Lipophilic gold(I) complexes with 1,3,4-oxadiazol-2-thione or 1,3-thiazolidine-2-thione moieties: synthesis and their cytotoxic and antimicrobial activities

Novel lipophilic gold(I) complexes containing 1,3,4-oxadiazol-2-thione or 1,3-thiazolidine-2-thione derivatives were synthesized and characterized by IR, high resolution mass spectrometry, and ¹H, ¹³C ³¹P NMR. The cytotoxicity of the compounds was evaluated considering cisplatin and/or auranofin as reference in different tumor cell lines: colon cancer (CT26WT), metastatic skin melanoma (B16F10), breast adenocarcinoma (MCF-7), cervical carcinoma (HeLa), glioblastoma (M059 J). Normal human lung fibroblasts (GM07492-A) and kidney normal cell (BHK-21) were also evaluated. The gold(I) complexes were more active than their respective free ligands and cisplatin. Furthermore, antibacterial activity was evaluated against Gram-positive bacteria Staphylococcus aureus ATCC 25213, Staphylococcus epidermidis ATCC 12228 and Gram-negative bacteria Escherichia coli ATCC 11229 and Pseudomonas aeruginosa ATCC 27853 and expressed as the minimum inhibitory concentration (MIC). The complexes exhibited lower MIC values when compared to the ligands and chloramphenicol against Gram-positive bacteria and Gram-negative bacteria. Escherichia coli was sensitive one to the action of gold(I) complexes.     

Structural flexibility of the macrophage dengue virus receptor CLEC5A: implications for ligand binding and signaling

The human C-type lectin-like molecule CLEC5A is a critical macrophage receptor for dengue virus. The binding of dengue virus to CLEC5A triggers signaling through the associated adapter molecule DAP12, stimulating proinflammatory cytokine release. We have crystallized an informative ensemble of CLEC5A structural conformers at 1.9-Å resolution and demonstrate how an on-off extension to a β-sheet acts as a binary switch regulating the flexibility of the molecule. This structural information together with molecular dynamics simulations suggests a mechanism whereby extracellular events may be transmitted through the membrane and influence DAP12 signaling. We demonstrate that CLEC5A is homodimeric at the cell surface and binds to dengue virus serotypes 1–4. We used blotting experiments, surface analyses, glycan microarray, and docking studies to investigate the ligand binding potential of CLEC5A with particular respect to dengue virus. This study provides a rational foundation for understanding the dengue virus-macrophage interaction and the role of CLEC5A in dengue virus-induced lethal disease.     

Glycoinositolphospholipids from Trypanosoma cruzi induce B cell hyper-responsiveness in vivo

The surface of the protozoan Trypanosoma cruzi, the etiologic agent of Chagas' disease, is covered by a dense glycolipid layer, composed mainly by a structurally related family of glycoinositolphospholipids (GIPLs). In the present study we evaluated the in vivo effects of the GIPL on B cell function and immunoglobulin (Ig) secretion. We observed that GIPL injection led to a sustained increase in circulating IgM levels. B cells from GIPL injected mice showed higher response when activated in vitro with either LPS or dextran-conjugated anti-IgD antibodies or purified cytokines. GIPL purified from T. cruzi also showed an adjuvant effect, since this glycophospholipid boosted a polysaccharide-(TNP-Ficoll) induced IgG response. Taken together, our data indicate that T. cruzi-derived GIPL could be at least partially responsible for the remarkable B cell activation observed during T. cruzi acute infection in vivo.     

The Unbearable Lightness of Health Science Reporting: A Week Examining Italian Print Media

Background

Although being an important source of science news information to the public, print news media have often been criticized in their credibility. Health-related content of press media articles has been examined by many studies underlining that information about benefits, risks and costs are often incomplete or inadequate and financial conflicts of interest are rarely reported. However, these studies have focused their analysis on very selected science articles. The present research aimed at adopting a wider explorative approach, by analysing all types of health science information appearing on the Italian national press in one-week period. Moreover, we attempted to score the balance of the articles.

