Enzymatic System of Metabolism and Detoxication of Xenobiotics as a Basis of Metabolic Portraiting during Prognostication of Risk of Pathological Processes

We studied intraspecific features of the main enzymes of metabolism and detoxication of xenobiotics on mice (eight inbred lines) and rats (five lines) for estimation of possible variants of complete or incomplete metabolic equality. Significant genetically determined intraspecific differences for activities of the enzymes of metabolism and detoxication of xenobiotics were described. Generalized criteria for comparison of the metabolic status were proposed on the basis of activities of the main enzymes: cytochrome P-450 (hydroxylation and epoxidation), epoxyhydrolase, glutathione-S-transferase, UDP-glucuronosyl transferase, and sulfotransferase. The proposed criteria for estimation of the metabolic parameters of an individual can serve as a basis of metabolic portraiting.     

Response of the mink reproductive system to hormonal stimulation in october as a prognostic criterion of folluculogenesis and fertility

The responsess of the mink reproductive systems in October to a single intramuscular injection of chorionic gonadotropin (CG, Profasi R, Italy) at doses of 10, 20, 50, and 100 IU was studied. The estrous cycle state, folliculogenesis, and reproductive parameters of the female minks were estimated. To evaluate functional polymorphism in the reproductive system of the females in response to the CG injection, a dose of 20 IU was chosen. On the sixth day after administration of this dose of CG, the females (n = 185) were distributed according to the stages of the estrous cycle as follows: anestrus—71 animals (38.4%), anestrus-proestrus—37 (20.0%), proestrus—30 (16.2%), proestrus-estrus—14 (7.6%), estrus—33 (17.8%). In the females of the “anestrus-proestrus” and “proestrus” groups as compared with the other groups as well as with control, a statistically significantly higher fertility was revealed. The study of folliculogenesis in the females with different parameters of the estrous cycle in November demonstrated the high level of fertility to be due to ability of these females to produce, under influence of the CG injection, the maximal number of mature follicles. A high heritable responsiveness of the reproductive system of the females to the CG injection (coefficient of realized heritabilityh = 0.64; the calculation made on the data for the sisters) indicates that this method may be an additional criterion in the selection of females for fertility.     

Discrete phenotypical variability of electrophoretical specters of one of system of myogens in the Acipenseridae family

Analysis of electrophoregrams of water-soluble proteins of white skeletal muscle of 10 species belonging to three genera of the Acipenseridae family has allowed revealing an earlier not described system that can serve as a biochemical marker. This protein system represents a set of five fractions (A, B, C, D, E). A part of the studied species is monomorphous for one of these fractions (sterlet, giant sturgeon, Caspian sturgeon, and Amu-Darya shovelnose had phenotype A, barbel sturgeon—phenotype C, Amur sturgeon—phenotype D). In all individuals of the Amur sturgeon the identical three-component specter (phenotype ACE) was revealed. In the Sakhalin, Siberian, and Russian sturgeons a clearly expressed polymorphism was observed. Among the studied species the Russian sturgeon was characterized by the highest degree of heterogeneity and polymorphism. In the studied sample of this species all five protein variants are found, whereas in the rest of them—only a part of this set.     

DNA fingerprinting of human cell lines using PCR amplification of fragment length polymorphisms

Summary Methods for monitoring cell line identification and authentication include species-specific immunofluorescence, isoenzyme phenotyping, chromosome analysis, and DNA fingerprinting. Most previous studies of DNA fingerprinting of cell lines have used restriction fragment length polymorphism analysis. In this study, we examined the utility of an alternative and simpler method of cell line DNA fingerprinting—polymerase chain reaction (PCR) amplification of fragment length polymorphisms. Fourteen human cell lines previously found by other methods to be either related or disparate were subjected to DNA fingerprinting by PCR amplification of selected fragment length polymorphism loci. Cell identification patterns by this method were concordant with those obtained by isoenzyme phenotyping and restriction fragment length polymorphism-DNA fingerprinting, and were reproducible within and between assays on different DNA extracts of the same cell line. High precision was achieved with electrophoretic separation of amplified DNA products on high resolution agarose or polyacrylamide gels, and with fragment length polymorphism (FLP) loci-specific “allelic ladders” to identify individual FLP alleles. Determination of the composite fingerprint of a cell line at six appropriately chosen fragment length polymorphism loci should achieve a minimum discrimination power of 0.999. The ability of PCR-based fragment length polymorphism DNA fingerprinting to precisely and accurately identify the alleles of different human cell lines at multiple polymorphic fragment length polymorphism loci demonstrates the feasibility of developing a cell line DNA fingerprint reference database as a powerful additional tool for future cell line identification and authentication.     

