[Animals (Animalia) in the system of organisms. 1. Typological systems].

Since times of Aristotle animals were considered as a group, opposing to plants. The last were distinguished by two characters. Plants as distinct from animals live the attached way of a life and all nutrients receive from a substratum on which live and from the surrounding air. Animals live an active way of life and exist due to digestion. Fungi at such definition belong to plants. Only in second half of XX centuries due to works of Whittaker and of Tachtadjan fungi have received the separate status equally with plants and animals. In this new system of a plant embraced either oxygenic phototrophs, or photosynthetic eukaryotes. The traditional characters distinguishing animals from plants and fungi are in detail analysed. Many of them appeared formal, not reflecting the structure of relationship. Comparing heterotrophs some authors saw in absorptive nutrition the main difference of fungi from animals. However on mechanisms of receipt of substances in a cell fungi, animals and plants do not differ. Phagocytosis and pinocytosis (clathrin-mediated endocytosis), considered as the most characteristic feature of animals, are revealed both in fungi, and in plants. On photosynthetic activity plants form heterogeneous group, differing on primary and secondary plastids. The last besides have the various origin connected to symbiogenesis of the host cell with red or green algae. Heterotrophy cannot be considered as a uniting attribute of fungi and animals. It is essentially different and focused on diverse food sources. Evolution of animals is connected to perfection of structure of a plasmatic membrane and saturation by its molecules allowing a cell, and through it all organism to be guided in an environment and adequally to be up to external irritants. At a cellular level animals use the various mechanisms of cellular activity connected to moving of cells, their combination in aggregates and complexes or, on the contrary, separation in new cellular configurations. The complex of cellular adaptations connected to the analysis of external signals and adequate response to them of cells, underlies the phenomenon of irritability. At a cellular level irritability is mediated through work of the actin apparatus. Lamarck in "Philosophie zoologique" considered irritability as the main distinctive feature of animals. Evolution of plants and fungi went in a direction of development of a secondary metabolism. The secondary metabolism, concerning synthesis of protective substances, is peculiar to all sedentary organisms, including the animals.

Insulin/IGF and target of rapamycin signaling: a TOR de force in growth control.

'They come in all sizes.' Apart from its origin and use in the clothing industry, this saying reflects the fact that the size of organisms spans an enormous range. Whether destined to be large or small, species grow in an organized fashion to reach their final specified size. For growth to proceed, food must be metabolized to liberate energy in the form of adenosine triphosphate (ATP) and protein building blocks in the form of amino acids. One major orchestrator of this complex growth process in diverse metazoan species is the insulin/insulin-like growth factor (IGF) system. This review summarizes current studies primarily from Drosophila regarding the function of the insulin/IGF system in the control of growth.

Anandamide activity and degradation are regulated by early postnatal aging and follicle-stimulating hormone in mouse Sertoli cells.

Anandamide (AEA), a prominent member of the endogenous ligands of cannabinoid receptors (endocannabinoids), is known to adversely affect female fertility. However, a potential role of AEA in male reproductive functions is unknown. Here we report evidence that immature mouse Sertoli cells have the biochemical tools to bind and inactivate AEA, i.e. a functional type-2 cannabinoid receptor (CB2R), a selective AEA membrane transporter, and an AEA-degrading enzyme fatty acid amide hydrolase. We show that, unlike CB2R, the activity of AEA membrane transporter and the activity and expression of FAAH decrease, whereas the apoptosis-inducing activity of AEA increases with age during the neonatal period. We also show that FSH reduces the apoptotic potential of AEA, but not that of its nonhydrolyzable analog methanandamide. Concomitantly, FSH enhances FAAH activity in a manner dependent on mRNA transcription and protein synthesis and apparently involving cAMP. These data demonstrate that Sertoli cells partake in the peripheral endocannabinoid system, and that FSH reduces the apoptotic potential of AEA by activating FAAH. Taken together, it can be suggested that the endocannabinoid network plays a role in the hormonal regulation of male fertility.

A Caenorhabditis elegans TGF-beta, DBL-1, controls the expression of LON-1, a PR-related protein, that regulates polyploidization and body length.

