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The functional changes in hormone-sensitive adenylyl cyclase (AC) signaling system of the central nervous system (CNS) and periphery play a crucial role in etiology and pathogenesis of diabetes mellitus (DM). The identification of these changes in AC signaling system and the abnormalities in AC signaling network are necessary for creation of the new strategies to treat and prevent diabetic pathology. In this chapter, our data and the results of other authors on the changes in hormone-sensitive adenylyl cyclase signaling system (ACSS) in the diabetic brain and heart and on their contribution to etiology and pathogenesis of DM and its complications, diabetic cardiomyopathy in particular, are presented and analyzed, and the promising approaches to treat DM and its complications, which are based on the restoration of AC signaling cascades and their functional interaction, are discussed.

Lentil (Lens culinaris Medikus subsp. culinaris) is an important dietary source of protein and other essential nutrients in South and West Asia, North and East Africa. Lentil crops are vulnerable to a number of diseases caused by fungi, viruses, nematodes, insect pests, parasitic plants and abiotic stresses. Among them, the most significant and serious soil-borne disease is Fusarium wilt (Fusarium oxysporum f.sp. lentis: Fol). Fusarium wilt causes yield loss up to 50% in farmers’ fields. The pathogen showed high levels of phenotypic and genotypic diversity in India, Algeria, Syria and Iran. The disease thrives at 22–25°C temperature and affect lentil either at seedling and vegetative or the reproductive stages of the crop. To minimize yield losses, an integrated management strategy comprising resistant/partial resistant cultivars, adjusting sowing time, bio-control and chemical seed treatments is the best approach to reduce the incidence of the Fusarium wilt of lentil. This review covers past achievements in managing the disease, pathogen diversity and identify gaps in managing Fusarium wilt to improve productivity and production of the crop.

The G protein-coupled receptors (GPCRs), a large family of the receptors that specifically interact with a number of signal molecules, play a key role in the regulation of fundamental cell processes, and the pharmacological action of over 40% of drugs is carried out through GPCRs. In the last years, a significant progress was made in the creation of selective regulators of GPCRs interacting with their allosteric sites, such as the synthetic peptides corresponding to intracellular regions of receptors (GPCR-peptides) and the low-molecular weight agonists and antagonists of GPCRs. This review describes the recent results obtained by us and other authors in the development of GPCR-peptides and low-molecular weight agonists and the prospects of their use in clinics.

In our experiments with an in vitro culture of rat cardiac cells, we identified and described for the first time the phenomenon of intracellular development of CSCs in mature CMs with formation of the “cell-in-cell structures” (CICSs). Recently, we have confirmed the reproducibility of our results and existence of this phenomenon in rats of different age groups, 1-year-old bull, adult mice and humans. Moreover, we demonstrated the 5–10 times increase in the amount of CICSs after exposure of in vitro cultures to hypoxia and acidosis, that is, these conditions stimulate intracellular development of CSCs. Our data strongly suggest that transitory amplifying cells (TACs), which release from CICSs, are present as a very rare cell population in adult and old rats. Therefore, we assume that TACs are important for renewal of myocardium during ontogenesis. TACs should be considered as the major source of cells that can reduce myocardial damage in adult mammals with various pathologies of the cardiovascular system. In conclusion, precise and exhaustive analysis of the phenomenon of intracellular development of CSCs, CICSs and TACs will pave the way for cell technologies of new generation in regenerative medicine.

In Mexico, high incidences of Fusarium affect common bean (Phaseolus vulgaris L.) production, reducing grain yields due to seedling death and crop standing reductions. Production of resistant germplasm could be an appropriate strategy for grain yield increasing. Bean breeding programs need the former analysis of plant-pathogen pathosystem to perform the selection of segregating populations with improved resistance to root rot pathogens and the best agroecosystem adaptation. Here, we report our results on characterization of genetic variability patterns of Fusarium solani f. sp. phaseoli (FSP) from Aguascalientes, México; the analysis of P. vulgaris germplasm reactions to highly and naturally FSP-infested field and controlled conditions; and the identification of genetic basis of resistance to FSP root rot in segregating common bean populations. Significant genetic variability in FSP isolates from Aguascalientes and other regions of México was found. Also, we found high variation on reactions to FSP root rots, resistance was more frequent on black seed-coated beans, and susceptibility was common in pinto beans. Resistance to FSP in BAT 477 seedlings was associated with one quantitative trait loci (QTL).