Polyamines and cellular metabolism in plants: transgenic approaches reveal different responses to diamine putrescine versus higher polyamines spermidine and spermine

Distribution of biogenic amines—the diamine putrescine (Put), triamine spermidine (Spd), and tetraamine spermine (Spm)—differs between species with Put and Spd being particularly abundant and Spm the least abundant in plant cells. These amines are important for cell viability and their intracellular levels are tightly regulated, which have made it difficult to characterize individual effects of Put, Spd and Spm on plant growth and developmental processes. The recent transgenic intervention and mutational genetics have made it possible to stably alter levels of naturally occurring polyamines and study their biological effects. We bring together an analysis of certain metabolic changes, particularly in amino acids, to infer the responsive regulation brought about by increased diamine or polyamine levels in actively growing poplar cell cultures (transformed with mouse ornithine decarboxylase gene to accumulate high Put levels) and ripening tomato pericarp (transformed with yeast S-adenosylmethionine decarboxylase gene to accumulate high Spd and Spm levels at the cost of Put). Our analysis indicates that increased Put has little effect on increasing the levels of Spd and Spm, while Spd and Spm levels are inter-dependent. Further, Put levels were positively associated with Ala (α and β), Ile and GABA and negatively correlated with Gln and Glu in both actively growing poplar cell cultures and non-dividing tomato pericarp tissue. Most amino acids showed positive correlations with Spd and Spm levels in actively growing cells. Collectively these results suggest that Put is a negative regulator while Spd–Spm are positive regulators of cellular amino acid metabolism.     

Rate of dehydration,state of subcellular organisation and nature of cryoprotection are critical factors contributing to the variable success of cryopreservation: studies on recalcitrant zygotic embryos of <Emphasis Type="Italic">Haemanthus montanus</Emphasis>

Effects of sequential procedures required for cryopreservation of embryos excised from the recalcitrant seeds of Haemanthus montanus were assessed ultrastructurally and in conjunction with respiratory activity and the rate of protein synthesis. Fresh material (water content, 5.05 ± 0.92 g g⁻¹ dry mass) afforded ultrastructural evidence of considerable metabolic activity, borne out by respiratory rates. Neither exposure to glycerol nor sucrose as penetrating and non-penetrating cryoprotectants, respectively, brought about degradative changes, although increased vacuolation and autophagy accompanied both, while respiratory and protein synthetic activity were not adversely affected. Glycerol-cryoprotected embryos flash dried to water contents >0.4 g g⁻¹ showed organised ultrastructural features and considerable autophagy consistent with metabolic activity, and although respiratory activity was lower, protein synthesis rate was enhanced relative to fresh material. However, at water contents <0.4 g g⁻¹, embryo tissue presented a mosaic of cells of variable density and ultrastructural status, but trends in rates of respiration and protein synthesis remained similar. Flash drying after sucrose exposure was accompanied by considerable ultrastructural abnormality particularly at water contents <0.4 g g⁻¹, lysis of individual and groups of cells and considerable depression of respiration, but not of protein synthesis. Success, assessed as ≥50% axes forming seedlings after cryogen exposure, was obtained only when glycerol-cryoprotected embryos at water contents >0.4 g g⁻¹—in which the degree of vacuolation remained moderate—were rapidly cooled. The outcomes of this study are considered particularly in terms of the stresses imposed by prolonged, relatively slow dehydration and ultimate water contents, on embryos showing considerable metabolic activity.     

Analysing the content of the European Ocean Biogeographic Information System (EurOBIS): available data, limitations, prospects and a look at the future

The European Ocean Biogeographic Information System—EurOBIS—is an integrated data system developed by the Flanders Marine Institute (VLIZ) for the EU Network of Excellence “Marine Biodiversity and Ecosystem Functioning” (MarBEF) in 2004. Its principle aims are to centralise the largely scattered biogeographical data on marine species collected by European institutions and to make these quality-controlled data freely available and easily accessible. It is in essence a distributed system in which individual datasets go through a series of quality control procedures before they are integrated into one large consolidated database. EurOBIS is freely available online at , where marine biogeographical data—with a focus on taxonomy, temporal and spatial distribution—can be consulted and downloaded for analyses. Over the last 6 years, EurOBIS has collected 228 datasets contributed by more than 75 institutes, representing over 13.6 million distribution records of which almost 12.5 million records are species level identifications. It is now the largest online searchable public source of European marine biological data, holding biogeographical information on 26,801 species and 9,221 genera. EurOBIS acts as the European node of OBIS, the Ocean Biogeographic Information System of the Census of Marine Life (CoML). EurOBIS shares its data with OBIS, which in its turn shares its content with the Global Biodiversity Information Facility (GBIF). This article describes the status of the European Ocean Biogeographic Information System, identifies data gaps, possible applications, uses and limitations. It also formulates a strategy for the growth and improvement of the system and wants to appeal for more contributions.     