Using cDNA-based array analysis combined with double-stranded RNA interference (dsRNAi), we have identified yk298h6 as a target gene of Caenorhabditis elegans TGF-beta signaling. Worms overexpressing dbl-1, a TGF-beta ligand, are 16% longer than wild type. Array analysis shows yk298h6 to be one of several genes suppressed in such worms. Disruption of yk298h6 function by dsRNAi also resulted in long worms, suggesting that it is a negative regulator of body length. yk298h6 was then mapped to, and shown to be identical to, lon-1, a known gene that affects body length. lon-1 encodes a 312 amino acid protein with a motif sequence that is conserved from plants to humans. Expression studies confirm that LON-1 is repressed by DBL-1, suggesting that LON-1 is a novel downstream component of the C.elegans TGF-beta growth regulation pathway. Consistent with this, LON-1 is expressed mainly in the larval and adult hypodermis and has dose-dependent effects on body length associated with changes in hypodermal ploidy, but not hypodermal cell proliferation.

Oxidative monensin metabolism and cytochrome P450 3A content and functions in liver microsomes from horses, pigs, broiler chicks, cattle and rats.

The oxidative metabolism of monensin, an ionophore antibiotic extensively used in veterinary practice as a coccidiostat and a growth promoter, was studied in hepatic microsomal preparations from horses, pigs, broiler chicks, cattle and rats. As assayed by the measurement of the amount of the released formaldehyde, the rate of monensin O-demethylation was nearly of the same order of magnitude in all species, but total monensin metabolism, which was estimated by measuring the rate of substrate disappearance by a high-performance liquid chromatography (HPLC) method, was highest in cattle, intermediate in rats, chicks and pigs, and lowest in horses. When expressed as turnover number (nmol of metabolized monensin/min nmol cytochrome P450-1), the catalytic efficiency (chick >> cattle >> pig approximately rat > horse) was found to correlate inversely with the well known interspecies differences in the susceptibility to the toxic effects of the ionophore, which is characterized by an oral LD50 of 2-3 mg/kg bodyweight (bw) in horses, 50-80 mg/kg bw in cattle and 200 mg/kg bw in chicks. Chick and cattle microsomes also displayed both the highest catalytic efficiency toward two P450 3A dependent substrates (erythromycin and triacetyloleandomycin) and the highest immunodetectable levels of proteins cross-reacting with anti rat P450 3A1/2. Further studies are required to define the role played by this isoenzyme in the oxidative biotransformation of the drug in food producing species.

[Transabiotic factors in an aqueous environment (a review)]. / Transabioticheskie faktory v vodnoi srede (obzor).

Excretion of metabolites is a characteristic feature of any alive organism. A big group of these products--second metabolites--because of their variability, quantity and physico-biological activity have a special importance in aquatic environment. Exometabolites of some organisms become an important part of environment for the others. The authors discussed the origin and evolution of exometabolites from simple waste products to biologically active substances. Quantitative and qualitative aspects of metabolic excretion by organisms in water conditions are analysed. The data on composition, origin and biological function of some second metabolites of different groups of aquatic organisms are presented. The authors propose a classification of second metabolites according to their functional significance. The role of metabolites and decay products in the development of chemical information streams in hydrobiocoenosis is analysed. Metabolites (soluble organic substances) form a field of chemical information for biotic community. The most important functions of this field are communication and conditioning. The authors emphasize the importance of investigations of chemical bioinformation field in aquatic ecosystems.

Genetic analysis of cadherin function in animal morphogenesis.

Cadherins are a superfamily of Ca(2+)-dependent adhesion molecules found in metazoans. Several classes of cadherins have been defined from which two - classic cadherins and Fat-like cadherins - have been studied by genetic approaches. Recent in vivo studies in Caenorhabditis elegans and Drosophila show that cadherins play an active role in a number of distinct morphogenetic processes. Classic cadherins function in epithelial polarization, epithelial sheet or tube fusion, cell migration, cell sorting, and axonal patterning. Fat-like cadherins are required for epithelial morphogenesis, proliferation control, and epithelial planar polarization.

Gamma-tubulin complexes: size does matter.

gamma-Tubulin is a conserved component of all microtubule-organizing centres and is required for these organelles to nucleate microtubule polymerization. However, the mechanism of nucleation is not known. In addition to its localization to organizing centres, a large pool of gamma-tubulin exists in the cytoplasm in a complex with other proteins. The size of the gamma-tubulin complex and number of associated proteins vary among organisms, and the functional significance of these differences is unknown. Recently, the nature of these gamma-tubulin complexes has been explored in different organisms, and this has led us closer to a molecular understanding of microtubule nucleation.

Metabolic depression in animals: physiological perspectives and biochemical generalizations.