Appendix: The Main Problems and Methods of Evolutionary Physiology—A Lecture by Leon A. Orbeli

Sugarcane is one of the most important crops for sugar production in sugarcane-growing areas. Many biotic and abiotic stresses affected the sugarcane production which leads to severe losses. Pokkah boeng is now playing a very important role due to its economic threats. Currently, the occurrence and rigorousness of pokkah boeng disease have been spread like wildfire from major sugarcane-growing countries. Pokkah boeng is a fungal disease that can cause serious yield losses in susceptible varieties. Infection of the disease is caused either by spores or ascospores. It may cause serious yield losses in commercial plantings. However, there have been many reported outbreaks of the disease which have looked spectacular but have caused trade and industry loss. Fusarium species complex is the major causal agent of this disease around the world, but some researchers have documented the increased importance of Fusarium. Three Fusarium species have been identified to cause the sugarcane pokkah boeng disease in China. Moreover, Fusarium may be accompanied of its mycotoxin production, genomic sequencing, and association with nitrogen application in China. Many studies on disease investigations, breeding of disease-resistant varieties, and strategy of disease control have also been carried out in China.

The problems and limitations of the control of diseases caused by phytopathogens through the use of fungicides, make the biological control present as an alternative method in the production of tomato plants in greenhouse, which is limited by the incidence of Fusarium oxysporum Schlechtend.:Fr., being the most worldwide destructive disease. The objective of the present investigation was to evaluate the effect of three Mexican strains of the genus Trichoderma against F. oxysporum on the production of tomato seedlings under greenhouse conditions, as well as to determine the antagonistic effect of the strains used. The Trichoderma harzianum strain had the highest antagonistic activity (81.50%) and the highest growth rate (1.25 cm/day), proving to be the most aggressive strain to control F. oxysporum. in addition the results of the interaction of the dual cultures paired, presented a visible overgrowth zone with hyphae of Trichoderma spp. Seeds inoculated with T. harzianum showed a survival of 84% and a mortality of 16%, lower than the control group, which present a mortality of 58%; however, the treatment inoculated with F. oxysporum had the highest incidence of “disease” with 83%, the lowest survival (17%) and a decrease of the green biomass with respect to the control.

Androstenedione (AD) is a steroid intermediate valuable for the production of steroid medicaments. Microbial biotransformation of phytosterol to produce AD is a well-researched area. However, low substrate solubility of phytosterol in aqueous media and nucleus degradation of AD to androstadienedione (ADD) or 9-hydroxy-AD are the major obstacles for AD production leading to detailed research for optimization of biotransformation process. In this review, microbial transformation of AD with respect to the existing methods of chemical or biochemical synthesis of AD are extensively discussed. This review examines the microbial biotransformation process and limitations for enhanced AD production. Factors affecting the effective biotransformation process to obtain AD are discussed and limitations are highlighted. The main content of this review focuses on the recent and futuristic biotechnological advances and strategies in techniques to enhance AD bioprocess.

Ion channels mediate selective passive transport of ions across biomembranes. They participate in diverse physiological processes and belong to distinct protein families. Understanding specific roles of different channels in physiology, pathology, and pharmacology requires knowledge of their origin and evolution. Traditional approaches include experimental physiological studies and analysis of sequences and genomes. In the last two decades, availability of 3D structures of many ion channel proteins revolutionized ion channel studies, including their evolution. In this chapter, we consider examples of how 3D structures provided clues for understanding evolutionary aspects of multi-domain organization, domain folding, and roles of highly conserved and variable residues. Such achievements are important for addressing practical problems including drug design, channelopathies, and acquired resistance to insecticides.

Traditionally, the evolution of flora and fauna on the Earth as well as the evolution of their physical and chemical environment are considered separately. At the same time, when considering the global evolutionary changes, it becomes clear that the evolution of all these components occurs in close relationship and that they together constitute a unified evolutionary process. Thus, we should talk about their co-evolution and that the whole biosphere is a united functional system. In this chapter, we briefly discuss some of the major “inventions” of ancient life that are responsible for global biosphere transformations and which “worked” in the biosphere until now (photosynthesis, eukaryotic cell, multicellular organism, and the other findings). The evolution of the Precambrian life as well as the Phanerozoic stage of the biosphere evolution are considered in this context.

