\r\n\tThe development of the interpersonal model and the Kleinian school in the second half of the last century allowed the emergence of an original understanding of the unconscious mind. Within the intersubjective paradigm, the psychoanalytic situation is conceptualized as an interpersonal field to which both the analyst and the patient contribute substantially. We have shown elsewhere how the failure to give a full account of such an intersubjective dimension in both psychoanalytic theory and practice amounts to a core liability in contemporary psychoanalytic discourse.
\r\n
\r\n\tThe present book will focus on a few areas where the insufficient development of our discipline is currently apparent: five wounds that mark the body of the psychoanalytic enterprise.
\r\n
\r\n\tNew contributions are particularly needed in the following areas: Current conceptualization of the unconscious mind is mechanistic and not suited to incorporate the full network of interpersonal exchanges which unfolds in the analytic room; Furthermore, the development of interpersonal psychoanalysis and the theory of the object relations warrants a greater appreciation of the impact of extratranference relations (e.g., couple, family, peers) on the patient's inner life both within and without the psychoanalytic situation.
\r\n
\r\n\tAn integration of theories and models from other psychological paradigms is clearly in order here; the book will also focus on Barangers’ theory of the bi-personal field that makes traditional unipersonal models of the psychoanalytic process untenable. Also, it will help in the understanding of the reciprocal interactions of the two partners in the psychoanalytic dyad in most psychoanalytic institutes the training format relies naively on models from the academic or the professional domains. This fosters rigidity, conformism, and a hierarchical organizational style in the institutional life; e) all over the long span of his creative life Freud showed consistent interest in the application of psychoanalysis to literature, the arts, religion, and politics. Contemporary psychoanalysis is getting more and shyer and is pressed at the margins of social and political debate. The psychoanalytic theory includes unique lore of knowledge about the conscious and unconscious mind. Without it, a comprehensive understanding of human reality will stay out of the reach of contemporary culture.
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1. Introduction
\n
In the last 20 years, the domestic dog has become one of the main animal models for the study of genetic disorders and congenital defects due to advances in genetics and genomics. The frequent occurrence of birth defects in dogs, with the cleft lip and palate being among the most common, is a byproduct of breeding practices. Since the mechanisms responsible for the morphogenesis of mammals are highly conserved and the genomic similarity between dogs and humans is high, in addition to sharing the same environment, spontaneous cases of cleft lip and palate in dogs are exceptionally useful for studies on the pathogenesis and genetics of oral clefts and the morphogenesis of the face [1–3].
\n
In this chapter, we present an overview of the medical and genetic aspects of cleft lip and palate in dogs, in the hope that it will be useful to veterinary clinicians, researchers, and other professionals interested in genetics and developmental biology.
\n
2. General considerations
\n
2.1. Considerations on homology
\n
It is easy even for a layperson to see that human anatomy and physiology have their equivalence throughout the zoological scale of vertebrates, especially when it comes to tetrapods. It is also not difficult to deduce that the mechanisms of development are similar or even identical, especially when we compare eutherian mammals. However, when we think of genes, genotypes, and their mechanisms of action, there is a tendency to conclude that everything is quite different. Nevertheless, in reality, “our genome” is not as exclusively ours as we generally imagine. Dogs and mice share over 90% of our genes [4], enabling us to suppose that genetic programs that control embryonic development are similar in the three species. Genes with a common evolutionary origin, maintaining the same function in different species, are known as orthologs (Figure 1). They are clear evidence that the homology of structures among species also have a molecular base. For instance, the ADAMTS20 gene is one of the necessary genes for the normal palatogenesis of mice, to the extent that homozygous individuals for a mutation with loss of function have a palatal cleft [5]. Recently, a recessive mutation in the canine ortholog was identified in dogs with a cleft palate [6].
\n
Figure 1.
Shared genome. Examples of orthologs with the respective chromosomal assignment in the dog (CFA) and man (HSA). In two of them (ADAMTS20 and DLX6), mutations are known that cause cleft lip and palate in a breed of dogs, while in the other three, mutations are known that have been associated with cleft lip and palate in humans.
Knowledge of the developmental biology and genetics of one species helps us to understand those of another. Much has been learned regarding craniofacial morphogenesis by studying chickens and mice [7–9]. The dog, which has contributed so much to the development of surgical techniques used today to correct oral defects, can also help to expand our knowledge of the pathogenesis and genetics of orofacial defects.
\n
2.2. Considerations on the morphogenesis of the lip and palate
\n
Orofacial development is a sequence of events in space and time that involve cellular multiplication, migration and differentiation, tissue fusion, and apoptosis and are dependent on the action of various signaling molecules and transcription factors [10].
\n
The primitive mouth is called the stomodeum. It emerges as a slight depression on the ectodermal surface, delimited by mesenchymal structures where cells from the neural crest proliferate. Although these cells are ectodermal in origin, they settle and integrate with the mesenchyme of the head of the embryo. They are fundamental to the development of the craniofacial structures. Five structures surround the stomodeum: frontonasal prominence, from which the primary palate will originate; right and left maxillary prominences, from which the secondary palate will originate; and right and left mandibular prominences, from which the mandible will originate (Figure 2). The maxillary and mandibular prominences are derived from the first branchial arch [10, 11].
Figure 2.
Palatogenesis. Semischematic drawing representing the formation of the primary and secondary palate in dogs.
\n
2.2.1. Formation of the primary palate
\n
The primary palate is the primordium of the hard palate (incisive bone) rostrally located at the incisive fissures (incisive foramen in humans). During development, the frontonasal prominence forms a pair of lateral and medial nasal processes. The fusion of the lateral and medial parts of each process delimits the nasal cavities that are forming. The medial processes are then lengthened and projected between the maxillary prominences, are fused with them, and transformed into the primary palate and medial part of the upper lip [11].
\n
2.2.2. Formation of the secondary palate
\n
The secondary palate is the primordium of the palate caudally located at the incisive fissures (hard palate and soft palate, so-called because its formation is completed after the formation of the primary palate). Initially, the maxillary prominences are projected vertically by the sides of the tongue, and are then raised and projected horizontally on the tongue until they meet. A fusion then occurs between the two in the medial line forming a continuous epithelial seam, which will subsequently disappear. Rostrally, the secondary palate is also fused with the primary palate and, dorsally, with the projection (nasal septum) formed by the united medial nasal processes. The maxillary prominences also form the lateral parts of the upper lip [11].
\n
At approximately 23 days of gestation, in the canine embryo it is possible to see the frontonasal, maxillary, and mandibular prominences. At approximately 28 days, the first ossification of the maxilla and mandible occurs [12].
\n
3. Medical aspects
\n
3.1. Frequency
\n
A cleft lip and/or palate can affect purebred dogs or mongrels. Any canine breed can be affected, especially if we consider cleft lip and palate caused by environmental teratogens. However, the relatively frequent occurrence in some breeds indicates a strong contribution of genetic factors [13].
\n
Indeed, certain breeds of dog are more likely to have cleft lip and palate, especially brachycephalic dogs [14]. At least, this is the clear impression of numerous veterinary practitioners who work with small animals worldwide. Unfortunately, no statistics are yet available that enable definitive statement regarding frequency in different breeds, nor in canine species as a whole.
\n
In boxers, a frequency of 0.6% has been recorded, while in beagles has been 0.11%, and in Pyrenees shepherd dogs, 2.2%. In Portuguese water dogs, cleft palate has been reported in 2.3% of litters [15–18].
\n
In some cases, the high frequency observed at veterinary clinics in certain breeds may be due to the popularity of those breeds at a given time. It is also possible that the frequency is high in certain lines due to constant inbreeding, but not high in the breed as a whole. In a lineage of old Spanish pointer dogs a frequency of 15–20% was found [19].
\n
Table 1 shows the breeds that are considered as having a predisposition to oral clefts or for which cases have been registered.
Successful communication between professionals (veterinary practitioners, geneticists, surgeons, dentists, etc.) who treat patients with CL/P depends on an appropriate and correct registration of these abnormalities adhering to common criteria by everyone involved. Thus, the adoption of a classification is highly important. Furthermore, a consistent register based on a classification helps to establish the cause, planned treatment, prognosis, and studies of comparative anatomy [24].
\n
The different classifications used in human medicine can be adapted for use with dogs, as has been done by some researchers based on the first classifications of human oral clefts [24, 25]. Many of the classifications of human clefts are modifications of the classification of Kernahan and Stark [26], which will be adopted here for the purposes of this chapter. It is based on the morphology and pattern of embryonic development of mammals. The clefts are clustered into three groups, each with three subgroups, with all of them considering the degree of impairment of the structures as total or partial (Figures 3 and 4):
Figure 3.
Types of cleft. In each group, complete unilateral or bilateral clefts are shown. However, a cleft from Group I can be left- or right-sided and affect only the lip, the lip and the alveolar process, or include the entire extension of the primary palate, as shown in the illustration. Likewise, a cleft from Group II may affect only the soft palate or the soft palate and the hard palate.
Figure 4.
Dogs with nonsyndromic (A–C) and syndromic (D) clefts. (A) Left-sided unilateral cleft, affecting the upper lip, alveolar process, and incisive bone (primary palate); (B) cleft palate only; (C) bilateral cleft (upper lip, hard palate, and soft palate); (D) anophthtalmia and CLP. Photographs (A–C) reprinted from Moura and Pimpão [35].
\n
Group I. Primary cleft palate (total or partial impairment)
\n
1 – unilateral left or right; 2 – medial; 3 – bilateral
\n
Group II. Secondary cleft palate only
\n
1 – total; 2 – partial; 3 – submucous
\n
Group III. Primary and secondary palate (total or partial impairment)
\n
1 – unilateral left or right; 2 – medial; 3 – bilateral
\n
The criteria for defining a cleft as partial (incomplete) or total (complete) is subjective. Thus, with broader objectives, especially for epidemiological studies and minute comparison with human clefts, we suggest using the numerical system adapted by Schwartz et al. [27] from the striped Y of Kernahan [28], known as the RPL system, or one of the others that are available.
\n
3.3. Etiology
\n
Cleft lip and/or palate (CL/P) in dogs, as in humans, are etiologically heterogeneous, and can be caused by genetic factors, environmental factors, or a combination of these two groups of factors [29, 30].
\n
Mutations in different genes, both in murine models and human beings, have been associated with CL/P [29]. As these genes have the respective homologs that are also present in the canine genome, the same situation is expected to occur in dogs (see Section 4).
\n
The environment of an embryo is represented by the amniotic sac, uterus, maternal body, and the place where the mother lives. Thus, the potentially negative influences of this environment include amniotic abnormalities, uterine abnormalities, maternal metabolic disease, viruses, chemical substances swallowed by or administered to the mother, and maternal exposure to chemical or physical environmental pollutants [31]. Few studies of dogs associate a given environmental factor to oral clefts. Furthermore, these studies focus on substances administered to the mother of the affected dogs during gestation, such as 6-diazo-5-oxo-l-norleucine, aspirin, and vitamin A [32–34]. However, it should be remembered that in the case of aspirin and vitamin A, excessive doses were used, much higher than therapeutic doses. Based on the data obtained in other species (mice, rats, cats, goats, etc.), or personal impressions, it has been suggested that maternal exposure to various substances such as hydroxyurea, griseofulvin, anabasine, metronidazole, primidone, sulphonamides, and corticosteroids can cause oral clefts in dogs [30]. Indeed, as the morphogenic processes are highly conserved [35], the same causes of oral dysmorphogenesis known in man can also be found in other species of mammals, including dogs, and vice versa (Table 2).
