming techniques",level:"1"},{id:"sec_26",title:"12. Conclusions",level:"1"}],chapterReferences:[{id:"B1",body:'Chen K, Arora R. Dynamics of the antioxidant system during seed osmopriming, post-priming germination, and seedling establishment in spinach (Spinacia oleracea). Plant Science. 2011;180:212-220. DOI:10.1016/j.plantsci.2010.08.007'},{id:"B2",body:'Paparella S, Araújo SS, Rossi G, Wijayasinghe M, Carbonera D, Balestrazzi A. Seed priming: state of the art and new prospectives. Plant Cell Reports. 2015;34:1281-1293. 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Study of seed priming mechanisms of three plant species used in revegetation of industrial sites. PhD Thesis, Université catholique de Louvain, Belgium. 2009. 253 p.'},{id:"B181",body:'Bonsager BC, Finnie C, Roepstorff P, Svensson B. Spatio-temporal changes in germination and radicle elongation of barley seeds tracked by proteome analysis of dissected embryo, aleurone layer, and endosperm tissues. Proteomics. 2007;7:4528-4540.'},{id:"B182",body:'Catusse J, Meinhard J, Job C, Strub JM, Fischer U, Pestova E, Westohoff P, Van Dorselaer A, Job D. Proteomics reveals potential boiomarkers of seed vigor in sugarbeet. Proteomics. 2011;11:1569-1580.'},{id:"B183",body:'Zhang H, Wang WQ, Liu SJ, Moller JM, Song SQ. Proteome analysis of poplar seed vigor. PLoS One. 2015;10:e0132509.'},{id:"B184",body:'Rajjou L, Belghazi M, Huguet R, Robin C, Moreau A, Job C, Job D. Proteomic investigation of the effect of salicylic acid an Arabidopsis seed germination and establishment of early defense mechanisms. Plant Physiology. 2006;141:910-923.'},{id:"B185",body:'Tanou G, Job C, Rajjou L, Arc E, Belghazi M, Diamentidis G, Molasiotis A, Job D. Proteomics reveals the overlapping roles of hydrogen peroxide and nitric oxide in the acclimation of citrus plants to salinity. Plant Journal. 2009;60:795-804.'},{id:"B186",body:'Wu X, Li N, Li H, Tang H. An optimized method for NMR-based plant seed metabolomics analysis with maximized polar metabolite extraction efficiency, signal-to-noise ratio, and chemical shift consistency. Analyst. 2014;139:1769-1778.'},{id:"B187",body:'Posmyk MM, Corbineau F, Vinel D, Bailly C, Côme D. Osmoconditioning reduces physiological and biochemical damage induced by chilling in soybean seeds. Physiologia Plantarum. 2001;111:473-482.'},{id:"B188",body:'Tallowin JRB, Rook AJ, Brookman SKE. The effect of osmoting resowing treatment on laboratory germination in a range of wild flower species. Annals of Applied Biology. 1994;124:363-370.'},{id:"B189",body:'Wright B, Rowse H, Whipps JM. Microbial population dynamics on seeds during drum and steeping priming. Plant and Soil. 2003;255:631-640.'},{id:"B190",body:'Chiu KY, Chen CL, Sung JM. Effects of priming temperature on storability of primed sh-2 sweet corn seeds. Crop Science. 2002;42:1996-2003.'},{id:"B191",body:'Hill HJ, Cunningham JD, Bradford KJ, Taylor AG. Primed lettuce seeds exhibit increased sensitivity to moisture content during controlled deterioration. HortScience. 2007;42:1436-1439.'},{id:"B192",body:'Schwember AR, Bradford KJ. Drying rate following priming affect temperature sensitivity of germination and longevity of lettuce seeds. HortScience. 2005;40:778-781.'},{id:"B193",body:'Hacisalihoglu G, Taylor AG, Paine DH, Hildebrand MB, Khan AA. Embryo elongation and germination rate as sensitive indicators of lettuce seed quality: priming and ageing studies. HortScience. 1999;34:1240-1243.'},{id:"B194",body:'Butler LH, Hay FR, Ellis RH, Smith RD, Murray TB. Priming and redrying improve the survival of mature seeds of Digitalis purpurea during storage. Annals of Botany. 2009;103;1261-1270.'},{id:"B195",body:'Hussain S, Zheng M, Khan F, Khaliq A, Fahad S, Peng S, Huang J, Cui K, Nie L. Benefits of rice seed priming are offset permanently by prolonged storage and the storage conditions. Scientific Reports. 2015;5:8101.'},{id:"B196",body:'Buitink J, Hemminga MA, Hoekstra FA. Is there a role for oligosaccharides in seed longevity? An assessment of intercellular glass stability. Plant Physiology. 2000;122:1217-1224.'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Stanley Lutts",address:"stanley.lutts@uclouvain.be",affiliation:'
Groupe de Recherche en Physiologie végétale (GRPV), Earth and Life Institute-Agronomy, Université catholique de Louvain, Louvain-la-Neuve, Belgium
Faculty of Biology, Department of Plant Physiology, Adam Mickiewicz University, Poznan, Poland
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1. Introduction
Extensive research in the chemical synthetic approaches has led to a huge increment in the poorly water-soluble drug’s development [1]. In the present scenario, statistical reports suggest that there are approximately 70% of poor water-soluble new chemical entities (NCEs) [2]. These newly developed drugs possess lipophilic characteristic and are challenging to deliver through the oral route. They have poor oral bioavailability, show variation in intra- as well as intersubject pharmacokinetics, have poor dose proportionality, and have erratic absorption [3]. Researchers have made many strategies to overcome the limitation of poor solubility and bioavailability. Different delivery system formulation development and chemical and/or physical modification of drug moiety can be used to solve the poor solubility issue of drugs. Though there are many drug delivery system approaches, lipid-based drug delivery system has gained much interest in lipophilic drug delivery. It includes macroemulsion, nanoemulsion, niosomes, self-emulsifying formulation, liposomes, solid-lipid nanoparticle, etc. Among all these formulation approaches, emulsion-based preparation can be considered an industrially feasible approach to overcome the limitation of poor bioavailability [4]. Nanoemulsion is capable of improving the topical drug absorption thereby increasing the bioavailability and permeability of lipophilic drug; thus, it can be a good alternative option for drug delivery [5]. Nanoemulsion is further incorporated into gel matrix to prepare nanoemulgel which has even better permeation and stability. So far, there is no review article reported on the promising future of nanoemulgel applications as a delivery system in the treatment of various diseases. This article is a complete package of nanoemulgel comprising information of potent selected formulation component, formulation procedure, advantages over other delivery system, and widespread possible application of nanoemulgel in the treatment therapy. In this article, we have mentioned only reported applications, and there are many to still go in the upcoming future.
Though oral route offers better patient compliance, it has various limitations like gastric irritation, unavoidable side effects, systemic toxicity, and hepatic first-pass metabolism [6]. To avoid all these issues, a nonirritating, non-painful, and a noninvasive topical drug delivery system can be a suitable alternative. It has several advantages over oral route such as targeted site-specific delivery of drug with least systemic toxicity, no gastric irritation, first-pass metabolism bypass, and improved bioavailability of a drug [7, 8]. Apart from many advantages, traditional topical formulations, namely lotions, creams, and ointments suffer from sticky nature, stability issue, low spreadability, etc. which affect the patient’s compliance. Whereas, modern transdermal preparations like transparent gel, nanogel, and (micro/nano) emulgel not only have shown improved patient compliance but also improves the formulation efficacy, stability, and safety. Several studies have reported that topical drug delivery system improves the bioavailability of the drug [9, 10]. Bioavailability of lacidipine given through transdermal route was found to be increased by 3.5-fold than the oral route. It may be due to the avoidance of the first-pass metabolism of the drug [9]. In another study conducted by Bhaskar and team, it was found that the topical nanoemulsion of flurbiprofen exhibits 4.4 times more bioavailability than oral delivery [10]. Thus, the bioavailability of a lipophilic drug can be enhanced by the topical drug delivery system. Topical delivery not only reduces the drug metabolism but also improves the permeation across the skin by maintaining longer steady-state delivery of the drug [9].
