Comparative analysis of sensitivity of proteases (chymotrypsin and trypsin) and cholinesterases of different origin to some organophosphorus inhibitors

The antichymotrypsin, antitrypsin, and anticholinesterase potencies of four homologous series of organophosphorus inhibitors are compared: O-(n-alkyl) methylthiophosphonates, O-(n-alkyl)-S-(n-butyl) methylthiophosphonates, O-(n-alkyl)-S-(β-ethylmercaptoethylene) methylth-iophosphonates, and their methylsulfomethylates. As sources of α-chymotrypsin and trypsin, commercial preparations from Worthington Biochemical Corporation and Leningrad Myasokombinat were tested. Bimolecular constant of the reaction rate was used as the measure of antienzyme potency. In all cases, the antichymotrypsin efficiency was lower, while the antitrypsin-essentially higher than the anticholinesterase activity of the studied inhibitors. These differences were found to much depend both on the inhibitor structure and on the nature of the cholinesterase preparations.     

Comparative analysis of sensitivity of cholinesterases of different origin to bis-onium reversible inhibitors

Analytical review of the literature data on interaction constant of cholinesterases from different animal (vertebrates and squids) with 45 bis-onium reversible inhibitors forming homologous series with regularly varied structure has been carried out. Values of the competitive, uncompetitive and generalized inhibitor constants are compared. Interspecies and intraspecies differences in sensitivity of ChE are revealed. Results of conformational analysis of the investigated ligand molecules are presented. The data on population of individual conformations are compared with the data on anticholinesterase potency. Conclusions are made on the action mechanism of the investigated compounds and predominant place of their sorption. The presented data are considered from the point of view of comparative biochemistry and in the light of current information about the active center structure of cholinesterases.     

Comparative analysis of sensitivity of cholinesterases of different origin to monoonium reversible inhibitors

The analytic review of the literature data on constants of interaction of cholinesterases of different animal (vertebrates and squids) with 89 onium (ammonium, phosphonium, sulfonium) reversible inhibitors constituting homologous series with regularly varied structure is carried out. Values of the competitive, uncompetitive and generalized inhibitor constants are compared. On the basis of that, conclusions about the mechanism of action of the studied compounds and primary place of their sorption—in “anionic” or peripheral “anionic” sites of enzymes—are made. The presented data are considered from the point of view of comparative biochemistry and in light of current concepts of cholinesterase active center structure.     

Comparative analysis of sensitivity of cholinesterases of different origin to reversible bis-onium inhibitors

Analytical review of literature data has been carried out about kinetic parameters of cholinesterases (ChE) of various animals (vertebrates and squids) with 45 reversible bis-onium inhibitors forming homologous series with regularly changing structure. Values of competitive, non-competitive, and generalized inhibitory constants are compared. Interspecies and intraspecies differences are revealed in sensitivity of ChE to bis-onium inhibitors. Results of conformational analysis of molecules of the studied ligands are presented. Data on population of individual conformations are compared with values of anticholinesterase efficiency. Conclusions are made about mechanisms of action of the studied compounds and the predominant site of their sorption. The presented data are discussed from the point of view of comparative enzymology and in the light of the current information about structure of active center of cholinesterases.     

Seasonal variations in the morphology of the coccolithophore Calcidiscus leptoporus off Bermuda (N. Atlantic)

Calcidiscus leptoporus is a cosmopolitan coccolithophore specieswith one of the longest fossil records. A previous morphometricstudy on coccoliths of C. leptoporus, carried out on a globalset of Holocene sediment samples, indicated that temperaturemight be a significant factor influencing the size distributionof C. leptoporus. In the present study, C. leptoporus morphologicalvariations and dynamics are studied in samples from HydrostationS time series, near Bermuda, over a 3 year interval (1991 to1994) with monthly sampling. Calcidiscus leptoporus was presentall year round in very low abundances but displayed strong variationsthrough the time-series, both in absolute abundances (maximum551 cells/l and minimum <10 cells/l) and in morphology. Nosignificant correlation between environmental parameters andC. leptoporus abundances was found. The seasonal dynamics ofC. leptoporus, therefore, appears to be the consequence of planktoncommunity interactions and, possibly, of life-cyle. The morphologicalstudy of C. leptoporus shows a sharp decrease in size and variabilityoccurring during the spring–summer transition at the onsetof water stratification. Our results give no conclusive evidenceas to whether C. leptoporus at Hydrostation S consists of anassemblage of different species or ecophenotypes. However, weprovide evidence for significant morphological plasticity linkedto seasonality and possibly temperature. More importantly, ourresults show a trend between temperature and morphology oppositeto the study of Knappertsbusch et al. (Knappertsbusch et al.,1997) based on Holocene sediments. These results emphasize thenecessity of plankton studies in order to interpret patternsobserved in sediments.     