Presumed or confirmed risk factors that have been associated with CL/P in humans.
Obs.: Not all the risk factors presented in this table are definitely associated with CL/P, and further studies are required. Several factors (amoxicillin, corticosteroids, maternal obesity, stress, etc.) have not shown a consistent association and there are discrepancies between the studies.
The interaction between genetic and environmental factors is a known underlying phenomenon of the development of certain phenotypes [38]. Evidence has already been found in humans, linking certain genetic markers to CL/P. For example, maternal smoking in combination with the variants of the GSTT1 and IRF6 genes increases the risk of clefts [29]. It should be remembered once again that dogs and humans have high genomic homology and share the same environment [1]. Therefore, similar or even identical interactions may occur.
\n
3.4. Pathogenesis
\n
Due to its etiology, a cleft lip or palate may be the result of an originally abnormal development process or negative interference in a normal development process, corresponding to the concepts of malformation and disruption, respectively, used in dysmorphology [35].
\n
The heterogeneous etiology, in cases of malformation and disruption, assumes varied mechanisms in the development of CL/P. While some mechanisms impair the morphogenesis of various structures in addition to the palate, resulting in syndromic clefts, others act only in the palatogenesis, resulting in nonsyndromic clefts [29, 35].
\n
Developmental field (or morphogenic field) theory aids understanding because different factors can cause the same type of defect. In the early stages, the whole embryo represents a developmental field (primary field). Later, a developmental field is a region or part of the body of the embryo which responds as a coordinated unit to embryonic induction and gives rise to multiple or complex anatomic structures [39, 40]. The induction depends on influences, both physical and chemical, that one developing tissue has on another (or others) in embryogenesis [39]. Developmental fields are systems that control the progressive differentiation of the structure and size, in addition to the temporal and spatial distribution of complex organ components [40]. During blastogenesis, the interactions of the primary field (embryo) generate the progenitor fields (primordia of the final structures) that, in turn, create the secondary fields that produce the final structures during organogenesis [41].
\n
Defects in a structure or in part of the body result from disturbances in one or more secondary fields and are known as monotopic field defects, such as nonsyndromic oral clefts. Multiple defects are the result of disturbances in the primary field or progenitor fields, as occurs in individuals with various defects, including CL/P (syndromic clefts). Correlated defects that emerge early during blastogenesis and affecting structures in different parts of the body are polytopic field defects [41].
\n
At any time during embryogenesis, disturbances in the developmental fields can reflect negatively on fusion mechanisms between the lateral and medial nasal processes, and the medial nasal processes with the maxillary processes (Group I clefts); and/or the mechanisms of development, elevation, and fusion of the palatal shelves and the disappearance of the midline epithelial seam (clefts in Groups II and III).
\n
3.5. Patient evaluation
\n
The diagnosis is conducted by visual inspection of the entire extension of the oral cavity, from the premaxilla (incisive bone) to the soft palate. Without this precaution, smaller clefts may go undetected, especially those that affect the soft palate only.
\n
Cleft lip is evident, however, it indicates the need for a thorough and detailed examination of the oral cavity of the patient and the entire organism in search of other congenital abnormalities to determine whether the cleft is an isolated (nonsyndromic) defect or part of a larger (syndromic) condition.
\n
In newborns, difficulty in nursing, nasal reflux of milk, and fault in development are frequent clinical signs. In older patients, in addition to delayed development, choking, coughing, and sneezing during feeding are common. Nasal discharge is also frequent, but the existence of one or more clinical signs and their intensity depends on the location and gravity of the cleft. It is important to be attentive to clinical manifestation resulting from complications, especially signs of pneumonia, a condition that requires immediate treatment.
\n
Detailed record of the oral cleft is essential for adequate planning of treatment, evaluation of postsurgery progress, and studies with different purposes.
\n
Evaluation of the general condition of the patient may include routine laboratory tests and X-rays. Computerized tomography may be useful for planning surgical treatment [3]. The simultaneous existence of oral cleft and other congenital defects justifies a karyotype test.
\n
Irrespective of the existence of obvious abnormalities or clinical signs, inspection of the oral cavity should be part of the physical examination of all newborns.
\n
3.6. Complications
\n
Cleft lip in general means no complications or complications limited to suction problems. However, clefts that affect the incisive bone and, above all, those that affect the secondary palate cause problems of feeding, breathing, and malocclusion. They cause rhinitis, rhinosinusitis, and occasionally otitis media [42, 43]. They can also cause aspiration pneumonia with risk of death. Malnutrition, dehydration, and accumulation of food in the cleft are commonplace.
\n
Unlike in humans and for obvious reasons, difficulty in emitting sounds is not important in dogs and speech defects do not exist.
\n
3.7. Treatment
\n
Cleft lip and palate require corrective surgery to enable adequate function and for esthetic reasons. However, the decision to undergo surgery falls to the owner of the dog. Although many opt for euthanasia, every day, people seek veterinary clinics to inquire about treatment for a dog born with a CL/P.
\n
If the owner opts for treatment, it is necessary for him to be fully aware of the intensive work involved before the patient is old enough for surgery. It is also important to give the owner careful guidelines regarding feeding and cleaning procedures for his dog. He should also be warned of the need to be constantly on the lookout for possible complications. Clefts that affect only the lip or the lip and the alveolar process require little of the owner, but the more extensive clefts may require a lot of dedication.
\n
An efficient and minimally invasive technique for feeding dogs with a cleft palate was described by Martínez-Sanz et al. [19] using baby bottle nipples and customized palatal prostheses made of dental thermoplastic plates. During the breastfeeding period, dogs were fed with a commercial maternal milk substitute using a baby bottle with a customized nipple. After weaning, which occurred during the fifth week of life, palatal prostheses were made every week in keeping with the development of the dogs. The palatal prosthesis was kept in the mouth during the day and removed at night. The technique did not impede oral development and the materials used are easily obtained from dental suppliers. The cost is relatively low and accessible to most veterinary clinics [19].
\n
In cases of severe clefts, it is necessary for the newborn to be fed through a stomach tube to ensure its height and weight development and good nourishment. It may even be necessary to create an esophageal or gastric stoma for feeding and hospitalize the patient [30]. These procedures can be found in several textbooks of veterinary hospital techniques.
\n
In any situation, the owner must be duly trained to deal with the patient’s condition and clean the oral cavity adequately after feeding. Alternatively, the owner should take the dog to a veterinary clinic every day for adequate care. A collaborative, patient, and well-informed owner is essential for dogs with cleft lip and palate to develop and be ready for a surgical procedure.
\n
The age that most surgeons consider appropriate for the first corrective procedure is between 4 and 6 months, i.e., it is advisable to await permanent dentition eruption. Before this time, dental development may be harmed. It is also important to consider that oral clefts tend to diminish with growth and become stable at around 6 months [30, 44, 45].
\n
The surgery should be carefully planned and all preoperative care should be taken, including stabilization of the nutritional status and the solution of any complications that may arise. Rhinitis or rhinosinusitis should be treated with antibiotics and secretolytic agents. The same medication is used to treat aspiration pneumonia together with oxygen, bronchodilators, and, in some cases, corticosteroids [30].
\n
Several techniques are available to correct cleft lip and cleft palate, ranging from those that use a mucosal flap or mucoperiosteal flap to autologous bone grafts and prostheses in the case of larger clefts. There are also promising procedures that use mesenchymal stem cells of the iliac bone with hydroxyapatite particles [44, 46–49]. When the correction is done in stages, the functional rehabilitation and esthetic results are better [50]. Although the main purpose is the rehabilitation of the patient, veterinary procedures in plastic surgery and dentistry are now available and would provide a really good esthetic effect in a final step.
\n
Like all surgery, postoperative care is essential for success. Thus, supportive measures and the administration of antibiotics, analgesics, and antiinflammatory medicine should be followed strictly. Care should also be taken regarding the patient’s feeding and hygiene.
\n
3.8. Prevention
\n
The prevention of oral clefts in dogs follows the same principles as prevention in humans. In other words, educating people regarding the risk factors and genetic counseling, with appropriate adaptations.
\n
Pregnant dogs should be given a balanced diet and their health should be monitored. They should also be protected from viral agents. The environment where they live should be free of chemical products. Breeders and owners should be warned of the risk to the embryo/fetus from the administration of certain medicines. Before prescribing medicine, veterinary practitioners should check the teratogenic potential of the drug.
\n
In humans, advanced parental age is linked to an increased probability of oral clefts in offspring [51]. However, in dogs, there are not studies on this aspect. Assuming that this is the case with dogs, a preventive measure is to use good sense and avoid crossing very young animals or much older ones.
\n
As in human medicine, in veterinary medicine, mineral and vitamin supplements have been recommended, especially folic acid and vitamins B6 and B12 [52, 53]. However, the results are not definitive and there have been discrepancies between studies [29, 54].
\n
A daily supplement of 5 mg of folic acid in pregnant French bulldogs, beginning on the 15th day and ending on the last day of pregnancy, reduced the frequency of cleft palate by 48.54% in a research period of 18 months [53]. In Boston terriers, a reduction of 76% was observed [52]. In pugs and Chihuahuas, there were reductions of 60 and 66.67%, respectively. A supplement of 5 mg/day was given to pugs and 2.5 mg/day to Chihuahuas from the beginning of estrus to the 40th day of gestation [55].
\n
Considerations on genetic counseling will be given later in Section 4.3.
\n
4. Genetic aspects
\n
The genetic basis of cleft lip and palate is extremely complex due to the potential number of genes involved, their behavior (mode of inheritance, gene interaction, penetrance, expressivity, etc.), number of alleles in each gene, independent segregation (two or more genes), epistasis, and gene linkage, in addition to environmental factors that might cause phenocopies. This complexity, added to the difficulties of maintaining and handling the affected animals, has severely limited clinical and genetic studies of orofacial clefts in dogs. Consequently, few are available and these will be summarized as follows.
\n
4.1. Syndromic and nonsyndromic clefts
\n
Canine oral clefts may be isolated abnormalities, affecting the lip, lip and palate, or only the palate. They may also coexist with abnormalities in other areas of the body. The former are nonsyndromic clefts and the latter are syndromic clefts. The term “syndromic,” as used here, is well established and corresponds to a syndrome in a general sense, i.e., a set of abnormalities that occur jointly, but does not necessarily correspond to the concept used in clinical genetics, in which a set of abnormalities can indeed be a syndrome, but also an association or sequence [39].
\n
In dogs, there are no conclusive data on the frequency of each of these two groups. However, the clear perception of veterinary practitioners is that the nonsyndromic forms are far more common than the syndromic. In humans, approximately 70% of cleft lip and palate are isolated abnormalities, while 30% are part of multiple abnormalities due to chromosome aberrations, monogenic inheritance, teratogens, or unknown causes [56].
\n
In veterinary clinics, the common procedure for dogs with multiple abnormalities is immediate euthanasia. This is often performed by the owners or breeders, with no records or study. Consequently, little is known about the syndromic forms of cleft lip and palate.
\n
4.1.1. Syndromic clefts
\n
We have seen bilateral anophthalmia and cleft lip and palate in mongrels, omphalocele, and cleft palate in Siberian huskies, and anencephaly and cleft palate in Yorkshire terriers, to name three examples. Most of the few reports available have to do with cases in which it was not possible to identify a cause. However, in four cases, a hereditary pattern was established or presumed and, in two cases, the mutation that was responsible was identified [6, 57–59].