Academician E.M. Kreps founded the Laboratory of Hyperbaric Physiology in 1960. Heads of the Laboratory were G.L. Zaltsman (1960–1972), A.I. Selivra (1972–1975), I.A. Aleksandrov (1975–1982) and I.T. Demchenko (1983–2009). In 2009, the Laboratory was merged with the Laboratory of Respiratory Physiology (A.I. Krivchenko). For more than five decades, Hyperbaric Laboratory has conducted basic and applied researches dealt with CNS oxygen toxicity, the high pressure nervous syndrome and nitrogen narcosis. Main achievements of basic researches are as follows: identified key mechanisms of adaptive responses of CNS and cardiorespiratory systems to breathing gas mixtures at high pressure, neurophysiological mechanisms of CNS oxygen toxicity and high pressure nervous syndrome, and pathogenesis of nitrogen narcosis. Main achievements of the translation of hyperbaric researches are as follows: new technology for 1000 m dive of animals (monkeys) using the gas mixture (He-N2-O2), new compression and decompression profiles for free escape of monkey from a depth of 700 m, use preconditional hypoxia and hyperthermia for the protection of nitrogen narcosis. Currently, main researches are focusing on the evaluation of molecular and cellular mechanisms of biological responses to extreme hyperbaric environments.

This review covers our recent advantages in studying the ontogenetic aspects of physiological mechanisms underlying regulation of rhythmic behavior. We have revealed that excitation patterns that emerged at early stages of phylogenetic development of life forms contribute greatly to the rhythmic activity of living vertebrates and invertebrates. These patterns govern spontaneous excitation, which is easily observed during the early stage of ontogenesis. The intensity and patterns of rhythmic activity are determined by nature and kinetics of certain metabolic reactions. During perinatal and sometimes postnatal periods (as in prematurely born animals), endogenic rhythmicity of developing physiological structures is strongly pronounced due to relatively stable living conditions. This rhythmic behavior is coordinated within an entire organism. Its integration in multiple systems is driven by amplitude and frequency modulation yielding rhythms of various frequency ranges. Indeed, it is the complex and conjoint functioning of physiological systems that maintains homeostasis in developing organisms. We present the results of our authentic research concerning the evolution and ontogeny of regulatory mechanisms of motor, cardiovascular, and respiratory systems. The aspects of intact and disrupted development are considered, involving the changes in dopaminergic, norepinephrinergic, and cholinergic system activation.

In recent years, there has been growing interest in computer modeling of the evolution of gene and cell regulatory networks, in general, and in computational studies of the classic ideas of Baldwin, Schmalhausen, Waddington, and followers, in particular. Two related aspects of Waddington’s evolutionary theories are the concepts of canalization and of genetic assimilation. Canalization is associated with the robust development of an individual to diverse perturbations and noise, though, when fluctuations in developmental factors exceed a particular limit, the normal developmental trajectory can be “thrown out” of the robust canal, resulting in an altered phenotype. If selective pressure favors the new phenotype, an initial individual loss of canalization can lead to phenotypic changes in the population (with canalization then becoming established for the new phenotype). Genetic assimilation is the subsequent genetic fixing of the new trait in the population. Recent experimental and theoretical works have established a quantitative basis for these classic concepts of Waddington; this chapter will review these new developments in systems evolutionary biology.

Mycoparasitic fungi, fungi preying on other fungal species, are prolific producers of volatile and non-volatile secondary metabolites. Several secondary metabolites are produced during mycoparasitism to weaken the host and support attack and parasitism. Further, evidence accumulated that some secondary metabolites also act as communication molecules. Besides their antagonistic activity, several fungal mycoparasites exhibit beneficial effects on plants and some of their secondary metabolites have plant growth-promoting and defense stimulating activities. As many secondary metabolism-associated gene clusters remain silent under standard laboratory conditions, the full variety as well as the underlying biosynthetic pathways employed by fungal mycoparasites for secondary metabolite production still await clarification. Nonetheless, the variety of currently known secondary metabolites and their range of activities is impressive already and they exhibit a great potential for agriculture, pharmacology and other industrial applications.

During the last 20 years, new data on the neurophysiological mechanisms underlying different types of cognitive activity, especially speech and its ontogenetic formation, were obtained in the Laboratory of Children’s Neurophysiology headed by Prof. M.N. Tsitseroshin. Using the analysis of the spatial-temporal structure of regional interactions of cortical bioelectric potentials (so-called functional connectivity), we investigated how specific language levels, such as phonology, grammar, and semantics, are represented in the brain. The data obtained in children vs. adults indicate that the speech perception and production require joint and extremely coordinated activities of both hemispheres, along with the obligatory and differentiated involvement of “classic” speech centers in the left hemisphere, especially Wernicke’s area. Another line of our research is to explore the differences, which arise during verbal processing in adults and children with impaired vs. non-impaired speech, particularly with alalia, dysarthria and stuttering, using behavioral and EEG data. Our data obtained in children vs. adults allow assessing the degree of maturity in the organization of the central processes of maintaining the studied types of verbal activity in children of different ages. These data allow expanding modern concepts about the brain mechanisms of verbal activity in children in the norm and pathology.

