\r\n\tThis book will intend to look at different migrant patterns, voluntary and involuntary migration, over the last three centuries. What influenced people to leave their home countries, family, and friends and settle somewhere else? The book may include histories of the 19th century, consider tragedies and movements activated by political events in the 20th century, and/or look at recent events of the 21st century. Push and pull factors are important points. While most of us may be influenced in a negative way by the current happenings in Eastern Europe, the Russian invasion and resulting tragedies also demonstrate some very positive human traits – the preparedness of Ukraine’s surrounding countries to help those in need and to provide a safe place for the present.
\r\n\tWhether one looks at voluntary or involuntary migration into any country, after a period of adjustment, migrants do play a positive role. The research found that migrants contribute to the economy (food, shelter, employment, tax) and enrich a country’s cultural norms. Prerequisites for successful settlements are that the host society adopts a tolerant approach and that the migrants recognize the law and the language of the host country. Nothing is ever easy or without controversy, but I am a migrant (German Australian), and life in Australia has been relatively harmonious. Issues that could be considered in the book are multicultural societies (do monocultural societies still exist?) and theories of acculturation versus integration (settlement processes).
\r\n\tTwo further issues are very important in relation to human migration. There is climate change, global warming, and the environment, which clearly affect people’s movement. Small island populations are very concerned about rising sea levels. 2021 has also seen floods costing human lives: Turkey (August 2021), Brazil (December 2021), Chile (January 2021), and South India (November 2021), to name but a few. In Australia (March 2022), farms and whole townships in New South Wales and Queensland have been flooded for the second time in five years, and plans to resettle these towns are considered. Official and social media provide ample coverage of the events, which leads me to the next issue. There is today’s very important role of the media, of the official and social media. We are constantly bombarded with images of human war tragedies and flood victims. People in industrialized, western countries must be the best-informed populace. How far do the images and up-to-date TV news influence us, make us change our behavior, and perhaps even consider us more generous than we have been?
\r\n\tClimate change and the media are relatively new to the human migration debate, but both issues play important parts, and some interesting discussions are appreciated.
\r\n\t
Amyotrophic lateral sclerosis (ALS) is a late-onset progressive neurodegenerative disorder affecting both the upper and lower motor neurons. It is characterized by increasing muscle weakness, paresis, and paralysis, and although the course of the disease may vary considerably, death usually occurs within 3–5 years due to respiratory failure. While almost all skeletal muscles, including the cranially innervated muscles responsible for speech and swallowing, are affected in ALS, oculomotor disturbances are not dominant or typical features of this disease, not even in patients with long-duration ALS, and eye movements may remain the only form of communication available to these patients at the end stages of the disease. The cranial nerve nuclei supplying the eye muscles appear rather normal in terminal ALS patients [1], and abnormalities in eye motility in ALS patients, when present, have been ascribed to supranuclear deficits [2].
The pathophysiology of the neurodegenerative process in ALS has been proposed to be due to a number of different causes. The traditional point of view has been that ALS is a motor neuron disease that progresses to the periphery where it affects the muscles, due to the typical loss of motor neurons in the anterior horns of the spinal cord and sclerosis of the lateral corticospinal tracts. However, a number of studies suggest an inverse course of events, with changes starting at the periphery and progressing along the motor neurons toward the CNS, reviewed by [3, 4, 5]. In SOD1G93A transgenic mice, it has been shown that peripheral denervation occurs in the limb muscles before the animals become clinically weak or motor neuron loss is detected [6]. Similar results were also reported for a patient with ALS who died unexpectedly, leading the authors to propose that motor neuron pathology in ALS begins at the distal axon end and proceeds in a “dying back” pattern [6]. Later, it has been shown that muscle-restricted expression of three different SOD1 gene variants can initiate the non-autonomous degeneration of motor neurons typical of ALS [7], truly showing that the muscle itself may be a major player in the early stages of ALS.
A unifying model compiling extensive experimental data from SOD1 transgenic models of ALS [3] proposes that although motor neuron degeneration and death are the primary causes of the progressive paralysis, neighboring nonneuronal cells are also involved in the toxicity and damage development. In this model, the earliest event is the retraction of motor axons from their muscle synapses, before any symptoms of the disease are present.
The extraocular muscles (EOMs) are unique in many respects and are considered a separate muscle class, allotype. They are both the fastest and the most fatigue-resistant muscles in the body, and their fiber-type composition is very complex [8, 9]. The unique properties of the EOMs are reflected in their expression profile that differs from that of limb muscle in over 300 genes [10]. However, the most striking property of EOMs is their varied behavior in disease. The EOMs are known to be selectively involved in certain diseases like mitochondrial myopathies, myasthenia gravis, and Miller Fisher syndrome, but preferentially spared in other devastating diseases like Duchenne muscular dystrophy and merosin-deficient muscular dystrophy, that affect all other muscles in the body [11, 12, 13].
The extraocular muscles are richly innervated, and their motor units are very small, with 7–25 muscle fibers, in contrast to the motor units of limb muscles, which typically contain hundreds of muscle fibers. The majority of the nerve fibers in the EOMs are large and myelinated and innervate a typical single “en plaque” endplate in the middle portion of each muscle fiber. The remaining 15–20% of the EOM nerve fibers are small and innervate many small, “en grappe” motor endplates along the length of a muscle fiber (the so-called multiply innervated muscle fibers, reviewed in [11]). This traditional description of the innervation of the EOMs has been significantly changed by the recent report of a subpopulation of muscle fibers that exhibit multiple large “en plaque” nerve endings [14]. The NMJs of the EOMs also differ from limb muscle in retaining expression of the fetal gamma subunit of the acetylcholine receptor (AChR), in addition to the adult epsilon subunit, typically present in mature motor endplates [14, 15]. We have shown that the NMJs of the human EOMs have a different immunoreactivity pattern than that seen in limb muscles for antibodies against gangliosides GQ1b, GT1a, and GD1b [16]. Gangliosides are a large family of sialylated glycosphingolipids highly enriched in neuronal and glial plasma membranes and important for the development, function, and maintenance of the nervous system. Complex gangliosides have neurotrophic factor-like activity and may regulate the expression levels of neurotrophic factors and their receptors [17]. Notably, there have been at least two case reports of ALS associated with antibodies against gangliosides [18, 19].
Given that the EOMs differ significantly from the limb and trunk muscles with respect to their response to disease and given the more recent view that the muscle itself may play a key role in the pathophysiology of ALS, we first investigated whether there are any major differences between the EOMs and the limb muscles of terminal ALS donors [20]. Thereafter, we investigated neuromuscular junction integrity [21, 22, 23], neurotrophic factors (BDNF, NT-3, NT-4, GDNF) and their receptors (p75NTR, TrkB, TrkC) [24, 25], and relevant Wnt isoforms (Wnt1, Wnt3a, Wnt5a, Wnt7a) [26], as possible important puzzle pieces to better understand the pathophysiology of ALS and the selective sparing of the EOMs in the disease.