2. Emulsion-based nano-carrier in topical application
Delivery of a lipophilic drug is a big obstacle for the conventional transdermal delivery system due to low therapeutic potential and poor skin permeability capability. Researches propose that nanoscale-sized transdermal preparation can increase the drug permeability by disrupting the skin bilayer of lipid [11] and extending the drug retention time at the site of action [12, 13]. Nanoemulsion can be a promising carrier delivery of hydrophobic drug, since it has greater thermodynamic stability and higher capability of drug solubilization over emulsion and other dispersion systems. It also has longer shelf life and requires a small amount of external energy for manufacturing [14]. Nanoemulsion is a dispersed system which consists of nanoscale-sized (20–200 nm diameter) droplets solvent composed of an oil phase and water phase and stabilized by the suitable surfactant. Drug is entrapped in the core which is surrounded by emulsifier layer as shown in Figure 1. Generally, permeation enhancers are not required when nanoemulsion is used as a carrier for delivery of the lipophilic drug [15]. It has less tendency of phase separation than other ordinary emulsions which makes it more stable [16]. Different studies have reported better permeation of drug into the skin through nanoemulsion delivery system than conventional ointment [17], cream [18], gel [19], and emulsion [20]. Depending on the type of nanoemulsion, viz. oil-in-water or water-in-oil, it can solubilize both hydrophobic and hydrophilic drug in its structure [21].
Figure 1.
Structure of nanoemulsion.
In spite of lots of advantages, nanoemulsion suffers from low spreadability, low viscosity, and poor skin retention issue [22]. Due to these, the clinical application of topical nanoemulsion is restrained [23]. Researchers converted nanoemulsion into nanoemulgel by incorporating it into the gel matrix and solved this problem.
2.1 Nanoemulgel as topical drug delivery system
Nanoemulgel is the fusion of two systems: nanoemulsion system and hydrogel system. Both the systems have some limitations, such as nanoemulsion that suffers low spreadability and poor retention, whereas hydrogels are incapable of incorporating lipophilic molecule [24, 25]. Nanoemulgel has different types of polymeric materials, surfactants, and fatty substances of natural, synthetic, and semisynthetic nature with a droplet size range from 5 to 500 nm [26]. Nanoemulgel has the capability to overcome the limitation of both the systems. The lipophilic drug is dissolved in the oil phase of nanoemulsion which is then added to hydrogel base to form nanoemulgel [27] which enables the incorporation of lipophilic drug into a hydrogel, simultaneously improving the viscosity of nanoemulsion. In transdermal drug delivery, nanoemulgel acts as a reservoir of the drug. The drug is first to release from the inner phase to the outer phase and from there into the skin surface. When applied on skin, oily droplets were released from the gel matrix of nanoemulgel, which then penetrate deep into the skin via stratum corneum, and there they directly deliver the drug moiety [23]. The mechanism of drug release depends on the crosslink density as well as the composition of a network of polymer chains [28].
2.2 Potent components for nanoemulgel formulation
Nanoemulgel is a fusion of two separate systems, viz. the nanoemulsion and a gel system. Nanoemulsion acting as a vehicle for drug delivery can be either water-in-oil or oil-in-water type. In both cases, it consists of an oil phase, aqueous phase, surfactant, and sometime cosurfactant. Overview of commonly used major components of nanoemulgel formulation has been apprehended in this section (Figure 2).
Figure 2.
Potent formulation component of nanoemulgel.
2.2.1 Oils
Oil is an important component of the nanoemulgel formulation that should be selected appropriately based on the solubility, stability, permeability, and viscosity of the formulation. Vegetable oils/edible oils are not frequently used in nanoemulgel formulation, since they had shown poor emulsification properties and drug solubility [29, 30, 31]. Thus, chemically modified oils such as mono or diglyceride or medium-chain triglycerides are commonly used as an oil phase in the nanoemulgel formulation for lipophilic drug delivery [15]. A medium-chain triglyceride, Labrafac, has been used by Syamala and his group to prepare butenafine nanoemulgel [32]. Capryol 90 is another example used as an oil phase in the preparation of nanoemulsion, which has shown better stability of the nanoemulsion formulation of leflunomide and paclitaxel [3, 33].
On the other hand, scientists are focusing on utilizing the supplementary benefit of natural oil in therapeutic effect. Antimicrobial activity of tea tree oil was combined with an antifungal agent itraconazole for a synergistic effect of nanoemulgel preparation against vaginal candidiasis [34]. Another nanoemulgel of curcumin has been reported by Jeengar and team with emu oil. Emu oil obtained from emu bird has analgesic, antipruritic, anesthetic, antioxidants, and anti-inflammatory properties, and it has shown the improvement in permeability of drug in the treatment of joint synovial [35]. Various oils used by different researchers in nanoemulgel preparation are listed in Table 1.
Active Drug
Oil
Surfactant
Cosurfactant
Gelling agents
Reference
Thymol
Caprylic acid, isopropyl myristate, and tea tree oil
Various components used in different nanoemulgel formulations.
2.2.2 Surfactant and cosurfactant
Surfactant reduces the interfacial tension between the mixtures of two immiscible liquids and changes the dispersion entropy, thus stabilizing thermodynamically unstable emulsion system. Selection of appropriate surfactant for nanoemulgel is based on the safety, stability, high drug loading capacity as well as good emulsification properties [31]. Also, the surfactant should be selected based on the solubility with oil like Tween 20 that was used on the basis of solubility of Capryol 90 and oleic acid [15, 40].
Cosurfactant may combine with surfactant and help in the emulsification process by disrupting the interfacial film. It may also help in solubilization of oil [15]. Depending on the physicochemical properties, most frequently used cosurfactants in nanoemulsion and nanoemulgel preparation are propylene glycol, PEG 400, ethanol, transcutol P, carbitol, etc. [35, 40]. Studies suggest that with the increase in the concentration of cosurfactant, the area of nanoemulsion in phase diagram decreases [48, 49].
2.2.3 Aqueous solvents
Aqueous solvents act as the aqueous phase in emulsion preparation. Worldwide widely used aqueous solvents are ethanol and water.
2.2.4 Gelling agents
Carbapol 934, Carbapol 940, and hydroxy propyl methyl cellulose (HPMC) are widely used gelling agent for nanoemulgel. They increased the thickness of the formulation and may interact with the surfactant to modify the viscosity of the formulation [41]. It is added to the nanoemulsion preparation to change the physical state of nanoemulsion formulation from liquid to gel, thus solving the problem of low spreadability, low viscosity, and poor skin retention issue of nanoemulsion.
2.2.5 Miscellaneous components
To protect the formulation from microbial attack and increase the shelf life of formulation, preservatives are added in the preparation. Most commonly used preservatives are methylparaben, benzoic acid, propylparaben, benzalkonium chloride, etc. Antioxidants like butylate hydroxyl toluene, butylate hydroxyl anisole, and ascorbyl palmitate are used to prevent oxidative degradation of formulation components and to prevent loss of moisture, glycerin and propylene glycol are used as humectants [50]. Hence, the stability of the nanoemulsion and nanoemulgel preparation increased.
2.3 Preparation of nanoemulgel formulation
Two steps are involved in the manufacturing of nanoemulgel. The first step is nanoemulsion formulation which is then incorporated into a gelling agent in the second step to form nanoemulgel. Figure 3 schematically represents the procedure of preparation of nanoemulgel.
Figure 3.
Procedure of nanoemulgel preparation.
Methods used for the preparation of nanoemulsion can be high-energy emulsification methods or low-energy emulsification methods [49, 51]. In high-energy emulsification methods, external energy is applied which rupture the oil phase to form nanosized droplets in the aqueous phase. It includes ultrasonic emulsification and high-pressure homogenization. Solvent displacement method, phase inversion composition method, and phase inversion temperature method are low-energy emulsification in which low energy is required for prepared nanoemulsion [21].