The evolution of caste polymorphism in social insects:0 Genetic release followed by diversifying evolution

Caste polymorphism, defined as the presence within a colony of two or more morphologically differentiated individuals of the same sex, is an important character of highly eusocial insects both in the Hymenoptera (ants, bees and wasps) and in the Isoptera (termites), the only two groups in the animal kingdom where highly eusocial species occur. Frequently, caste polymorphism extends beyond mere variations in size (although the extent of variations in size can be in the extreme) and is accompanied by allometric variations in certain body parts. How such polymorphism has evolved and why, in its extreme form, it is essentially restricted to the social insects are questions of obvious interest but without satisfactory answers at the present time. I present a hypothesis entitled ‘genetic release followed by diversifying evolution’, that provides potential answers to these questions. I argue that genetic release followed by diversifying evolution is made possible under a number of circumstances. One of them I propose is when some individuals in a species begin to rely on the indirect component of inclusive fitness while others continue to rely largely on the direct component, as workers and queens in social insects are expected to do. Thus when queens begin to rely on workers for most of the foraging, nest building and brood care, and workers begin to rely increasingly on queens to lay eggs—when queen traits and worker traits do not have to be expressed in the same individual—I postulate the relaxation of stabilizing selection and new spurts of directional selection on both queen-trait genes and worker-trait genes (in contrasting directions) leading to caste polymorphism.     

Role of physiological factors in prognosis of the risk of oncological diseases development on the basis of xenobiotic metabolism enzyme system polymorphism

Summarised data about polymorphism of xenobiotic metabolism enzyme system (XMES) have been presented. Metabolic molecular mechanisms and the role of genetic polymorphism in metabolic transformation of different xenobiotics are reviewed. Significance of X-transport proteins and nuclear receptors in regulation of XMES-activity are discussed. Possible connection of XMES polymorphism with the development of cancer was examined. Experimental modeling of different levels of epoxide syntase and epoxide hydratase activites has revealed their connection with cancer development. Physiological factors should be considered when evaluation of risk extent for cancer development is carried out.     

From metabolism to comparative biochemistry of toxic organophosphorus compounds

The main stages of scientific biography of Professor Viktor Iosifovich Rozengart are exposed: his works on muscle bioenergetics, discovery of the pathway of synthesis of creatinine, his development of new concepts of pathways of metabolism of organophosphorus xenobiotics, creation of biochemical grounds of selective toxicity as well as studies in the new field, of which he was one of founders,—comparative biochemistry of toxic organophosphorus compounds.     

Partitioning of yeast RNA in aqueous two-phase system

Summary The partition behaviour of RNA extracted from yeast was examined using three types of aqueous two-phase systems: potassium phosphate—polyethyleneglycol (PEG) system, ammonium sulphate—PEG system and dextran sulphate—PEG—NaCl system. The molecular weight of PEG showed rather remarkable effects of RNA partition than did the electrolyte. High molecular weight RNA was concentrated at the interface in these systems. This suggests the possibility of its simple concentration or extraction.     

New RAPD markers of tomato spotted wilt virus (TSWV) resistance in Lycopersicon esculentum Mill

The selection of TSWV resistant individuals can be facilitated by molecular markers. RAPD analysis was carried out on three forms (Stevens × Rodade — resistant; Rey de los Tempranos — moderately tolerant; Potentat — susceptible) with the use of 271 primers. Out of 271 primers 28 generated stable polymorphism and so they were tested for linkage to resistance gene. Bulk segregant analysis (BSA) was applied to F₂ segregating progeny developed from resistant × susceptible parents. As a result, 5 primers enabling us to distinguish between resistant and susceptible forms were detected. Only one of them had previously been reported by Chague et al. (1996). The analysis should be repeated on a larger population to confirm the results obtained.     