We compared the general morphology, fiber-type content, fiber area and myosin heavy chain (MyHC) composition of EOM, biceps brachii, vastus lateralis, and tibialis anterior muscle samples collected from eight terminal ALS donors (age 58–80 years) and from three age-matched (age 72–86 years) and a younger (age 26 years) control, with ethical approval, using immunohistochemistry and SDS-PAGE [20]. There were five cases of sporadic ALS and three cases of familial ALS. The MyHC isoforms are the major determinants of key contractile and biochemical characteristics of the myofibers including shortening velocity and power and therefore very good markers of the physiological properties of myofibers. Our study showed that the morphology of the ALS limb muscle samples is clearly pathological. All limb muscle samples from terminal ALS donors exhibit typical signs of myofiber type grouping, myofiber splitting, necrosis, increased connective tissue, fatty replacement, and ongoing regeneration, with a very wide range of myofiber areas. In contrast, the EOM samples from the same donors show remarkably well-preserved morphology. In 18 out of the 43 EOM samples examined, larger variation in fiber area was apparent than in the control samples and irrespectively of being sporadic or familial ALS cases. In fact, areas that appear well preserved reveal a general atrophy of all myofiber types, whereas areas that appear more affected generally show atrophy of the myofibers containing MyHCslow and hypertrophy of the myofibers containing MyHCfast2A. In 20 EOM samples, increased connective tissue amounts were noted, either around individual myofibers or around groups of myofibers. The changes noticed vary among donors and among different EOM samples from a given donor. Centrally placed nuclei are rarely detected. The MyHC content, determined with SDS-PAGE of whole EOM extracts, varies among ALS donors, whereas it is rather similar among control EOM samples [20]. This variation in MyHC content at the whole muscle level can be interpreted as reflecting different levels of involvement, and, to a lesser degree, naturally occurring variation among subjects [8].
Given that this first study clearly shows that the human EOMs are remarkably well preserved at the end stage of ALS [20] and because the EOMs are known to show a divergent behavior in disease, we decided to further investigate these muscles in ALS, comparing the EOMs and limb muscle samples from human donors and from mouse models of ALS, taking a “muscle perspective” to study the pathophysiology of the disease.
In the SOD1G93A mouse, the most widely used mouse model of ALS, it has been shown that loss of contact between the axons and the myofibers, at the neuromuscular junctions, occurs early in the course of the disease and indeed precedes detection of loss of motor neurons in the spinal cord [6]. Similar findings have been reported in ALS patients who died of other reasons early in the course of ALS [6]. Furthermore, data show that muscle-specific alterations are sufficient to trigger neuromuscular pathology and distal degeneration of motor neurons [5, 7], suggesting that the muscle itself may play an important role in the pathophysiology of ALS.
We investigated [21] whether there are signs of loss of contact between the axons and the myofibers, at the neuromuscular junctions of the EOMs, extensor digitorum longus, tibialis anterior, and gastrocnemius and soleus muscles from seven SOD1G93A transgenic and six control mice. We used triple labeling immunohistochemistry with antibodies against neurofilament protein and synaptophysin to identify the axonal side of the neuromuscular junctions and their axons and alpha-bungarotoxin, to identify the muscle side of the neuromuscular junctions, in the same muscle section. Our study confirmed that, as described above for the human EOMs of terminal ALS donors, the eye muscles in this animal model of ALS also show rather well-preserved morphological features, in clear contrast to the limb muscles of the same animal, at the end stage of the disease. We could confirm previously reported findings [6] of significant loss of contact between the nerve and myofiber in approximately 33% of the neuromuscular junctions in limb muscles of the ALS mouse model, whereas in the limb muscles of the control animals, only approximately 4.6% of the neuromuscular junctions lack contact with the supplying nerve (p = 0.0071). In contrast, the number of neuromuscular junctions lacking nerve contacts in the EOMs is extremely low and similar between transgenic (1.9%) and control (1.7%) animals (p = 0.659) [21].
Similarly, the neuromuscular junctions of the EOMs of terminal ALS donors show maintenance of their integrity [22, 23]. In a study of 7 terminal ALS donors (age 58–80 years, three cases with SOD1D90A genotype) and 10 controls (adults aged 34–53 years and elderly aged 69–83 years), we compared the EOMs and the limb muscles with respect to the presence and distribution of neurofilament light subunit (marker of the axons in nerves and at the neuromuscular junction), synaptophysin (marker of synaptic vesicles and thereby of functioning neuromuscular junctions), S100B, p75NTR and glial fibrillary acidic protein (GFAP) which are markers of terminal Schwann cells at the neuromuscular junction, and alpha-bungarotoxin, which labels the muscle side of the synapse [23]. GFAP and p75NTR are upregulated in Schwann cells after injury [27, 28, 29]. Two groups of control donors (adult and elderly) were included in this and all our studies of ALS in order to distinguish between the effects of normal aging and those related to ALS. This pioneer study showed that there is a dramatic decrease in the number of neuromuscular junctions and nerve axons containing neurofilament light subunit in limb muscles of terminal ALS donors, whereas the EOMs maintain neurofilament light subunit in their neuromuscular junctions and nerves. There is also a significant decrease in neuromuscular junctions labeled with synaptophysin in the limb muscles but not in the EOMs of terminal ALS donors. Together, these results confirm that there is a marked loss of nerve-muscle contacts in the limb muscles of terminal ALS donors, whereas the EOMs succeed in maintaining their neuromuscular junctions until the end stage of the disease. The neuromuscular junctions of limb muscles show also massive loss of S100B and p75NTR in ALS, whereas the staining pattern of GAFP is maintained. In contrast, the neuromuscular junctions in the EOMs of terminal ALS donors also show loss of S100B but have an unchanged pattern regarding the other two Schwann cell markers, GFAP and p75NTR. The loss of S100B can be interpreted as due to downregulation rather than a sign of loss of Schwann cells, given that the other two markers remain unchanged. It may also indicate a disturbed calcium homeostasis as an early step toward the loss of the neuromuscular junction in ALS. In summary, this study shows fundamental differences between the limb muscles and the EOMs of terminal ALS donors with a significant impact of the disease on important synaptic proteins normally present in the motor axons and terminal Schwann cells in the limb muscles, whereas the neuromuscular junctions in the EOMs are only very mildly affected [23].
Another study has in addition revealed fragmentation of the postsynaptic membrane, decreased density of acetylcholine receptors, and absence of nerve sprouting in denervated neuromuscular junctions in the limb muscles of the SOD1G93A mouse model of ALS, whereas no such changes are present in the neuromuscular junctions of the EOMs of the same animals [30].
In the context of motor axon retraction from the muscle synapse being an early event in the pathogenesis of ALS, it is of particular interest to further investigate the cellular and molecular microenvironment of the neuromuscular junctions of the extraocular muscles, as they may provide cues to the unique resistance of the EOMs to ALS.