\n
In 2015, Wolf et al. [6] studied 13 cases of CL/P with a phenotypic spectrum ranging from bilateral cleft in the nasal wings to complete CLP in Nova Scotia duck tolling retrievers. Furthermore, 10 of the affected animals had syndactyly in the third and fourth toes, varying from incomplete in only one paw to complete in all four paws. As for the other three dogs, whether they had syndactyly was not known. These abnormalities were the result of autosomal recessive inheritance and were a syndromic form of CL/P with variable expressivity. A mutation in the ADAMTS20 gene was associated with this phenotype. In 2014, Wolf et al. [57] had already identified another mutation in the same breed: an insertion of a LINE-1 in the DLX6 gene, causing CP and brachygnathia with a pattern of autosomal recessive inheritance. More details on these mutations are given in the section on molecular aspects.
\n
In 1998, Villagómez and Alonso [58] described four individuals from a litter of six Saint Bernard dogs, the offspring of normal parents. They had a cleft palate, bilateral anotia, supernumerary vertebrae and ribs, bifid tongue, and bilateral pedal preaxial polydactyly. In two of these dogs, there was also a cleft lip and one did not have polydactyly. The parents, in four previous gestations, had 28 offspring, 22 of which were normal and 6 had the same clinical phenotype as the four affected individuals. As the parents were normal and had affected male and female offspring, the authors of this report concluded that the abnormalities could be a recessive mutation of an autosomal gene, although the action of teratogens could not be discarded.
\n
In 1985, Sponenberg and Bowling [59] studied a family of Australian shepherds in which there was a syndrome lethal only to the males. The affected animals had a cleft palate and multiple skeletal defects (scoliosis, brachygnathia, short tibia and fibula, polydactyly, syndactyly). In the females, the defects were less severe and there was no cleft palate. The authors of this report raised the hypothesis of X-linked inheritance.
\n
There are also brief reports of omphalocele and bilateral cleft of primary palate in Yorkshire terriers [23], cleft lip and unilateral left-sided anophthalmia in a French bulldog [60], and bilateral cleft of the primary palate, anencephaly, and macroglossia in a dog of unspecified breed [61].
\n
4.1.2. Nonsyndromic clefts
\n
Most genetic nonsyndromic clefts occur in families in accordance with the multifactorial inheritance model. However, there are cases in which a Mendelian pattern of inheritance has been documented.
\n
Monogenic inheritance. Monogenic inheritance is one that depends on a single gene and the type that has so far been confirmed in dogs is autosomal recessive. In other words, the phenotype only manifests if the individual has two copies of the mutant allele. Like all monogenic inheritance, it has a characteristic pattern as follows and is shown in Figure 5 [62]:
Figure 5.
Autosomal recessive inheritance. Consanguineous unions increase the probability that both individuals are heterozygotes, such as couple III-3 X III-4. The risk of recurrence in the offspring of this couple is 25%. The likelihood of having more heterozygous descendants is 2/4 (50%). However, for any one of the normal descendants (male or female) that have already been born, the likelihood is 2/3 (67%).
\n
The phenotype occurs approximately with the same frequency in males and females;
The parents of an affected individual are generally heterozygotes (Aa × Aa) and thus phenotypically normal; although there is the possibility of an affected individual having one or both parents affected, such situations are improbable;
The phenotype tends to skip generations;
The risk of recurrence in descendants of the parents of an affected individual is 25%;
There is a 50% chance of the parents of an affected having heterozygous descendants like them;
Normal siblings of an affected individual have a chance of approximately 67% of being heterozygotes; and
Consanguineous unions increase the chance of the phenotype occurring.
\n
This pattern of inheritance was registered in cases of nonsyndromic CL/P in dogs of the Brittany spaniel, Pyrenees shepherd, and boxer breeds.
\n
In Brittany spaniels, Richtsmeier et al. [63] studied dogs belonging to an intensely inbred colony. In 12 litters, 52 individuals were born, 14 of which had a cleft palate (CP). One of them also had a cleft lip (CL). In 10 of these 12 litters, the number of males and females was registered (15 males and 29 females). Of those affected (11), there were more females than males (9 females and 2 males). In all crossings, the parents were normal.
\n
In Pyrenees shepherd dogs, Kemp et al. [17] analyzed the records of a club for this breed over a 20-year period (1984–2004), corresponding to a population of 2104 dogs. They found 47 cases (24 males and 23 females) born in 37 litters with a total of 163 pups and normal parents. Some were only affected by a CP, while others had a cleft lip with or without a cleft palate (CL ± P).
\n
In boxers, Moura et al. [64] found four affected dogs (two males and two females) in two litters with 11 pups born of a consanguineous union (uncle and niece) between normal individuals. All the dogs had essentially the same phenotype (bilateral CLP). Previously, Turba and Willer [15] had raised the hypothesis that in this breed, CLP had a monogenic autosomal recessive pattern of inheritance.
\n
Bleicher et al. [65] reported a case of cleft palate in a beagle together with its pedigree, which is suggestive of autosomal recessive inheritance. There were five affected individuals of both sexes and, in all crossings, the parents were normal.
\n
An older report on cleft palate is suggestive of autosomal recessive inheritance in bulldogs. It presents 33 pups (24 normal and nine affected) born in six litters of a supposedly heterozygous couple [66].
\n
Regarding autosomal dominant inheritance, two reports have described possible cases in which there was nasal cleft, cleft lip, and cleft palate, occurring separately or in association in Bernese mountain dogs (Bernese sennenhund). An affected male that crossed with a normal female and then with a female German shepherd fathered 26 pups, 11 of which were affected [67, 68]. An abnormality with some similarity was also observed in a Portuguese pointer [69]. However, no further data were published to confirm the mode of inheritance in these dogs.
\n
It should be remembered that, in principle, clefts with different patterns of inheritance could be present in the same lineage, which would hinder the interpretation of the gene segregation mechanism.
\n
Multifactorial inheritance. Nonsyndromic clefts are normally distributed in families without following any monogenic pattern of inheritance, but recurrence in generations is undeniable evidence of a genetic basis. The theoretical model that explains this inheritance assumes the contribution of several genes (polygenic inheritance) with an additive effect. The presence of a determined number of liability alleles would create a critical threshold and different degrees of expression of the phenotype, which can also depend on the influence of environmental factors. For instance, if we represent four genes, segregating independently and with the liability alleles identified by the number 2, and that from five number 2 alleles the critical threshold emerges, then several genotypes would be possible (A1A2 B1B2 C1C2 D2D2; A2A2 B1B2 C2C2 D1D2; A1A2 B2B2 C2C2 D2D2;A1A1 B2B2 C2C2 D1D2; etc.). Thus, with any combination of five number 2 alleles, the cleft would occur, and the higher the quantity of these alleles, the more serious it would be, with environmental factors also contributing to this. Figure 6 illustrates this example. There may also be a principal gene that would have a greater effect than the others. In real situations, the number involved is probably much higher than four genes.
Figure 6.
Polygenic inheritance. In this hypothetical pedigree, the individual who inherited at least five number 2 alleles shows the clinical phenotype.
\n
When canine families with high degrees of consanguinity are considered, the critical threshold is more frequent than in families with less or no inbreeding (Figure 7). Likewise, the artificial selection process that formed certain breeds led to an increased frequency of liability alleles, making the critical threshold closer than in other breeds and, consequently, leading to a higher frequency of CL/P. As stated previously, there may be a principal gene that increases the risk, as occurs in brachycephalic breeds [70].
Figure 7.
Distribution of genotypes in polygenic inheritance. Comparison of the threshold between the general population and consanguineous relatives or inbred lines.
\n
4.2. Molecular aspects
\n
Modern molecular biology techniques and the use of murine models have enabled the identification of many genes that may be associated with CL/P, and, with each new study, the number of candidate genes grows. The evidence suggests that mutations in these genes, in addition to environmental factors, can act alone or interact with several signaling pathways, negatively interfering in the development of the lip and palate [10]. These genes, and the complex signaling pathways with which they interact, are generally highly conserved in vertebrates and therefore a high degree of homology between man and dog is expected. The identification of mutations in canine genes opens up possibilities for identifying human genes and vice versa, as has happened with the discovery of mutations in mice genes [71]. Table 3 shows several examples of candidate genes related to CL/P in humans and, potentially, in dogs.
Gene (abbrev.)
Gene name
Chromosomal assignment (human)
Chromosomal assignment (dog)
IRF6
Interferon regulatory factor 6
1
7
VAX1
Ventral anterior homeobox 1
10
28
BMP4
Bone morphogenetic protein 4
14
8
FGFR2
Fibroblast growth factor receptor 2
10
28
FOXE1
Forkhead box E1
9
11
MAFB
MAF bZIP transcription factor B
20
24
MSX1
msh homeobox 1
4
3
CRISPLD2
Cysteine rich secretory protein LCCL domain containing 2
16
5
FGF8
Fibroblast growth factor 8
10
28
GSTT1
Glutathione S-transferase theta-1-like
22
26
MTHFR
Methylenetetrahydrofolate reductase (NAD(P)H)
1
2
PDGFC
Platelet derived growth factor C
4
15
PVRL1
Poliovirus receptor-related 1 (herpesvirus entry mediator C)
11
5
SUMO1
Small ubiquitin-like modifier 1
2
37
TGFA
Transforming growth factor alpha
2
10
TGFB3
Transforming growth factor beta 3
14
8
Table 3.
Examples of genes (human and dog orthologs) that have been associated with CL/P in humans.
Recently, in Nova Scotia duck tolling retrievers (NSDTR) with a cleft palate and other abnormalities, mutations have been identified in two genes: DLX6, located in chromosome 14 of the dog (CFA 14), and ADAMTS20, located in chromosome 27 (CFA 27).
\n
In the DLX6 gene, a LINE-1 insertion was found in the intron 2 jointly segregating with the phenotype (CP and brachygnathia) and obeying an autosomal recessive pattern of inheritance. The presence of the LINE-1 insertion disrupts the transcription of the DLX6 gene in such a way that only 25% of the normal levels of expression occur, which is not sufficient to prevent CP and mandibular abnormalities. It is located in a noncoding region that is highly conserved, disturbing a binding domain for SUZ12, a molecule that plays a significant regulatory role in the development of the embryo [57]. Dlx genes form an important family for the development of the first branchial arch, regulating genetic programs that direct the formation of the pattern of the maxilla and mandible [72]. The inactivation of Dlx5 and Dlx6 in mice causes serious defects in the craniofacial, axial, and appendicular skeleton, leading to perinatal death [73].
\n
In the ADAMTS20 gene, a deletion of two nucleotides (AA) was found, segregating together with the phenotype (CL/P and syndactyly) and adhering to an autosomal recessive pattern of inheritance. This deletion represents a frameshift mutation in the metalloprotease domain and should cause the truncation of 1461 amino acids of a protein of 1916 amino acids [6]. The ADAMTS20 gene is a member of a gene family that encode zinc-dependent proteases. In mouse embryos, its expression is detected in the first branchial arch and between the medial nasal processes [74]. In the palatal mesenchyme, it directs the formation and extension of the palatal shelves [5].
\n
In parallel with the study on NSDTR dogs, Wolf et al. [6] conducted a family-based genome-wide association analysis in a population of native Guatemalans. They identified a significant association between cases of CL/P and the ADAMTS20 gene, lengthening the list of candidate genes for the etiology of oral clefts in humans.