Methodology/Principal Findings

We collected 146 health science communication articles defined as articles aiming at improving the reader''s knowledge on health from a scientific perspective. Articles were evaluated by 3 independent physicians with respect to different divulgation parameters: benefits, costs, risks, sources of information, disclosure of financial conflicts of interest and balance. Balance was evaluated with regard to exaggerated or non correct claims. The selected articles appeared on 41 Italian national daily newspapers and 41 weekly magazines, representing 89% of national circulation copies: 97 articles (66%) covered common medical treatments or basic scientific research and 49 (34%) were about new medical treatments, procedures, tests or products. We found that only 6/49 (12%) articles on new treatments, procedures, tests or products mentioned costs or risks to patients. Moreover, benefits were always maximized and in 16/49 cases (33%) they were presented in relative rather than absolute terms. The majority of stories (133/146, 91%) did not report any financial conflict of interest. Among these, 15 were shown to underreport them (15/146, 9.5%), as we demonstrated that conflicts of interest did actually exist. Unbalanced articles were 27/146 (18%). Specifically, the probability of unbalanced reporting was significantly increased in stories about a new treatment, procedure, test or product (22/49, 45%), compared to stories covering common treatments or basic scientific research (5/97, 5%) (risk ratio, 8.72).

Conclusions/Significance

Consistent with prior research on health science communication in other countries, we report undisclosed costs and risks, emphasized benefits, unrevealed financial conflicts of interest and exaggerated claims in Italian print media. In addition, we show that the risk for a story about a new medical approach to be unbalanced is almost 9 times higher with respect to stories about any other kind of health science-related topics. These findings raise again the fundamental issue whether popular media is detrimental rather than useful to public health.     

Derivation in culture of primordial germ cells from cells of the mouse epiblast: phenotypic induction and growth control by Bmp4 signalling

Primordial germ cells (PGCs) are the embryonic precursors of the gametes of the adult. PGCs derive from cells of the most proximal part of the cup-shaped epiblast corresponding to the presumptive region of the extraembryonic mesoderm. At 7.2 days post coitum (dpc) a small group of PGCs located at the base of the allantois can be recognised due to a strong alkaline phosphatase activity. Thus far, scant information was available on the mechanism(s) controlling the lineage of PGCs in the mouse embryo. However, results obtained in mice defective for bone morphogenetic protein-4 (Bmp4) secreted molecule revealed that this growth factor has important functions for the derivation of PGCs from extraembryonic mesoderm cells. In this paper, we have studied the effects in culture of Bmp4 on epiblast cells obtained from egg-cylinder stage mouse embryos (5.5-6.0 dpc) and PGCs from 11.5 dpc embryos. We found that Bmp4 treatment enables recruitment of pluripotent cells to a PGC phenotype by a multi-step process involving an initial pre-commitment of epiblast cells and a following stage of PGC phenotypic determination. We further provide evidences that Bmp4 may promote the growth of gonadal PGCs through a Smad1/4 signalling.     

Molecular dynamics studies of human receptor molecule in hemagglutinin of 1918 and 2009 H1N1 influenza viruses

Molecular dynamics (MD) simulations were carried out to study the behavior of human receptor molecule in the hemagglutinin (HA) of 1918 and 2009 H1N1 influenza viruses respectively. The 2009 HA model was obtained by virtually mutating the 1918 HA crystal structure based on A/Mexico City/MCIG01/2009(H1N1) segment 4 sequence. We found that human receptor molecule has no binding preference between the 2009 HA and the 1918 HA. In addition, among the four sugar moieties in the human receptor molecule, sialic acid contributes the most to the electrostatic and non-polar interaction energy during binding. Furthermore, the hydrogen bonds between sialic acid and the surrounding residues in 1918 HA are preserved in 2009 HA. We also found that the mutated residues contribute to a more favorable binding of hemagglutinin to the human receptor molecule.     