Effective mitochondria bioenergetics requires the proper functioning of various intra-organelle dehydrogenases. By providing pyridine and flavin adenine dinucleotides to the electron chain, or Acyl-CoA for the reactions of the tris-carboxylic acid cycle, or the acylation of fatty acids to undergo β-oxidation, these dehydrogenases preside to the organelle production of ATP, required for a variety of cellular functions under physiological conditions. The operation of the various dehydrogenases is mainly regulated by hormones through changes in intra-mitochondrial cation levels and ratios, namely Ca2+ and Mg2+. Dysregulation of specific dehydrogenases under pathological conditions results in marked changes in the energetic level of the organelle and ultimately the cell. The present review will attempt to highlight the role of the main mitochondrial dehydrogenases and their regulation, and provide a general assessment of their dysfunction and associated consequences under some of the most common human pathologies.

This chapter summarizes the phylogenetic and ontogenetic approaches for studying cognitive disorders such as Alzheimer’s disease. It gives an extended example of evaluation of animal behavior and brain properties using an original model of prenatal hypoxia in rats by various physiological, behavioral, immunohistochemical, molecular biological, and biochemical techniques at different stages of postnatal development, which provide a better understanding of the pathological processes in the human brain during the development of neurodegeneration.

Herbal medicine is gaining acceptance worldwide for their effective pharmacological effects and relative safety. Plants have metabolic pathways that lead to the production and accumulation of secondary metabolites such as alkaloids, glycosides, and terpenoids that exhibit various biological activities. Plant secondary metabolites have been the major foci of investigation for several years and have been successfully used against a number of communicable and noncommunicable diseases such as diabetes, cancer, and viral infections. This chapter will explore Malaysian plants, their secondary metabolites, and their biological/medicinal properties with a particular focus on some selected species under a national project. Other aspects such as plant tissue culture to produce secondary metabolites and a case study on the use of secondary metabolites in the prevention and treatment of dengue fever are also described. While a lot of effort has been put in, further research and development into plant secondary metabolites are needed including using the plant tissue culture approach toward reaching high-value herbal industry.

Cyanobacteria are a diverse group of photosynthetic bacteria found in marine, freshwater and terrestrial habitats. Secondary metabolites are produced by cyanobacteria enabling them to survive in a wide range of environments including those which are extreme. Often production of secondary metabolites is enhanced in response to abiotic or biotic stress factors. The structural diversity of secondary metabolites in cyanobacteria ranges from low molecular weight, for example, with the photoprotective mycosporine-like amino acids to more complex molecular structures found, for example, with cyanotoxins. Here a short overview on the main groups of secondary metabolites according to chemical structure and according to functionality. Secondary metabolites are introduced covering non-ribosomal peptides, polyketides, ribosomal peptides, alkaloids and isoprenoids. Functionality covers production of cyanotoxins, photoprotection and antioxidant activity. We conclude with a short introduction on how secondary metabolites from cyanobacteria are increasingly being sought by industry including their value for the pharmaceutical and cosmetics industries.

Plants are a remarkable source of high-value secondary metabolites with applications in various domains. Plant cell and tissue culture techniques appear as environmentally friendly alternatives for the production of secondary metabolites when natural supply is limited or chemical synthesis is unviable. In this chapter, the main advantages of using plant cell and tissue culture techniques for the production of plant secondary metabolites are presented as well as the different biotechnological approaches available to improve their production. In addition, the production of anticancer compounds (camptothecin, podophyllotoxin, taxol, vinblastibe, and vincristine) and metabolites from Lamiaceae spp. (phenolics as rosmarinic acid) were selected as examples to be highlighted. The study reviewed shows that undifferentiated cells are the preferred culture system used for the production of high-value secondary metabolites in vitro although there are many examples reporting the production in differentiated tissues particularly in hairy roots. Efforts have been made to scale up the production, and several strategies have been successfully applied to increase the production yields at the laboratorial scale. Nevertheless, there are only few examples of plant secondary metabolites production at commercial level, and further in-depth studies are still required.

