Synthesis,Antimicrobial Activity and Molecular Docking Study of Novel α‐(Diphenylphosphoryl)‐ and α‐(Diphenylphosphorothioyl)cycloalkanone Oximes

A series of novel α‐(diphenylphosphoryl)‐ and α‐(diphenylphosphorothioyl)cycloalkanone oximes have been synthesized in search for novel bioactive molecules. Their structures were characterized by various spectroscopic methods including IR, NMR (¹H, ³¹P, ¹³C), mass spectrometry and single crystal X‐ray diffraction. The newly synthesized phosphorus‐containing oximes were screened for their in vitro antimicrobial activity against Gram‐positive bacteria (Staphylococcus aureus and Bacillus subtilis), Gram‐negative bacteria (Escherichia coli and Salmonella typhimurium) and fungal strains (Candida albicans and Candida glabrata). The biological assays showed that all the studied compounds exhibited high antibacterial and antifungal activities at only 0.1–2.1 μg/mL. In silico molecular docking studies in FabH enzyme active site were performed in order to predict the possible interaction modes and binding energies of the drug candidates at the molecular level.     

In vitro inhibition of cytosolic carbonic anhydrases I and II by some new dihydroxycoumarin compounds

A new series of 6, 7-dihydroxy-3-(methylphenyl) chromenones, including three new derivatives, i.e. 6,7-dihydroxy-3-(2-methylphenyl)-2H-chromen-2-one (OPC); 6,7-dihydroxy-3-(3-methylphenyl)-2H-chromen-2-one (MPC); 6,7-dihydroxy-3-(4-methylphenyl)-2H-chromen-2-one (PPC) and one previously described, namely 6,7-dihydroxy-3-phenyl-2H-chromen-2-one (DPC), were synthesized. These compounds were investigated as inhibitors of human carbonic anhydrase I (hCA-I) and human carbonic anhydrase II (hCA-II) which had been purified from human erythrocytes on an affinity gel comprised of L-tyrosine-sulfonamide-Sepharose 4B.     

Very fine‐scale population genetic structure of sympatric asterinid sea stars with benthic and pelagic larvae: influence of mating system and dispersal potential

The present study investigated the fine‐scale population genetic structure of sympatric asterinid sea stars with contrasting modes of larval development (benthic versus pelagic). Parvulastra exigua lacks a dispersive life phase yet is one of the worlds most widely distributed and abundant sea stars, whereas Meridiastra calcar, a sea star with a dispersive larva, has a more limited regional scale distribution. Populations of P. exigua sampled from tide pools on three adjacent headlands showed significant genetic substructure (mitochodrial DNA control region) at fine spatial scales (tide pools < 300 m apart: F_ST = 0.249, P < 0.01; headlands 5–15 km apart: F_ST = 0.125, P = 0.04). As expected, M. calcar populations sampled from the same headlands did not exhibit significant genetic structuring (F_ST = 0.029, P = 0.14). The life‐history traits of P. exigua, a mixed mating system (selfing + outcrossing), pseudocopulation among closely‐related conspecifics, and an entirely benthic life cycle with a philopatric larva, undoubtedly influence its strong genetic structure across fine spatial scales. Localized genetic structure, especially at the very fine‐scale of tide pools, would not be detected in the more typical regional scale approaches adopted by most studies of marine invertebrate populations. © 2013 The Linnean Society of London, Biological Journal of the Linnean Society, 2013, ●●, ●●–●●.     

Towards a conceptualization of ETL and physical storage of semantic data warehouses as a service

The data warehouse technology has become the incontestable tool for businesses and organizations to make strategic decisions to ensure their competitively. The construction of a data warehouse ( $\mathcal{D}\mathcal{W}$ ) passes by selecting relevant information sources, extracting relevant data and loading them into the $\mathcal{D}\mathcal{W}$ . These processes require a precise expertise from designers related to logical and physical implementations of information sources, which is not usually an easy task. The diversity and heterogeneity of information sources makes the construction process of the $\mathcal{D}\mathcal{W}$ complex and time consuming. Domain ontologies have been proposed to reduce heterogeneity between sources, platforms, services, etc. They resolve syntax and semantic conflicts. The phenomenon of adopting domain ontologies by organizations creates a new type of databases, called semantic databases ( $\mathcal{S}\mathcal{D}\mathcal{B}$ ). As a consequence, they become a candidate for building the semantic $\mathcal{D}\mathcal{W}$ ( $\mathcal{S}\mathcal{D}\mathcal{W}$ ). To handle the diversity of information sources and hide the implementations aspects of sources, proposing a generic framework for constructing $\mathcal{D}\mathcal{W}$ becomes a necessity. In this paper, we first proposed an ontology-based approach for designing $\mathcal{S}\mathcal {D}\mathcal{B}$ . Secondly, ETL phases are defined at ontological level to hide the implementation details. Thirdly, a storage service for ontologies and its associated data is given. Finally, our proposal is validated through a case study and a tool.     

Protocol of a prospective study on the diagnostic value of transcranial duplex scanning of the substantia nigra in patients with parkinsonian symptoms

Background  

Parkinson's disease (PD) is the second most common neurodegenerative disorder. As there is no definitive diagnostic test, its diagnosis is based on clinical criteria. Recently transcranial duplex scanning (TCD) of the substantia nigra in the brainstem has been proposed as an instrument to diagnose PD. We and others have found that TCD scanning of substantia nigra duplex is a relatively accurate diagnostic instrument in patients with parkinsonian symptoms. However, all studies on TCD so far have involved well-defined, later-stage PD patients, which will obviously lead to an overestimate of the diagnostic accuracy of TCD.     

