The Anopheles gambiae salivary protein gSG6: An anopheline-specific protein with a blood-feeding role

The Anopheles gambiae salivary gland protein 6 (gSG6) is a small protein specifically found in the salivary glands of adult female mosquitoes. We report here the expression of a recombinant form of the protein and we show that in vivo gSG6 is expressed in distal-lateral lobes and is secreted with the saliva while the female mosquito probes for feeding. Injection of gSG6 dsRNA into adult A. gambiae females results in decreased gSG6 protein levels, increased probing time and reduced blood feeding ability. gSG6 orthologs have been found so far only in the salivary glands of Anopheles stephensi and Anopheles funestus, both members of the Cellia subgenus. We report here the gSG6 sequence from five additional anophelines, four species of the A. gambiae complex and Anopheles freeborni, a member of the subgenus Anopheles. We conclude that gSG6 plays some essential blood feeding role and was recruited in the anopheline subfamily most probably after the separation of the lineage which gave origin to Cellia and Anopheles subgenera.     

Synthesis,cannabinoid receptor affinity,molecular modeling studies and in vivo pharmacological evaluation of new substituted 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides. 2. Effect of the 3-carboxamide substituent on the affinity and selectivity profile

New substituted 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides were synthesized by replacing the 2,4-dichlorobenzyl and cyclohexyl moieties at the 3-carboxamide nitrogen of the previously reported CB₁ receptor antagonists/inverse agonists 4 and 5. Several ligands showed potent affinity for the hCB₁ receptor, with K_i concentrations comparable to the reference compounds 1, 4 and 5, and exhibited CB₁ selectivity comparable to 1 and 2. Docking experiments and molecular dynamics (MD) simulations explained the potent hCB₁ binding affinity of compounds 31 and 37. According to our previous studies, 31 and 37 formed a H-bond with K3.28(192), which accounted for the high affinity for the receptor inactive state and the inverse agonist activity. The finding of inhibition of food intake following their acute administration to rats, supported the concept that the CB₁ selective compounds 4 and 52 act as antagonists/inverse agonists.     

Partitioning of functional diversity reveals the scale and extent of trait convergence and divergence

Questions: Trait differentiation among species occurs at different spatial scales within a region. How does the partitioning of functional diversity help to identify different community assembly mechanisms? Location: Northeastern Spain. Methods: Functional diversity can be partitioned into within‐community (α) and among‐communities (β) components, in analogy to Whittaker's classical α and β species diversity concept. In light of ecological null models, we test and discuss two algorithms as a framework to measure α and β functional diversity (the Rao quadratic entropy index and the variance of trait values). Species and trait (specific leaf area) data from pastures under different climatic conditions in NE Spain are used as a case study. Results: The proposed indices show different mathematical properties but similarly account for the spatial components of functional diversity. For all vegetation types along the climatic gradient, the observed α functional diversity was lower than expected at random, an observation consistent with the hypothesis of trait convergence resulting from habitat filtering. On the other hand, our data exhibited a remarkably higher functional diversity within communities compared to among communities (α?β). In contrast to the high species turnover, there was a limited functional diversity turnover among communities, and a large part of the trait divergence occurred among coexisting species. Conclusions: Partitioning functional diversity within and among communities revealed that both trait convergence and divergence occur in the formation of assemblages from the local species pool. A considerable trait convergence exists at the regional scale in spite of changes in species composition, suggesting the existence of ecological redundancy among communities.     

X-Ray crystal structure of GarR—tartronate semialdehyde reductase from Salmonella typhimurium

Tartronate semialdehyde reductases (TSRs), also known as 2-hydroxy-3-oxopropionate reductases, catalyze the reduction of tartronate semialdehyde using NAD as cofactor in the final stage of d-glycerate biosynthesis. These enzymes belong to family of structurally and mechanically related β-hydroxyacid dehydrogenases which differ in substrate specificity and catalyze reactions in specific metabolic pathways. Here, we present the crystal structure of GarR a TSR from Salmonella typhimurium determined by the single-wavelength anomalous diffraction method and refined to 1.65 Å resolution. The active site of the enzyme contains l-tartrate which most likely mimics a position of a glycerate which is a product of the enzyme reaction. The analysis of the TSR structure shows also a putative NADPH binding site in the enzyme.     

Kinetic and Thermodynamic Solubility Values of Some Bioactive Compounds

Thermodynamic solubility is a decisive physicochemical property in drug development. The Chasing Equilibrium method offers an alternative to the classical procedures to measure the solubility of compounds with acid–base properties. The method is fast and yields accurate results. In this work, the solubility of several compounds including acids and bases was determined through the Chasing Equilibrium approach. A study of experimental conditions in terms of sample weight was performed to measure solubilities. The study shows that only a limited range of weights, depending on the nature and solubility of the compounds, is adequate to obtain reliable results.     

Acetate metabolism in Escherichia coli strains lacking phosphoenolpyruvate: carbohydrate phosphotransferase system; evidence of carbon recycling strategies and futile cycles

The ptsHIcrr operon was deleted from Escherichia coli wild-type JM101 to generate strain PB11 (PTS(-)). In a mutant derived from PB11 that partially recovered its growth capacity on glucose by an adaptive evolution process (PB12, PTS(-)Glc(+)), part of the phosphoenolpyruvate not used in glucose transport has been utilized for the synthesis of aromatic compounds. In this report, it is shown that on acetate as a carbon source, PB11 displayed a specific growth rate (mu) higher than PB12 (0.21 and 0.13 h(-1), respectively) while JM101 had a mu of 0.28 h(-1). To understand these growth differences on acetate, we compared the expression profiles of central metabolic genes by RT-PCR analysis. Obtained data revealed that some gluconeogenic genes were downregulated in both PTS(-) strains as compared to JM101, while most glycolytic genes were upregulated in PB12 in contrast to PB11 and JM101. Furthermore, inactivation of gluconeogenic genes, like ppsA, sfcA, and maeB,and poxB gene that codes for pyruvate oxidase, has differential impacts in the acetate metabolism of these strains. Results indicate that growth differences on acetate in the PTS(-) derivatives are due to potential carbon recycling strategies, mainly in PB11, and futile carbon cycles, especially in PB12.     

Molecular models for intrastrand DNA G-quadruplexes

Background  

Independent surveys of human gene promoter regions have demonstrated an overrepresentation of G₃X _n1G3X _n2G₃X _n3G₃ motifs which are known to be capable of forming intrastrand quadruple helix structures. In spite of the widely recognized importance of G-quadruplex structures in gene regulation and growing interest around this unusual DNA structure, there are at present only few such structures available in the Nucleic Acid Database. In the present work we generate by molecular modeling feasible G-quadruplex structures which may be useful for interpretation of experimental data.