\n
4.3. Genetic counseling
\n
Like any genetic abnormality, the main recommendation in cases of CLP in dogs is that affected individuals should not be crossed, nor should normal couples with affected descendants ever be crossed again. As the majority of oral clefts in dogs appear to be multifactorial or recessive, it should be noted that owners of normal dogs who have had affected offspring are not always willing to follow this recommendation, especially when the dogs have characteristics of their breed that are highly valued. Therefore, if the owners/breeders decide to cross them again, and are sure that the cleft lip or palate is genetic in nature, the risk of recurrence should be seriously taken into consideration [35].
\n
To avoid autosomal recessive clefts, an important strategy is never to cross individuals that are known to be heterozygotes one with another, such as those that have already had affected offspring. When there is a family history of recessive cleft and the zygosity of an individual is not known, consanguineous unions should be avoided. For X-linked recessive phenotypes, normal female offspring of affected father are all carriers, i.e., heterozygotes, and should not be crossed even when the males are normal. For multifactorial clefts, the main strategy is to avoid crossing dogs that have any relationship. This will reduce the probability of reaching the critical threshold [35].
\n
5. Final considerations
\n
Always bearing in mind that greater knowledge results in a correct diagnosis, suitable management of each case, and definition of criteria that give consistency to guidelines for prevention of CLP, the first step to expand knowledge is appropriate details when publishing new canine cases, using one of the classifications established in human medicine. This will facilitate international communication between professionals from the different fields in question.
\n
Breeds, lineages, or families of dogs in which CLP occurs more frequently are a valuable source of information on the molecular biology and genetics of oral clefts. Genome-wide association studies (GWAS) with genotyping using arrays based on single nucleotide polymorphisms (SNP) are powerful means for mapping of regions of interest. The current technologies of next-generation sequencing (NGS), with increasingly robust platforms and increasingly expanded panels, facilitate the identification of candidate genes, allowing studies that confirm the role of these genes in the etiology of oral clefts.
\n
It should also be remembered that a chromosomal analysis in syndromic cases should be routine. Analyses with fluorescence in situ hybridization (FISH) and comparative genomic hybridization (GCH) may identify chromosomal aberrations and describe new syndromes, as well as establishing a correlation with human syndromes.
\n
An interface of knowledge on human and canine species opens up new paths in both veterinary and human medicine. This promotes quality and more humane and competent clinical practice. It is also clearly reflected in the fields of genetics, developmental biology, and evolutionary biology.
\n',keywords:"dog, cleft lip, cleft palate, cleft lip and palate, oral clefts, genetics",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/53715.pdf",chapterXML:"https://mts.intechopen.com/source/xml/53715.xml",downloadPdfUrl:"/chapter/pdf-download/53715",previewPdfUrl:"/chapter/pdf-preview/53715",totalDownloads:7372,totalViews:1773,totalCrossrefCites:4,totalDimensionsCites:7,totalAltmetricsMentions:2,impactScore:5,impactScorePercentile:93,impactScoreQuartile:4,hasAltmetrics:1,dateSubmitted:"April 9th 2016",dateReviewed:"November 24th 2016",datePrePublished:null,datePublished:"March 22nd 2017",dateFinished:"December 31st 2016",readingETA:"0",abstract:"The same types of cleft lip and/or cleft palate (CL/P) that affects humans also naturally affect dogs. Therefore, the dog has become an important spontaneous animal model for the study of human oral clefts. In order to provide an overview of CL/P in dogs to people with an interest in this area, we present in this chapter the main medical aspects, ranging from the etiology to the prevention, and also the main genetic aspects, including inheritance mechanisms and highlighting the homology between the two species, and the most recent molecular findings.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/53715",risUrl:"/chapter/ris/53715",book:{id:"5428",slug:"designing-strategies-for-cleft-lip-and-palate-care"},signatures:"Enio Moura and Cláudia Turra Pimpão",authors:[{id:"91097",title:"Prof.",name:"Enio",middleName:null,surname:"Moura",fullName:"Enio Moura",slug:"enio-moura",email:"enio.moura@pucpr.br",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/91097/images/3044_n.jpg",institution:{name:"Pontifícia Universidade Católica do Paraná",institutionURL:null,country:{name:"Brazil"}}},{id:"194711",title:"Dr.",name:"Cláudia",middleName:null,surname:"Pimpão",fullName:"Cláudia Pimpão",slug:"claudia-pimpao",email:"claudia.pimpao@pucpr.br",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. General considerations",level:"1"},{id:"sec_2_2",title:"2.1. Considerations on homology",level:"2"},{id:"sec_3_2",title:"2.2. Considerations on the morphogenesis of the lip and palate",level:"2"},{id:"sec_3_3",title:"2.2.1. Formation of the primary palate",level:"3"},{id:"sec_4_3",title:"2.2.2. Formation of the secondary palate",level:"3"},{id:"sec_7",title:"3. Medical aspects",level:"1"},{id:"sec_7_2",title:"3.1. Frequency",level:"2"},{id:"sec_8_2",title:"3.2. Classification",level:"2"},{id:"sec_9_2",title:"3.3. Etiology",level:"2"},{id:"sec_10_2",title:"3.4. Pathogenesis",level:"2"},{id:"sec_11_2",title:"3.5. Patient evaluation",level:"2"},{id:"sec_12_2",title:"3.6. Complications",level:"2"},{id:"sec_13_2",title:"3.7. Treatment",level:"2"},{id:"sec_14_2",title:"3.8. Prevention",level:"2"},{id:"sec_16",title:"4. Genetic aspects",level:"1"},{id:"sec_16_2",title:"4.1. Syndromic and nonsyndromic clefts",level:"2"},{id:"sec_16_3",title:"4.1.1. Syndromic clefts",level:"3"},{id:"sec_17_3",title:"4.1.2. Nonsyndromic clefts",level:"3"},{id:"sec_19_2",title:"4.2. Molecular aspects",level:"2"},{id:"sec_20_2",title:"4.3. Genetic counseling",level:"2"},{id:"sec_22",title:"5. Final considerations",level:"1"}],chapterReferences:[{id:"B1",body:'Shearin AL, Ostrander EA. Leading the way: canine models of genomics and disease. Dis Model Mech. 2010;3(1–2):27–34. doi: 10.1242/dmm.004358.'},{id:"B2",body:'Schoenebeck JJ, Ostrander EA. Insights into morphology and disease from the dog genome project. Annu Rev Cell Dev Biol. 2014;30:535–560. doi: 10.1146/annurev-cellbio-100913-012927.'},{id:"B3",body:'Nemec A, Daniaux L, Johnson E, Peralta S, Verstraete FJ. Craniomaxillofacial abnormalities in dogs with congenital palatal defects: computed tomographic findings. 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In: Perez-Marin CC, editor. A Bird\'s-Eye View of Veterinary Medicine. Rijeka: InTech; 2012. p. 71–98. DOI: 10.5772/32344'},{id:"B36",body:'Mossey PA, Little J, Munger RG, Dixon MJ, Shaw WC. Cleft lip and palate. Lancet. 2009;374(9703):1773–1785. doi: 10.1016/S0140-6736(09)60695-4.'},{id:"B37",body:'Lin KJ, Mitchell AA, Yau WP, Louik C, Hernández-Díaz S. Maternal exposure to amoxicillin and the risk of oral clefts. Epidemiology. 2012;23(5):699–705. doi: 10.1097/EDE.0b013e318258cb05.'},{id:"B38",body:'Zhu H, Kartiko S, Finnell RH. Importance of gene-environment interactions in the etiology of selected birth defects. Clin Genet. 2009;75(5):409–423. doi: 10.1111/j.1399-0004.2009.01174.x.'},{id:"B39",body:'Spranger J, Benirschke K, Hall JG, Lenz W, Lowry RB, Opitz JM, Pinsky L, Schwarzacher HG, Smith DW. Errors of morphogenesis: concepts and terms. Recommendations of an international working group. 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Influences of different surgical procedures on growth of dentomaxillary complex in dogs with artificially created cleft palate. Ann Plast Surg. 1978;1(5):460–465.'},{id:"B46",body:'Marretta SM. Cleft palate repair techniques. In: Verstraete FJ, Lommer MJ, editors. Oral and Maxillofacial Surgery in Dogs and Cats. 1st edition. Edinburgh: Saunders; 2012. p. 351–362.'},{id:"B47",body:'Ishikawa Y, Goris RC, Nagaoka K. Use of a cortico-cancellous bone graft in the repair of a cleft palate in a dog. Vet Surg. 1994;23(3):201–205.'},{id:"B48",body:'Lee JI, Kim YS, Kim MJ, Lee J, Choi JH, Yeom DB, Park JM, Hong SH. Application of a temporary palatal prosthesis in a puppy suffering from cleft palate. J Vet Sci. 2006;7(1):93–95.'},{id:"B49",body:'Yoshioka M, Tanimoto K, Tanne Y, Sumi K, Awada T, Oki N, Sugiyama M, Kato Y, Tanne K. Bone regeneration in artificial jaw cleft by use of carbonated hydroxyapatite particles and mesenchymal stem cells derived from iliac bone. Int J Dent. 2012;2012:352510. doi: 10.1155/2012/352510.'},{id:"B50",body:'Bardach J, Kelly KM, Salyer KE. Relationship between the sequence of lip and palate repair and maxillary growth: an experimental study in beagles. Plast Reconstr Surg. 1994;93(2):269–278.'},{id:"B51",body:'Herkrath AP, Herkrath FJ, Rebelo MA, Vettore MV. Parental age as a risk factor for non-syndromic oral clefts: a meta-analysis. J Dent. 2012;40(1):3–14. doi: 10.1016/j.jdent.2011.10.002.'},{id:"B52",body:'Elwood JM, Colquhoun TA. Observations on the prevention of cleft palate in dogs by folic acid and potential relevance to humans. N Z Vet J. 1997;45(6):254–256.'},{id:"B53",body:'Guilloteau A, Servet E, Biourge V, Ecochard C. Folic acid and cleft palate in brachycephalic dogs. Waltham Focus. 2006;16(2):30–33.'},{id:"B54",body:'Shaw GM, Vollset SE, Carmichael SL, Yang W, Finnell RH, Blom H, Ueland PM. Nested case-control study of one-carbon metabolites in mid-pregnancy and risks of cleft lip with and without cleft palate. Pediatr Res. 2009;66(5):501–506. doi: 10.1203/PDR.0b013e3181b9b544.'},{id:"B55",body:'Domosławska A, Jurczak A, Janowski T. Oral folic acid supplementation decreases palate and/or lip cleft occurrence in Pug and Chihuahua puppies and elevates folic acid blood levels in pregnant bitches. Pol J Vet Sci. 2013;16(1):33–37.'},{id:"B56",body:'Stanier P, Moore GE. Genetics of cleft lip and palate: syndromic genes contribute to the incidence of non-syndromic clefts. Hum Mol Genet. 2004;13 Spec No 1:R73-81.'},{id:"B57",body:'Wolf ZT, Leslie EJ, Arzi B, Jayashankar K, Karmi N, Jia Z, Rowland DJ, Young A, Safra N, Sliskovic S, Murray JC, Wade CM, Bannasch DL. A LINE-1 insertion in DLX6 is responsible for cleft palate and mandibular abnormalities in a canine model of Pierre Robin sequence. PLoS Genet. 2014;10(4):e1004257. doi: 10.1371/journal.pgen.1004257.'},{id:"B58",body:'Villagómez DA, Alonso RA. A distinct Mendelian autosomal recessive syndrome involving the association of anotia, palate agenesis, bifid tongue, and polydactyly in the dog. Can Vet J. 1998;39(10):642–643.'},{id:"B59",body:'Sponenberg DP, Bowling AT. Heritable syndrome of skeletal defects in a family of Australian shepherd dogs. J Hered. 1985;76(5):393–394.'},{id:"B60",body:'Pereira JS; Pereira ABFS. Anophthalmia and cleft lip in a dog - a case report (Original in Portuguese: Anoftalmia e lábio leporino em um cão – relato de caso). Centro de Estudos, Pesquisa e Oftalmologia Veterinária.'},{id:"B61",body:'Wammes JCS, Filadelpho AL, Birck AJ, Peres JA, Pinto e Silva JRC, Guazzelli Filho J, Barcelos RP. Anencephaly, cleft lip and macroglossia in a dog: a case report (Original in Portuguese: Anencefalia, macroglossia e fenda labial em cão: relato de caso). Revista Eletrônica de Medicina Veterinária. 