Use of in vivo and in vitro systems to select Leishmania amazonensis expressing green fluorescent protein

Various Leishmania species were engineered with green fluorescent protein (GFP) using episomal vectors that encoded an antibiotic resistance gene, such as aminoglycoside geneticin sulphate (G418). Most reports of GFP-Leishmania have used the flagellated extracellular promastigote, the stage of parasite detected in the midgut of the sandfly vector; fewer studies have been performed with amastigotes, the stage of parasite detected in mammals. In this study, comparisons were made regarding the efficiency for in vitro G418 selection of GFP-Leishmania amazonensis promastigotes and amastigotes and the use of in vivo G418 selection. The GFP-promastigotes retained episomal plasmid for a prolonged period and G418 treatment was necessary and efficient for in vitro selection. In contrast, GFP-amastigotes showed low retention of the episomal plasmid in the absence of G418 selection and low sensitivity to antibiotics in vitro. The use of protocols for G418 selection using infected BALB/c mice also indicated low sensitivity to antibiotics against amastigotes in cutaneous lesions.     

Activation of TGF-beta by Leishmania chagasi: importance for parasite survival in macrophages

TGF-beta is a potent regulatory cytokine that suppresses expression of inducible NO synthase and IFN-gamma, and suppresses Th1 and Th2 cell development. We examined whether functionally active TGF-beta is present in the local environment surrounding the invading protozoan Leishmania chagasi. Our prior data showed that TGF-beta levels are significantly increased in L. chagasi-infected mice. In the current study, we found TGF-beta was also abundant in bone marrows of humans with acute visceral leishmaniasis but not in those of uninfected controls. Furthermore, L. chagasi infection caused an increase in biologically active TGF-beta in human macrophage cultures without changing the total TGF-beta. Therefore, we investigated the means through which leishmania could augment activated but not total TGF-beta. Incubation of latent TGF-beta with Leishmania sp. promastigotes caused active TGF-beta to be released from the latent complex. In contrast, the nonpathogenic protozoan Crithidia fasciculata could not activate TGF-beta. TGF-beta activation by leishmania was prevented by inhibitors of cysteine proteases and by the specific cathepsin B inhibitor CA074. Physiologic concentrations of TGF-beta inhibited killing of intracellular L. chagasi in macrophages, although the phagocytosis-induced respiratory burst remained intact. In contrast, supraphysiologic concentrations of TGF-beta had no effect on parasite survival. We hypothesize that the combined effect of abundant TGF-beta stores at extracellular sites during infection, and the ability of the parasite to activate TGF-beta in its local environment, leads to high levels of active TGF-beta in the vicinity of the infected macrophage. Locally activated TGF-beta could, in turn, enhance parasite survival through its effects on innate and adaptive immune responses.     

Sexual selection drives the evolution of antiaphrodisiac pheromones in butterflies

Competition for mates has resulted in sophisticated mechanisms of male control over female reproduction. Antiaphrodisiacs are pheromones transferred from males to females during mating that reduce attractiveness of females to subsequent courting males. Antiaphrodisiacs generally help unreceptive females reduce male harassment. However, lack of control over pheromone release by females and male control over the amount transferred provides males an opportunity to use antiaphrodisiacs to delay remating by females that have returned to a receptive state. We propose a model for the evolution of antiaphrodisiacs under the influence of intrasexual selection, and determine whether changes in this signal in 11 species of Heliconius butterflies are consistent with two predictions of the model. First, we find that as predicted, male-contributed chemical mixtures are complex and highly variable across species, with limited phylogenetic signal. Second, differences in rates of evolution in pheromone composition between two major clades of Heliconius are as expected: the clade with a greater potential for male-male competition (polyandrous) shows a faster rate of divergence than the one with typically monoandrous mating system. Taken together, our results provide evidence that for females, antiaphrodisiacs can be both honest signals of receptivity (helping reduce harassment) and chastity belts (a male-imposed reduction in remating).     

A single 1-h bout of evening exercise increases basal FFA flux without affecting VLDL-triglyceride and VLDL-apolipoprotein B-100 kinetics in untrained lean men

Our group (Magkos F, Wright DC, Patterson BW, Mohammed BS, Mittendorfer B, Am J Physiol Endocrinol Metab 290: E355-E362, 2006) has recently demonstrated that a single, prolonged bout of moderate-intensity cycling (2 h at 60% of peak oxygen consumption) in the evening increases basal whole-body free fatty acid (FFA) flux and fat oxidation, decreases hepatic VLDL-apolipoprotein B-100 (apoB-100) secretion, and enhances removal efficiency of VLDL-triglyceride (TG) from the circulation the following day in untrained, healthy, lean men. In the present study, we investigated the effect of a single, shorter-duration bout of the same exercise (1 h cycling at 60% of peak oxygen consumption) on basal FFA, VLDL-TG, and VLDL-apoB-100 kinetics in seven untrained, healthy, lean men by using stable isotope-labeled tracer techniques. Basal FFA rate of appearance in plasma and plasma FFA concentration were approximately 55% greater (P < 0.05) the morning after exercise than rest, whereas resting metabolic rate and whole-body substrate oxidation rates were not different after rest and exercise. Exercise had no effect on plasma VLDL-TG and VLDL-apoB-100 concentrations, hepatic VLDL-TG and VLDL-apoB-100 secretion rates, and VLDL-TG and VLDL-apoB-100 plasma clearance rates (all P > 0.05). We conclude that in untrained, healthy, lean men 1) the exercise-induced changes in basal whole-body fat oxidation, VLDL-TG, and VLDL-apoB-100 metabolism during the late phase of recovery from exercise are related to the duration of the exercise bout; 2) single sessions of typical recreational activities appear to have little effect on basal, fasting plasma TG homeostasis; and 3) there is a dissociation between systemic FFA availability and VLDL-TG and VLDL-apoB-100 secretion by the liver.