Alterations in the expression of target-derived neurotrophic factors and in their signaling pathways have been reported in ALS. Neurotrophic factors are important for survival and maintenance of neurons [31, 32, 33]. Target-derived neurotrophic factors can be transported to lower motor neurons from other cells, including the muscle cells, by retrograde transport, and from upper motor neurons, by anterograde transport, and act as signaling molecules [31, 32, 33]. Among neurotrophic factors, brain-derived neurotrophic factor (BDNF) is of particular interest due to its capacity to promote motor neuron survival and motor axon growth [32, 33, 34]. Glial cell line-derived neurotrophic factor (GDNF) is also relevant as it is capable of rescuing motor neurons from injury-induced cell death [35], and neurothrophin-4 (NT-4) plays a role in growth and remodulation of adult motor neurons [36, 37], whereas NT-3 is of particular importance for sensory neurons.
Data on the SOD1G93A mouse model of ALS show important differences between the EOMs and the limb muscles over time regarding the levels of expression of neurotrophic factors [24]. The authors compared the expression levels of BDNF, GDNF, NT-3, and NT-4, determined with quantitative RT-PCR, in limb (soleus and gastrocnemius) and extraocular muscles at the early stage (50 days) and at the end stage (150 days) of the disease. Starting with the control animals, the EOMs differ from the limb muscles by having significantly lower levels of BDNF and NT-3 mRNA at age 50 days. At 150 days, the control EOMs have significantly lower levels of BDNF and NT-4 mRNA than the limb muscles from the same animals. In the limb muscles of control animals, mRNA levels of BDNF increase significantly from 50 to 150 days of age, whereas the levels of NT-3 decrease dramatically. In the control EOMs, the mRNA levels of BDNF, GDNF, NT-3, and NT-4 remain unchanged from 50 to 150 days of age [24].
In the transgenic animals, the expression levels of BDNF increase significantly from 50 to 150 days, that is, from the early stage of ALS, when the limb muscle morphology is still normal, to the end stage of the disease, when the limb muscles are extremely affected. Compared to the controls, the limb muscles of the transgenic animals show significantly lower levels of NT-4 at 50 days and significantly higher levels of GDNF at 150 days. The transgenic EOMs show no change in the levels of expression of BDNF or GDNF and show significant decrease in NT-3 and increase in NT-4, over time between 50 and 150 days, and the morphology is comparable to that of the age-matched controls. Compared to the controls, the EOMs of the G93A animals show significantly higher levels of GDNF and NT-3 at 50 days, whereas no significant differences are detectable at 150 days. Finally, comparison between the EOMs and limb muscles of transgenic animals shows no significant differences in the levels of expression of any of the four neurotrophic factors at 50 days but significantly higher levels of BDNF in the limb muscles at 150 days [24].
Because no significant changes in the levels of expression of BDNF detected with quantitative RT-PCR are apparent in either the limb or EOMs of the transgenic animals at any stage, the authors dismiss a possible role for this neurotrophic factors on ALS. The BDNF results obtained in the SOD1G93A mice are in agreement with a previous report from muscle samples of ALS patients [38]. In contrast, the GDNF mRNA levels are significantly upregulated in the EOMs of the SOD1G93A mice at 50 days, and the authors suggest that this early upregulation is triggered by the disease and seminal for the maintenance of the general morphology of the EOMs and in particular for their capacity of keeping intact neuromuscular junctions. They interpret the upregulation of GDNF in the end stage in the limb muscles as reflecting the advanced motor neuron degeneration. Similarly, the upregulation of NT-3 in the EOMs detected at 50 days is also proposed to be triggered by ALS and to protect the EOMs, whereas early downregulation of NT-4 in the limb muscles is suggested to be detrimental and contribute to the loss of axonal contact at the neuromuscular junctions [24].
At the cellular level, there are also important differences in the patterns of distribution of neurotrophic factors between the EOMs and limb muscles, both among controls and among SOD1G93A animals at 50 and 150 days [25]. In the limb muscles of control animals, GDNF, BDNF, NT-3, and NT-4 are present in the vast majority of the neuromuscular junctions at 50 and 150 days, whereas that is the case in only a little over half of the neuromuscular junctions in the control EOMs, at 50 and 150 days. The proportion of neuromuscular junctions containing BDNF and NT-4 is significantly higher in the limb muscles than in the EOMs of control animals at 50 days, and the same is true for the proportion of neuromuscular junctions containing BDNF and GDNF at 150 days. Particularly noteworthy is that the limb muscles of SOD1G93A animals show a significant decrease in the proportion of neuromuscular junctions containing BDNF, GDNF, and NT-4 at 150 days, whereas the EOMs maintain their pattern. The same is true for the presence of the receptors p75NTR, TrkB, and TrkC, which decline significantly in the neuromuscular junctions of the limb muscles of the SOD1G93A animals at 150 days, but not in their EOMs. TrkB is a high-affinity tyrosine kinase receptor specific for BDNF and NT-4, TrkC is a high-affinity tyrosine kinase receptor specific for NT-3, and p75NTR is a low-affinity receptor for BDNF, NT-3, and NT-4 [39]. There are only discrete differences between the control and the SOD1G93A animals with respect to patterns of neurotrophic factors in the nerve axons and the myofibers of both EOM and limb muscles [25].
Taken together, these studies [24, 25] clearly show both at the mRNA level and immunohistochemically that the EOMs have lower neurotrophic factor levels than the limb muscles, in control mice. One possible explanation resides in the differences in innervation between these muscles, as the EOMs have a rich population of multiply innervated myofibers, in contrast to the exclusively twitch myofibers of limb muscles, and the developmental fates of these different types of axons are dependent upon target-derived neurotrophic factors [40]. They also show that the significant changes in neurotrophic factors in limb muscles of transgenic animals are not related to normal aging.
Studies of neurotrophic factors in muscle tissue pose a technical challenge and clinical trials in ALS have not led to the desired effects, but the early detection of alterations in the levels of expression of neurotrophic factors and the distinct patterns observed in the EOMs versus limb muscles indicate that it is too early to dismiss their possible roles in the pathophysiology of ALS and in particular in the selective capacity of the EOMs to maintain neuromuscular junctions and remain rather unaffected in the disease.
Several Wnt proteins, including Wnt1, Wnt3a, Wnt 5a, and Wnt7a, are highly expressed at the neuromuscular junction, in muscle fibers, and in motor neurons, and abnormal Wnt signaling has been reported in ALS and a number of other neuromuscular conditions [41, 42, 43, 44, 45, 46]. In particular, Wnt1 has been assigned important roles in muscle regeneration and in synaptic plasticity, acting on both sides of the synapse [41, 47]. Wnt3a modulates the formation of neuromuscular junctions and promotes nerve outgrowth [48, 49, 50], whereas Wnt5a is important for motor neuron survival during development [51]. Wnt7a plays an important role in synaptic assembly and plasticity and remodeling of incoming axons [52] and has also been shown to have positive effects on the myofibers [53, 54]. Furthermore, Riluzole, the only medical treatment available for ALS, enhances Wnt/beta catenin signaling.