2.3.1 Procedure for nanoemulsion preparation
The selected surfactant is dissolved in either the aqueous phase or the oil phase. Based on the solubility, the drug is then added and solubilized in the oil phase or aqueous phase followed by heating. Then one phase is gradually added into another with continuous stirring till the temperature of the mixture reaches to room temperature.
2.3.2 Procedure for nanoemulgel preparation
The appropriate gelling agent is dissolved in distilled water with continuous stirring to prepare gel base. The pH of prepared gel is adjusted, then the nanoemulsion system is incorporated slowly into the prepared gel at a particular ratio with continuous stirring to get nanoemulgel preparation.
2.4 Advantages of nanoemulgel
Nanoemulgel preparations have various advantages over other topical as well as conventional preparation. Some of the advantages are listed as follows (Figure 4).
Figure 4.
Advantages of nanoemulgel preparation.
2.4.1 Incorporation of lipophilic drug
The lipophilic drug moieties base show improper drug release mechanism in the gel due to its insolubility in aqueous base. Fusion of the hydrogel system with emulsion system enables the incorporation of lipophilic drug into the aqueous base, thus improving the release mechanism of the drug. Lipophilic drug is dissolved in the oil phase of emulsion which is then incorporated into hydrogel system [52].
2.4.2 Better loading capacity
Better loading capacity has been observed by nanoemulgel as compared to than other novel drug delivery systems. Due to its nanoscale size, it has a larger surface area and better entrapment efficiency which enable it to load more amount of drugs in its network-like system [52].
2.4.3 Better stability
Nanoemulgel system is more stable than other transdermal drug delivery system, because it decreases the interfacial as well as the surface tension of the formulation, which make it superior from a conventional transdermal delivery system [53].
2.4.4 Controlled release
Nanoemulgel acts as a drug reservoir and has shown prolong residence time leading to sustain release of the drug. Thus, it is beneficial for the drugs having shorter half-life [52].
2.4.5 Better pharmacokinetic profile
Nanoemulgel formulation gives higher Tmax and peak plasma concentration of lipophilic drugs than the conventional gel as well as oral formulation. Thereby, nanoemulgel preparation improves the bioavailability of lipophilic drug many folds than the other lipophilic drug formulations [53].
2.4.6 Better pharmacodynamics activity
2.4.7 Improved permeability of nanoemulgel preparation through the skin enables more drugs to penetrate into the site of action. This enhances the pharmacodynamic activity of the drug increasing its therapeutic efficacy [53]
2.4.8 Better patient compliance
Major issue with the transdermal preparation is the sticky nature and low spreading coefficient which require rubbing mechanism. Nanoemulgel being nonsticky and easily spreadable preparation results in better patient compliance than other transdermal preparations [28].
2.4.9 Enhanced drug permeability through skin
Nanoemulgel has shown significant enhancement in the permeability of the drug through skin than other formulation since from nanoemulgel preparation, the drug can permeate the skin layer through both paracellular and transcellular route, whereas, in nanoemulsion, only transcellular permeation route is seen [53]. Comparison of cumulative drug permeability through the skin from different formulation is represented in Figure 5 [24].
Figure 5.
Comparative representation of cumulative cyclosporine permeated through the skin of albino rat from different formulations. Regenerated from [24].
2.4.10 Better safety profile
Nanoemulgel bypasses the first-pass metabolism, thus solving one of the major problems of drug, that is, the oral side effect. It does not cause skin irritation or any toxicity on the application [53].
3. Health claim
A significant number of the nanoemulgel formulation of drugs has been carried out and reported by various researchers to show its application as a more potent and effective drug delivery system. Some of the studies have shown outstanding result over the conventional oral drug delivery system, suggesting a promising future of nanoemulgel application.
3.1 Acne and pimple
Thymol nanoemulgel formulation for acne vulgaris, a common chronic skin disease, was prepared by Ahmad and team. The preparation showed better efficacy [36].
3.2 Psoriasis
It is the skin condition in which skin cells build up and form itchy, dry patches, and scales. A nanoemulgel formulation of leflunomide by Pund and team showed considerably higher anti-psoriatic and anti-melanoma activity in human keratinocyte cell line due to improved permeability of drug. Amount of drug deposited in the skin after 12 hours by nanoemulgel was found to be sixfold more than ordinary gel [33]. In another study by Somagoni and team, nanoemulgel showed 3.22- and 2.01-fold more reduction of ear swelling than drug solution and marketed product, respectively, in psoriatic-like model [43].
3.3 Fungal infection
High skin permeability of nanoemulgel has made it a better alternative for the faster treatment of fungal infection. Syamala has reported that it took only 12 days to Butenafine nanoemulgel to cure fungus-infected rat skin, whereas cream took 16 days [32]. Nanoemulgel has also shown a notable increase in antifungal activity of the drug. Higher area of inhibition zone was observed with Ketoconazole nanoemulgel than drug solution when incubated for 48 hours [38]. Nanoemulgel of Amphotericin B can overcome formulation limitation of Amphotericin B making it a better alternative to painful intravenous administration. It could be used as a stable, effective, and safe carrier for sustained and enhanced localized delivery of Amphotericin B against fungal infection [42].
3.4 Inflammation and pain due to osteoarthritis and rheumatic arthritis
Nanoemulgel is a better alternative for poor water-soluble anti-inflammatory drugs, and it also bypasses the related oral side effects of drugs like gastrointestinal irritation, renal, and cardiovascular problems, etc. Many researchers have reported remarkably higher activity of anti-inflammatory drugs in nanoemulgel formulation than other drug carrier system [35, 40, 54, 55, 56, 57]. Nanoemulgel of ketoprofen, an extensively utilized non steroidal anti inflammatory drugs (NSAIDs) for rheumatoid arthritis and osteoarthritis treatment, was developed by Arora and team. Along with enhancing the skin permeability and solubility of ketoprofen, it also bypasses the problems related to chronic oral delivery of ketoprofen. Comparison of the optimized formulation with the marketed product and drug solution showed 1.5- and 2-fold higher permeability, respectively [40].
Another common drug used in osteoarthritis and rheumatoid arthritis is piroxicam. It is also used in the treatment of the musculoskeletal and joint disorder. It also possesses the problem of poor solubility along with undesirable side effect on stomach and kidney. Dhawan and team reported that piroxicam nanoemulgel can be used as a feasible alternative [41].
Apart from these, attempt has also made to establish the stability, efficacy, and safety of certain drugs with anti-inflammatory activity which has poor solubility and permeability profile and/or oral side effect like curcumin [35], Swietenia macrophylla [27], Lornoxicam [54], Nimesulide [55], mangosteen [56], and diclofenac diethylamine [57]. Figure 6 represents the comparison of anti-inflammatory effect of flurbiprofen nanoemulgel by Radhika and Guruprasad with marketed preparation [37].
Figure 6.
Graphical representation of improvement in anti-inflammatory effect of nanoemulgel of flurbiprofen. Regenerated from [56].
3.5 Periodontal disease
Dental nanoemulgel preparation is intended for periodontal delivery of drug to treat chronic bacterial infection of the gum and bone supporting teeth. Periodontal disease causes inflammation of gum forming pockets which may lead to gum tissue and bone damage. Srivastava and team formulated syringeable ketoprofen nanoemulgel for intra-pocket delivery and found satisfied pharmaceutical characterization offering sustained release of ketoprofen into the pocket. Significant reduction was observed in alveolar bone loss, gingival index, and tooth motility by ketoprofen nanoemulgel due to decreased cytokine levels [58]. Whereas, the study of Nayak and team suggested that controlled released delivery of Quercetin nanoemulgel can be used successfully in periodontitis [59].
3.6 Corneal fungus infection
Ocular nanoemulgel can be better alternative drug delivery system to the conventional eye drops to cure corneal fungal infection. Permeation of fluconazole from nanoemulgel preparation was found four times that of commercial fluconazole eye drop due to high permeation, sustained release of drug, and prolongation in the precorneal residence time. Prolong release was achieved by in situ gelation of Gellan gum due to its crosslinking with tear fluid. Fluconazole nanoemulgel formulation showed no sign of any ocular irritation and tissue damage [60]. Whereas, Tayel used a rabbit model to successfully control the release rate of terbinafine-HCL nanoemulgel, which can be an effective alternative to conventional eye drop for ocular fungal infection, into the rabbit aqueous humor [61].