Inhibition of arginine gingipains (RgpB and HRgpA) with benzamidine inhibitors: zinc increases inhibitory potency

We assayed several benzamidine derivatives for inhibition potency with HRgpA and RgpB gingipains, enzymes which are involved in the pathogenesis of gingivitis and periodontal disease. The benzamidine derivatives proved to be effective inhibitors of HRgpA and RgpB, with the best inhibitor being a bis-benzamidine with a urea linker (Ki=30 microM). The inhibition potency was increased 2-3 fold in the presence of low concentrations of zinc with the benzamidines containing a urea moiety linking the two aromatic rings. We propose an inhibition model involving a tetrahedral zinc atom coordinated with the active site Cys and His of gingipain and the urea linker in the benzamidine inhibitor. In summary, we have discovered a new series of effective inhibitors for the gingipains and found a novel way to increase inhibitor potency with the HRgpA and RgpB gingipains using zinc.     

Polyanionic inhibitors of phosphoglycerate mutase: combined structural and biochemical analysis.

The effects that the inhibitors inositol hexakisphosphate and benzene tri-, tetra- and hexacarboxylates have on the phosphoglycerate mutases from Saccharomyces cerevisiae and Schizosaccharomyces pombe have been determined. Their Kivalues have been calculated, and the ability of the inhibitors to protect the enzymes against limited proteolysis investigated. These biochemical data have been placed in a structural context by the solution of the crystal structures of S. cerevisiae phosphoglycerate mutase soaked with inositol hexakisphosphate or benzene hexacarboxylate. These large polyanionic compounds bind to the enzyme so as to block the entrance to the active-site cleft. They form multiple interactions with the enzyme, consistent with their low Kivalues, and afford good protection against limited proteolysis of the C-terminal region by thermolysin. The inositol compound is more efficacious because of its greater number of negative charges. The S. pombe phosphoglycerate mutase that is inherently lacking a comparable C-terminal region has higher Kivalues for the compounds tested. Moreover, the S. pombe enzyme is less sensititive to proteolysis, and the presence or absence of the inhibitor molecules has little effect on susceptibility to proteolysis.     

Non-peptidic, non-prenylic bisubstrate farnesyltransferase inhibitors. Part 3: structural requirements of the central moiety for farnesyltransferase inhibitory activity

Recently, we have described non-peptidic, non-prenylic bisubstrate analogues as a novel type of farnesyltransferase inhibitor composed of a farnesyl-mimetic, a linker and an AAX-peptidomimetic substructure. With this study, we showed that the amide function connecting the farnesyl-mimetic and the linking substructures of our inhibitors is crucial for their activity. We suggest that the amide is bound to the essential zinc ion in the farnesyltransferases active center. We identified succinic and glutaric acid, respectively, in addition to the initially used 1-alanyl moiety as suitable linking structures. Glycine can also be used in this function provided the distance between the alpha-amide group and the center of the peptidomimetic substructure is enlarged by introduction of an additional methylene unit into the peptidomimetic substructure.     

Distribution of coccidians (Coccidea) among different groups of hosts

Approximately 3660 species of Coccidea belonging to 73 genera and 29 families parasitize representatives of the Metazoa kingdom. Coccidea were discovered in 10 of 35 phyla of Metazoa; in the most cases a direct correlation between the number of species in a host group and the number of Coccidea known from that group is clearly traced. Host groups, which are most archaic phylogenetically, are also parasitized by the archaic Coccidea groups. Evolutionarily derived hosts are parasitized by groups of Coccidea, which are the youngest phylogenetically. Parallel development of Coccidea and their hosts may be used for an indirect determination the time of origin of different Coccidea groups.     

Urease inhibitory isoflavonoids from different parts of Calopogonium mucunoides (Fabaceae)

The dichloromethane-methanol (1:1) soluble part of Calopogonium mucunoides (Fabaceae) resulted in the isolation of 10 isoflavones (4′-O-methylalpinumisoflavone, 4′-O-methylderrone, alpinumisoflavone, daidzeine, Calopogonium isoflavone A, atalantoflavone, 2′,4′,5′,7-tetramethoxyisoflavone, 7-O-methylcuneantin, cabreuvin and 7-O-methylpseudobaptigenin) and a rotenoid (6a,12a-dehydroxydegueline). Among these, daidzeine, 7-O-methylcuneantin, atalantoflavone and 6a, 12a-dehydroxydegueline have been isolated for the first time from C. mucunoides while remaining are already reported from this source. Structures of all the isolated constituents were elucidated with the aid of NMR spectroscopic and mass spectrometric techniques. Among all the isolated constituents, nine were evaluated for their urease inhibitory potential. However, six were found potent. These include 4′-O-methylderrone, daidzeine, atalantoflavone, 2′,4′,5′,7-tetramethoxyisoflavone, 7-O-methylcuneantin and 6a, 12a-dehydroxydegueline.     

Circadian variations in the committed stem cell responsiveness to granulopoiesis inhibitory factor (chalone) in vitro

The effect of inhibitory extracts of human granulocytes (chalone) on the circadian rhythm of myelopoietic colony formation in soft agar (CFUc) was studied over one year. Normally, the number of bone marrow CFUc shows a strong circadian rhythm. Preincubation of the cells with the extracts before plating modulated this rhythm with phase shifts and modifications of amplitude. The effects of the extracts oscillated between significant inhibition and stimulation over a 24 h period. No significant seasonal variations in the inhibitory effects were found.     