A minimal principle in biomechanics

Expenditure of energy under several simultaneous forms (mechanical, chemical, etc.) is associated with all muscular activity. The energy is directly related to what is commonly called exertion or effort. This paper defines “muscular effort” quantitatively in terms of some of the elements of the dynamics of the human (and animal) body. It postulates that in all likelihood the individual will, consciously or otherwise, determine his motion (or his posture, if at rest) in such a manner as to reduce his total muscular effort to a minimum consistent with imposed conditions, or “constraints”. The principle, formulated in mathematical terms, is sufficient to ascribe to the moments at all body joints—a matter generally of free choice on the part of the individual—their most likely magnitudes. It therefore renders the equations of human (and animal) motion determinate within this context. The paper also describes briefly an iteration method for the solution of these equations, once they have been made determinate. A simple illustrative application of the principle is included.     

Role of PPARs and their isoforms in metabolic disorders related to insulin resistance and diabetes

PPARs play a key role in energy homeostasis, inflammation, development of insulin resistance, and the metabolic syndrome. Therefore, special attention is paid to the synthesis of PPAR ligands (fibrates, thiazolidinediones). Three isoforms of PPARs are activated by fatty acids and their derivatives—eicosanoids. The Pro12Ala polymorphism of the PPARG2 gene is associated with insulin sensitivity of tissues and risks of developing diabetes. It is assumed that PPAR polymorphisms are related to differential responses to pharmacotherapy; this is the basis for the development of personalized medicines and assessments of prognoses.     

Mitochondrial haplogroups associated with Japanese Alzheimer’s patients

The relationships between Japanese Alzheimer’s disease (AD) patients and their mitochondrial single nucleotide polymorphism (mtSNP) frequencies at individual mtDNA positions of the entire mitochondrial genome are described using the radial basis function (RBF) network and the modified method. Japanese AD patients are associated with the haplogroups G2a, B4c1, and N9b1. In addition, to compare mitochondrial haplogroups of the AD patients with those of other classes of Japanese people, the relationships between four classes of Japanese people (i.e., Japanese centenarians, Parkinson’s disease (PD) patients, type 2 diabetic (T2D) patients, and non-obese young males) and their mtSNPs are also described. The four classes of people are associated with following haplogroups: Japanese centenarians—M7b2, D4b2a, and B5b; Japanese PD patients—M7b2, B4e, and B5b; Japanese T2D patients—B5b, M8a1, G, D4, and F1; and Japanese healthy non-obese young males—D4g and D4b1b. The haplogroups of the AD patients are therefore different from those of the other four classes of Japanese people. As the analysis method described in this article can predict a person’s mtSNP constitution and the probabilities of becoming an AD patient, centenarian, PD patient, or T2D patient, it may be useful in initial diagnosis of various diseases.     

Assessing impact of forest landscape dynamics on migratory corridors: a case study of two protected areas in Himalayan foothills

Contiguity of protected areas (PAs) is a critical factor to promote well being of the native flora, fauna and life support system to humans. Such contiguity cannot be guaranteed without providing a path or ‘a corridor’ through forested landscapes that includes natural land cover and undisturbed patches. Incidentally, the Himalayan foothills have greater pressure on these landscapes due to high human dependence for livelihood. This pressure is expected to increase in the coming years altering the potential corridors between PAs. The PA managers need flexible processing, modeling and decision tools to propose a range of acceptable corridors between the PAs and ensure their sustainable health. Such flexible tools can be utilized in future to modify for taking decision to conserve the patches connecting patches and adapt as per changing landscapes. This article describes utility of geospatial modeling tools to assess the status of corridors in light of changing landscapes between Rajaji and Jim Corbett National Park, the two most important PAs in the Himalayan foothills. The work has been carried out in four stages, first—using satellite data land use land cover (LULC) maps were prepared for year 1990, 2000 and 2005, second—Land Change Modeler (LCM) was used for LULC change analysis, third—Multi Layer Perceptron Neural Network (MLPNN) was used to predict the status of LULC for 2015 and 2020, and fourth—using temporal morphology of the areas behaving both as barrier and easiness, friction surface cost was calculated to identify least cost pathways (LCPs)/migratory corridors between the PAs. The LULC maps for 1990, 2000 and 2005 were evaluated using accuracy assessment (80%) and Khat statistics (>0.79). The change prediction model was validated by comparing actual LULC of 2005 with predicted LULC of 2005 and the agreement was 71%. The LCP has shifted with the predicted change in the classes. The corridor has shifted by 0.5–3 km towards the south and has come closer to the agriculture fields and river channels.     