3.7 Vaginal candidiasis
A thermo-sensitive nanoemulgel of itraconazole with tea tree oil was prepared for patients suffering from periodic vaginal candidiasis. Antimicrobial activity of itraconazole and tea tree oil combined to give synergistic effect covering cure for wide range microbial infection [34].
3.8 Alopecia
Minoxidil is the commonly used drug for the treatment of hair loss also known as alopecia. Nanoemulgel is capable of increasing solubility and permeability of drug through the skin; hence, nanoemulgel preparation of minoxidil will be more effective and safer than conventional preparation present in the market for the treatment of alopecia areata [62].
3.9 Insomnia
Nasal nanoemulgel of zaleplon was formulated by Hosny and Banjar for the treatment of insomnia. The main objective was to solve the problem with marketed zaleplon tablet. Zaleplon tablet suffers from poor bioavailability due to extensive first-pass metabolism and delayed onset of action due to poor aqueous solubility. Nasal zaleplon nanoemulgel showed eight times more bioavailability than the marketed zaleplon tablet [63].
3.10 Parkinson’s disease
Selegiline HCL-loaded nanoemulgel possess better sustains release effect of the drug and higher bioavailability than the conventional gel and a marketed tablet. Bioavailability was reported to be 5.53 and 6.56 times that of normal gel and tablet [64]. Microemulgel loaded with rotigotine has also shown significantly higher bioavailability than marketed patch of rotigotine in the treatment of Parkinson’s disease [65].
3.11 Cosmetics
Use of nanotechnology in cosmetics is very common. Fullerenes, solid-lipid nanoparticle, liposomes, nanosomes, etc., are already nourishing in cosmetic industries. Ferulic acid nanoemulgel was developed by Harwansh and team to protect the skin damage from harmful UV radiation. Ferulic acid strongly absorbs the UV radiation. Its incorporation into nanoemulgel system made it effective for more than 4 hours on the UV-exposed skin [39].
Currently available marketed emulgel products for the treatment of acne and pimple, inflammation, and pain caused by osteoarthritis and rheumatoid arthritis and skin infection have been listed in Table 2.
Product brand name
Active pharmaceutical ingredient(s)
Manufacturers
Application
Benzolait AZ emulgel
Benzoylperoxide
Roydermal
Pimple and blacks on skin
Coolnac Gel emulgel 1%
Diclofenac diethyl ammonium
Chumchon
Inflammation and pain due to trauma
Diclobar emulgel
Diclofenac diethyl amine
Barakat Pharma
Inflammation due to trauma and rheumatic diseases
Levorage emulgel
Liquorice, hibiscus, and natural extract
THD Ltd
Anal fissures
Meloxic emulgel
Meloxicum
Laboratories Provet
Musculoskeletal pain management and inflammation
Miconaz-H-emulgel
Miconazole nitrate, hydrocortisone
Medical Union Pharmaceutics
Skin infection by candida
Reumadep emulgel
Ashwagandha, myrrh, arnica, rosemary, mint, and cloves
Erbozeta
Inflammation and pain due to trauma
Voltaren emulgel
Diclofenac diethyl ammonium
Novartis Pharma
Osteoarthritis joint pain
Voveron emulgel
Diclofenac diethyl amine
Novartis Pharma
Osteoarthritis joint pain
Table 2.
Available marketed emulgel preparations.
4. Mechanism involved to enhance permeability and bioavailability from nanoemulgel preparations
The skin permeability as well as bioavailability of nanoemulgel may be enhanced by various mechanisms. Some of the studied mechanisms with types of nanoemulgel are listed in Table 3.
Types of nanoemulgel
Mechanism of permeability/bioavailability
References
Conjugate of curcumin
Induced apoptosis in cancer cells, suppressing the expression of NF-κB, TNF-α, and COX-2 cellular targets
Nanoemulgel has been found to be extraordinarily good vehicle system for hydrophobic drug delivery. High drug loading due to better solubilizing efficacy, improved bioavailability due to better permeability, and capability to control the release of drug make it a potent alternative delivery system in the treatment of various diseases. Application of nanoemulgel preparation in the treatment of acne, pimple, psoriasis, fungal infection, and inflammation due to osteoarthritis as well as rheumatoid arthritis has shown significantly higher efficacy. Besides transdermal application, it can also be applied for ocular, vaginal, dental, and nose to brain delivery of drug for the treatment of diverse local and systemic ailments such as alopecia, periodontitis, and Parkinson’s disease. Nanoemulgel has also shown its application in the cosmetic industries as a UV absorber nanoemulgel to protect skin from sunburn. Precisely, the nanoemulgel system has a marvelous ability to be applied in various local and systemic ailments. Some preparations are already present in the market, whereas others need a further clinical study to launch the product in the market.
\n',keywords:"nanoemulgel, lipophilic, bioavailability, permeability",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/81214.pdf",chapterXML:"https://mts.intechopen.com/source/xml/81214.xml",downloadPdfUrl:"/chapter/pdf-download/81214",previewPdfUrl:"/chapter/pdf-preview/81214",totalDownloads:81,totalViews:0,totalCrossrefCites:0,dateSubmitted:"January 29th 2022",dateReviewed:"February 22nd 2022",datePrePublished:"April 11th 2022",datePublished:null,dateFinished:"April 11th 2022",readingETA:"0",abstract:"Nanoemulgel delivery system is a fusion of two different delivery systems, wherein the physical state of drug containing nanoemulsion is changed by adding it to the gel matrix, thus enabling more lipophilic drugs to be used in treatment therapies. It solves the major issues such as limiting use of lipophilic drugs, poor oral bioavailability, and unpredictable pharmacokinetic and absorption variations. Simultaneously, its nongreasy nature and easily spreading ability support the patient compliance. Nanoemulgel can be widely used in the treatment of acne, pimple, psoriasis, fungal infection, and inflammation cause by osteoarthritis and rheumatoid arthritis. The delivery of drug via ocular, vaginal, dental, and nose to brain routes for the treatment of diverse local and systemic ailments for instance alopecia, periodontitis, and Parkinson’s are possible. In the cosmetic industries, UV absorber nanoemulgel protected skin from sunburn.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/81214",risUrl:"/chapter/ris/81214",signatures:"Nazneen Sultana, Juber Akhtar, Badruddeen, Mohammad Irfan Khan, Usama Ahmad, Muhammad Arif, Mohammad Ahmad and Tanmay Upadhyay",book:{id:"11091",type:"book",title:"Drug Development Life Cycle",subtitle:null,fullTitle:"Drug Development Life Cycle",slug:null,publishedDate:null,bookSignature:"Prof. Juber Akhtar, Dr. Badruddeen, Dr. Mohammad Ahmad and Dr. Mohammad Irfan Khan",coverURL:"https://cdn.intechopen.com/books/images_new/11091.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80356-048-9",printIsbn:"978-1-80356-047-2",pdfIsbn:"978-1-80356-049-6",isAvailableForWebshopOrdering:!0,editors:[{id:"345595",title:"Prof.",name:"Juber",middleName:null,surname:"Akhtar",slug:"juber-akhtar",fullName:"Juber Akhtar"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Emulsion-based nano-carrier in topical application",level:"1"},{id:"sec_2_2",title:"2.1 Nanoemulgel as topical drug delivery system",level:"2"},{id:"sec_3_2",title:"2.2 Potent components for nanoemulgel formulation",level:"2"},{id:"sec_3_3",title:"Table 1.",level:"3"},{id:"sec_4_3",title:"2.2.2 Surfactant and cosurfactant",level:"3"},{id:"sec_5_3",title:"2.2.3 Aqueous solvents",level:"3"},{id:"sec_6_3",title:"2.2.4 Gelling agents",level:"3"},{id:"sec_7_3",title:"2.2.5 Miscellaneous components",level:"3"},{id:"sec_9_2",title:"2.3 Preparation of nanoemulgel formulation",level:"2"},{id:"sec_9_3",title:"2.3.1 Procedure for nanoemulsion preparation",level:"3"},{id:"sec_10_3",title:"2.3.2 Procedure for nanoemulgel preparation",level:"3"},{id:"sec_12_2",title:"2.4 Advantages of nanoemulgel",level:"2"},{id:"sec_12_3",title:"2.4.1 Incorporation of lipophilic drug",level:"3"},{id:"sec_13_3",title:"2.4.2 Better loading capacity",level:"3"},{id:"sec_14_3",title:"2.4.3 Better stability",level:"3"},{id:"sec_15_3",title:"2.4.4 Controlled release",level:"3"},{id:"sec_16_3",title:"2.4.5 Better pharmacokinetic profile",level:"3"},{id:"sec_17_3",title:"2.4.6 Better pharmacodynamics activity",level:"3"},{id:"sec_18_3",title:"2.4.7 Improved permeability of nanoemulgel preparation through the skin enables more drugs to penetrate into the site of action. This enhances the pharmacodynamic activity of the drug increasing its therapeutic efficacy [53]",level:"3"},{id:"sec_19_3",title:"2.4.8 Better patient compliance",level:"3"},{id:"sec_20_3",title:"2.4.9 Enhanced drug permeability through skin",level:"3"},{id:"sec_21_3",title:"2.4.10 Better safety profile",level:"3"},{id:"sec_24",title:"3. Health claim",level:"1"},{id:"sec_24_2",title:"3.1 Acne and pimple",level:"2"},{id:"sec_25_2",title:"3.2 Psoriasis",level:"2"},{id:"sec_26_2",title:"3.3 Fungal infection",level:"2"},{id:"sec_27_2",title:"3.4 Inflammation and pain due to osteoarthritis and rheumatic arthritis",level:"2"},{id:"sec_28_2",title:"3.5 Periodontal disease",level:"2"},{id:"sec_29_2",title:"3.6 Corneal fungus infection",level:"2"},{id:"sec_30_2",title:"3.7 Vaginal candidiasis",level:"2"},{id:"sec_31_2",title:"3.8 Alopecia",level:"2"},{id:"sec_32_2",title:"3.9 Insomnia",level:"2"},{id:"sec_33_2",title:"3.10 Parkinson’s disease",level:"2"},{id:"sec_34_2",title:"3.11 Cosmetics",level:"2"},{id:"sec_36",title:"4. Mechanism involved to enhance permeability and bioavailability from nanoemulgel preparations",level:"1"},{id:"sec_37",title:"5. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Weissig V, Lizano C, Torchilin VP. Selective DNA release from DQAsome/DNA complexes at mitochondria-like membranes. 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Enhanced topical delivery and anti-inflammatory activity of methotrexate from an activated nanogel. European Journal of Pharmaceutics and Biopharmaceutics. 2010;76(2):275-281'},{id:"B70",body:'Elmataeeshy ME, Sokar MS, Bahey-El-Din M, Shaker DS. Enhanced transdermal permeability of terbinafine through novel nanoemulgel formulation; development, in vitro and in vivo characterization. Future Journal of Pharmaceutical Sciences. 2018;4(1):18-28'},{id:"B71",body:'Qian Q , Shi L, Gao X, Ma Y, Yang J, Zhang Z, et al. A paclitaxel-based mucoadhesive nanogel with multivalent interactions for cervical cancer therapy. Small. 2019;15(47):1903208'},{id:"B72",body:'Javed H, Shah SNH, Iqbal FM. Formulation development and evaluation of diphenhydramine nasal nano-emulgel. AAPS PharmSciTech. 2018;19(4):1730-1743'},{id:"B73",body:'Zakir F, Ahmad A, Mirza MA, Kohli K, Ahmed FJ. Exploration of a transdermal nanoemulgel as an alternative therapy for postmenopausal osteoporosis. Journal of Drug Delivery Science and Technology. 2021;65:102745'},{id:"B74",body:'Ma Q , Zhang J, Lu B, Lin H, Sarkar R, Wu T, et al. Nanoemulgel for improved topical delivery of desonide: Formulation design and characterization. AAPS PharmSciTech. 2021;22(5):1-4'},{id:"B75",body:'Mahtab A, Anwar M, Mallick N, Naz Z, Jain GK, Ahmad FJ. Transungual delivery of ketoconazole nanoemulgel for the effective management of onychomycosis. AAPS PharmSciTech. 2016;17(6):1477-1490'},{id:"B76",body:'Chin LY, Tan JYP, Choudhury H, Pandey M, Sisinthy SP, Gorain B. Development and optimization of chitosan coated nanoemulgel of telmisartan for intranasal delivery: A comparative study. Journal of Drug Delivery Science and Technology. 2021;62:102341'},{id:"B77",body:'Abioye AO, Issah S, Kola-Mustapha AT. Ex vivo skin permeation and retention studies on chitosan–ibuprofen–gellan ternary nanogel prepared by in situ ionic gelation technique—A tool for controlled transdermal delivery of ibuprofen. International Journal of Pharmaceutics. 2015;490(1-2):112-130'},{id:"B78",body:'Dhawan B, Aggarwal G, Harikumar SL. Enhanced transdermal permeability of piroxicam through novel nanoemulgel formulation. International Journal of Pharmaceutical Investigation. 2014;4(2):65'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Nazneen Sultana",address:null,affiliation:'
Faculty of Pharmacy, Integral University, Lucknow, India
Faculty of Pharmacy, Integral University, Lucknow, India
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Today’s coherent, solid-state radars (either of the phased array type or of the single-radiator type as air traffic control or marine radars) transmit a set of deterministic signals with relatively large duty cycles, an order of 10%, calling for pulse compression to get the required range resolution. Often, power budget calls for different pulse lengths (e.g., short, medium, and long waveforms with a rectangular envelope) to cover the whole radar range. The first part of the chapter includes the topic of mitigating the effect of unwanted side lobes, inherent to every pulse compression, which is achieved both by a careful and optimal design of the waveform and by a (possibly mismatched) suitable processing. The second part of the chapter deals with the novel noise radar technology, not yet used in commercial radar sets but promising: (1) to prevent radar interception and exploitation by an enemy part and (2) to limit the mutual interferences of nearby radars, as in the marine environment. In this case, the design includes a tailoring of a set of pseudo-random waveforms, generally by recursive processing, to comply with the system requirements.",signatures:"Gaspare Galati and Gabriele Pavan",authors:[{id:"213346",title:"Prof.",name:"Gaspare",surname:"Galati",fullName:"Gaspare Galati",slug:"gaspare-galati",email:"gaspare.galati@uniroma2.it"},{id:"213352",title:"Dr.",name:"Gabriele",surname:"Pavan",fullName:"Gabriele Pavan",slug:"gabriele-pavan",email:"gabriele.pavan@uniroma2.it"}],book:{id:"6347",title:"Topics in Radar Signal Processing",slug:"topics-in-radar-signal-processing",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"124222",title:"Prof.",name:"Mihai",surname:"Datcu",slug:"mihai-datcu",fullName:"Mihai Datcu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"German Aerospace Center",institutionURL:null,country:{name:"Germany"}}},{id:"211960",title:"M.Sc.",name:"Tamás",surname:"Pető",slug:"tamas-peto",fullName:"Tamás Pető",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Budapest University of Technology and Economics",institutionURL:null,country:{name:"Hungary"}}},{id:"212964",title:"Prof.",name:"Alexander",surname:"Totsky",slug:"alexander-totsky",fullName:"Alexander Totsky",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Aerospace University – Kharkiv Aviation Institute",institutionURL:null,country:{name:"Ukraine"}}},{id:"212966",title:"Prof.",name:"Karen",surname:"Egiazarian",slug:"karen-egiazarian",fullName:"Karen Egiazarian",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"217664",title:"Dr.",name:"Octavian",surname:"Dumitru",slug:"octavian-dumitru",fullName:"Octavian Dumitru",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"217666",title:"Mr.",name:"Gottfried",surname:"Schwarz",slug:"gottfried-schwarz",fullName:"Gottfried Schwarz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"German Aerospace Center",institutionURL:null,country:{name:"Germany"}}},{id:"217736",title:"Dr.",name:"Daniela",surname:"Espinoza-Molina",slug:"daniela-espinoza-molina",fullName:"Daniela Espinoza-Molina",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"German Aerospace Center",institutionURL:null,country:{name:"Germany"}}},{id:"217737",title:"Prof.",name:"Herman",surname:"Hummel",slug:"herman-hummel",fullName:"Herman Hummel",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Royal Netherlands Institute for Sea Research",institutionURL:null,country:{name:"Netherlands"}}},{id:"217738",title:"Dr.",name:"Christiaan",surname:"Hummel",slug:"christiaan-hummel",fullName:"Christiaan Hummel",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Royal Netherlands Institute for Sea Research",institutionURL:null,country:{name:"Netherlands"}}},{id:"221376",title:"Dr.",name:"Rudolf",surname:"Seller",slug:"rudolf-seller",fullName:"Rudolf Seller",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Budapest University of Technology and Economics",institutionURL:null,country:{name:"Hungary"}}}]},generic:{page:{slug:"attribution-policy",title:"Attribution Policy",intro:"
Definition of Terms:
\n\n
Book - collection of Works distributed in a book format, whose selection, coordination, preparation, and arrangement has been performed and published by IntechOpen, and in which the Work is included in its entirety in an unmodified form along with one or more other contributions, each constituting separate and independent sections, but together assembled into a collective whole.