Protein reabsorption in the renal proximal tubule (PT) is a vitally important process which prevents the loss of filtered proteins and provides their participation in subsequent metabolism. Despite considerable changes in renal structure and function in the process of evolution, very little is known about the functional similarities or specifics of tubular protein reabsorption in the kidney of lower vertebrates compared with the mammalian and human kidney. This article presents an overview of our recent studies on protein reabsorption in the kidney of amphibians, which are used as one of the main animal models for current biological and biomedical research. In frogs, newts, and rats, the absorption capacity of epithelial PT cells was studied after the introduction of green fluorescent protein (GFP), yellow fluorescent protein (YFP), and lysozyme. Molecular mechanisms of receptor-mediated protein endocytosis were also investigated by immunohisto- and immunocytochemistry, electron, fluorescent, and laser scanning confocal microscopy.

Plants produce secondary metabolites that are essential for survival of the producing plants such as to attract insect for pollination and defend against pest and environmental stress. Plant secondary metabolites are widely exploited by the mankind especially for medicine, one of which is to protect against infection by microorganism including fungi. Many medicinal plants have been traditionally used and/or studied for the fungicidal activity. Most of the plants studied or traditionally used as antifungi show antiphytophthora activity and some of them also active as antifusarium. Higher concentration plant extract is needed to inhibit the growth of Fusarium than Phytophthora. Considering the concentration in plant and activity as antifungi, eugenol is considered to be the most effective to be used as antiphytophthora and antifusarium. The presence of aromatic moiety, orthodioxy substitution, and double bond in the terminal of site chain is considered to be essential for the antifungal activity of the eugenol derivative.

T-2 toxin and its major metabolite HT-2 toxin are type A trichothecene mycotoxins produced by the Fusarium moulds, present mainly in cereals and cereal-based products. The studies quoted under this chapter bring data on the incidence of T-2 and HT-2 toxin in unprocessed cereals (n = 285) harvested in Croatia during a two-year period. They also demonstrate the influence of certain thermal food processing methods on the reduction of T-2 and HT-2 toxin in naturally contaminated cereals. In analysed cereals, the highest percentage of T-2- and HT-2-positive samples was determined in oat samples (56.9%), followed by triticale (34.5%), maize (32.1%) and barley samples (22.7%), whereas the highest mean (94.8 ± 63.7 μg/kg) and maximal concentration (420 μg/kg) of the toxins in reference were determined in maize. The summary T-2/HT-2 concentrations found in one maize and one triticale sample were higher than the indicative levels, necessitating further sampling and investigations of conditions under which the production of these toxins takes place. Thermal food processing in terms of roasting (which enabled 28.8–54.4%-toxin reduction) and especially extrusion (which enabled 73.0–92.5%-toxin reduction) efficiently reduces T-2/HT-2 levels, whereas cooking does not significantly aid in their reduction (< 10%-toxin reduction achieved).

Plant secondary metabolites are synthesized for their protection and regulation purposes. Quite often, due to their properties, these metabolites have relevant organoleptic and biological properties and can play important roles in human health and general well-being. A relevant case study in this context is berries and flowers from Sambucus nigra L., which have been used for generations in folk medicine. Although those effects are mainly linked to phenolic compounds, mono and sesquiterpenic secondary metabolites may also play a key role. Despite their potential, S. nigra mono and sesquiterpenic compounds are yet largely unexplored. Complex and dynamic external and internal plant-related phenomena deeply affect terpenes profile, as metabolism, abiotic and biotic stresses, and understanding these phenomena is the first step for S. nigra berries and flowers’ valuation. This chapter will cover aspects linked to elder plant uses, mono and sesquiterpenic composition, and the influence of preharvest and postharvest effects over these metabolites. This knowledge is crucial for scientists and industries to understand and improve the quality of S. nigra-based products.

Introductory Chapter: Fusarium: Pathogenicity, Infections, Diseases, Mycotoxins and Management

In brain gangliosides and phospholipids of stenothermal cold-water teleost fishes, higher content of polyenoic and monoenoic fatty acids was revealed than in brain gangliosides and phospholipids of warm-water stenothermal teleosts. The changes in fatty acid composition of lipids during adaptation of fishes to living in cold water (or at great water depth) are directed to the maintenance of liquid-crystalline state of cell membranes and their optimal fluidity, physical state, and microheterogeneity. The results of cluster analysis of the data on composition of carbohydrate component of brain gangliosides of various ectothermic vertebrates were used to create the dendrogram. This dendrogram was found to correspond appreciably to the tree of classical taxonomy of vertebrates. The changes in molecular organization of brain gangliosides in the course of evolution of vertebrates are suggested to contribute to differentiation of brain and complication of its functions in phylogenesis. The main brain gangliosides (GM1, GD1a, GD1b, GT1b) may be considered to be typical adaptogens. They protect neurons against the action of excitatory amino acids, hydrogen peroxide, amyloid β-peptide, and other toxins. Protective effect of gangliosides against these toxins depends on activation of Trk receptor tyrosine kinase and downstream protein kinases.