We have performed a comprehensive immunohistochemical study comparing the distribution of Wnt1, Wnt3a, Wnt5a, and Wnt7a in the EOMs and limb muscle samples (biceps brachii, vastus lateralis, and tibialis anterior) from six terminal ALS donors, younger controls (mean age 41 years for EOMs and 33 years for limb muscles, referred to as adult controls), and older controls (mean age 75 years for EOM and 76 years for limb, referred to as elderly controls), and we have reported significant differences and suggested a role for Wnts in the different behaviors of EOMs and limb muscles in ALS [26].
In the adult control EOMs, roughly 71% of the axons are Wnt1 positive, and in the elderly controls, merely 12% of the axons contain Wnt1, whereas in the EOMs of terminal ALS donors, 43% of axons are labeled for Wnt1, clearly showing that they preferentially maintain Wnt1 in their nerves. The limb muscles of terminal ALS donors contain significantly less Wnt1-positive axons than the EOMs, with extremely high variation among the different donors. No statistically significant differences between the three limb muscle groups are detectable regarding the presence of Wnt1 in the motor nerves. Wnt1 is present in almost 40% of the myofibers in the EOMs of adult controls and almost in all myofibers of terminal ALS donors, whereas it is not present in limb myofibers of adult controls or terminal ALS donors.
With regard to Wnt3a, it is present in the vast majority of axons in both the EOMs of adult controls and ALS terminal donors, but again it is significantly lower in the elderly control EOMs. In the limb muscles of all groups, the percentage of axons containing Wnt3a is significantly lower than in the EOMs, with approximately 75% fewer Wnt3a axons. Approximately 17% of the myofibers contain Wnt3a in adult control EOM, whereas almost all myofibers in the EOMs of terminal ALS donors are positive. Higher levels of Wnt3a are present in adult control limb myofibers, but in contrast Wnt3a is practically absent in the limb muscle fibers of terminal ALS donors.
Wnt5a is present in practically all EOM axons both in adult controls and terminal ALS donors and is somewhat lower in the EOMs of elderly controls. Similarly, practically all limb muscle axons, irrespective of group, are Wnt5a positive. Wnt5a, seen as weak immunostaining, is present in almost all myofibers of control adult EOMs and terminal ALS donors, whereas it is not present in limb myofibers of adult controls or terminal ALS donors.
A very large proportion of the axons in the EOMs of adult controls and terminal ALS donors are Wnt7a positive, whereas a significantly lower number is found in the EOMs of the elderly controls. A similar proportion of Wnt7a-positive axons are present in the limb muscles of both adult controls and terminal ALS donors, but a significantly higher number of positive axons are found in the limb muscles of elderly controls. Only approximately 20% of the myofibers in the adult control EOMs contain Wnt7a, but in the EOMs of terminal ALS donors, this number increases significantly almost 60%. In the limb muscles, Wnt7a is present in more than half of the myofibers of the adult controls and practically in all myofibers in the elderly controls. The differences found between adult controls and terminal ALS donors regarding Wnt7a in limb myofibers are not significant, probably due to large interindividual variation among the donors.
Data collected in controls and in the SOD1G93A mouse model of ALS [26] indicates that practically all neuromuscular junctions in control EOMs and limb muscles express Wnt1, Wnt3a, Wnt5a, and Wnt7 at 50 and 150 days. The same is true for the transgenic EOMs at both 50 and 150 days and the transgenic limb muscles at 50 days, whereas a significantly decrease in the proportion of neuromuscular junctions co-expressing the different Wnt isoforms is clearly apparent in the transgenic limb samples at 150 days.
In summary, the EOMs remain remarkably well preserved until the end stages of ALS, both in human terminal donors and in mouse models of ALS. They maintain the composition of their neuromuscular junctions and do not loose contact with the supplying axon. Furthermore, important differences exist between the EOMs and the limb muscles with respect to neurotrophic factors and Wnts:
The mRNA levels of BDNF, NT-4, and NT-3 and the detection of BDNF, NT-4, NT-3, and GDNF at the protein level are lower in the EOMs than in the limb muscles of control animals at 50 and/or 150 days.
NT-3 is upregulated in the EOMs of SOD1G93A mice at 50 days and may be protective. A similar difference in GDNF may also be advantageous for the EOMs and protect their motor neurons.
There is early downregulation of NT-4 in the limb muscles of SOD1G93A mice compared to the controls at the same age, which coincides with the timing of early loss of motor axon occupancy at the neuromuscular junctions of limb muscles in this ALS model [6].
The proportion of neuromuscular junctions in the EOMs positive for BDNF, GDNF, and NT-4 is not changed between the controls and the transgenic mice at 150 days, whereas there is a significant decrease in the limb muscles of the SOD1G93A animals compared to the controls at late stage and there is also a significant decrease over the course of the disease in the limb muscles of the transgenic mice. Again, these changes in neurotrophic factors parallel the loss of axonal occupancy at the neuromuscular junctions of the limb muscles of transgenic animals and these neurotrophic factors are known to play crucial roles in regulating the synapses [55, 56].
There is a significant decrease in the neurotrophic factor receptors p75NTR, TrkB, TrkC, and GFR-alpha1 in the neuromuscular junctions of terminal SOD1G93A mice, whereas they are maintained in the neuromuscular junctions of terminal transgenic EOMs.
Wnt1 and Wnt3a are present in a larger proportion of axons in the human control EOMs than in the limb muscles. The myofibers in the control EOMs contain higher Wnt1 and Wnt5a and lower Wnt3a and Wnt7a than the myofibers of limb muscles, and although the exact implications of these intrinsic differences in Wnt isoform profiles remain to be determined, they may be relevant for the selective sparing of the EOMs in ALS.
Wnt1 and Wnt3a are present at significantly higher levels in the axons and the muscle fibers of the EOMs than in the axons or muscle fibers of the limb muscles of terminal ALS donors. Because Wnt1 plays a role in synaptic plasticity and muscle regeneration and in neuromuscular junction formation during fetal development and Wnt3a has similar roles, these differences between EOMs and limb muscles are likely to be of importance for the selective sparing of the EOMs, and in particular of their neuromuscular junctions, in ALS.
Altogether, these data show important differences between the EOMs and limb muscles with regard to neurotrophic factors and four different Wnt isoforms, both at base line and in ALS, that likely play a role in the selective sparing of the EOMs in ALS. These data also suggest that muscle itself may provide a door for the development of new treatment strategies in the future.
There are no conflicts of interest.