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Work - a book Chapter (as well as Conference Papers), including any and all content, graphics, images and/or other materials forming part of, or accompanying, the Chapter/Conference Paper.
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Attribution – appropriate credit for the used Work or book.
\\n\\n
Creative Commons licenses – enable licensors to retain copyright while allowing others to use their Works in an appropriate way.
\\n\\n
Rules of Attribution for Works Published by IntechOpen
\\n\\n
With the purpose of protecting Authors' copyright and the transparent reuse of OA (Open Access) content, IntechOpen has developed Rules of Attribution of Works licensed under Creative Commons licenses.
\\n\\n
\\n\\t
All Chapters published in IntechOpen books prior to October 2011 are licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported license (CC BY-NC-SA 3.0);
\\n\\t
All Chapters published in IntechOpen books after October 2011 are licensed under the Creative Commons Attribution 3.0 Unported license (CC BY 3.0);
\\n
\\n\\n
In case you reuse or republish any of the Works licensed under CC licenses, you must abide by the guidelines outlined below:
\\n\\n
1. Rules for reusing of books in their entirety or significant parts of books
\\n\\n
All rights to Books and other compilations published on the IntechOpen platform and in print are reserved by IntechOpen. The Copyright to Books and other compilations is subject to a separate Copyright from any that exists in the included Works.
\\n\\n
A Book in its entirety or a significant part of a Book cannot be translated freely without specific written consent by the publisher. Further information can be obtained at permissions@intechopen.com.
\\n\\n
In instances where permission is obtained from the publisher for reusing or republishing the Book, or significant parts of the Book, all of the following conditions apply:
\\n\\n
\\n\\t
Information about the first publisher must be provided – please note the fact that the material was originally published by IntechOpen as an OA (Open Access) publication must be acknowledged;
\\n\\t
All original Academic Editor(s) must be credited;
\\n\\t
Since you are reusing content that someone else created and allowed you to use freely, you must credit all Authors involved;
\\n\\t
The type of license that is available for the Works must be indicated, as well as a link to the license provided, so that others can investigate the terms of the license. You will be aware that the material can be used for free in consequence of the CC license attribution, so you must acknowledge that fact. It is not sufficient that the material is Creative Commons, because that says nothing about how the material can actually be used. There are different CC licenses and you have to identify the specific license that is being used;
\\n\\t
Any original Copyright Notices associated, with the Works which constitute the Book must be kept intact;
\\n\\t
Provision of the original title of the Book, as well as the original titles of any individual Works;
\\n\\t
Provision of the URL where the Book is hosted, with a notice to the effect that the Book is an OA (Open Access) publication;
\\n\\t
Provision of the URL to every individual Work which constitutes the Book with a notice that the Work is an OA (Open Access) publication. As the material has been accessed for free, it is incumbent upon you to provide the source so that others can also access it for free.
\\n
\\n\\n
Every single Work that is used has to be attributed in the way described. If you are unsure about proper attribution, please write to permissions@intechopen.com.
\\n\\n
2. Rules of attribution for works published by IntechOpen
\\n\\n
Individual Works originally published in IntechOpen books are licensed under Creative Commons licenses and can be freely used under terms of the respective CC license, if properly attributed. In order to properly attribute the Work you must respect all the conditions outlined below:
\\n\\n
\\n\\t
Credit all Authors – since you are reusing contents that someone created and allowed you to use freely, you have to acknowledge authorship;
\\n\\t
Indicate the type of license under which the Work is available and provide the URL to the license so others can find out the license terms. Preferably keep intact any original Copyright Notice associated with the Chapter (if any). You will be aware that the material can be used for free in consequence of the CC license attribution, so you must acknowledge that fact. It is not sufficient that the material is Creative Commons, because that says nothing about how the material can actually be used. There are different CC licenses and you have to identify the specific license that is being used;
\\n\\t
Provide the URL where the Work is hosted, preferably providing the original title of the Work, as well as the original title of the Book with a notification that the Work is an OA (Open Access) publication. As the material has been accessed for free, it is incumbent upon you to provide the source so that others can also access it for free;
\\n\\t
Provide information about the first publisher – please note the fact that the material was originally published by IntechOpen as an OA (Open Access) Work must be acknowledged.
\\n
\\n\\n
Every single Work that is used has to be attributed in the way as described. If you are unsure about proper attribution, please contact Us at permissions@intechopen.com.
\\n\\n
In the event that you use more than one of IntechOpen's Works published in one or more books (but not a significant part of the book that is under separate Copyright), each of these have to be properly attributed in the way described.
\\n\\n
IntechOpen does not have any claims on newly created copyrighted Works, but the Works originally published by IntechOpen must be properly attributed.
\\n\\n
All these rules apply to BOTH online and offline use.
\\n\\n
Parts of the Rules of Attribution are based on Work Attributing Creative Commons Materials published by the Australian Research Council Centre of Excellence for Creative Industries and Innovation, in partnership with Creative Commons Australia, which can be found at creativecommons.org.au licensed under Creative Commons Attribution 2.5 Australia license, and Best practices for attribution published by Creative Commons, which can be found at wiki.creativecommons.org under the Creative Commons Attribution 4.0 license.
\\n\\n
All the above rules are subject to change, IntechOpen reserves the right to take appropriate action if any of the conditions outlined above are not met.
Work - a book Chapter (as well as Conference Papers), including any and all content, graphics, images and/or other materials forming part of, or accompanying, the Chapter/Conference Paper.
\n\n
Attribution – appropriate credit for the used Work or book.
\n\n
Creative Commons licenses – enable licensors to retain copyright while allowing others to use their Works in an appropriate way.
\n\n
Rules of Attribution for Works Published by IntechOpen
\n\n
With the purpose of protecting Authors' copyright and the transparent reuse of OA (Open Access) content, IntechOpen has developed Rules of Attribution of Works licensed under Creative Commons licenses.
\n\n
\n\t
All Chapters published in IntechOpen books prior to October 2011 are licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported license (CC BY-NC-SA 3.0);
\n\t
All Chapters published in IntechOpen books after October 2011 are licensed under the Creative Commons Attribution 3.0 Unported license (CC BY 3.0);
\n
\n\n
In case you reuse or republish any of the Works licensed under CC licenses, you must abide by the guidelines outlined below:
\n\n
1. Rules for reusing of books in their entirety or significant parts of books
\n\n
All rights to Books and other compilations published on the IntechOpen platform and in print are reserved by IntechOpen. The Copyright to Books and other compilations is subject to a separate Copyright from any that exists in the included Works.
