Design,synthesis and evaluation of novel triazole core based P-glycoprotein-mediated multidrug resistance reversal agents

A novel series of triazol-N-ethyl-tetrahydroisoquinoline based compounds were designed and synthesized via click chemistry. Most of the synthesized compounds showed P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) reversal activities. Among them, compound 7 with little cytotoxicity towards GES-1 cells (IC₅₀ >80 μM) and K562/A02 cells (IC₅₀ >80 μM) exhibited more potency than verapamil (VRP) on increasing anticancer drug accumulation in K562/A02 cells. Moreover, compound 7 could significantly reverse MDR in a dose-dependent manner and also persist longer chemo-sensitizing effect than VRP with reversibility. Further mechanism studies revealed that compound 7 in reversing MDR revealed that it could remarkably increase the intracellular accumulation of both rhodamine-123 (Rh123) and adriamycin (ADM) in K562/A02 cells as well as inhibit their efflux from the cells. These results suggested that compound 7 showed more potency than the classical P-gp inhibitor VRP under the same conditions, which may be a promising P-gp-mediated MDR modulator for further development.     

尿液常规干化学法测定影响因素的探讨

目的：通过分析尿液常规检验中标本采集后放置时间和标本中污染细菌后对结果的影响,来探讨尿液分析的标准化。方法：按全国临床检验操作规程（第三版）的推荐方法在1 h之内进行尿液干化学分析, 根据结果分为阳性标本组,阴性标本组,阴性标本接种大肠埃希菌组和阴性标本接种粪肠球菌组,然后放置在室温（约20℃）,每隔1 h 进行尿液干化学分析直至留取标本后5 h。结果：尿液干化学分析结果受多种影响因素,阴性标本接种大肠埃希菌后尿隐血、亚硝酸盐产生假阳性,阳性标本室温放置后尿胆原、蛋白质、白细胞、维生素C阳性减弱或产生假阴性。结论：在实际工作中必须遵照标准化的操作规程的要求,正确地留取标本并及时送检,排除多种影响因素干拢,才能保证结果的准确性,更好地为临床服务。     

Fat & fabulous: Bifunctional lipids in the spotlight

Understanding biological processes at the mechanistic level requires a systematic charting of the physical and functional links between all cellular components. While protein–protein and protein–nucleic acid networks have been subject to many global surveys, other critical cellular components such as membrane lipids have rarely been studied in large-scale interaction screens. Here, we review the development of photoactivatable and clickable lipid analogues–so-called bifunctional lipids–as novel chemical tools that enable a global profiling of lipid–protein interactions in biological membranes. Recent studies indicate that bifunctional lipids hold great promise in systematic efforts to dissect the elaborate crosstalk between proteins and lipids in live cells and organisms. This article is part of a Special Issue entitled Tools to study lipid functions.     

Ant diversity partitioning across spatial scales: Ecological processes and implications for conserving Tropical Dry Forests

Several ecological and evolutionary processes can drive changes in diversity at different spatial scales. To determine the scale at which these processes are most influential, we hypothesized that (i) broad‐scale differences between ecoregions had greater influence on ant species richness and species turnover than local differences among fragments within ecoregions; and (ii) the degree of dissimilarity in ant species composition is larger between Tropical Dry Forest fragments and the surrounding vegetations than among Tropical Dry Forests located in different ecoregions, indicating that extant Tropical Dry Forests are relicts of a broader distribution of this vegetation. To examine ant diversity patterns, we built a nested hierarchical design on three spatial scales, ranging from fragments (local scale), Tropical Dry Forest + surroundings vegetation (landscape scale) and Brazilian ecoregions (regional scale). We used 450 sampling units (45 sampling units × two fragments × five ecoregions = 450). A null model based on the sample was used to identify variations in the random distribution across spatial scales. Spatial partitioning of ant diversity showed that observed β₁ diversity (between fragments) and β₂ diversity (among ecoregions) were higher than expected by chance. When the partitioning was analysed separately for each region, the observed β₁ diversity (Tropical Dry Forest and surrounding vegetation) was higher than expected by the null hypothesis in all ecoregions of Brazil. Based on species composition and diversity patterns, we stress the importance of creating more protected areas throughout the coverage area of Tropical Dry Forests, favouring a more efficient conservation process.     

Does a sap feeding marsupial choose trees with specific chemical characteristics?

