Solid-phase synthesis of polymyxin B1 and analogues via a safety-catch approach.

As part of a program towards the development of novel antibiotics, a convenient method for solid-phase synthesis of the cyclic cationic peptide polymyxin B1 and analogues thereof is described. The methodology, based on cleavage-by-cyclization using Kenner's safety-catch linker, yields crude products with purities ranging from 37-67%. Antibacterial assays revealed that analogues 23-26, in which the (S)-6-methyloctanoic acid moiety is replaced with shorter acyl chains, exhibit distinct antimicrobial activity. The results suggest that the length of the acyl chain is rather critical for antimicrobial activity. On the other hand, substitution of the hydrophobic ring-segment D-Phe-6/Leu-7 in polymyxin B1 with dipeptide mimics (i.e. analogues 27-33) resulted in almost complete loss of antimicrobial activity.     

Ecological description of ground beetle communities (Coleoptera, Carabidae) in northern taiga meadows of Arkhangelsk Region

Species composition and ecological structure of ground beetle population was studied in northern taiga meadows of the Arkhangelsk Region. Meadows in the northern forest zone proved to harbor 91 ground beetle species. Carabid complexes formed in the intrazonal biocenoses of the northern forest zone can be as rich as the family topical groups in the southern forest zone by the number of species and ecological diversity. Ecological properties of the fauna and ground beetle population proved similar in different parts of the forest zone. The proportion of stenobiotic meadow species proved to decrease while that of ecologically plastic ones increased from south to north. The proportion of the genus Harpalus decreased in the ground beetle population while the number of Amara species remained unaltered and their abundance increased. The changes in the species composition caused no transformation of the ecological structure of ground beetle population since they were limited to a single life form or guild.     

Excision repair does not protect Bacillus subtilis cells from inactivation by sunlight]

Exponentially growing Bacillus subtilis cells are highly sensitive to inactivating action of sunlight, the strain deficient in excision repair being every more sensitive than the uvr1 mutant. The inactivating effect is connected with the action of irradiation located in the left part of the spectrum (the whole UV region and some zones of the visible one). Increased sensitivity to sunlight disappeared when cells were exposed to sunlight in a liquid medium with casaminoacids (2 g/l). The inactivating effect was probably of photodynamic nature and was caused either by DNA lesions that were not removed by excision repair or by the damage which arose not in DNA.     

An Immunohistochemical Study of Localization of the Calcium-Binding Protein Recoverin in Retina of the Newt Pleurodeles waltl

The presence and localization of the calcium-binding protein recoverin, initially found in photoreceptors of the bovine eye, were immunochemically studied in retina of the new Pleurodeles waltl. Polyclonal monospecific antibodies against recoverin were raised and the methods of immunoblotting and indirect immunofluorescence were used. A protein with an apparent molecular mass of 26 kDa was found in the retina extract, which was specifically stained by the antibodies against recoverin. Localization of recoverin was studied on the retina sections: an intense reaction was found in the inner segments and a weak reaction was found in the basal part of the outer segments of photoreceptors and in Landolt's clubs of displaced bipolars. The results we obtained suggest for the first time the presence of recoverin in the retina of a representative of the Urodeles and indicate to interspecific conservativeness of this protein and differences of its localization in the retina photoreceptors in different species. The data obtained open a possibility of using recoverin as a marker protein of photoreceptors and displaced bipolars in studies of retina regeneration in newts.     

Charging of Dust Grains in a Nuclear-Induced Plasma at High Pressures

The process of dust-grain charging in plasmas produced by radioactive decay products or spontaneous fission fragments in air and xenon at high pressures is studied numerically in the hydrodynamic approximation. It is shown that, at sufficiently high rates of gas ionization, the dust grains in air are charged by electrons rather than ions, so that the grain charge in air is comparable to that in electropositive gases. The results of numerical calculations based on a complete model agree well with the experimental data. The time evolution of the grain charge is investigated, and the characteristic time scales on which the grains acquire an electric charge are established. The validity of approximate theories of dust-grain charging in electropositive and electronegative gases at high pressures is examined.     

Peptidomimetic glutathione analogues as novel gammaGT stable GST inhibitors.

Elevated levels of glutathione-S-transferase (GST) isoenzymes are found in many tumor cells and are thought to play a role in the onset of multidrug resistance (MDR). To evaluate the contribution of GST to this process, inhibitors are needed. Glutathione (GSH) conjugates, although good GST inhibitors, cannot be used in vivo, because they are eliminated rapidly. In this paper, we describe the synthesis of a series of novel peptidomimetic glutathione analogues that are stabilized against peptidase mediated breakdown. The peptide bonds in GSH were replaced by isosteres, such as the 'reduced' amide (which was prepared using a novel method), N-methylamide, urethane, and methylene linkages. The in vitro evaluation of the compounds focuses on GST inhibition and stability towards gamma-glutamyl-transpeptidase (gammaGT), the main enzyme involved in GSH breakdown. The compounds were conjugated to the model electrophile ethacrynic acid (EA) to resemble GS-EA, an efficient GST inhibitor. All novel GSH-analogues were shown to inhibit rat liver cytosolic GSTs. Furthermore, peptidomimetic changes of the gamma-glutamyl-cysteine amide bond greatly improved stability towards gammaGT. These compounds may therefore be useful in the design of novel in vivo applicable GST inhibitors.     

CO2 mass transfer and acid-base balance under conditions of muscular activity at sea level and in the mountains

The state of the blood acid-base balance and dynamics of carbonic acid gas mass transfer were studied in sportsmen at the sea level and in mountains. It is shown that at the sea level due to an intensive muscular activity large amounts of CO2 are formed and excreted; the mass transfer of this gas is multiply accelerated, simultaneously, a pronounced decompensated metabolic acidosis is observed which in some cases is complicated respiratory acidosis. The similar exercises in mountains are followed by a more pronounced disturbance in the acid-base balance and a more intensified mass-transfer of CO2. After 12-day acclimatization and training in mountains the buffer blood capacity increases, the metabolic acidosis under conditions of muscular activity is less pronounced.     

Long-term ant-species-dependent dynamics of a myrmecochorous plant community

Myrmecochory or seed dispersal by ants is a widely spread phenomenon, and myrmecochorous plants constitute a large portion of species in many ecosystems. Since the ant species complex in the ecosystem is continuously changing in time and space, the long-term effects of such ant–plant interactions on the plant community remained unclear. The manifold information obtained in numerous previous studies from one ecosystem in the deciduous forests of Central Ukraine allowed us to simulate the possible scenarios for plant survival and distribution in the ecosystem after a reduction in the number or local extinction of one of the ant species. The results of the virtual long-term experiment show that the abundance and spatial distribution of myrmecochorous plants strongly depends on both the abundance of ants and their species composition in the ecosystem. The positive role of ant species diversity for maintaining myrmecochorous plant species diversity is shown. Competition between plant species for seed dispersers is influenced by the ant community in such a way that the disappearance of one ant species may lead to the reduction or even local extinction of a particular plant population.