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The aim of this chapter was to show the different aspects of non-Saccharomyces species that may play a positive incidence in the biotechnological process to conduct to wine elaboration.",book:{id:"5253",slug:"grape-and-wine-biotechnology",title:"Grape and Wine Biotechnology",fullTitle:"Grape and Wine Biotechnology"},signatures:"Margarita García, Braulio Esteve-Zarzoso and Teresa Arroyo",authors:[{id:"182064",title:"Dr.",name:"Teresa",middleName:null,surname:"Arroyo",slug:"teresa-arroyo",fullName:"Teresa Arroyo"},{id:"182068",title:"Ms.",name:"Margarita",middleName:null,surname:"García",slug:"margarita-garcia",fullName:"Margarita García"},{id:"182089",title:"Dr.",name:"Esteve-Zarzoso",middleName:null,surname:"Braulio",slug:"esteve-zarzoso-braulio",fullName:"Esteve-Zarzoso Braulio"}]},{id:"52380",doi:"10.5772/65055",title:"Influence of Yeasts in Wine Colour",slug:"influence-of-yeasts-in-wine-colour",totalDownloads:2371,totalCrossrefCites:11,totalDimensionsCites:25,abstract:"Colour is the first impression that the consumer receives from wine and it influences the taste. Colour gives an idea about wine quality, age, oxidation and structure, so it has an important repercussion on the consumer perception of wine. Yeasts promote the formation of stable pigments by the production and release of fermentative metabolites affecting the formation of vitisin A and B type pyranoanthocyanins. The hydrox- and ycinnamate decarboxylase activity showed by some yeast strains produces highly reactive vinylphenols stimulating the formation of vinylphenolic pyranoanthocyanins from grape anthocyanin precursors during fermentation. Some yeasts also influence the formation of polymeric pigments by unclear mechanisms that can include the production of linking molecules such as acetaldehyde. Grape anthocyanins adsorbed in yeast cell walls during fermentation are removed from wine after racking processes affecting final pigment content. Moreover, the intensive use of non‐Saccharomyces yeasts in current oenology makes it interesting to assess the effect of new species in the improvement of wine colour.",book:{id:"5253",slug:"grape-and-wine-biotechnology",title:"Grape and Wine Biotechnology",fullTitle:"Grape and Wine Biotechnology"},signatures:"Morata Antonio, Loira Iris and Suárez Lepe Jose Antonio",authors:[{id:"180952",title:"Prof.",name:"Antonio",middleName:null,surname:"Morata",slug:"antonio-morata",fullName:"Antonio Morata"},{id:"186423",title:"Dr.",name:"Iris",middleName:null,surname:"Loira",slug:"iris-loira",fullName:"Iris Loira"},{id:"186424",title:"Prof.",name:"Jose Antonio",middleName:null,surname:"Suárez Lepe",slug:"jose-antonio-suarez-lepe",fullName:"Jose Antonio Suárez Lepe"}]},{id:"44142",doi:"10.5772/52933",title:"The Current Status of Wild Grapevine Populations (Vitis vinifera ssp sylvestris) in the Mediterranean Basin",slug:"the-current-status-of-wild-grapevine-populations-vitis-vinifera-ssp-sylvestris-in-the-mediterranean-",totalDownloads:4159,totalCrossrefCites:11,totalDimensionsCites:19,abstract:null,book:{id:"3143",slug:"the-mediterranean-genetic-code-grapevine-and-olive",title:"The Mediterranean Genetic Code",fullTitle:"The Mediterranean Genetic Code - Grapevine and Olive"},signatures:"Rosa A. Arroyo García and Eugenio Revilla",authors:[{id:"154744",title:"Dr.",name:"Rosa Adela",middleName:null,surname:"Arroyo-Garcia",slug:"rosa-adela-arroyo-garcia",fullName:"Rosa Adela Arroyo-Garcia"},{id:"164824",title:"Prof.",name:"Eugenio",middleName:null,surname:"Revilla",slug:"eugenio-revilla",fullName:"Eugenio Revilla"}]},{id:"52244",doi:"10.5772/65102",title:"Aroma Compounds in Wine",slug:"aroma-compounds-in-wine",totalDownloads:3120,totalCrossrefCites:9,totalDimensionsCites:20,abstract:"Volatile aroma compounds are very important to grape wine quality. In order to understand the flavor of wine, a multitude of scientific investigations was carried out and a number of appropriate analytical tools for flavor study were developed in the past few decades. This chapter deals with major achievements reported in wine aroma and flavor. Firstly, we illustrate the existing knowledge on aroma compounds contributing to wine flavor, as well as the types of wine aroma compounds. Furthermore, the main factors affecting flavor quality in wine are discussed. Finally, the genomics and biotechnology of wine flavor are also summarized. This chapter broadens the discussion of wine aroma compounds to include more modern concepts of biotechnology and also provides relevant background and offers directions for future study.",book:{id:"5253",slug:"grape-and-wine-biotechnology",title:"Grape and Wine Biotechnology",fullTitle:"Grape and Wine Biotechnology"},signatures:"Fengmei Zhu, Bin Du and Jun Li",authors:[{id:"180555",title:"Dr.",name:"Fengmei",middleName:null,surname:"Zhu",slug:"fengmei-zhu",fullName:"Fengmei Zhu"},{id:"180943",title:"Dr.",name:"Bin",middleName:null,surname:"Du",slug:"bin-du",fullName:"Bin Du"},{id:"180945",title:"Prof.",name:"Jun",middleName:null,surname:"Li",slug:"jun-li",fullName:"Jun Li"}]}],mostDownloadedChaptersLast30Days:[{id:"52017",title:"Grape Drying: Current Status and Future Trends",slug:"grape-drying-current-status-and-future-trends",totalDownloads:2961,totalCrossrefCites:12,totalDimensionsCites:17,abstract:"With high moisture and sugar content, fresh grapes respire and transpire actively after harvest, which contribute to quality loss. Drying can process grapes into raisins for longer shelf-life as well as dehydrated grapes, which can be used for wines or juice production. The pre-treatments, drying method and drying conditions, can significantly influence the quality of final products. In this chapter, firstly, different pre-treatments as a necessary operation previous to the drying of grapes into raisins is introduced. These pre-treatments include chemical pre-treatment, physical pre-treatment, and blanching. In addition, the quality and drying characteristics of different pre-treatments is summarized too. Secondly, the current status of different technologies for grape drying and their effects on drying kinetics and quality attributes of seedless grapes are described to highlight the advantages and disadvantages of each drying method. These drying methods include the traditional open sun drying, shade drying, hot-air drying, freezing drying, microwave drying, as well as the vacuum impulsed drying. Thirdly, influences of drying on bioactive substances (flavonoids, phenolics, anthocyanin, and resveratrol) and antioxidant capacity of grape by-products including seed, skin, stem, and stalk are also examined. Finally, the future research trends of grape and its by-product drying are indentified and discussed.",book:{id:"5253",slug:"grape-and-wine-biotechnology",title:"Grape and Wine Biotechnology",fullTitle:"Grape and Wine Biotechnology"},signatures:"Jun Wang, Arun S. Mujumdar, Weisong Mu, Jianying Feng,\nXiaoshuan Zhang, Qian Zhang, Xiao-Ming Fang, Zhen-Jiang Gao\nand Hong-Wei Xiao",authors:[{id:"28871",title:"Dr.",name:"Zhenjiang",middleName:null,surname:"Gao",slug:"zhenjiang-gao",fullName:"Zhenjiang