Phytochemical analysis and in vitro antiviral activities of the essential oils of seven Lebanon species

The chemical composition of the essential oils of Laurus nobilis, Juniperus oxycedrus ssp. oxycedrus, Thuja orientalis, Cupressus sempervirens ssp. pyramidalis, Pistacia palaestina, Salvia officinalis, and Satureja thymbra was determined by GC/MS analysis. Essential oils have been evaluated for their inhibitory activity against SARS-CoV and HSV-1 replication in vitro by visually scoring of the virus-induced cytopathogenic effect post-infection. L. nobilis oil exerted an interesting activity against SARS-CoV with an IC(50) value of 120 microg/ml and a selectivity index (SI) of 4.16. This oil was characterized by the presence of beta-ocimene, 1,8-cineole, alpha-pinene, and beta-pinene as the main constituents. J. oxycedrus ssp. oxycedrus oil, in which alpha-pinene and beta-myrcene were the major constituents, revealed antiviral activity against HSV-1 with an IC(50) value of 200 microg/ml and a SI of 5.     

New uses for old drugs. Auranofin, a clinically established antiarthritic metallodrug, exhibits potent antimalarial effects in vitro: Mechanistic and pharmacological implications

The clinically established gold-based antiarthritic drug auranofin (AF) manifests a pronounced reactivity toward thiol and selenol groups of proteins. In particular, AF behaves as a potent inhibitor of mammalian thioredoxin reductases causing severe intracellular oxidative stress. Given the high sensitivity of Plasmodium falciparum to oxidative stress, we thought that auranofin might act as an effective antimalarial agent. Thus, we report here new experimental results showing that auranofin and a few related gold complexes strongly inhibit P. falciparum growth in vitro. The observed antiplasmodial effects probably arise from direct inhibition of P. falciparum thioredoxin reductase. The above findings and the safe toxicity profile of auranofin warrant rapid evaluation of AF for malaria treatment in animal models.     

Phytochemical analysis and in vitro evaluation of the biological activity against herpes simplex virus type 1 (HSV-1) of Cedrus libani A. Rich.

Cedrus libani are widely used as traditional medicine in Lebanon for treatment of different infection diseases. In the present study we reported the phytochemical composition analyzed by GC-MS of wood essential oil and cones and leaves ethanol extracts. The main components of wood essential oil were himachalol (22.50%), beta-himachalene (21.90%), and alpha-himachalene (10.50%). Leaves ethanol extract was characterized by a high content of germacrene d (29.40%). The same extract obtained from cones essentially contained alpha-pinene (51.0%) and beta-myrcene (13.0%). Moreover, we investigated extracts, essential oil, and identified compounds for their in vitro antiviral activities against herpes simplex virus type 1 (HSV-1). Cytotoxicity was evaluated by MTT assay in Vero cells. Cones and leaves ethanol extracts exhibited an interesting activity with IC50 of 0.50 and 0.66 mg/ml, respectively, at non-cytotoxic concentration. A comparable activity was found when essential oil was tested (IC50 of 0.44 mg/ml).     

Identification by time-resolved EPR of the peridinins directly involved in chlorophyll triplet quenching in the peridinin-chlorophyll a-protein from Amphidinium carterae

The mechanism of triplet-triplet energy transfer in the peridinin-chlorophyll-protein (PCP) from Amphidinium carterae was investigated by time-resolved EPR (TR-EPR). The approach exploits the concept of spin conservation during triplet-triplet energy transfer, which leads to spin polarization conservation in the observed TR-EPR spectra. The acceptor (peridinin) inherits the polarization of the donor (chlorophyll) in a way which depends on the relative geometrical arrangement of the donor-acceptor couple. Starting from the initially populated chlorophyll triplet state and taking the relative positions among Chls and peridinins from the X-ray structure of PCP, we calculated the expected triplet state polarization of any peridinin in the complex. Comparison with the experimental data allowed us to propose a path for triplet quenching in the protein. The peridinin-chlorophyll pair directly involved in the triplet-triplet energy transfer coincides with the one having the shortest center to center distance. A water molecule, which is coordinated to the central Mg atom of the Chl, is also placed in close contact with the peridinin. The results support the concept of localization of the triplet state mainly in one specific peridinin in each of the two pigment subclusters related by a pseudo C2 symmetry.     