2013; 21(1):1–8. http://revistas.bvs-vet.org.br/rcemv/article/view/27833/29221. [Accessed: 2016-07-23]'},{id:"B62",body:'Moura E. Mendel’s laws and inheritance patterns of genetic diseases (Original in Portuguese: Leis de Mendel e padrões de herança das doenças genéticas). In: Trevilatto PC, Werneck RI, editors. Dental Genetics (Genética Odontológica). São Paulo: Artes Médicas; 2014. p. 45–63.'},{id:"B63",body:'Richtsmeier JT, Sack GH Jr, Grausz HM, Cork LC. Cleft palate with autosomal recessive transmission in Brittany spaniels. Cleft Palate Craniofac J. 1994;31(5):364–371.'},{id:"B64",body:'Moura E, Cirio SM, Pimpão CT. Nonsyndromic cleft lip and palate in boxer dogs: evidence of monogenic autosomal recessive inheritance. Cleft Palate Craniofac J. 2012;49(6):759–760. doi: 10.1597/11-110.'},{id:"B65",body:'Bleicher N, Sloan RF, Gault IG, Ashley FL. Cleft palate in a dog. Cleft Palate J. 1965; 45:56–61.'},{id:"B66",body:'Wriedt, 1925. Apud Hutt FB. Genetics for Dogs Breeders. San Francisco: W. H. Freeman and Company; 1979. p. 86.'},{id:"B67",body:'Weber 1955, 1959. Apud Burns M, Fraser MN. Genetics of the Dog. Philadelphia: J.B. Lippincott Company; 1966. p. 80.'},{id:"B68",body:'Weber, 1959. Apud Richtsmeier JT, Sack GH Jr, Grausz HM, Cork LC. Cleft palate with autosomal recessive transmission in Brittany spaniels. Cleft Palate Craniofac J. 1994;31(5):364–371.'},{id:"B69",body:'Costa-Guerreiro, 1950. Apud Burns M, Fraser MN. Genetics of the Dog. Philadelphia: J.B. Lippincott Company; 1966. p. 80.'},{id:"B70",body:'Bannasch D, Young A, Myers J, Truvé K, Dickinson P, Gregg J, Davis R, Bongcam-Rudloff E, Webster MT, Lindblad-Toh K, Pedersen N. Localization of canine brachycephaly using an across breed mapping approach. PLoS One. 2010;5(3):e9632. doi: 10.1371/journal.pone.0009632.'},{id:"B71",body:'Ferretti E, Li B, Zewdu R, Wells V, Hebert JM, Karner C, Anderson MJ, Williams T, Dixon J, Dixon MJ, Depew MJ, Selleri L. A conserved Pbx-Wnt-p63-Irf6 regulatory module controls face morphogenesis by promoting epithelial apoptosis. Dev Cell. 2011;21(4):627–641. doi: 10.1016/j.devcel.2011.08.005.'},{id:"B72",body:'Jeong J, Li X, McEvilly RJ, Rosenfeld MG, Lufkin T, Rubenstein JL. Dlx genes pattern mammalian jaw primordium by regulating both lower jaw-specific and upper jaw-specific genetic programs. Development. 2008;135(17):2905–2916. doi: 10.1242/dev.019778.'},{id:"B73",body:'Robledo RF, Rajan L, Li X, Lufkin T. The Dlx5 and Dlx6 homeobox genes are essential for craniofacial, axial, and appendicular skeletal development. Genes Dev. 2002;16(9):1089–1101.'},{id:"B74",body:'Rao C, Foernzler D, Loftus SK, Liu S, McPherson JD, Jungers KA, Apte SS, Pavan WJ, Beier DR. A defect in a novel ADAMTS family member is the cause of the belted white-spotting mutation. Development. 2003;130(19):4665–4672.'},{id:"B75",body:'HomoloGene. National Center for Biotechnology Information. http://www.ncbi.nlm.nih.gov/homologene. [Accessed: 2016-07-23]'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Enio Moura",address:"enio.moura@pucpr.br",affiliation:'
Service of Medical Genetics, Faculty of Veterinary Medicine, School of Life Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil
Department of Animal Science, School of Life Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil
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1. Introduction
In the current era of dynamism, Space is also one of the many products that humans consume, and hence just like any other product, space and its meaning is always in continuous transformation. Our attitude and behavior towards fellow humans extensively depends on our life’s physical/material aspects that we value or bestow significance. The typology of our needs and wants determines the typology of our relationships with the people around us. What are the ‘things/spaces’ that set value in our lives? - is a question with a very dynamic answer that is always evolving- with every generation, every innovation, and society’s ever-changing cultural values. These changing aspirations and lifestyles also change the expectations humans have from the built environment that they regularly occupy. Most designs and spatial research revolves around examination of built as singular entity responsible for driving the functions around it. Edward W Soja mentioned in his book ‘The political organisation of space’ that while human activity and behavior are analyzed as if they occur in a “spaceless environment devoid of terrestrial location, distance and directional relationships and other characteristics associated with a geographic context”. All too often, traditionally induced behavior patterns become inherent part of an individuals lifestyle and play an important role in the way people interact with the spatial order that surrounds them and the fellow users of that space [1]. Hence, undoubtedly the Built environment plays an essential role in determining our behavior towards the people with whom we share this space, simultaneously the culturally induced behavior determines our relationship with the built environment. As a result, the meaning of human interactions and human relationships evolves with time, culture, and innovation, leading to the transformation of the typology or quality of the interpersonal relationships that exist in a particular space because of its spatial order.
Figure 1.
Human response to spatial order, source: Author.
Figure 2.
Spatial levels of permeability (privacy), source: Author.
Figure 3.
Types of space surrounding an individual, source: Author.
Figure 4.
Human interaction, source: Author.
2. Setting of the background
History has witnessed many transformations in its built environment which is responsible for a paradigm shift in human behavior and interpersonal relationships. As the agrarian society shifted into being an industrial society, our cities evolved into dense concrete forests of industries- polluting and yet looking down upon the rest of the less industrialized built environment. As humans invented lifts and cranes, the buildings started to grow taller, and as we invented faster modes of transport, the distances started seeming shorter yet growing larger. Humans started traveling more considerable distances to meet friends and move further away from family because of work and leisure. Narrow streets lined with short buildings were replaced with wide streets lined with tall structures, allowing vehicles to take over pedestrians and, steel and concrete to replace grasslands. As cities started to densify, both homes and families became smaller. In the 19th–20th century, the world experienced another shift, i.e., from the industrial society to a service society that commodified lifestyles and made our cities into nothing but a prominent market place. Every family dinner or a friendly get together was now incomplete without ‘Dining out’ hence upgrading food to a commodity of leisure and luxury from merely a necessity. Malls became the new hangout destination for friends, and shopping was rendered into a leisurely act, not something merely driven by necessity. Today, in a world before the pandemic, we would hang out with our friends and family in restaurants, malls, and shopping streets. We tend to connect with them over things we own and can afford, not over the nostalgia of the past or mere bonding of emotional compatibility. This paradigm shift in perception of reality is because of the built infrastructure that our cities present us with, a spatial order that prioritizes ‘having’ over ‘being’. Streets are designed for vehicles to undermine pedestrians, establishing the superiority of car owners—making the concept of owning a car not a need-based act but rather a social symbol of superiority; this ultimately transformed into a necessity as our streets glorified the mechanical modes of transport.
Today, we find streets lined with large billboards displaying the hopes of having a better life by moving into a villa in the countryside which offers its residents an out of the world experience and lifestyle, with spaces more than adequate, amenities beyond usefulness. These elitist encounters of an individual, while navigating through the city in his day to day life, reinforce the concept of commodifying living. As physical distances increase, emotional attachment is converted into responsibility. Humans no longer make friends at a bus stop because we do not know what to expect from our fellow travelers - a warm smile or a cold stare? As people skills have degraded technological skills have taken over our spatial requirements and expectations. At an airport, we look for a seat closer to a charging point and not to a person who has shared with us a warm smile. Sometimes even co- travelers known to each other tend to sit apart if they need access to charging points located far away from each other. The above examples are not a judgment on the cultural change taken over our society, but an expression of acknowledgment of the transformations that drive our spatial needs today. Hence, to maintain healthy interpersonal relationships, today’s spatial designers must capture the need of the hour and design spaces with uninterrupted access to gadgets so that the co-travelers need not distance themselves from each other to remain virtually connected with the rest of the world. The ‘New Normal’ imposed by this unexpected COVID 19 does question, to an extent, the old social ways of gathering with friends and families in restaurants or other physical spaces. This has given birth to a new typology of virtual space, devoid of a spatial order which was public, and has rather driven humans to create cozy private corners that help them abide in a synchronous way with this virtual space.
Spatial organization’s power can be used to communicate both positive or negative attitudes by affirming or denying a particular language or behavior and facilitating the setting of the tone of a space or an organization. “Building design can influence language by how spaces are configured and how access to various locations determines who may speak to whom, when, and where. For example, simply by what it takes to gain access to certain spaces in a community, and whether they are designated as public or private (for example, a door marked “private“ clearly conveys the message that we are not to enter), residents and employees can feel a part of or left out of the various aspects of the community” [2]. Users must be wary of such messages in any place while using it. “Honouring the cues given by the built environment—such as where to have private conversations—can help keep everybody comfortable” [2]. Space that comprises many such messages of the prohibition or forbidden spaces leads to an undermined sense of community and hurts the residents’ social life. Navigating through our cities exposes us to various such messages, and for a better experience and a better understanding of the prevailing culture, designers need to make sure that these cues are easily readable and cater to the users’ social and privacy needs.
3. Human space
Cities are an expression of coexistence, an agglomeration of culture that continually evolves and continuously transforms lifestyle. Today’s cities illustrate a dichotomy of the aspirations of 21st-century users and the conventional life processes that the city’s built environment caters. Every place is designed by The space created around the building/physical entity placed in it, the use of the building itself, and the users who use it. The spatial order of the built environment imposes a specific behavior in its users. This behavior governs the relationships that the stakeholders/users of the space develop. The influence of spatial order on human relationships remains a lesser-explored parameter in the study of interpersonal relationships. This facet is strongly impacted by situational aspects of the era and its culturally induced behavior.