Depression of metabolic rate has been recorded for virtually all major animal phyla in response to environmental stress. The extent of depression is usually measured as the ratio of the depressed metabolic rate to the normal resting metabolic rate. Metabolic rate is sometimes only depressed to approx. 80% of the resting value (i.e. a depression of approx. 20% of resting); it is more commonly 5-40% of resting (i.e. a depression of approx. 60-95% of resting); extreme depression is to 1% or less of resting, or even to an unmeasurably low metabolic rate (i.e. a depression of approx. 99-100% of resting). We have examined the resting and depressed metabolic rate of animals as a function of their body mass, corrected to a common temperature. This allometric approach allows ready comparison of the absolute level of both resting and depressed metabolic rate for various animals, and suggests three general patterns of metabolic depression. Firstly, metabolic depression to approx. 0.05-0.4 of rest is a common and remarkably consistent pattern for various non-cryptobiotic animals (e.g. molluscs, earthworms, crustaceans, fishes, amphibians, reptiles). This extent of metabolic depression is typical for dormant animals with 'intrinsic' depression, i.e. reduction of metabolic rate in anticipation of adverse environmental conditions but without substantial changes to their ionic or osmotic status, or state of body water. Some of these types of animal are able to survive anoxia for limited periods, and their anaerobic metabolic depression is also to approx. 0.05-0.4 of resting. Metabolic depression to much less than 0.2 of resting is apparent for some 'resting', 'over-wintering' or diapaused eggs of these animals, but this can be due to early developmental arrest so that the egg has a low 'metabolic mass' of developed tissue (compared to the overall mass of the egg) with no metabolic depression, rather than having metabolic depression of the entire cell mass. A profound decrease in metabolic rate occurs in hibernating (or aestivating) mammals and birds during torpor, e.g. to less than 0.01 of pre-torpor metabolic rate, but there is often no intrinsic metabolic depression in addition to that reduction in metabolic rate due to readjustment of thermoregulatory control and a decrease in body temperature with a concommitant Q10 effect. There may be a modest intrinsic metabolic depression for some species in shallow torpor (to approx. 0.86) and a more substantial metabolic depression for deep torpor (approx. 0.6), but any energy saving accruing from this intrinsic depression is small compared to the substantial savings accrued from the readjustment of thermoregulation and the Q10 effect. Secondly, a more extreme pattern of metabolic depression (to < 0.05 of rest) is evident for cryptobiotic animals. For these animals there is a profound change in their internal environment--for anoxybiotic animals there is an absence of oxygen and for osmobiotic, anhydrobiotic or cryobiotic animals there is an alteration of the ionic/osmotic balance or state of body water. Some normally aerobic animals can tolerate anoxia for considerable periods, and their duration of tolerance is inversely related to their magnitude of metabolic depression; anaerobic metabolic rate can be less than 0.005 of resting. The metabolic rate of anhydrobiotic animals is often so low as to be unmeasurable, if not zero. Thus, anhydrobiosis is the ultimate strategy for eggs or other stages of the life cycle to survive extended periods of environmental stress. Thirdly, a pattern of absence of metabolism when normally hydrated (as opposed to anhydrobiotic or cryobiotic) is apparently unique to diapaused eggs of the brine-shrimp (Artemia spp., an anostracan crustacean) during anoxia. The apparent complete metabolic depression of anoxic yet hydrated cysts (and extreme metabolic depression of normoxic, hypoxic, or osmobiotic, yet hydrated cysts), is an obvious exception to the above patterns. (ABST

Regulation analysis of energy metabolism.

This paper reviews top-down regulation analysis, a part of metabolic control analysis, and shows how it can be used to analyse steady states, regulation and homeostasis in complex systems such as energy metabolism in mitochondria, cells and tissues. A steady state is maintained by the variables in a system; regulation is the way the steady state is changed by external effectors. We can exploit the properties of the steady state to measure the kinetic responses (elasticities) of reactions to the concentrations of intermediates and effectors. We can reduce the complexity of the system under investigation by grouping reactions into large blocks connected by a small number of explicit intermediates-this is the top-down approach to control analysis. Simple titrations then yield all the values of elasticities and control coefficients within the system. We can use these values to quantify the relative strengths of different internal pathways that act to keep an intermediate or a rate constant in the steady state. We can also use them to quantify the relative strengths of different primary actions of an external effector and the different internal pathways that transmit its effects through the system, to describe regulation and homeostasis. This top-down regulation analysis has been used to analyse steady states of energy metabolism in mitochondria, cells and tissues, and to analyse regulation of energy metabolism by cadmium, an external effector, in mitochondria. The combination of relatively simple experiments and new theoretical structures for presenting and interpreting the results means that top-down regulation analysis provides a novel and effective way to analyse steady states, regulation and homeostasis in intricate metabolic systems.

Crystal structure at 2.4 angstroms resolution of the complex of transducin betagamma and its regulator, phosducin.