This chapter is a continuation of our previous study of the forebrain evolution in vertebrates using some new tests allowing evolutionary transformations to be revealed. As such tests, we chose the expression of calcium-binding proteins as neuronal functional markers and the metabolic activity of cytochrome oxidase, characterizing the level of neuronal activity. Here, we report the results of our study of the thalamic visual and auditory centers in reptiles (turtles, Emys orbicularis and Testudo horsfieldii) and birds (pigeon, Columba livia) with a special focus on differences in their parallel visual thalamofugal and tectofugal channels and auditory lemniscal and extralemniscal channels. A comparison with data obtained in other Sauropsida amniotes was drawn to elucidate the role of phylogenetic and functionally adaptive factors determining variable distribution of calcium-binding proteins and metabolic activity, as well as to identify evolutionary conservative and plastic traits in the organization of these thalamic sensory centers.

Introduction: The 60th Anniversary of the Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Saint Petersburg

The genus Fusarium is a group of fungi producing several types of toxins with toxicological effect in both humans and animals. Such fungi are commonly found in soils so it can contaminate various types of crops, preferably cereals, leading to significant economic losses. Relative humidity, storage temperature and various handling in cereales increase the possibility of contamination by Fusarium toxins. Cereals naturally have secondary metabolites that may help attenuate contamination by these toxins, but it is necessary to know strategies and mechanisms that generate inactivation mycotoxins. This chapter reviews relevant information about cereal mycotoxin contamination, as well as the production of cereal secondary metabolites as a strategy to reduce the possibility of mycotoxin contamination.

Historically, Fusarium has been important because: (i) taxonomy of Fusarium species has been a controversial issue, (ii) Fusarium species are among the most important plant pathogens in the world, and (iii) many Fusarium species produce mycotoxins that cause animal and human diseases. The genus Fusarium was introduced by Link in 1809. “Die Fusarien” was published by Wollenweber and Reinking in 1935, described 65 species, 55 varieties, and 22 forms of Fusarium. In 1945, Snyder and Hansen reduced number of species of Fusarium to nine. In 1990s, the application of phylogenic species concept based on the DNA sequencing resulted in introducing new species of Fusarium that cannot be distinguished morphologically. In 2006, Leslie and Summerell integrated the morphological, biological, and phylogenic species concepts and published “The Fusarium Laboratory Manual,” which provides details of identification of 70 Fusarium species. Although considerable research studies on Fusarium have been accomplished in the past 200 years, yet Fusarium diseases continue to be among the most important plant diseases. Fusarium fungi are the most widespread in cereal-growing areas of the world and produce a diversity of mycotoxins, including zearalenone, fumonisin, moniliformin, and trichothecenes, which cause various disorders, including cancer, in animals and humans.

Fusarium oxysporum causes vascular wilt disease in a broad range of crops, including tomato (Solanum lycopersicum). Tomato, a major and important vegetable crop, is susceptible to F. oxysporum f. sp. lycopersici (FOL), a biotrophic pathogen that is the causal agent of tomato wilt resulting in significant yield losses each year. Development of disease in susceptible tomato plants requires FOL to advance through a series of transitions, beginning with spore germination and culminating with establishment of a systemic infection. In addition, many host attributes, including the composition of root exudates, the structure of the root cortex, and the capacity to recognize and respond quickly to invasive growth of a pathogen, can impede the development of FOL. FOL divides into races on the basis of the ability of individual strains to overcome specific genes. This implies the presence of avirulence genes (Avr) in the fungus that is recognized by products of the corresponding genes. In tomato, resistance (R) genes against the wilt-inducing FOL are called immunity genes, and the interaction between these genes will determine the success of the infection.

An Introductory Chapter: Secondary Metabolites

This article describes a philosophy of an arising multicellularity on the basis of division of functions between cells. Laws of the division are discussed in elementary multicellularity units, called histions. There is a variety of the histions that have different social structures. Several parameters have been proposed to describe them quantitatively and to systematize them by means of a periodic table. Consideration is given to the rules that govern polymerization of histions as well as the formation of regular cellular networks using them. It is shown that these types of networks could serve as biological tissue models that enable one to predict the tissue development. It has been found that arising multicellularity can result in a drastically decreased metabolites production per cell and thus creates the need in their economically justified unequal distribution.