The response of cortical neurons to in vivo-like input current: theory and experiment: II. Time-varying and spatially distributed inputs

The response of a population of neurons to time-varying synaptic inputs can show a rich phenomenology, hardly predictable from the dynamical properties of the membrane’s inherent time constants. For example, a network of neurons in a state of spontaneous activity can respond significantly more rapidly than each single neuron taken individually. Under the assumption that the statistics of the synaptic input is the same for a population of similarly behaving neurons (mean field approximation), it is possible to greatly simplify the study of neural circuits, both in the case in which the statistics of the input are stationary (reviewed in La Camera et al. in Biol Cybern, 2008) and in the case in which they are time varying and unevenly distributed over the dendritic tree. Here, we review theoretical and experimental results on the single-neuron properties that are relevant for the dynamical collective behavior of a population of neurons. We focus on the response of integrate-and-fire neurons and real cortical neurons to long-lasting, noisy, in vivo-like stationary inputs and show how the theory can predict the observed rhythmic activity of cultures of neurons. We then show how cortical neurons adapt on multiple time scales in response to input with stationary statistics in vitro. Next, we review how it is possible to study the general response properties of a neural circuit to time-varying inputs by estimating the response of single neurons to noisy sinusoidal currents. Finally, we address the dendrite–soma interactions in cortical neurons leading to gain modulation and spike bursts, and show how these effects can be captured by a two-compartment integrate-and-fire neuron. Most of the experimental results reviewed in this article have been successfully reproduced by simple integrate-and-fire model neurons.     

Modelling metapopulations with stochastic membrane systems

Metapopulations, or multi-patch systems, are models describing the interactions and the behavior of populations living in fragmented habitats. Dispersal, persistence and extinction are some of the characteristics of interest in ecological studies of metapopulations. In this paper, we propose a novel method to analyze metapopulations, which is based on a discrete and stochastic modelling framework in the area of Membrane Computing. New structural features of membrane systems, necessary to appropriately describe a multi-patch system, are introduced, such as the reduction of the maximal parallel consumption of objects, the spatial arrangement of membranes and the stochastic creation of objects. The role of the additional features, their meaning for a metapopulation model and the emergence of relevant behaviors are then investigated by means of stochastic simulations. Conclusive remarks and ideas for future research are finally presented.     

The Interrelationships of the Gastrotricha Using Nuclear Small rRNA Subunit Sequence Data, with an Interpretation Based on Morphology

Gastrotrichs are meiobenthic invertebrates of obscure origin and unclear phylogenetic alliances. Uncertainties also plague the intra-group relationship with major contrasts between the evolutionary scenarios inferred from morphology or molecules. In this study we analysed partial sequences of the 18S rDNA gene of 18 taxa (14 new and 4 published) to test morphological estimates of gastrotrich phylogeny and to verify whether controversial interrelationships from previous molecular data are due to poor sampling. Data were analysed using both maximum parsimony and maximum likelihood. MP topology was then forced to reflect published morphological estimates and the most parsimonious solutions from each constraint analysis was statistically compared against the unconstrained solution. MP analysis yielded a single tree with few nodes well supported by bootstrap resampling. These included the monophyly of the Chaetonotidae and the internal relationships of the members of this family, with Aspidiophorus appearing as the most basal member. The monophyly of the Turbanellidae was also well supported with some suggestion that its sister group might be Mesodasys. Lepidodasyidae was found to be an unnatural taxon with Lepidodasys forming a separated clade but unrelated also to the Thaumastodermatidae. With the exception of genera Lepidodasys and Neodasys, the Macrodasyida appeared to be resolved separately from the Chaetonotida, and Dactylopodola was resolved as the most basal macrodasyid. ML analysis yielded a tree not too dissimilar from MP, although Dactylopodola and Xenodasys were resolved as a clade. Statistics indicate that the output from our MP analysis is compatible with the classical view placing representatives of the two orders within two distinct evolutionary lines. Most of the constrained solutions, except the shortest, corroborate the monophyly of the two orders, whereas all five constrained solutions support also the notion that sees Neodasys as an early divergent clade along the Chaetonotida branch. Thus, results are generally compatible with the hypothesised evolutionary scenario based on morphological data, but are in contrast with previous findings from molecules. Future research should consider using the complete SSU rDNA gene sequence in their analysis and additional genes for deeper resolution.     

Bile acids in asymmetric synthesis and chiral discrimination

An overview on the use of bile acid‐based compounds able to catalyze transformations, control the stereochemical course of a given reaction, recognize and bind other molecules, is presented. The recent developments in inclusion discrimination of chiral and achiral guests and enantioselective recognition achieved by bile acid are described with suitable examples. Chirality 2010. © 2009 Wiley‐Liss, Inc.