The crystal structure of transducin's betagamma subunits complexed with phosducin, which regulates Gtbetagamma activity, has been solved to 2.4 angstroms resolution. Phosducin has two domains that wrap around Gtbetagamma to form an extensive interface. The N-terminal domain binds loops on the "top" Gtbeta surface, overlapping the Gtalpha binding surface, explaining how phosducin blocks Gtbetagamma's interaction with Gtalpha. The C-terminal domain shows structural homology to thioredoxin and binds the outer strands of Gtbeta's seventh and first blades in a manner likely to disrupt Gtbetagamma's normal orientation relative to the membrane and receptor. Phosducin's Ser-73, which when phosphorylated inhibits phosducin's function, points away from Gtbetagamma, toward a large flexible loop. Thus phosphorylation is not likely to affect the interface directly, but rather indirectly through an induced conformational change.

Conservation within the myosin motor domain: implications for structure and function.

BACKGROUND: Myosins are motors that use energy supplied by ATP to travel along actin filaments. The structure of myosin is known, but the actin-binding site is not well defined, and the mechanisms by which actin activates ATP hydrolysis by myosin, and myosin moves relative to the actin filament, developing force, are not fully understood. Previous phylogenetic analyses of the motor domain of myosins have identified up to twelve classes. We set out to analyse the positions of conserved residues within this domain in detail, and relate the conserved residues to the myosin structure. RESULTS: Our analysis indicates that there are at least thirteen myosin classes. Conserved residues in the motor domain have been positioned within the framework provided by the recent crystal structures, thus helping to define those residues involved in actin and ATP binding, in hydrolysis and in conformational change. This has revealed remarkably poor overall conservation at the site thought to be involved in actin binding, but several highly conserved residues have been identified that may be functionally important. CONCLUSIONS: Information from such a sequence analysis is a useful tool in the further interpretation of X-ray structures. It allows the position of crucial residues from other members of a superfamily to be determined within the framework provided by the known structures and the functional significance of conserved or mutated residues to be assessed.

The form and bioavailability of non-ionic organic chemicals in sewage sludge-amended agricultural soils.

The application of sewage sludges to agricultural land may increase the concentrations of many toxic organic chemicals in soils which could have adverse effects on wildlife and human health if these compounds enter foodchains. Chlorobenzenes (CBs), polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) are amongst those compounds currently receiving most attention. The "form' in which these, and other organic chemicals, are present in soils and their potential to be lost by various processes including leaching, volatilisation and (bio)degradation is shown to be dependent on the physicochemical characteristics of the soil and sewage sludge, environmental conditions and the properties of the chemicals themselves. The distinction is made between those compounds that are labile, reversibly sorbed and irreversibly sorbed by sewage sludge-amended soils. The implications of the form in which the chemicals are present in soil for their "availability' to transfer from the soil to bacteria, fungi, earthworms, grazing livestock and food crops followed by the potential for further transfers, metabolism or bioaccumulation are discussed. The importance of the timing and method of sewage sludge application to soil on "form' and "availability' are also considered.

Structural and functional homology between periplasmic bacterial molecular chaperones and small heat shock proteins.

The periplasmic Yersinia pestis molecular chaperone Caf1M belongs to a superfamily of bacterial proteins for one of which (PapD protein of Escherichia coli) the immunoglobulin-like fold was solved by X-ray analysis. The N-terminal domain of Caf1M was found to share a 20% amino acid sequence identity with an inclusion body-associated protein IbpB of Escherichia coli. One of the regions that was compared, was 32 amino acids long, and displayed more than 40% identity, probability of random coincidence was 1.2 x 10(-4). IbpB is involved in a superfamily of small heat shock proteins which fulfil the function of molecular chaperone. On the basis of the revealed homology, an immunoglobulin-like one-domain model of IbpB three-dimensional structure was designed which could be a prototype conformation of sHsp's. The structure suggested is in good agreement with the known experimental data obtained for different members of sHsp's superfamily.

Structure, function and evolution of seryl-tRNA synthetases: implications for the evolution of aminoacyl-tRNA synthetases and the genetic code.

Two aspects of the evolution of aminoacyl-tRNA synthetases are discussed. Firstly, using recent crystal structure information on seryl-tRNA synthetase and its substrate complexes, the coevolution of the mode of recognition between seryl-tRNA synthetase and tRNA(ser) in different organisms is reviewed. Secondly, using sequence alignments and phylogenetic trees, the early evolution of class 2 aminoacyl-tRNA synthetases is traced. Arguments are presented to suggest that synthetases are not the oldest of protein enzymes, but survived as RNA enzymes during the early period of the evolution of protein catalysts. In this view, the relatedness of the current synthetases, as evidenced by the division into two classes with their associated subclasses, reflects the replacement of RNA synthetases by protein synthetases. This process would have been triggered by the acquisition of tRNA 3' end charging activity by early proteins capable of activating small molecules (e.g., amino acids) with ATP. If these arguments are correct, the genetic code was essentially frozen before the protein synthetases that we know today came into existence.