Soil contains enzymes, constantly interacting with soil constituents, e.g. minerals, rhizosphere and numerous nutrients. Enzymes, in turn, catalyse important biochemical reactions for rhizobacteria and plants, stabilize the soil by degrading wastes and mediate nutrient recycling.The available enzymes inside soil could originate from plants, animals or microbes. The enzymes that are produced from these organism could exhibit intracellular activities, at the cell membrane, interacting therefore with soil and its constituents, or extracellularly (so freely available). Therefore, vis-à-vis to plant nutrition, the (extra or sub) cellular localization has a key role. Typical major enzymes available in soil can be listed as dehydrogenases, hydrogenases, oxidases, catalases, peroxidases, phenol o-hydroxylase, dextransucrase, aminotransferase, rhodanese, carboxylesterase, lipase, phosphatase, nuclease, phytase, arylsulphatase, amylase, cellulase, inulase, xylanase, dextranase, levanase, poly-galacturonase, glucosidase, galactosidase, invertase, peptidase, asparaginase, glutaminase, amidase, urease, aspartate decarboxylase, glutamate decarboxylase and aromatic amino acid decarboxylase. An interesting strategy for improving the nutritional quality of the soil would be to inoculate microorganism to soil while giving attention to mineral or other compounds that affect enzyme activity in soil. Since, some elements or compounds could show both activation and inhibitory effect, such as Fe, Na, etc. metals, the regulation of their bioavailability is crucial.

There is much interest in the study and production of nondigestible oligosaccharides (NDOs), due to their bioactivities and beneficial effects to the human health. The main approach in the production of NDOs relies on the action of glycosidases performing hydrolysis or transglycosylation of polysaccharides and sugars. In this chapter, a description of the main microbial glycosidases used for NDOs production, their sources, their principal properties, and a description of the production processes with the better results obtained are discussed.

Nanoparticles (NPs) are included in many products of daily life and present in the environment. Due to the potential of NPs to improve quality and stability of consumer and health and medical products, it is expected that the exposure of humans to engineered NPs will rather increase than decrease in the future. Although NPs did not act acutely cytotoxic on these concentrations, they may cause adverse effects upon chronic exposure. Cytotoxicity testing in long-term cultures and analysis of organelle function could identify such effects. Cells take up NPs mainly via active mechanisms, and these routes deliver their payload predominantly to lysosomes. Acute exposure of cells to NPs can have adverse effects on lysosome morphology and function, but lysosomes are also potential targets for accumulation. The chapter explains the role of lysosomes and describes techniques for labeling and assessment of their function. Examples for co-localization studies and vital dye staining are shown. A variety of techniques are available to characterize effects of NPs on lysosomes, but care has to be taken in the choice of the proper technique because NPs may interfere with the detection.

The studies of free radicals in melanin and the human melanoma malignum cells by an X-band (9.3 GHz) electron paramagnetic resonance (EPR) spectroscopy were presented. The original results were compared with those published earlier. The aim of this work was application of the advanced spectral analysis to determine free radical properties in melanin biopolymers obtained from different melanotic tumor cells and free radicals existing in the human melanoma cells. Magnetic spin-lattice interactions in melanin samples were tested. The evolution of lineshape of tumor cells with increasing of microwave power was determined to confirm their complex free radical system. The useful shape parameters were proposed. The shape of melanotic tumor cells was analyzed. EPR spectra of free radicals in the melanin isolated from different tumor cells measured in the wide range of microwave power were analyzed. The melanins were obtained from the control tumor cells and the cells cultured with the several antitumor substances. The usefulness of the electron paramagnetic resonance spectroscopy was confirmed.

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are two devastating neurodegenerative diseases. Several lines of evidence suggest that these diseases are part of a continuum with common genetic factors. As researchers uncover more genes associated with ALS/FTLD, studies have shown that majority of these genes regulate lysosome‐related processes. Lysosomes play important roles in clearing damaged organelles and proteins through the autophagy‐lysosome pathway and clearing extracellular debris by the endolysosomal pathway. Disruption of both the autophagy and endolysosomal pathways has been implicated in ALS/FTLD pathogenesis.