Parasite communities of the spotted rose snapper Lutjanus guttatus (Perciformes: Lutjanidae) off the Mexican Pacific coasts: Spatial and long-term inter-annual variations

A total of 802 individuals of Lutjanus guttatus (Steindachner, 1869) specimens were collected over a 10-year period (August 2012 to February 2021) from four locations on the south-central Pacific coast of Mexico. Their parasite communities were quantified and analyzed to determine if they experience significant spatial and inter-annual variations.Thirty-two taxa of metazoan parasite were recovered and identified: four species of Digenea, four Monogenea, one Cestoda, two Acanthocephala, seven Nematoda, one Hirudinea, and nine of Crustacea (six Copepoda, and three Isopoda). Species richness was greatest among the digenean group, which represented 25% of the total species recovered, followed by the nematodes (22% of total species). Species richness at the component community level (10 to 20 species) was similar to reported richness in other Lutjanus spp. The component communities and infracommunities exhibited a similar pattern: low species richness and diversity, and dominance by a single species, mainly the monogenean Haliotrematoides guttati. Parasite community structure and species composition varied through the years, as well as between sampling locations. Variations were possibly caused by a combination of biotic and abiotic factors which generated notable changes in the infection levels of several component species. However, the similarity in the parasite species composition was high locally for short-term periods (one or two years). This result, therefore, suggests that parasite communities of L. guttatus may be more predictable locally, but only for short-term periods.     

Ancient hybrid origin of the eastern wolf not yet off the table: a comment on Rutledge et al. (2015)

A recent study of North American canids by Rutledge et al. (Biol. Lett. 11, 20150303 (doi:10.1098/rsbl.2015.0303)) refutes the hypothesized hybrid origin of the eastern wolf (EW) based on genomic evidence against very recent hybridization. However, the analyses do not rule out the possibility of more ancient hybridization. Claims to have resolved the evolutionary origin of the EW are therefore inappropriate. Importantly, though, we plead that uncertainty about the ancient history of the taxon should not affect current conservation policy.     

Evolution of the major histocompatibility complex: independent origin of nonclassical class I genes in different groups of mammals

The class I major histocompatibility complex genes are composed of classical and nonclassical genes, the latter being largely nonfunctional. To understand the evolutionary relationships of the two groups of class I genes, a phylogenetic analysis of DNA sequences was conducted using 45 genes from six mammalian and one avian species. The results indicate that nonclassical genes in one species are more closely related to classical genes from the same species than to nonclassical genes from a species belonging to a different order or family. This indicates that the differentiation of classical and nonclassical genes occurs rather rapidly in the genome. Classical genes are apparently duplicated with a high frequency in the evolutionary process, and many of the duplicated genes seem to degenerate into nonclassical genes as a result of deleterious mutation. The nonclassical Qa genes in the mouse have sequences homologous to regulatory sequences involved in the universal expression of classical class I genes, but they have accumulated numerous nucleotide substitutions in these sequences. The pattern of nucleotide substitution in nonclassical genes is different from that in classical genes. In nonclassical genes, the rate of nonsynonymous substitution is higher in the antigen recognition site than in other gene regions, as is true of classical genes. However, unlike the case of classical genes, the nonsynonymous rate does not always exceed the synonymous rate in the antigen recognition site. Nonclassical proteins further differ from classical proteins in having amino acid replacements in conserved antigen recognition site positions. These observations are consistent with the hypothesis that nonclassical genes have originated from classical genes but have lost classical class I function because of deleterious mutation.     

不同地理种群烟蚜形态特征差异分析

烟蚜Myzus persicae是一种世界性的重要农业害虫。为探讨我国不同地理种群烟蚜形态特征变异情况, 本研究测量了我国18个地理种群烟蚜的体长、 体宽、 头宽、 各足腿节长、 各足胫节长等18个形态性状度量特征和Q值, 并进行方差分析和基于欧氏距离与地理距离和海拔差距的Mantel Test, 利用各形态特征与体长的比值构成的比例特征进行系统聚类和主成分分析。结果表明： 部分地理种群烟蚜的形态性状差异显著。系统聚类和主成分分析表明, 18个烟蚜地理种群中贵州贞丰种群（ZF-GZ）与其他种群相比差异最大, 陕西南泥湾（NNW-SX）、 湖南慈利（CL-HN）、 安徽谯城（QC-AH）和重庆武隆（WL-CQ）种群差异最小, 其他种群间的差异程度介于这两者之间。Mantel Test显示欧氏距离与地理距离、 海拔高度差距都不具有相关性。烟蚜种群的形态分化不符合地理隔离模式, 地理气候条件对种群形态有一定影响, 种群形态差异的形成是多种因素综合作用的结果, 但具体作用机制尚不明确。