MHD plasma stabilization in a chain of axisymmetric adiabatic open mirror cells

Conditions for convective plasma instability in a chain of axisymmetric adiabatic mirror cells with different signs of magnetic field curvature are analyzed. The boundaries of the region that can be occupied by a stable hollow plasma in a system of two connected cells—a nonparaxial simple mirror cell and a semicusp—are determined, as well as the interval of allowed values of the ratio between the pressures in the cells. Because of the large magnetic field curvature in the component cells, the safety factor that is achieved at both—external and internal—plasma boundaries in accordance with the average min-B principle can be high. It is assumed that the unperturbed pressure in each cell is almost isotropic, in which case the mirror ratio should necessarily be large. A key role in the stability of the plasma is played by its compressibility. A comparison is made between the conditions for complete plasma stabilization against arbitrary perturbations and the conditions for stability of individual cells against the global mode. The stability of the cells against the global mode is sufficient, but not necessary, for stabilizing the chain. The analysis is done by using orthogonal coordinates associated with the unperturbed magnetic field (flux variables). Numerical simulations were carried out for nonparaxial cells from a certain three-parameter family.     

Pharmacogenomics: Catechol O-Methyltransferase to Thiopurine S-Methyltransferase

1. Pharmacogenomics is the study of the role of inheritance in variation in the drug response phenotype—a phenotype that can vary from adverse drug reactions at one end of the spectrum to lack of therapeutic efficacy at the other.2. The thiopurine S-methyltransferase (TPMT) genetic polymorphism represents one of the best characterized and most clinically relevant examples of pharmacogenomics. This polymorphism has also served as a valuable “model system” for studies of the ways in which variation in DNA sequence might influence function.3. The discovery and characterization of the TPMT polymorphism grew directly out of pharmacogenomic studies of catechol O-methyltransferase (COMT), an enzyme discovered by Julius (Julie) Axelrod and his coworkers.4. This review will outline the process by which common, functionally significant genetic polymorphisms for both COMT and TPMT were discovered and will use these two methyltransferase enzymes to illustrate general principles of pharmacogenomic research—both basic mechanistic and clinical translational research—principles that have been applied to a series of genes encoding methyltransferase enzymes.     

The relevance of xenobiotic metabolism in the interindividual susceptibility to chemicals

Biotransformation enzymes may catalyze either detoxication or bioactivation reactions; indeed, many xenobiotics exert their toxic effects after metabolic activation to electrophilic chemicals, interacting with nucleophilic sites on cellular macromolecules. On the other hand, by increasing xenobiotic hydrophilicity, the drug-metabolizing enzymes favors excretion of lipophilic chemicals, not allowing their bioaccumulation up to toxic levels. The expression of the enzymes of the drug-metabolizing system is modulated by genetic, pathological, developmental, environmental and dietary factors. Genetic polymorphism resulting in interindividual and interethnic variation in xenobiotic metabolism is responsible for differences in the susceptibility to chemical-induced toxicity and carcinogenicity, allowing the identification of people at increased risk. Moreover, differences in drug metabolism may correspond to variability in drug response during pharmacological therapy, which can be manifest either as adverse reactions or as a lack of benefit.     

Expression in promoter variant of the ERα gene in bos taurus liver

Due to the variant functions that estrogens play in the regulation of reproduction, development of the mammary gland, growth and differentiation of cells, estrogen receptors and their genes are considered as a candidates for the markers of production and functional traits in farm animals, including cattle. In the earliest study, a 2853-bp bovine ER gene 5′-region was PCR amplified and sequenced. Moreover, for the first time, a polymorphism was described within 5′ region of the bovine ERα gene—A/G transition lying upstream at position 2591 from acceptor splice site +85, possibly within its promoter—which could be recognized with RFLP-BglI. In other study we are found second polymorphism—A/G transition at position 1213 from acceptor splice site +85, located in promoter for exon B. We have examined the specific mRNA expression of ERα in various genotypes using real-time RT-PCR. We used four animals from each genotype group—AG, GG for BglI and AA, AG for SnaBI—to analyse liver ERα expression at the level of Real-time PCR. Liver samples were taken from the 16 young Friesian bulls of the different ERα genotypes, slaughtered at the local abattoir. As shown by Real-Time PCR, on the livers of animals with different genotype ERα mRNA for BglI polymorphism we didn’t found variability, but for SnaBI we have found variability between AG and AA genotypes.