The most recent and widely experienced example of this pandemic is the utilization of public spaces. As “Social Distancing” is the principal motto for self-preservation today, sharing of benches in a park, which used to lead to casual chit-chat and sometimes a lifetime of friendship, is just a concept of the past. Today, people tend to walk past each other on streets without recognizing acquaintances- as people have half-hidden faces and have started maintaining large distances from each other. Redundancy of the street furniture has led to a transformation in establishing relationships with unknown people, and this is just a minor step towards the changing space. A paradigm shift in the design and placement of street furniture is needed to cater to interpersonal interaction needs when social predicaments dictate public space use. It is, therefore, safe to conclude that the built environment of a place dramatically impacts human behavior and most importantly the ‘human to human’ interaction, signifying that the relationships that people can establish on streets and any other private, public or semi-public space are greatly influenced by the specific spatial order that exists in that place. Another similar instance that reinforces this concept is the notion that supports the implication of urban design in achieving a socially sound city or a neighborhood. For instance, one can meet prospective business clients or develop deep, meaningful relationships by meeting strangers in a place of comfortable shade, but one can even miss-out on noticing an old friend while navigating through a very congested street that has uncontrolled light and noise levels.
Humans develop a cognitive relationship with the environment surrounding them, and this relationship dramatically impacts their behavior and attitude towards others around them. Psychologists refer to cognition as the mental activity of processing information and using that information in judgment [3]. Social cognition helps us perceive and predict the behavior of the people who surround us and our response to their actions. Spatial cognition involves the active interpretation of symbols and events happening in the space around us. This cognitive relationship can be at various levels- starting from the scale of a dwelling, to a neighborhood, to a city and even the burgeoning urban context. People’s interaction with their physical space is a result of their cognitive abilities and expresses a lot about their desire or willingness to communicate with the others around them - this is known as immediacy. For example, most gathering spaces are designed as vast enclosed or semi-enclosed spaces clear of visual obstructions to ensure that every person in the room is put on display, so it becomes easier for the other to notice, meet and greet. An introvert would tend to stand in a corner, taking the support of a wall to display his lack of interest in interaction. This is is way of non verbally communicating with people surrounding him to convey his disinterest in mingling. On the other hand, an extrovert attending the event to network with more people will tend to be in the centre of the room occupying more space, hence non verbally communicating his desire to mingle (see Figure 1).
Humans tend to develop defensible spaces around themselves, and one of the City planner Oscar Newman developed the concept of ‘defensible spaces.’ He used this to define “how public and semi-public areas in public housing can be brought under the control of residents. The two major components of defensible space are surveillance and territoriality. Good surveillance is achieved by proper positioning of windows and video cameras. Residents’ feelings of territoriality are enhanced by real and symbolic barriers that mark areas as belonging to particular buildings” [4]. “Territoriality is a pattern of behaviour and attitudes held by an individual or group that is based on perceived, attempted, or actual control of a definable physical space, object, or idea. It may involve habitual occupation, defence, personalisation, and marking of that space” [5]. A person sitting on a park bench is always more approachable to a stranger than someone sitting on their private porch. A classic display of territoriality can be seen in the street hawking zones where the hawkers tend to place their display to mark their business space and deflect encroachment from other hawkers and other stakeholders. It can be perceived as an individual’s relationship with their physical space and their behavior with the fellow humans in that space. “Personal factors, physical and social aspects of situations, and culture can lead to territoriality. For example, males generally manifest more territoriality than females.
Defensible space theory argues that physical arrangements increase territoriality feelings and behavior and that this increase leads to a decline in territorial invasions. These physical arrangements may be at the block or neighborhood level (e.g., altering traffic flow) or at the house level (e.g., fences and plantings)” [5]. ‘A house’ is the most private space that any human owns, and hence he establishes space defenses around it to safeguard his privacy, and it is assumed that all human-human interactions in this space are personal or intimate. Bill Bryson, in his book ‘At Home,’ suggests that every small aspect in a home is intensely thought. He also talks about homes as spaces with a varied typology of built spaces but catering to the similar typology of relationships. “Houses are quite odd things. They have almost no universally defining qualities: they can be practically any shape, incorporate virtually any material, be of almost any size. However, wherever we go in the world, we know houses and recognize them domestically when we see them. This aura of homeliness is, it turns out, is extremely ancient” [6]. There are many privacy levels inside this personal space, and it can be defined by how the spaces inside the home are demarcated and circulation patterns between them are designed.
Every human surrounds themselves with four levels of usable space, categorized based on the territoriality level that they intend to maintain in any given space (see Figure 2). Usable Human Space can be defined as the expanse surrounding an individual that can be used for communication and interaction. These can be categorized into 1. intimate space for close conversations, whispers, embraces, and touching, 2. Personal space is used for interaction with close friends and kins 3. Social space for group interactions among acquaintances or the once taking place in a standard setup, 4. Public space is the one that comes into the picture at large gatherings for public speaking. The generally built construct around us defines the category of human space that is being put into use by an individual, hence defining the typology of interaction that is expected to take place among them. “Culture is one factor contributing to people’s perception of how proxemics should be used. People from different cultures have different views on what proper personal space should be” [7]. The following Figure 3 illustrates these hierarchies in the types of spaces.
4. Spatial order
The pattern in which things are arranged or organized in a particular space is known as spatial order. “In composition, spatial order is an organizational structure in which details are presented as they are (or were) located in space—from left to right or top to bottom. Also known as a place or space structure, spatial order describes things as they appear when observed. In descriptions of places and objects, spatial order determines the perspective from which readers observe details” [8]. The spatial order of a built environment sends out messages to its users. These messages are perceived by the users in a way that they have culturally learned. The concepts of Spatial Semiotics can be used to read these messages. They evoke specific behavior among the users, and this behavior becomes the essence of the association that develops between two or more people in that space. For example, while walking down a street, a pedestrian never maintains the same pace; he tends to walk through an abandoned, dilapidated establishment at a much faster pace compared to a long shop frontage, which is engaging, involving, and buzzing. We can therefore conclude that “people usually feel differently in vast open spaces, in a cathedral, museum or palace, and have a different set of feelings in their former primary school, childhood home or living room” [2].
Spatial order can be inviting or intimidating, comfortable or uncomfortable, pleasing or apprehensive, and this is responsible for determining how users interact with their fellow users in the given spatial order. Spatial organization is responsible for transforming cultural patterns, which induce meaning to the space that eventually responds to users’ needs and fancies. User behavior and beliefs, in turn, impose onto the space around them a specific order which reformulates the spatial organization in such a way that space becomes more user friendly and dynamic.
Accompanying a friend to an art gallery, located in an enclosed building with air-conditioning, we unknowingly tend to maintain distance between each other, seldom interact to comment on an exhibit, and incline towards whispering in in case we need to communicate. However, visiting a street art festival with the same friend evokes a different standard of interaction. We tend to visit each exhibit together while indulging in rigorous discussions about the exhibits. In the above situation, the gallery’s spatial order - enclosed and controlled environment induces a controlled and proper behavior and relationship among the friends, as opposed to the open, free, and informal interaction imposed by the spatial order of the street art exhibition. Similarly, an art gallery ensures minimal interaction with the artist that includes formal complementarities; whereas, a street art exhibition will incline towards a more informal and cozy conversation with a friendly exchange of complementarities (see Figure 4).
In the above diagram, the Art gallery’s spatial order imposes a norm of maintaining a certain social distance level. Cross-referencing Figure 3, we can conclude that people marked in green inside the art gallery occupy each other’s social space only, while on the street, the art exhibition imposes a more cozy and informal interaction. Here, in most instances, visitors occupy each other’s intimate space and, in some instances, also share their personal space with the artist. Here the spatial order induces a behavior leading to non-verbal communication expressed using body language, and this nonverbal communication becomes the driving force for verbal communication. The verbal communication inside the gallery is limited to the exchange of whispers used to pass on short important messages but, in the street exhibition area, it extends to long discussions carried out in higher decibel levels.
Space and society are two independent concepts that function in total entanglement. When space becomes a place when its given a name. Henri Lefebvre in his book “The Production of Space” discusses how the meaning of space ‘historically’ was merely referring to an empty area and was a mathematical concept. Social space at that time was an unknown idea. With a strong backing of existentialism he argued that space as a concept wasn’t absolute. Eventually, mathematicians tried to categories the concept of space into various types or sets of spaces, but failing to do so with complete logic they abandoned this concept for the philosophers to overtake. As Leonardo da Vinci suggests, it became in no time ‘a mental thing’ . This ‘mental thing’ or better termed as ‘ the mental space’ is the one which gives meaning to the real or physical space. The combination of mental space and physical space formulate the social space [7]. For instance, while planning an outing with friends in a nearby park we cannot refer to the park as ‘just the park’, it either needs a name or a point of reference. For example, let us meet at the park near my office, here ‘my office’ is the point of reference that gives a social meaning to the space. This recognition is never singular but always shared with a larger group, and in this act, the social dimension inevitably comes into the picture [1]. In an attempt to decode the relationship between spaces and human interaction, he states that; “the conjunction between space as a geometrical form, and society conceived generally as a bundle of relations, has been conceptualized in four ways: – organized spaces affect society (ecological approaches); – society molds spaces which become territories or organized spaces;– society and spaces are united in specific circumstances to form an indistinct whole (fusion or conflation approach); – space and society are circular: they are distinct but interactive, and produce a cumulative effect” [1]. An individual tends to establish a cognitive association with the space surrounding them, and this relationship is responsible for the user’s behavior in a given space. This cognitive association is in the same hierarchy as the definition of types of space, intimate or personal is the house, social space construes the neighborhood while the city is a vast public space. An individual’s relation to the surrounding urban context, as explained earlier, is also very much culture driven. The users can respond differently to the same spatial order, immediate (neighborhood) or enlarged (city) if they come from different cultural backgrounds.
5. Conclusion
This chapter is an attempt to develop a narrative that can provide a multi-dimensional overview of the diverse spatial order and its impact of the relationships that humans develop while navigating through these spaces. It is a fusion of spatial and social studies which attempts to empower spatial design with social causes. An amalgamation which has been long due, this chapter intends to introduce the vast prospects of this fusion. As the society has started viewing ‘Human Space’ as a product, a consumer good which has an ever increasing value, it is very important to make sure that this product is capable of inducing behavior and relationships that are socially and culturally sound. This chapter aims to act as an aid of initiation for amalgamating social and spatial studies so that a user friendly and an inclusive built environment can be created.
Acknowledgments
I would like to take the opportunity to express my gratitude towards the people who have helped me nurture the concept of connecting spatial studies and social studies and encouraged me to plunge onto an un-traversed path.
I would like to thank all those who were very supportive of the mission and enabled my research towards cause in spite of their hectic schedules. My parents who have contributed not just with their support and blessing, but also by supporting with partial funding towards this publication. I thank IRDS Team who helped put the remaining funds together through some other private design projects. A big thank you specially to IntechOpen for having given me this amazing opportunity.
Conflict of interest
The author declares no conflict of interest.