Biomass and nutritive value of Spirulina (Arthrospira fusiformis) cultivated in a cost-effective medium

Introduction

Cultivation of spirulina at commercial-scales relies on analytical grade–based media, which are expensive and so are the product.

Purpose

This study assessed the biomass, proximate composition, and other useful compounds in Spirulina (Arthrospira fusiformis) produced with a cost-effective culture medium (LCMA), and the results were compared with those from a standard Zarrouk medium–grown spirulina.

Methods

The LCMA medium was formulated by using a commercial NPK10-20-20 fertilizer as a source of the three major nutrients for spirulina growth, and other three ingredients from Zarrouk medium. The experiment was conducted for 28 days in the glass aquaria under indoor conditions. Standard analytical methods were applied for the determination of proximate composition, chlorophyll, minerals, and vitamins in the spirulina biomass.

Result

The LCMA medium showed the best growth conditions by accumulating higher chlorophyll content (0.99 ± 0.02%) and dry weight (0.75 ± 0.01 g/100 ml) as well as attaining higher optical density (2.06 at day 15) earlier than the Zarrouk medium. The results of the proximate analysis for spirulina cultured in the LCMA medium were of good quality, with the protein contributing more than 50% of its dry matter. It was further noticed that the LCMA was an ideal medium for optimization of vitamins and some minerals since it recorded a significant amount of most of the analyzed vitamins together with the minerals sodium and potassium compared with the Zarrouk medium.

Conclusion

It is suggested that LCMA medium could be used as the alternative and cheap medium for maximization of biomass and production of useful biochemical compounds in spirulina species.

     

Clustering of Vector Control Interventions Has Important Consequences for Their Effectiveness: A Modelling Study

Vector control interventions have resulted in considerable reductions in malaria morbidity and mortality. When universal coverage cannot be achieved for financial or logistical reasons, the spatial arrangement of vector control is potentially important for optimizing benefits. This study investigated the effect of spatial clustering of vector control interventions on reducing the population of biting mosquitoes. A discrete-space continuous-time mathematical model of mosquito population dynamics and dispersal was extended to incorporate vector control interventions of insecticide treated bednets (ITNs), Indoor residual Spraying (IRS), and larviciding. Simulations were run at varying levels of coverage and degree of spatial clustering. At medium to high coverage levels of each of the interventions or in combination was more effective to spatially spread these interventions than to cluster them. Suggesting that when financial resources are limited, unclustered distribution of these interventions is more effective. Although it is often stated that locally high coverage is needed to achieve a community effect of ITNs or IRS, our results suggest that if the coverage of ITNs or IRS are insufficient to achieve universal coverage, and there is no targeting of high risk areas, the overall effects on mosquito densities are much greater if they are distributed in an unclustered way, rather than clustered in specific localities. Also, given that interventions are often delivered preferentially to accessible areas, and are therefore clustered, our model results show this may be inefficient. This study provides evidence that the effectiveness of an intervention can be highly dependent on its spatial distribution. Vector control plans should consider the spatial arrangement of any intervention package to ensure effectiveness is maximized.     

Chemical characterization of new oxylipins from Cestrum parqui, and their effects on seed germination and early seedling growth

Isolation, chemical characterization, and phytotoxicity of five new oxylipins, together with seven already known related compounds, from Cestrum parqui L' Hérl. is reported. All the structures were elucidated on the basis of their spectral data, especially 1D-(1H- and 13C-NMR, DEPT) and 2D-NMR (COSY, TOCSY, HSQC, HMBC, and NOESY). The configurations of the stereogenic C-atoms were determined by the Mosher's method. The compounds have been assayed for their phytotoxicity on Lactuca sativa at concentrations ranging between 10(-4) and 10(-8) M. The results of the phytotoxicity tests on the germination and growth of the test species, obtained by a cluster analysis, showed interesting relationship between the chemical structures of the compounds and their biological effects.