Rat mammary-gland transferrin: nucleotide sequence, phylogenetic analysis and glycan structure.

The complete cDNA for rat mammary-gland transferrin (Tf) has been sequenced and also the native protein isolated from milk in order to analyse the structure of the main glycan variants present. A lactating-rat mammary-gland cDNA library in lambda gt10 was screened with a partial cDNA copy of rat liver Tf and subsequently rescreened with 5' fragments of the longest clones. This produced a 2275 bp insert coding for an open reading frame of 695 amino acid residues. This includes a 19-amino acid signal sequence and the mature protein containing 676 amino acids and one N-glycosylation site in the C-terminal domain at residue 490. Phylogenetic analysis was carried out using 14 translated Tf nucleotide sequences, and the derived evolutionary tree shows that at least three gene duplication events have occurred during Tf evolution, one of which generated the N- and C-terminal domains and occurred before separation of arthropods and chordates. The two halves of human melanotransferrin are more similar to each other than to any other sequence, which contrasts with the pattern shown by the remaining sequences. Native rat milk Tf is separated into four bands on native PAGE that differ only in their sialic acid content: one biantennary glycan is present containing either no sialic acid residues or up to three. The complete structures of the two major variants were determined by methylation, m.s. and 400 MHz 1H-n.m.r. spectroscopy. They contain either one or two neuraminic acid residues (alpha 2-->6)-linked to galactose in conventional biantennary N-acetyl-lactosamine-type glycans. Most contain fucose (alpha 1-->6)-linked to the terminal non-reducing N-acetylglucosamine.

Mutations within a highly conserved sequence present in the X region of phosphoinositide-specific phospholipase C-delta 1.

Phosphoinositide-specific phospholipase C (PI-PLC) enzymes have considerable structural similarity within limited regions (X and Y) implicated in catalysis. The role of residues contained within a highly conserved sequence present in the X region was investigated by site-directed mutagenesis of PLC-delta 1 isoenzyme. Seven residues (Ser-308, Ser-309, Ser-310, His-311, Thr-313, Tyr-314, and Gln-319) were individually replaced by alanine or glutamine (His-311). Replacement of two residues, His-311 and Tyr-314, resulted in a dramatic reduction of enzyme activity. The kcat of hydrolysis of phosphatidylinositol 4,5-bisphosphate by H311A and Y314A mutants was reduced 1000- and 10-fold respectively, with little effect on Km. Further analysis of H311A and Y314A mutants, using limited proteolysis and circular dichroism, had shown that no major structural alterations had occurred. Since site-directed mutagenesis demonstrated the importance of histidine residues, their role in enzyme function was also analysed by chemical modification with diethyl pyrocarbonate. This modification of histidine residues resulted in the reduction of enzyme activity and also indicated that more than one residue could be important.

Influence of the energy relationships of trophic levels and of elements on bioaccumulation.

A concern of ecotoxicology is to predict to which trophic levels in biocenoses bioaccumulation of compounds or of elements occurs. Transformity, a measure of the energy required to produce and maintain a component or a flow resulting from an energy transformation process, may help predict bioaccumulation potential. This notion derives from two concepts. First, common substances are more likely to be processed by the biosphere. Moreover, the uptake of rare ones from the physical environment by organisms of low trophic levels makes them less unusual to organisms of high trophic levels, which may evolve a capability of processing them. Second, transformity expresses energy relationships between parts of a system. Substances that require more energy to form or concentrate are also the more unusual. The hypothesis was formulated that there is a correlation between the rarity, complexity, and energy required for concentrating a substance, and thus its transformity, and the transformity of the trophic level to which it bioaccumulates. This hypothesis was tested for a set of elements with published data on their biogeochemistry and bioaccumulation and on energy transfers between trophic levels in ecosystems. The transformities of the elements were calculated from the energy required by the biosphere for maintaining a difference in concentration compared to its physical environment. Transformities of corresponding trophic levels were calculated from the energy driving the energy flows. There was a significant rank correlation between the transformity of elements and that of trophic levels. This may be an important generalization in ecotoxicology because it may lead to the possibility of predicting bioaccumulation tendency.