Gao"},{id:"180873",title:"Prof.",name:"Hong-Wei",middleName:null,surname:"Xiao",slug:"hong-wei-xiao",fullName:"Hong-Wei Xiao"},{id:"181023",title:"Dr.",name:"Jun",middleName:null,surname:"Wang",slug:"jun-wang",fullName:"Jun Wang"},{id:"186411",title:"Prof.",name:"Arun S",middleName:null,surname:"Mujumdar",slug:"arun-s-mujumdar",fullName:"Arun S Mujumdar"},{id:"186412",title:"Prof.",name:"Xiaoshuan",middleName:null,surname:"Zhang",slug:"xiaoshuan-zhang",fullName:"Xiaoshuan Zhang"},{id:"186413",title:"Prof.",name:"Weisong",middleName:null,surname:"Mu",slug:"weisong-mu",fullName:"Weisong Mu"},{id:"186414",title:"Prof.",name:"Qian",middleName:null,surname:"Zhang",slug:"qian-zhang",fullName:"Qian Zhang"},{id:"186415",title:"Dr.",name:"Xiao-Ming",middleName:null,surname:"Fang",slug:"xiao-ming-fang",fullName:"Xiao-Ming Fang"}]},{id:"52146",title:"Grape and Wine Metabolites: Biotechnological Approaches to Improve Wine Quality",slug:"grape-and-wine-metabolites-biotechnological-approaches-to-improve-wine-quality",totalDownloads:2988,totalCrossrefCites:5,totalDimensionsCites:8,abstract:"Grape metabolites can be affected by many extrinsic and intrinsic factors, such as grape variety, ripening stage, growing regions, vineyard management practices, and edaphoclimatic conditions. However, there is still much about the in vivo formation of grape metabolites that need to be investigated. The winemaking process also can create distinct wines. Nowadays, wine fermentations are driven mostly by single-strain inoculations, allowing greater control of fermentation. Pure cultures of selected yeast strains, mostly Saccharomyces cerevisiae, are added to grape must, leading to more predictable outcomes and decreasing the risk of spoilage. Besides yeasts, lactic acid bacteria also play an important role, in the final wine quality. Thus, this chapter attempts to present an overview of grape berry physiology and metabolome to provide a deep understanding of the primary and secondary metabolites accumulated in the grape berries and their potential impact in wine quality. In addition, biotechnological approaches for wine quality practiced during wine alcoholic and malolactic fermentation will also be discussed.",book:{id:"5253",slug:"grape-and-wine-biotechnology",title:"Grape and Wine Biotechnology",fullTitle:"Grape and Wine Biotechnology"},signatures:"Fernanda Cosme, Berta Gonçalves, António Inês, António M. Jordão\nand Alice Vilela",authors:[{id:"60559",title:"Prof.",name:"Berta",middleName:null,surname:"Gonçalves",slug:"berta-goncalves",fullName:"Berta Gonçalves"},{id:"181011",title:"Dr.",name:"Alice",middleName:null,surname:"Vilela",slug:"alice-vilela",fullName:"Alice Vilela"},{id:"186819",title:"Prof.",name:"Fernanda",middleName:null,surname:"Cosme",slug:"fernanda-cosme",fullName:"Fernanda Cosme"},{id:"186820",title:"Prof.",name:"António",middleName:null,surname:"Inês",slug:"antonio-ines",fullName:"António Inês"},{id:"186821",title:"Prof.",name:"António",middleName:null,surname:"M. Jordão",slug:"antonio-m.-jordao",fullName:"António M. Jordão"}]},{id:"52244",title:"Aroma Compounds in Wine",slug:"aroma-compounds-in-wine",totalDownloads:3119,totalCrossrefCites:9,totalDimensionsCites:19,abstract:"Volatile aroma compounds are very important to grape wine quality. In order to understand the flavor of wine, a multitude of scientific investigations was carried out and a number of appropriate analytical tools for flavor study were developed in the past few decades. This chapter deals with major achievements reported in wine aroma and flavor. Firstly, we illustrate the existing knowledge on aroma compounds contributing to wine flavor, as well as the types of wine aroma compounds. Furthermore, the main factors affecting flavor quality in wine are discussed. Finally, the genomics and biotechnology of wine flavor are also summarized. This chapter broadens the discussion of wine aroma compounds to include more modern concepts of biotechnology and also provides relevant background and offers directions for future study.",book:{id:"5253",slug:"grape-and-wine-biotechnology",title:"Grape and Wine Biotechnology",fullTitle:"Grape and Wine Biotechnology"},signatures:"Fengmei Zhu, Bin Du and Jun Li",authors:[{id:"180555",title:"Dr.",name:"Fengmei",middleName:null,surname:"Zhu",slug:"fengmei-zhu",fullName:"Fengmei Zhu"},{id:"180943",title:"Dr.",name:"Bin",middleName:null,surname:"Du",slug:"bin-du",fullName:"Bin Du"},{id:"180945",title:"Prof.",name:"Jun",middleName:null,surname:"Li",slug:"jun-li",fullName:"Jun Li"}]},{id:"52240",title:"Grapevine Biotechnology: Molecular Approaches Underlying Abiotic and Biotic Stress Responses",slug:"grapevine-biotechnology-molecular-approaches-underlying-abiotic-and-biotic-stress-responses",totalDownloads:2489,totalCrossrefCites:3,totalDimensionsCites:6,abstract:"Grapevine is one of the most abundant crops worldwide, with varieties destined for fresh and dry consumption, as well as wine production. Unfortunately, grapevine plants are affected by both biotic and abiotic stresses, generating significant economic losses. These conditions can negatively impact grape cultivation at different stages: plant and berry development during pre- and post-harvest, production, fresh fruit processing and export, along with wine quality. Most of the grapevine varieties are susceptible to several pathogens and within this chapter, particular attention is given to fungi (Botrytis cinerea and Erysiphe necator) and viruses, since they are a worldwide concern. Within the latter, special focus is given to the grapevine leafroll disease, a complex and destructive infection. On the other hand, abiotic stress is also relevant in grapevine, and in this chapter it will be exemplified by UV-B radiation and its impact on growth and fruit development, plant adaptive responses and its relationship with the quality of grape berries for winemaking. The main biotic and abiotic grapevine stress factors are reviewed in this chapter, considering a special focus on biotechnological approaches carried out in order to address them and minimize their detrimental consequences.",book:{id:"5253",slug:"grape-and-wine-biotechnology",title:"Grape and Wine Biotechnology",fullTitle:"Grape and Wine Biotechnology"},signatures:"Grace Armijo, Carmen Espinoza, Rodrigo Loyola, Franko Restovic,\nClaudia Santibáñez, Rudolf Schlechter, Mario Agurto and Patricio\nArce-Johnson",authors:[{id:"181474",title:"Dr.",name:"Patricio",middleName:null,surname:"Arce-Johnson",slug:"patricio-arce-johnson",fullName:"Patricio Arce-Johnson"},{id:"182101",title:"Dr.",name:"Grace",middleName:null,surname:"Armijo",slug:"grace-armijo",fullName:"Grace Armijo"},{id:"182102",title:"Dr.",name:"Carmen",middleName:null,surname:"Espinoza",slug:"carmen-espinoza",fullName:"Carmen Espinoza"},{id:"182108",title:"Dr.",name:"Rodrigo",middleName:null,surname:"Loyola",slug:"rodrigo-loyola",fullName:"Rodrigo Loyola"},{id:"186721",title:"Dr.",name:"Franko",middleName:null,surname:"Restovic",slug:"franko-restovic",fullName:"Franko Restovic"},{id:"186722",title:"MSc.",name:"Claudia",middleName:null,surname:"Santibáñez",slug:"claudia-santibanez",fullName:"Claudia Santibáñez"},{id:"186723",title:"MSc.",name:"Rudolf",middleName:null,surname:"Schlechter",slug:"rudolf-schlechter",fullName:"Rudolf Schlechter"},{id:"186724",title:"MSc.",name:"Mario",middleName:null,surname:"Agurto",slug:"mario-agurto",fullName:"Mario Agurto"}]},{id:"44143",title:"Production of Anthocyanins in Grape Cell Cultures: A Potential Source of Raw Material for Pharmaceutical, Food, and Cosmetic Industries",slug:"production-of-anthocyanins-in-grape-cell-cultures-a-potential-source-of-raw-material-for-pharmaceuti",totalDownloads:7962,totalCrossrefCites:24,totalDimensionsCites:72,abstract:null,book:{id:"3143",slug:"the-mediterranean-genetic-code-grapevine-and-olive",title:"The Mediterranean Genetic Code",fullTitle:"The Mediterranean Genetic Code - Grapevine and Olive"},signatures:"Anthony Ananga, Vasil Georgiev, Joel Ochieng, Bobby Phills and Violeta Tsolova",authors:[{id:"74792",title:"Dr.",name:"Joel W.",middleName:null,surname:"Ochieng",slug:"joel-w.