Reactive oxygen species (ROS) is harmful to our health, and SOD, CAT, and GPX are the major antioxidant enzymes that defend us from effects of ROS. In medicine, food, and dairy industries, antioxidant enzymes often surround complex environments. For better utilization of these enzymes, the inhibitors (including competitive inhibitors and noncompetitive inhibitors) and activators of SOD, CAT, and GPX are descripted in detail in this chapter. Also, the structure and catalytic mechanism of these antioxidants are summarized.

Lignocellulolytic enzymes have been extensively studied due to their potential for industrial applications such as food, textile, pharmaceutical, paper, and, more recently, energy. The influence of metal ions, chemical agents, and organic compounds on these enzyme activities are addressed in this chapter, based on data available in the scientific literature.

Epithelial cells develop tight junctions (TJs) and cell polarity. Both properties are sensitive to environmental signals such as the epidermal growth factor (EGF) and the cardiotonic steroid ouabain. EGF is regarded as the main protector against injuries in epithelia, and ouabain is a hormone that regulates blood pressure, natriuresis, cell survival, and cell adhesion. After treatment with epidermal growth factor or ouabain, epithelial dog kidney MDCK cells undergo a drastic remodeling that includes changes in the transcription, translation, localization, and degradation of cell junction proteins. Degradation of these proteins involves selective and nonselective autophagy as well as endocytic lysosomal and proteasomal routes. The remodeling mechanism of tight junction’s proteins includes the activation of Src and ERK1/ERK2 kinases, the phosphorylation and translocation into the nucleus of the transcription factor STAT3, the activation of PKC to induce the endocytosis of claudin-2, and the delivery of this protein to the lysosomes. Whole communicating junctions and desmosomes are internalized by one cell and sent to degradation by nonselective autophagy. Nonselective and selective autophagies in epithelial cells are very context dependent; nevertheless, it is clear that, together with endocytic lysosomal and proteasomal degradation, they play a key role in the remodeling and functioning of cell junctions.

Enzyme inhibitory agents are attractive because of their application in treating different ailments. The absence of enzymes produce a number of diseases. Medicinal plants are a rich source of producing secondary metabolites which showed broad-spectrum enzyme inhibitory potential. The position of enzyme inhibitors as new drugs is vast since these compounds have been used for the treatment of various physiological disorders. Bioactive secondary metabolites can deliver excellent pharmacophore patterns for drugs related to numerous illnesses. This book chapter is planned to document the enzyme inhibitory potential of natural compounds, medicinal plant extract, and its isolated compounds.

Lysosomal exoglycosidases gradually degrade oligosaccharide chains of glycoconjugates (glycoproteins, glycolipids, glycosaminoglycans) in cell lysosomes. Defect in the activity of suitable lysosomal exoglycosidase stops degradation of oligosaccharide chains on sugar molecules not released by deficient exoglycosidase, and nondegraded oligosaccharide chains are stored in enlarged lysosomes. Enlarged lysosomes damage remaining cell structures and disturb the function of involved tissues, causing storage diseases. An increase in the activity of exoglycosidases in tissues and body fluids is observed in the reconstruction of damaged tissues. Exoglycosidase activity is an inexpensive and sensitive marker in diagnostics and monitoring of many diseases.

High isostatic pressure (HIP) and high-pressure homogenization (HPH) are considered important physical technologies that able to induce changes on enzymes. HIP and HPH are emerging food processing technologies that involve the use of ultra high pressures (up to 1200 MPa for HIP and up to 400 MPa for HPH), where the first process is based on the principle that the maintenance of a product inside vessels at high pressures induces changes in the molecules conformation and, consequently, in the functionality of polysaccharides, proteins and enzymes. To the contrary, for HPH process, the high shear and sudden pressure drop are the responsible phenomena for the changes on the processed product. This chapter aims to evaluate comparatively the effects of HIP and HPH on the activity of enzymes currently applied in food industry and to identify the main structural changes induced by each process. The overall evaluation of the results shows that mild conditions of both processes were recently highlighted as able to improve the activity and the stability of several enzymes, whereas extreme process conditions (pressure, time and temperature) induce enzyme denaturation with consequent reduction of biological activity. Considering the complexity and diversity involved in the enzyme structure and its ability to react, it is not possible to determine specific conditions that each process is able to promote increase or reduction of enzyme activity, being necessary to evaluate HIP and HPH for each enzyme. Finally, in terms of molecular structure, the effect of HIP and HPH on enzymes can be explained by the alterations in the quaternary, tertiary and secondary structures of enzymes, which directly affects its active site configuration.