\n',keywords:"human space, spatial order, built environment, social empathy, interpersonal relationships",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/75234.pdf",chapterXML:"https://mts.intechopen.com/source/xml/75234.xml",downloadPdfUrl:"/chapter/pdf-download/75234",previewPdfUrl:"/chapter/pdf-preview/75234",totalDownloads:242,totalViews:0,totalCrossrefCites:0,dateSubmitted:"December 18th 2020",dateReviewed:"January 23rd 2021",datePrePublished:"April 14th 2021",datePublished:null,dateFinished:"February 12th 2021",readingETA:"0",abstract:"Space truly becomes a place not merely because of the built and the unbuilt that design it, but also because of the way its users use it, behave around it, interact with it, and interact with each other in it. Space that surrounds every individual, in which an individual exists, interacts and performs, is known as “Human Space”. Organization of the Built environment around the users within their ‘human space’ is known as “Spatial Order” which is the key to formulation of non-verbal communication. Non verbal communication refers to the body language an individual adopts in order to convey a message to the fellow users of the space. This Non-verbal language subsequently becomes the basis of verbal communication that lays the foundation of Human Behavior within a particular spatial order.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/75234",risUrl:"/chapter/ris/75234",signatures:"Vaidehi Raipat",book:{id:"7827",type:"book",title:"Interpersonal Relationships",subtitle:null,fullTitle:"Interpersonal Relationships",slug:null,publishedDate:null,bookSignature:"Dr. Martha Peaslee Levine",coverURL:"https://cdn.intechopen.com/books/images_new/7827.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-83962-695-1",printIsbn:"978-1-83962-694-4",pdfIsbn:"978-1-83962-696-8",isAvailableForWebshopOrdering:!0,editors:[{id:"186919",title:"Dr.",name:"Martha",middleName:null,surname:"Peaslee Levine",slug:"martha-peaslee-levine",fullName:"Martha Peaslee Levine"}],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. Setting of the background",level:"1"},{id:"sec_3",title:"3. Human space",level:"1"},{id:"sec_4",title:"4. Spatial order",level:"1"},{id:"sec_5",title:"5. Conclusion",level:"1"},{id:"sec_6",title:"Acknowledgments",level:"1"},{id:"sec_9",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Osti, G. (2015). Socio-spatial relations: an attempt to move space near society (4th ed.). Italy: EUT Edizioni Università di Trieste'},{id:"B2",body:'Ronch, J. (2020). Spaces and interpersonal communication - I Advance Senior Care. Retrieved 23 September 2020, from https://www.iadvanceseniorcare.com/spaces-and-interpersonal-communication/'},{id:"B3",body:'Stangor, D. (2020). Affect, Behavior, and Cognition. Retrieved 26 November 2020, from- https://opentextbc.ca/socialpsychology/chapter/affect-behavior-and-cognition/'},{id:"B4",body:'Robert Sommer, in Encyclopedia of Applied Psychology, 2006'},{id:"B5",body:'R. Gifford, in Encyclopedia of Human Behavio[r (Second Edition), 2012'},{id:"B6",body:'Bryson, B. (2016). At home. London: Black Swan'},{id:"B7",body:'Luthans, Fred, and Jonathan P. Doe 2009 International Management: Culture, Strategy, and Behavior. p. 201 New York: McGraw-Hill Irwin'},{id:"B8",body:'Nordquist, R. (2020). What Does Spatial Order Mean in Composition?. Retrieved 24 September 2020, from https://www.thoughtco.com/spatial-order-composition-1691982'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Vaidehi Raipat",address:"vaidehi.urb.arc@gmail.com",affiliation:'
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UK Research and Innovation (former Research Councils UK (RCUK) - including AHRC, BBSRC, ESRC, EPSRC, MRC, NERC, STFC.) Processing charges for books/book chapters can be covered through RCUK block grants which are allocated to most universities in the UK, which then handle the OA publication funding requests. It is at the discretion of the university whether it will approve the request.)
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The term UAVs broadly encompasses drones, micro-, and nanoair/aerial vehicles. UAVs are largely made up of a main control unit, mounted with one or more fans or propulsion system to lift and push them through the air. Though initially developed and used by the military, UAVs are now used in surveillance, disaster management, firefighting, border-patrol, and courier services. In this chapter, applications of UAVs in agriculture are of particular interest with major focus on their uses in livestock and crop farming. This chapter discusses the different types of UAVs, their application in pest control, crop irrigation, health monitoring, animal mustering, geo-fencing, and other agriculture-related activities. Beyond applications, the advantages and potential benefits of UAVs in agriculture are also presented alongside discussions on business-related challenges and other open challenges that hinder the wide-spread adaptation of UAVs in agriculture.",book:{id:"6864",slug:"autonomous-vehicles",title:"Autonomous Vehicles",fullTitle:"Autonomous Vehicles"},signatures:"Chika Yinka-Banjo and Olasupo Ajayi",authors:null},{id:"66432",doi:"10.5772/intechopen.85566",title:"Model of the Optimal Maneuver Route",slug:"model-of-the-optimal-maneuver-route",totalDownloads:901,totalCrossrefCites:7,totalDimensionsCites:9,abstract:"The chapter deals with the mathematical model for planning the optimal movement route, which has been implemented in the Tactical Decision Support System (TDSS). The model processes and evaluates the data contained in the five raster layers, which are tactically relevant for planning the movement route of troops or autonomous vehicles on the battlefield. The basis for calculating the optimal movement route is a ground surface layer, which is then modified by algorithmic and criterion relationships with the layers of hypsometry, weather attack, and the activities of enemy and friendly units. The result of mathematical model calculations is a time-optimized and safe movement route displayed on the topographic basis. The experiments realized have verified the function of the optimal movement route model when neither the reconnaissance group nor the autonomous vehicle was observed by the enemy. The total time of the UGV with the use of the TDSS to cover the route of maneuver was 67 minutes shorter than the real time of the BRAVO group movement with the use of the TDSS and 105 minutes shorter than the real time of the ALFA group without the use of the TDSS. The comparison of responses to the attack shows that the BRAVO group using the Maneuver Control System (MCS CZ) as part of the TDSS has destroyed the attackers faster by 71 seconds than the ALFA group without the use of the TDSS.",book:{id:"7779",slug:"path-planning-for-autonomous-vehicles-ensuring-reliable-driverless-navigation-and-control-maneuver",title:"Path Planning for Autonomous Vehicle",fullTitle:"Path Planning for Autonomous Vehicles - Ensuring Reliable Driverless Navigation and Control Maneuver"},signatures:"Jan Nohel, Petr Stodola and Zdeněk Flasar",authors:[{id:"162332",title:"Prof.",name:"Petr",middleName:null,surname:"Stodola",slug:"petr-stodola",fullName:"Petr Stodola"},{id:"286639",title:"Dr.",name:"Jan",middleName:null,surname:"Nohel",slug:"jan-nohel",fullName:"Jan Nohel"},{id:"287297",title:"Prof.",name:"Zdenek",middleName:null,surname:"Flasar",slug:"zdenek-flasar",fullName:"Zdenek Flasar"}]},{id:"51781",doi:"10.5772/64730",title:"Application of Sampling-Based Motion Planning Algorithms in Autonomous Vehicle Navigation",slug:"application-of-sampling-based-motion-planning-algorithms-in-autonomous-vehicle-navigation",totalDownloads:2372,totalCrossrefCites:7,totalDimensionsCites:7,abstract:"With the development of the autonomous driving technology, the autonomous vehicle has become one of the key issues for supporting our daily life and economical activities. One of the challenging research areas in autonomous vehicle is the development of an intelligent motion planner, which is able to guide the vehicle in dynamic changing environments. In this chapter, a novel sampling-based navigation architecture is introduced, which employs the optimal properties of RRT* planner and the low running time property of low-dispersion sampling-based algorithms. Furthermore, a novel segmentation method is proposed, which divides the sampling domain into valid and tabu segments. The resulted navigation architecture is able to guide the autonomous vehicle in complex situations such as takeover or crowded environments. The performance of the proposed method is tested through simulation in different scenarios and also by comparing the performances of RRT and RRT* algorithms. The proposed method provides near-optimal solutions with smaller trees and in lower running time.",book:{id:"5285",slug:"autonomous-vehicle",title:"Autonomous Vehicle",fullTitle:"Autonomous Vehicle"},signatures:"Weria Khaksar, Khairul Salleh Mohamed Sahari and Tang Sai Hong",authors:[{id:"182534",title:"Dr.",name:"Weria",middleName:null,surname:"Khaksar",slug:"weria-khaksar",fullName:"Weria Khaksar"}]},{id:"70899",doi:"10.5772/intechopen.90552",title:"Traditional and New Types of Passive Flow Control Techniques to Pave the Way for High Maneuverability and Low Structural Weight for UAVs and MAVs",slug:"traditional-and-new-types-of-passive-flow-control-techniques-to-pave-the-way-for-high-maneuverabilit",totalDownloads:953,totalCrossrefCites:2,totalDimensionsCites:7,abstract:"Prevailing utilization of airfoils in the design of micro air vehicles and wind turbines causes to gain attention in terms of determination of flow characterization on these flight vehicles operating at low Reynolds numbers. Thus, these vehicles require flow control techniques to reduce flow phenomena such as boundary layer separation or laminar separation bubble (LSB) affecting aerodynamic performance negatively. This chapter presents a detailed review of traditional passive control techniques for flight vehicle applications operating at low Reynolds numbers. In addition to the traditional methods, a new concept of the pre-stall controller by means of roughness material, flexibility and partial flexibility is highlighted with experimental and numerical results. Results indicate that passive flow control methods can dramatically increase the aerodynamic performance of the aforementioned vehicles by controlling the LSB occurring in the pre-stall region. The control of the LSB with new concept pre-stall control techniques provides lift increment and drag reduction by utilizing significantly less matter consumption and low energy. In particular, new types of these methods presented for the first time by the chapter’s authors have enormously influenced the progress of separation and LSB, resulting in postponing of the stall and enhancing the aerodynamic performance of wind turbine applications.",book:{id:"6864",slug:"autonomous-vehicles",title:"Autonomous Vehicles",fullTitle:"Autonomous Vehicles"},signatures:"Mustafa Serdar Genç, Kemal Koca, Hacımurat Demir and Halil Hakan Açıkel",authors:null},{id:"50979",doi:"10.5772/64064",title:"Cloud Robotics and Autonomous Vehicles",slug:"cloud-robotics-and-autonomous-vehicles",totalDownloads:2387,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"Recently, a good amount of research has been focused on the development of the autonomous vehicles. Autonomous vehicles possess great potential in numerous challenging applications, for example, autonomous armoured fighting vehicles, automated highway systems, etc. To enable the usage of autonomous vehicles in such challenging applications, it is important to ensure the safety, efficiency, reliability and robustness of the system. Most of the existing implementations of the autonomous vehicles operate as standalone systems limited to onboard capabilities (computations, memory, data, etc.), which limit their potential and performance in real-world applications. The advent of the Internet and emerging advances in the cloud infrastructure suggests new methodologies where vehicles are not limited to onboard capabilities. Processing is also performed remotely on cloud to support different operations and to increase the proficiency of decision-making. This chapter surveys the research to date in the evolution of autonomous vehicles, cloud and cloud-enabled autonomous vehicles, with the limitations of existing systems, research challenges and possible future directions. The chapter can help new researchers in the field to understand and evaluate different approaches for the design of the autonomous vehicular systems.",book:{id:"5285",slug:"autonomous-vehicle",title:"Autonomous Vehicle",fullTitle:"Autonomous Vehicle"},signatures:"Khuram Shahzad",authors:[{id:"176926",title:"Mr.",name:"Khuram",middleName:null,surname:"Shahzad",slug:"khuram-shahzad",fullName:"Khuram