\n\n
A Book in its entirety or a significant part of a Book cannot be translated freely without specific written consent by the publisher. Further information can be obtained at permissions@intechopen.com.
\n\n
In instances where permission is obtained from the publisher for reusing or republishing the Book, or significant parts of the Book, all of the following conditions apply:
\n\n
\n\t
Information about the first publisher must be provided – please note the fact that the material was originally published by IntechOpen as an OA (Open Access) publication must be acknowledged;
\n\t
All original Academic Editor(s) must be credited;
\n\t
Since you are reusing content that someone else created and allowed you to use freely, you must credit all Authors involved;
\n\t
The type of license that is available for the Works must be indicated, as well as a link to the license provided, so that others can investigate the terms of the license. You will be aware that the material can be used for free in consequence of the CC license attribution, so you must acknowledge that fact. It is not sufficient that the material is Creative Commons, because that says nothing about how the material can actually be used. There are different CC licenses and you have to identify the specific license that is being used;
\n\t
Any original Copyright Notices associated, with the Works which constitute the Book must be kept intact;
\n\t
Provision of the original title of the Book, as well as the original titles of any individual Works;
\n\t
Provision of the URL where the Book is hosted, with a notice to the effect that the Book is an OA (Open Access) publication;
\n\t
Provision of the URL to every individual Work which constitutes the Book with a notice that the Work is an OA (Open Access) publication. As the material has been accessed for free, it is incumbent upon you to provide the source so that others can also access it for free.
\n
\n\n
Every single Work that is used has to be attributed in the way described. If you are unsure about proper attribution, please write to permissions@intechopen.com.
\n\n
2. Rules of attribution for works published by IntechOpen
\n\n
Individual Works originally published in IntechOpen books are licensed under Creative Commons licenses and can be freely used under terms of the respective CC license, if properly attributed. In order to properly attribute the Work you must respect all the conditions outlined below:
\n\n
\n\t
Credit all Authors – since you are reusing contents that someone created and allowed you to use freely, you have to acknowledge authorship;
\n\t
Indicate the type of license under which the Work is available and provide the URL to the license so others can find out the license terms. Preferably keep intact any original Copyright Notice associated with the Chapter (if any). You will be aware that the material can be used for free in consequence of the CC license attribution, so you must acknowledge that fact. It is not sufficient that the material is Creative Commons, because that says nothing about how the material can actually be used. There are different CC licenses and you have to identify the specific license that is being used;
\n\t
Provide the URL where the Work is hosted, preferably providing the original title of the Work, as well as the original title of the Book with a notification that the Work is an OA (Open Access) publication. As the material has been accessed for free, it is incumbent upon you to provide the source so that others can also access it for free;
\n\t
Provide information about the first publisher – please note the fact that the material was originally published by IntechOpen as an OA (Open Access) Work must be acknowledged.
\n
\n\n
Every single Work that is used has to be attributed in the way as described. If you are unsure about proper attribution, please contact Us at permissions@intechopen.com.
\n\n
In the event that you use more than one of IntechOpen's Works published in one or more books (but not a significant part of the book that is under separate Copyright), each of these have to be properly attributed in the way described.
\n\n
IntechOpen does not have any claims on newly created copyrighted Works, but the Works originally published by IntechOpen must be properly attributed.
\n\n
All these rules apply to BOTH online and offline use.
\n\n
Parts of the Rules of Attribution are based on Work Attributing Creative Commons Materials published by the Australian Research Council Centre of Excellence for Creative Industries and Innovation, in partnership with Creative Commons Australia, which can be found at creativecommons.org.au licensed under Creative Commons Attribution 2.5 Australia license, and Best practices for attribution published by Creative Commons, which can be found at wiki.creativecommons.org under the Creative Commons Attribution 4.0 license.
\n\n
All the above rules are subject to change, IntechOpen reserves the right to take appropriate action if any of the conditions outlined above are not met.
\n\n
Policy last updated: 2016-06-09
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. 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Various textile production methods used for the formation of textile preforms are explained. Composite fabrication methods are introduced. Engineering properties of textile composites are reviewed with regard to specific application areas. 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\r\n\tTransforming our World: the 2030 Agenda for Sustainable Development endorsed by United Nations and 193 Member States, came into effect on Jan 1, 2016, to guide decision making and actions to the year 2030 and beyond. Central to this Agenda are 17 Goals, 169 associated targets and over 230 indicators that are reviewed annually. The vision envisaged in the implementation of the SDGs is centered on the five Ps: People, Planet, Prosperity, Peace and Partnership. This call for renewed focused efforts ensure we have a safe and healthy planet for current and future generations.
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\r\n\t
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\r\n\tThis Series focuses on covering research and applied research involving the five Ps through the following topics:
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\r\n\t
\r\n
\r\n\t1. Sustainable Economy and Fair Society that relates to SDG 1 on No Poverty, SDG 2 on Zero Hunger, SDG 8 on Decent Work and Economic Growth, SDG 10 on Reduced Inequalities, SDG 12 on Responsible Consumption and Production, and SDG 17 Partnership for the Goals
\r\n
\r\n\t
\r\n
\r\n\t2. Health and Wellbeing focusing on SDG 3 on Good Health and Wellbeing and SDG 6 on Clean Water and Sanitation
\r\n
\r\n\t
\r\n
\r\n\t3. Inclusivity and Social Equality involving SDG 4 on Quality Education, SDG 5 on Gender Equality, and SDG 16 on Peace, Justice and Strong Institutions
\r\n
\r\n\t
\r\n
\r\n\t4. Climate Change and Environmental Sustainability comprising SDG 13 on Climate Action, SDG 14 on Life Below Water, and SDG 15 on Life on Land
\r\n
\r\n\t
\r\n
\r\n\t5. Urban Planning and Environmental Management embracing SDG 7 on Affordable Clean Energy, SDG 9 on Industry, Innovation and Infrastructure, and SDG 11 on Sustainable Cities and Communities.
\r\n
\r\n\t
\r\n
\r\n\tThe series also seeks to support the use of cross cutting SDGs, as many of the goals listed above, targets and indicators are all interconnected to impact our lives and the decisions we make on a daily basis, making them impossible to tie to a single topic.