Only about 20 vertebrate species are known to feed regularly on tree sap. One of these is the yellow‐bellied glider (Petaurus australis), a marsupial that obtains between 16% and 80% of its diet from eucalypt sap. We reviewed the literature on sap feeding by the yellow‐bellied glider and identified 10 species from which it most frequently obtains sap. These species come mainly from a few sections of the subgenus Symphyomyrtus, which accounts for two‐thirds of over 2000 sap trees reported, but more specifically sections Latoangulatae and Maidenii within this subgenus. Some of these key species contain relatively high concentrations of foliar nutrients and each is an important food tree for at least one of the arboreal folivores – koala (Phascolarctos cinereus), greater glider (Petauroides volans), and common ringtail (Pseudocheirus peregrinus) and brushtail possums (Trichosurus vulpecula). Because yellow‐bellied gliders, like the arboreal folivores, prefer to feed from certain individuals within a species, we hypothesized that these trees possess a unique chemical signature that links sap‐feeding with the concentrations of available nitrogen and formylated phloroglucinol compounds in leaves – the nutritive and defensive chemicals that influence feeding on these species by marsupial folivores. We tested this hypothesis in samples of leaves and bark collected from E. punctata and E. viminalis but found no link between chemistry and sap feeding and conclude that other aspects of an individual tree, such as sap flow or sap chemistry, determine whether gliders will target it for sap.     

Testate Amoeba (Arcellinida,Euglyphida) Ecology along a Poor‐Rich Gradient in Fens of Western Poland

We investigated the relationships between testate amoebae (Arcellinida, Euglyphida), vegetation and water chemistry along environmental gradients in minerotrophic peatlands (fens) in western Poland. We hypothesized that: a) hydrochemistry significantly influences structure of testate amoeba communities, and b) testate amoeba communities are more closely correlated with the hydrochemical variables (environment) than with the vegetation data. Testate amoeba communities and vegetation from 71 sample plots were investigated together with the hydro‐chemistry and hydrology based on 16 environmental variables and vegetation composition. Testate amoeba communities revealed a distinctive poor‐rich gradient in analysed fens. Mineral‐rich habitats, which were dominated by brown mosses, were preferred by a higher number of taxa than acidic habitats, which were dominated by Sphagnum. We recorded a total of 107 testate amoebae taxa. The average species richness of testate amoebae for brown mosses was higher (20) than for Sphagnum (13). We found that testate amoebae communities were similarly correlated with vascular plants, mosses and environmental parameters. Results of direct ordination demonstrate that hydrology, pH, Mg²⁺ and sodium remain the most important environmental control for the entire data set. CCA showed that in case of brown mosses hydrology, sodium and oxygen affect testate amoeba communities significantly whereas in Sphagnum only sodium emerge as most significant determining testate amoeba assemblages. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Differential plant growth and osmotic effects of two maize (<Emphasis Type="Italic">Zea mays</Emphasis> L<Emphasis Type="Italic">.</Emphasis>) cultivars to exogenous glycinebetaine application under drought stress

We investigated the effects of exogenous glycinebetaine (GB) and drought stress (DS) on grain yield (GY) and production of dry matter (DM) and osmolytes in two maize (Zea mays L.) cultivars i.e. Shaandan 9 (S₉) and Shaandan 911 (S₉₁₁) during the entire growing period. Drought stress substantially reduced DM and GY but increased free proline, endogenous GB, soluble sugar and K⁺ concentrations in leaves of both cultivars. The DM production, GY, drought index (DI) and concentrations of these osmolytes were greater for S₉ than those for S₉₁₁ under DS. The significant differences in these parameters suggested that S₉ was more drought-tolerant as compared to S₉₁₁. Additionally, foliar application of GB increased the concentrations of all osmolytes measured, DM and GY of both cultivars under DS. These positive responses of exogenous GB spray were more pronounced in S₉₁₁ as compared to those in S₉. Further correlation analysis involving a number of parameters indicated that maize production was tighterly correlated with accumulation of the osmolytes measured during DS rather than well-watered controls. Accordingly, this study demonstrated the notion of an anti-drought role of exogenous GB by osmoregulation under DS, particularly in this drought sensitive cultivar. Thus, exogenous GB application might be firstly used with drought sensitive species/cultivars when exposed to DS.     

Efficient Reconstruction of Metabolic Pathways by Bidirectional Chemical Search

One of the main challenges in systems biology is the establishment of the metabolome: a catalogue of the metabolites and biochemical reactions present in a specific organism. Current knowledge of biochemical pathways as stored in public databases such as KEGG, is based on carefully curated genomic evidence for the presence of specific metabolites and enzymes that activate particular biochemical reactions. In this paper, we present an efficient method to build a substantial portion of the artificial chemistry defined by the metabolites and biochemical reactions in a given metabolic pathway, which is based on bidirectional chemical search. Computational results on the pathways stored in KEGG reveal novel biochemical pathways. This work has been partially supported by the Spanish CICYT project TIN2004-07925-C03-01 GRAMMARS, by Spanish DGI projects MTM2006-07773 COMGRIO and MTM2006-15038-C02-01, and by EU project INTAS IT 04-77-7178.