-ochieng",fullName:"Joel W. Ochieng"},{id:"126149",title:"Dr.",name:"Anthony",middleName:null,surname:"Ananga",slug:"anthony-ananga",fullName:"Anthony Ananga"},{id:"136830",title:"Dr.",name:"Devaiah",middleName:null,surname:"Kambiranda",slug:"devaiah-kambiranda",fullName:"Devaiah Kambiranda"},{id:"137412",title:"Dr.",name:"Violetka",middleName:null,surname:"Tsolova",slug:"violetka-tsolova",fullName:"Violetka Tsolova"},{id:"165414",title:"Dr.",name:"Vasil",middleName:null,surname:"Georgiev",slug:"vasil-georgiev",fullName:"Vasil Georgiev"},{id:"165415",title:"Dr.",name:"Bobby",middleName:null,surname:"Phills",slug:"bobby-phills",fullName:"Bobby Phills"}]}],onlineFirstChaptersFilter:{topicId:"344",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:90,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:320,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:133,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:107,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:17,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. 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",coverUrl:"https://cdn.intechopen.com/series/covers/22.jpg",latestPublicationDate:"June 27th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:1,editor:{id:"356540",title:"Prof.",name:"Taufiq",middleName:null,surname:"Choudhry",slug:"taufiq-choudhry",fullName:"Taufiq Choudhry",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000036X2hvQAC/Profile_Picture_2022-03-14T08:58:03.jpg",biography:"Prof. Choudhry holds a BSc degree in Economics from the University of Iowa, as well as a Masters and Ph.D. in Applied Economics from Clemson University, USA. In January 2006, he became a Professor of Finance at the University of Southampton Business School. He was previously a Professor of Finance at the University of Bradford Management School. He has over 80 articles published in international finance and economics journals. His research interests and specialties include financial econometrics, financial economics, international economics and finance, housing markets, financial markets, among others.",institutionString:null,institution:{name:"University of Southampton",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:6,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",isOpenForSubmission:!0,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"26",title:"Machine Learning and Data Mining",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",isOpenForSubmission:!0,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. 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Heshmati",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313921/images/system/313921.jpg",biography:"Dr. Hassan Massoud Heshmati is an endocrinologist with 46 years of experience in clinical research in academia (university-affiliated hospitals, Paris, France; Mayo Foundation, Rochester, MN, USA) and pharmaceutical companies (Sanofi, Malvern, PA, USA; Essentialis, Carlsbad, CA, USA; Gelesis, Boston, MA, USA). His research activity focuses on pituitary tumors, hyperthyroidism, thyroid cancers, osteoporosis, diabetes, and obesity. He has extensive knowledge in the development of anti-obesity products. Dr. Heshmati is the author of 299 abstracts, chapters, and articles related to endocrinology and metabolism. 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He was also the recipient of the Australian Government Endeavour Research Fellowship for postdoctoral research as an adjunct senior researcher at the University of Tasmania, Australia. Dr. Hasanuzzaman’s current work is focused on the physiological and molecular mechanisms of environmental stress tolerance. Dr. Hasanuzzaman has published more than 150 articles in peer-reviewed journals. He has edited ten books and written more than forty book chapters on important aspects of plant physiology, plant stress tolerance, and crop production. According to Scopus, Dr. Hasanuzzaman’s publications have received more than 10,500 citations with an h-index of 53. He has been named a Highly Cited Researcher by Clarivate. He is an editor and reviewer for more than fifty peer-reviewed international journals and was a recipient of the “Publons Peer Review Award” in 2017, 2018, and 2019. He has been honored by different authorities for his outstanding performance in various fields like research and education, and he has received the World Academy of Science Young Scientist Award (2014) and the University Grants Commission (UGC) Award 2018. He is a fellow of the Bangladesh Academy of Sciences (BAS) and the Royal Society of Biology.",institutionString:"Sher-e-Bangla Agricultural University",institution:{name:"Sher-e-Bangla Agricultural University",country:{name:"Bangladesh"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",biography:"Kusal K. Das is a Distinguished Chair Professor of Physiology, Shri B. M. Patil Medical College and Director, Centre for Advanced Medical Research (CAMR), BLDE (Deemed to be University), Vijayapur, Karnataka, India. Dr. Das did his M.S. and Ph.D. in Human Physiology from the University of Calcutta, Kolkata. His area of research is focused on understanding of molecular mechanisms of heavy metal activated low oxygen sensing pathways in vascular pathophysiology. He has invented a new method of estimation of serum vitamin E. His expertise in critical experimental protocols on vascular functions in experimental animals was well documented by his quality of publications. He was a Visiting Professor of Medicine at University of Leeds, United Kingdom (2014-2016) and Tulane University, New Orleans, USA (2017). For his immense contribution in medical research Ministry of Science and Technology, Government of India conferred him 'G.P. Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. in Chemistry in July 2000, and his Ph.D. in Physical Chemistry in 2007 from the University of Khartoum, Sudan. In 2009 he joined the Dr. Ron Clarke research group at the School of Chemistry, Faculty of Science, University of Sydney, Australia as a postdoctoral fellow where he worked on the Interaction of ATP with the phosphoenzyme of the Na+, K+-ATPase, and Dual mechanisms of allosteric acceleration of the Na+, K+-ATPase by ATP. He then worked as Assistant Professor at the Department of Chemistry, University of Khartoum, and in 2014 was promoted to Associate Professor ranking. In 2011 he joined the staff of the Chemistry Department at Taif University, Saudi Arabia, where he is currently active as an Assistant Professor. His research interests include:\r\n(1) P-type ATPase Enzyme Kinetics and Mechanisms; (2) Kinetics and Mechanism of Redox Reactions; (3) Autocatalytic reactions; (4) Computational enzyme kinetics; (5) Allosteric acceleration of P-type ATPases by ATP; (6) Exploring of allosteric sites of ATPases and interaction of ATP with ATPases located in the cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. Pakistan Institute of Nuclear Science & Technology (PINSTECH) Islamabad, Punjab Institute of Nuclear Medicine (PINM), Faisalabad and Institute of Nuclear Medicine and Radiology (INOR) Abbottabad are the main collaborating institutes.",institutionString:"Government College University",institution:{name:"Government College University, Faisalabad",country:{name:"Pakistan"}}},{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",country:{name:"Hungary"}}},{id:"277367",title:"M.Sc.",name:"Daniel",middleName:"Martin",surname:"Márquez López",slug:"daniel-marquez-lopez",fullName:"Daniel Márquez López",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/277367/images/7909_n.jpg",biography:"Msc Daniel Martin Márquez López has a bachelor degree in Industrial Chemical Engineering, a Master of science degree in the same área and he is a PhD candidate for the Instituto Politécnico Nacional. His Works are realted to the Green chemistry field, biolubricants, biodiesel, transesterification reactions for biodiesel production and the manipulation of oils for therapeutic purposes.",institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",country:{name:"Argentina"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",biography:"Francisco Javier Martín-Romero (Javier) is a Professor of Biochemistry and Molecular Biology at the University of Extremadura, Spain. He is also a group leader at the Biomarkers Institute of Molecular Pathology. Javier received his Ph.D. in 1998 in Biochemistry and Biophysics. At the National Cancer Institute (National Institute of Health, Bethesda, MD) he worked as a research associate on the molecular biology of selenium and its role in health and disease. After postdoctoral collaborations with Carlos Gutierrez-Merino (University of Extremadura, Spain) and Dario Alessi (University of Dundee, UK), he established his own laboratory in 2008. The interest of Javier's lab is the study of cell signaling with a special focus on Ca2+ signaling, and how Ca2+ transport modulates the cytoskeleton, migration, differentiation, cell death, etc. He is especially interested in the study of Ca2+ channels, and the role of STIM1 in the initiation of pathological events.",institutionString:null,institution:{name:"University of Extremadura",country:{name:"Spain"}}},{id:"198499",title:"Dr.",name:"Daniel",middleName:null,surname:"Glossman-Mitnik",slug:"daniel-glossman-mitnik",fullName:"Daniel Glossman-Mitnik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/198499/images/system/198499.jpeg",biography:"Dr. Daniel Glossman-Mitnik is currently a Titular Researcher at the Centro de Investigación en Materiales Avanzados (CIMAV), Chihuahua, Mexico, as well as a National Researcher of Level III at the Consejo Nacional de Ciencia y Tecnología, México. His research interest focuses on computational chemistry and molecular modeling of diverse systems of pharmacological, food, and alternative energy interests by resorting to DFT and Conceptual DFT. He has authored a coauthored more than 270 peer-reviewed papers, 32 book chapters, and 4 edited books. He has delivered speeches at many international and domestic conferences. He serves as a reviewer for more than eighty international journals, books, and research proposals as well as an editor for special issues of renowned scientific journals.",institutionString:null,institution:null},{id:"217323",title:"Prof.",name:"Guang-Jer",middleName:null,surname:"Wu",slug:"guang-jer-wu",fullName:"Guang-Jer Wu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217323/images/8027_n.jpg",biography:null,institutionString:null,institution:null},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/148546/images/4640_n.jpg",biography:null,institutionString:null,institution:null},{id:"272889",title:"Dr.",name:"Narendra",middleName:null,surname:"Maddu",slug:"narendra-maddu",fullName:"Narendra Maddu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272889/images/10758_n.jpg",biography:null,institutionString:null,institution:null},{id:"242491",title:"Prof.",name:"Angelica",middleName:null,surname:"Rueda",slug:"angelica-rueda",fullName:"Angelica Rueda",position:"Investigador Cinvestav 3B",profilePictureURL:"https://mts.intechopen.com/storage/users/242491/images/6765_n.jpg",biography:null,institutionString:null,institution:null},{id:"88631",title:"Dr.",name:"Ivan",middleName:null,surname:"Petyaev",slug:"ivan-petyaev",fullName:"Ivan Petyaev",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Lycotec (United Kingdom)",country:{name:"United Kingdom"}}},{id:"428313",title:"Dr.",name:"Sambangi",middleName:null,surname:"Pratyusha",slug:"sambangi-pratyusha",fullName:"Sambangi Pratyusha",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"CGIAR",country:{name:"France"}}},{id:"423869",title:"Ms.",name:"Smita",middleName:null,surname:"Rai",slug:"smita-rai",fullName:"Smita Rai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424024",title:"Prof.",name:"Swati",middleName:null,surname:"Sharma",slug:"swati-sharma",fullName:"Swati Sharma",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"439112",title:"MSc.",name:"Touseef",middleName:null,surname:"Fatima",slug:"touseef-fatima",fullName:"Touseef Fatima",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}}]}},subseries:{item:{id:"12",type:"subseries",title:"Human Physiology",keywords:"Anatomy, Cells, Organs, Systems, Homeostasis, Functions",scope:"Human physiology is the scientific exploration of the various functions (physical, biochemical, and mechanical properties) of humans, their organs, and their constituent cells. The endocrine and nervous systems play important roles in maintaining homeostasis in the human body. Integration, which is the biological basis of physiology, is achieved through communication between the many overlapping functions of the human body's systems, which takes place through electrical and chemical means. Much of the basis of our knowledge of human physiology has been provided by animal experiments. Because of the close relationship between structure and function, studies in human physiology and anatomy seek to understand the mechanisms that help the human body function. The series on human physiology deals with the various mechanisms of interaction between the various organs, nerves, and cells in the human body.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11408,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. 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