Shahzad"}]}],mostDownloadedChaptersLast30Days:[{id:"70899",title:"Traditional and New Types of Passive Flow Control Techniques to Pave the Way for High Maneuverability and Low Structural Weight for UAVs and MAVs",slug:"traditional-and-new-types-of-passive-flow-control-techniques-to-pave-the-way-for-high-maneuverabilit",totalDownloads:953,totalCrossrefCites:2,totalDimensionsCites:7,abstract:"Prevailing utilization of airfoils in the design of micro air vehicles and wind turbines causes to gain attention in terms of determination of flow characterization on these flight vehicles operating at low Reynolds numbers. Thus, these vehicles require flow control techniques to reduce flow phenomena such as boundary layer separation or laminar separation bubble (LSB) affecting aerodynamic performance negatively. This chapter presents a detailed review of traditional passive control techniques for flight vehicle applications operating at low Reynolds numbers. In addition to the traditional methods, a new concept of the pre-stall controller by means of roughness material, flexibility and partial flexibility is highlighted with experimental and numerical results. Results indicate that passive flow control methods can dramatically increase the aerodynamic performance of the aforementioned vehicles by controlling the LSB occurring in the pre-stall region. The control of the LSB with new concept pre-stall control techniques provides lift increment and drag reduction by utilizing significantly less matter consumption and low energy. In particular, new types of these methods presented for the first time by the chapter’s authors have enormously influenced the progress of separation and LSB, resulting in postponing of the stall and enhancing the aerodynamic performance of wind turbine applications.",book:{id:"6864",slug:"autonomous-vehicles",title:"Autonomous Vehicles",fullTitle:"Autonomous Vehicles"},signatures:"Mustafa Serdar Genç, Kemal Koca, Hacımurat Demir and Halil Hakan Açıkel",authors:null},{id:"70496",title:"Sky-Farmers: Applications of Unmanned Aerial Vehicles (UAV) in Agriculture",slug:"sky-farmers-applications-of-unmanned-aerial-vehicles-uav-in-agriculture",totalDownloads:1835,totalCrossrefCites:10,totalDimensionsCites:18,abstract:"Unmanned aerial vehicles (UAVs) are unpiloted flying robots. The term UAVs broadly encompasses drones, micro-, and nanoair/aerial vehicles. UAVs are largely made up of a main control unit, mounted with one or more fans or propulsion system to lift and push them through the air. Though initially developed and used by the military, UAVs are now used in surveillance, disaster management, firefighting, border-patrol, and courier services. In this chapter, applications of UAVs in agriculture are of particular interest with major focus on their uses in livestock and crop farming. This chapter discusses the different types of UAVs, their application in pest control, crop irrigation, health monitoring, animal mustering, geo-fencing, and other agriculture-related activities. Beyond applications, the advantages and potential benefits of UAVs in agriculture are also presented alongside discussions on business-related challenges and other open challenges that hinder the wide-spread adaptation of UAVs in agriculture.",book:{id:"6864",slug:"autonomous-vehicles",title:"Autonomous Vehicles",fullTitle:"Autonomous Vehicles"},signatures:"Chika Yinka-Banjo and Olasupo Ajayi",authors:null},{id:"63245",title:"Autonomous Underwater Vehicle Guidance, Navigation, and Control",slug:"autonomous-underwater-vehicle-guidance-navigation-and-control",totalDownloads:1255,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"A considerable volume of research has recently blossomed in the literature on autonomous underwater vehicles accepting recent developments in mathematical modeling and system identification; pitch control; information filtering and active sensing, including inductive sensors of ELF emissions and also optical sensor arrays for position, velocity, and orientation detection; grid navigation algorithms; and dynamic obstacle avoidance among others. In light of these modern developments, this article develops and compares integrative guidance, navigation, and control methodologies for the Naval Postgraduate School’s Phoenix, a submerged autonomous vehicle. The measure of merit reveals how well each of several methodologies cope with known and unknown disturbance currents that can be constant or harmonic while maintaining safe passage distance from underwater obstacles, in this case submerged mines.",book:{id:"6864",slug:"autonomous-vehicles",title:"Autonomous Vehicles",fullTitle:"Autonomous Vehicles"},signatures:"Timothy Sands and Kevin Bollino",authors:[{id:"258189",title:"Prof.",name:"Timothy",middleName:null,surname:"Sands",slug:"timothy-sands",fullName:"Timothy Sands"}]},{id:"70382",title:"Lunar Science: Internet for Space Tourism",slug:"lunar-science-internet-for-space-tourism",totalDownloads:670,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The increased interest in space exploration drives the development of novel technologies that are useful in other areas, such as aviation. The use of these technologies gives rise to new challenges and applications. Space tourism is an emerging application due to advances in space exploration technologies. This paper addresses two challenges aimed at ensuring continued internet access in space tourism. The first is designing network architecture to ensure continued internet access for space tourists aboard a space vehicle. The second is using aerial vehicle technology to enhance access to cloud content in areas with poor telecommunication infrastructure. The paper proposes the distributed handover algorithm ensuring that the space vehicle can execute handover from terrestrial wireless networks to aerial platforms and satellites as a last mile connection. It also proposes the concept of aerial diversity ensuring low cost access to cloud content. Performance simulation shows that the use of the distributed handover algorithm enhances channel capacity by 18.4% on average and reduces latency by 11.6% on average. The use of the cloud content access system incorporating aerial diversity enhances the channel capacity of terrestrial wireless networks by up to 85% on average.",book:{id:"6864",slug:"autonomous-vehicles",title:"Autonomous Vehicles",fullTitle:"Autonomous Vehicles"},signatures:"Ayodele Abiola Periola",authors:[{id:"278676",title:"Dr.",name:"Periola",middleName:null,surname:"Ayodele",slug:"periola-ayodele",fullName:"Periola Ayodele"}]},{id:"62626",title:"Virtual Simulation Platform for Training Semi-Autonomous Robotic Vehicles’ Operators",slug:"virtual-simulation-platform-for-training-semi-autonomous-robotic-vehicles-operators",totalDownloads:1150,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"This chapter covers the development of a virtual simulation platform for training a semiautonomous robotic vehicle (SARV) operator via an open-source game engine called Unity3D. The SARV such as remotely operated vehicles (ROVs) is becoming increasingly popular in the maritime industry for risky jobs in inhospitable environments. The primary element in carrying out underwater missions in a hostile environment lies within the skills and experience of an ROV pilot. Training for ROV pilots is essential to prevent damage to expensive field equipment during the real operations. The proposed simulator differs from the existing simulators in the market is the use of modern game engine software to develop a “serious game” for ROV pilot trainee at much lower cost and shorter time-to-market. The results revealed that proposed virtual simulator can develop a high-fidelity virtual reality training for the underwater operation guided by classification society.",book:{id:"6864",slug:"autonomous-vehicles",title:"Autonomous Vehicles",fullTitle:"Autonomous Vehicles"},signatures:"Cheng Siong Chin, Xionghu Zhong, Rongxin Cui, Chenguang Yang and Mohan Venkateshkumar",authors:null}],onlineFirstChaptersFilter:{topicId:"1284",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:106,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"June 29th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:32,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:36,paginationItems:[{id:"82195",title:"Endoplasmic Reticulum: A Hub in Lipid Homeostasis",doi:"10.5772/intechopen.105450",signatures:"Raúl Ventura and María Isabel Hernández-Alvarez",slug:"endoplasmic-reticulum-a-hub-in-lipid-homeostasis",totalDownloads:2,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"82409",title:"Purinergic Signaling in Covid-19 Disease",doi:"10.5772/intechopen.105008",signatures:"Hailian Shen",slug:"purinergic-signaling-in-covid-19-disease",totalDownloads:3,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82374",title:"The Potential of the Purinergic System as a Therapeutic Target of Natural Compounds in Cutaneous Melanoma",doi:"10.5772/intechopen.105457",signatures:"Gilnei Bruno da Silva, Daiane Manica, Marcelo Moreno and Margarete Dulce Bagatini",slug:"the-potential-of-the-purinergic-system-as-a-therapeutic-target-of-natural-compounds-in-cutaneous-mel",totalDownloads:9,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82103",title:"The Role of Endoplasmic Reticulum Stress and Its Regulation in the Progression of Neurological and Infectious Diseases",doi:"10.5772/intechopen.105543",signatures:"Mary Dover, Michael Kishek, Miranda Eddins, Naneeta Desar, Ketema Paul and Milan Fiala",slug:"the-role-of-endoplasmic-reticulum-stress-and-its-regulation-in-the-progression-of-neurological-and-i",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}}]},overviewPagePublishedBooks:{paginationCount:32,paginationItems:[{type:"book",id:"7006",title:"Biochemistry and Health Benefits of Fatty Acids",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7006.jpg",slug:"biochemistry-and-health-benefits-of-fatty-acids",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Viduranga Waisundara",hash:"c93a00abd68b5eba67e5e719f67fd20b",volumeInSeries:1,fullTitle:"Biochemistry and Health Benefits of Fatty Acids",editors:[{id:"194281",title:"Dr.",name:"Viduranga Y.",middleName:null,surname:"Waisundara",slug:"viduranga-y.-waisundara",fullName:"Viduranga Y. Waisundara",profilePictureURL:"https://mts.intechopen.com/storage/users/194281/images/system/194281.jpg",biography:"Dr. Viduranga Waisundara obtained her Ph.D. in Food Science\nand Technology from the Department of Chemistry, National\nUniversity of Singapore, in 2010. She was a lecturer at Temasek Polytechnic, Singapore from July 2009 to March 2013.\nShe relocated to her motherland of Sri Lanka and spearheaded the Functional Food Product Development Project at the\nNational Institute of Fundamental Studies from April 2013 to\nOctober 2016. She was a senior lecturer on a temporary basis at the Department of\nFood Technology, Faculty of Technology, Rajarata University of Sri Lanka. She is\ncurrently Deputy Principal of the Australian College of Business and Technology –\nKandy Campus, Sri Lanka. She is also the Global Harmonization Initiative (GHI)",institutionString:"Australian College of Business & Technology",institution:null}]},{type:"book",id:"6820",title:"Keratin",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6820.jpg",slug:"keratin",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Miroslav Blumenberg",hash:"6def75cd4b6b5324a02b6dc0359896d0",volumeInSeries:2,fullTitle:"Keratin",editors:[{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}}]},{type:"book",id:"7978",title:"Vitamin A",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7978.jpg",slug:"vitamin-a",publishedDate:"May 15th 2019",editedByType:"Edited by",bookSignature:"Leila Queiroz Zepka, Veridiana Vera de Rosso and Eduardo Jacob-Lopes",hash:"dad04a658ab9e3d851d23705980a688b",volumeInSeries:3,fullTitle:"Vitamin A",editors:[{id:"261969",title:"Dr.",name:"Leila",middleName:null,surname:"Queiroz Zepka",slug:"leila-queiroz-zepka",fullName:"Leila Queiroz Zepka",profilePictureURL:"https://mts.intechopen.com/storage/users/261969/images/system/261969.png",biography:"Prof. Dr. Leila Queiroz Zepka is currently an associate professor in the Department of Food Technology and Science, Federal University of Santa Maria, Brazil. She has more than fifteen years of teaching and research experience. She has published more than 550 scientific publications/communications, including 15 books, 50 book chapters, 100 original research papers, 380 research communications in national and international conferences, and 12 patents. She is a member of the editorial board of five journals and acts as a reviewer for several national and international journals. 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