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She is also Invisalign certified. She’s working as a Senior Lecturer in the Department of Orthodontics, SRM Dental College since November 2019. She is actively involved in teaching orthodontics to the undergraduates and the postgraduates. Her clinical research topics include new orthodontic brackets, fixed appliances and TADs. She’s published 4 articles in well renowned indexed journals and has a published patency of her own. Her private practice is currently limited to orthodontics and works as a consultant in various clinics.",institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"323731",title:"Prof.",name:"Deepak M.",middleName:"Macchindra",surname:"Vikhe",slug:"deepak-m.-vikhe",fullName:"Deepak M. Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. His research interests include root canal morphology, functionally graded concept, dental biomaterials, epidemiology and dental education, biomimetic restoration, finite element analysis and endodontic regeneration. Dr. Madfa has numerous international publications, full articles, two patents, a book and a book chapter. Furthermore, he won 14 international scientific awards. Furthermore, he is involved in many academic activities ranging from editorial board member, reviewer for many international journals and postgraduate students' supervisor. Besides, I deliver many courses and training workshops at various scientific events. Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\r\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\r\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Orthodontist, Assoc Prof in the Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. After graduating from TED Ankara College in 1986, she attended the Hacettepe University, Faculty of Dentistry in Ankara. \nIn 1993 she attended the Gazi University, Faculty of Dentistry, Department of Orthodontics for her PhD education. After finishing the PhD education, she worked as orthodontist in Ankara Dental Hospital under the Turkish Government, Ministry of Health and in a special Orthodontic Clinic till 2011. Between 2011 and 2016, Dr. Deniz Uzuner worked as a specialist in the Department of Orthodontics, Faculty of Dentistry, Gazi University in Ankara/Turkey. In 2016, she was appointed associate professor. Dr. Deniz Uzuner has authored 23 Journal Papers, 3 Book Chapters and has had 39 oral/poster presentations. She is a member of the Turkish Orthodontic Society. Her knowledge of English is at an advanced level.",institutionString:null,institution:null},{id:"332914",title:"Dr.",name:"Muhammad Saad",middleName:null,surname:"Shaikh",slug:"muhammad-saad-shaikh",fullName:"Muhammad Saad Shaikh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jinnah Sindh Medical University",country:{name:"Pakistan"}}},{id:"315775",title:"Dr.",name:"Feng",middleName:null,surname:"Luo",slug:"feng-luo",fullName:"Feng Luo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sichuan University",country:{name:"China"}}},{id:"344229",title:"Dr.",name:"Sankeshan",middleName:null,surname:"Padayachee",slug:"sankeshan-padayachee",fullName:"Sankeshan Padayachee",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"315727",title:"Ms.",name:"Kelebogile A.",middleName:null,surname:"Mothupi",slug:"kelebogile-a.-mothupi",fullName:"Kelebogile A. Mothupi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"423519",title:"Dr.",name:"Sizakele",middleName:null,surname:"Ngwenya",slug:"sizakele-ngwenya",fullName:"Sizakele Ngwenya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"337613",title:"Mrs.",name:"Tshakane",middleName:null,surname:"R.M.D. Ralephenya",slug:"tshakane-r.m.d.-ralephenya",fullName:"Tshakane R.M.D. Ralephenya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419270",title:"Dr.",name:"Ann",middleName:null,surname:"Chianchitlert",slug:"ann-chianchitlert",fullName:"Ann Chianchitlert",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419271",title:"Dr.",name:"Diane",middleName:null,surname:"Selvido",slug:"diane-selvido",fullName:"Diane Selvido",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419272",title:"Dr.",name:"Irin",middleName:null,surname:"Sirisoontorn",slug:"irin-sirisoontorn",fullName:"Irin Sirisoontorn",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}}]}},subseries:{item:{id:"2",type:"subseries",title:"Prosthodontics and Implant Dentistry",keywords:"Osseointegration, Hard Tissue, Peri-implant Soft Tissue, Restorative Materials, Prosthesis Design, Prosthesis, Patient Satisfaction, Rehabilitation",scope:"
\r\n\tThe success of dental implant treatment is not solely dependent on the osseointegration around the implant. Aside from the criteria used to describe the hard tissue response at the implant level, the success criteria in implant dentistry include three additional aspects: peri-implant soft tissue, prosthesis, and patient’s satisfaction.
\r\n
\r\n\tThe Prosthodontics and Implant Dentistry topic will provide readers with up-to-date resources on the prosthodontics factors such as aesthetics, restorative materials, the design of prosthesis, case selection, occlusion, oral rehabilitation, among others, all of which play an important role in determining the success of a well osseointegrated implant. With the help of digital dental technology, these can now be accomplished more predictably.
\r\n
\r\n\tThe end goal of prosthesis is always considered when planning successful implant placement. The readers in this field will be able to learn more about taking a holistic approach when treating their dental implant cases.
",coverUrl:"https://cdn.intechopen.com/series_topics/covers/2.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11398,editor:{id:"179568",title:"Associate Prof.",name:"Wen Lin",middleName:null,surname:"Chai",slug:"wen-lin-chai",fullName:"Wen Lin Chai",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRHGAQA4/Profile_Picture_2022-05-23T14:31:12.png",biography:"Professor Dr. Chai Wen Lin is currently a lecturer at the Department of Restorative Dentistry, Faculty of Dentistry of the University of Malaya. She obtained a Master of Dental Science in 2006 and a Ph.D. in 2011. Her Ph.D. research work on the soft tissue-implant interface at the University of Sheffield has yielded several important publications in the key implant journals. She was awarded an Excellent Exchange Award by the University of Sheffield which gave her the opportunity to work at the famous Faculty of Dentistry of the University of Gothenburg, Sweden, under the tutelage of Prof. Peter Thomsen. In 2016, she was appointed as a visiting scholar at UCLA, USA, with attachment in Hospital Dentistry, and involvement in research work related to zirconia implant. In 2016, her contribution to dentistry was recognized by the Royal College of Surgeon of Edinburgh with her being awarded a Fellowship in Dental Surgery. She has authored numerous papers published both in local and international journals. She was the Editor of the Malaysian Dental Journal for several years. Her main research interests are implant-soft tissue interface, zirconia implant, photofunctionalization, 3D-oral mucosal model and pulpal regeneration.",institutionString:null,institution:{name:"University of Malaya",institutionURL:null,country:{name:"Malaysia"}}},editorTwo:{id:"479686",title:"Dr.",name:"Ghee Seong",middleName:null,surname:"Lim",slug:"ghee-seong-lim",fullName:"Ghee Seong Lim",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003ScjLZQAZ/Profile_Picture_2022-06-08T14:17:06.png",biography:"Assoc. Prof Dr. Lim Ghee Seong graduated with a Bachelor of Dental Surgery from University of Malaya, Kuala Lumpur in 2008. He then pursued his Master in Clinical Dentistry, specializing in Restorative Dentistry at Newcastle University, Newcastle, UK, where he graduated with distinction. He has also been awarded the International Training Fellowship (Restorative Dentistry) from the Royal College of Surgeons. His passion for teaching then led him to join the faculty of dentistry at University Malaya and he has since became a valuable lecturer and clinical specialist in the Department of Restorative Dentistry. He is currently the removable prosthodontic undergraduate year 3 coordinator, head of the undergraduate module on occlusion and a member of the multidisciplinary team for the TMD clinic. He has previous membership in the British Society for Restorative Dentistry, the Malaysian Association of Aesthetic Dentistry and he is currently a lifetime member of the Malaysian Association for Prosthodontics. Currently, he is also the examiner for the Restorative Specialty Membership Examinations, Royal College of Surgeons, England. He has authored and co-authored handful of both local and international journal articles. His main interest is in prosthodontics, dental material, TMD and regenerative dentistry.",institutionString:null,institution:{name:"University of Malaya",institutionURL:null,country:{name:"Malaysia"}}},editorThree:null,series:{id:"3",title:"Dentistry",doi:"10.5772/intechopen.71199",issn:"2631-6218"},editorialBoard:null},onlineFirstChapters:{paginationCount:25,paginationItems:[{id:"82654",title:"Atraumatic Restorative Treatment: More than a Minimally Invasive Approach?",doi:"10.5772/intechopen.105623",signatures:"Manal A. 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Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},subseries:[{id:"7",title:"Bioinformatics and Medical Informatics",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine",scope:"Bioinformatics aims to help understand the functioning of the mechanisms of living organisms through the construction and use of quantitative tools. The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",annualVolume:11403,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",fullName:"Alexandros Tzallas",profilePictureURL:"https://mts.intechopen.com/storage/users/5886/images/system/5886.png",institutionString:"University of Ioannina, Greece & Imperial College London",institution:{name:"University of Ioannina",institutionURL:null,country:{name:"Greece"}}},{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",institutionString:"Shenzhen Technology University",institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"225387",title:"Prof.",name:"Reda R.",middleName:"R.",surname:"Gharieb",fullName:"Reda R. Gharieb",profilePictureURL:"https://mts.intechopen.com/storage/users/225387/images/system/225387.jpg",institutionString:"Assiut University",institution:{name:"Assiut University",institutionURL:null,country:{name:"Egypt"}}}]},{id:"8",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.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"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",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",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"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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Valarmathi",profilePictureURL:"https://mts.intechopen.com/storage/users/69697/images/system/69697.jpg",institutionString:"Religen Inc. | A Life Science Company, United States of America",institution:null},{id:"205081",title:"Dr.",name:"Marco",middleName:"Vinícius",surname:"Chaud",fullName:"Marco Chaud",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSDGeQAO/Profile_Picture_1622624307737",institutionString:null,institution:{name:"Universidade de Sorocaba",institutionURL:null,country:{name:"Brazil"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/213346",hash:"",query:{},params:{id:"213346"},fullPath:"/profiles/213346",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)}()