Synthesis and characterization of platinum-sterol hydrazone complexes with biological activity against Leishmania (L.) mexicana

Leishmaniasis is a parasitic zoonosis caused by protozoans of the genus Leishmania transmitted by insects known as phlebotomines, which are found in wild or urban environments. The disease occurs in tropical and sub-tropical areas, mainly in Asia, Europe, Africa and the Americas. At present, there is no effective treatment for this disease. In the search for new rational chemotherapeutic alternatives, two novel trans [Pt(Hpy1)₂(Cl)₂] (1) and trans [Pt(Hpy2)₂ (Cl)₂] (2) complexes were synthesized by the reaction of K₂PtCl₄ with sterol hydrazone ligands 20-hydrazone-pyridin-2-yl-5α-pregnan-3β-ol (Hpy1) and 22-hydrazone-pyridin-2-yl-chol-5-ene-3β-ol (Hpy2). These organic compounds are specific inhibitors of sterol methyl transferase (SMT). The new platinum complexes were characterized by a combination of ESI-MS (electrospray ionization-mass spectroscopy), UV-vis, infrared and NMR spectroscopies; elemental analysis and molar conductivity. Promastigotes of Leishmania (L.) mexicana were treated for 48 h with 10 μM of the sterol hydrazones Hpy1 or Hpy2 alone or coordinated to Pt. Hpy1 produced higher leishmanistatic activity than Hpy2 (39% growth inhibition vs. 16%), which significatively increased (71%, p < 0.001) when the complex trans-[Pt(Hpy1)₂(Cl)₂] was used. This complex represents a new chemotherapeutic alternative to be evaluated in depth in experimental models of leishmaniasis.     

Mechanisms and cellular roles of local protein synthesis in mammalian cells

After the export from the nucleus it turns out that all mRNAs are not treated equally. Not only is mRNA subject to translation, but also through RNA-binding proteins and other trans-acting factors, eukaryotic cells interpret codes for spatial sorting within the mRNA sequence. These codes instruct the cytoskeleton and translation apparatus to make decisions about where to transport and when to translate the intended protein product. Signaling pathways decode extra-cellular cues and can modify transport and translation factors in the appropriate cytoplasmic space to achieve translation locally. Identifying regulatory sites on transport factors as well as novel physiological functions for well-known translation factors has provided significant advances in how spatially controlled translation impacts cell function.     

Loss of PPAR gamma in immune cells impairs the ability of abscisic acid to improve insulin sensitivity by suppressing monocyte chemoattractant protein-1 expression and macrophage infiltration into white adipose tissue

Abscisic acid (ABA) is a natural phytohormone and peroxisome proliferator-activated receptor gamma (PPARgamma) agonist that significantly improves insulin sensitivity in db/db mice. Although it has become clear that obesity is associated with macrophage infiltration into white adipose tissue (WAT), the phenotype of adipose tissue macrophages (ATMs) and the mechanisms by which insulin-sensitizing compounds modulate their infiltration remain unknown. We used a loss-of-function approach to investigate whether ABA ameliorates insulin resistance through a mechanism dependent on immune cell PPARgamma. We characterized two phenotypically distinct ATM subsets in db/db mice based on their surface expression of F4/80. F4/80(hi) ATMs were more abundant and expressed greater concentrations of chemokine receptor (CCR) 2 and CCR5 when compared to F4/80(lo) ATMs. ABA significantly decreased CCR2(+) F4/80(hi) infiltration into WAT and suppressed monocyte chemoattractant protein-1 (MCP-1) expression in WAT and plasma. Furthermore, the deficiency of PPARgamma in immune cells, including macrophages, impaired the ability of ABA to suppress the infiltration of F4/80(hi) ATMs into WAT, to repress WAT MCP-1 expression and to improve glucose tolerance. We provide molecular evidence in vivo demonstrating that ABA improves insulin sensitivity and obesity-related inflammation by inhibiting MCP-1 expression and F4/80(hi) ATM infiltration through a PPARgamma-dependent mechanism.     

Growth, delayed fluorescence and pigment composition of four Prorocentrum minimum strains growing at two salinities

Prorocentrum minimum is a potentially harmful and widely distributed marine dinoflagellate. Several P. minimum strains have already been studied, showing phylogenetical relations of strains isolated from the same geographical regions. Similarity among the strains was further examined on the basis of their physiology. Pigment composition and concentration, as well as delayed fluorescence (DF) decay kinetics and intensity, were measured in four P. minimum strains isolated from the Baltic and Adriatic Seas. The strains were grown at two salinities characteristic of the Baltic (8 PSU) and North Adriatic Seas (32 PSU). Strain differences in DF decay kinetics and growth did not always follow their genetic relations. While two strains showed similarities to the previously described strains from the Baltic and Adriatic Seas in DF parameters, the other two strains seemed to be specific. The differences among strains isolated from the same sea could stem from adaptations to conditions in the specific habitats. Cluster analysis based on the ratio of individual carotenoid pigments concentrations to the chlorophyll a concentration or to total carotenoids were not conclusive in showing relations among the strains. Among the measured pigments, only peridinin concentration depended on salinity in all st.     

The “Beauty Myth” Is No Myth

The phenomenon of apparently greater emphasis on human female physical attractiveness has spawned an array of explanatory responses, but the great majority can be broadly categorized as either evolutionary or social constructivist in nature. Both perspectives generate distinct and testable predictions. If, as Naomi Wolf (The beauty myth: How images of female beauty are used against women. New York: William Morrow, [originally published in 1991], 2002) and others have argued, greater emphasis on female attractiveness is part of a predominantly Western “beauty myth,” then an analysis of a culturally diverse sample should reveal marked fluctuation in gendered attractiveness emphasis: there should be significant numbers of cultures in which male and female attractiveness are equally emphasized, and cultures in which male attractiveness receives more emphasis. On the other hand, an evolutionary perspective suggests that disproportionate emphasis on female attractiveness will be a universal or near-universal phenomenon. To test these hypotheses, we tallied references to male versus female attractiveness in 90 collections of traditional folktales from 13 diverse cultural areas. The results are consistent with the evolutionary predictions and inconsistent with the constructivist predictions. Across culture areas information on physical attractiveness was much more likely to be conveyed for female characters. Together with other recent studies, these results suggest that the main elements of the beauty myth are not myths: there are large areas of overlap in the attractiveness judgments of diverse populations, and cross-cultural emphasis on physical attractiveness appears to fall principally upon women.     

Collapse of a Planktothrix agardhii perennial bloom and microcystin dynamics in response to reduced phosphate concentrations in a temperate lake

Planktothrix agardhii dynamics, microcystin concentration and limnological variables were monitored every 2 weeks for 2 years (2004-2006) in a shallow hypereutrophic artificial lake (BNV, Viry-Chatillon, France). Time-series analysis identified two components in the P. agardhii biomass dynamics: (1) a significant decreasing trend in P. agardhii biomass (65% of the overall variance) and (2) a residual component without significant seasonal periodicity. A path-analysis model was built to determine the main factors controlling the P. agardhii dynamics over the period studied. The model explained 66% of P. agardhii biomass changes. The decreasing trend in P. agardhii biomass was significantly related to a decrease in the PO4(3-) concentration resulting from an improved treatment of the incoming watershed surface water. The residual component was related to zooplankton dynamics (cyclopoid abundances), supporting the hypothesis of a top-down control of P. agardhii, but only when the biomass was low. Forty-nine percent of the variability in the microcystin (MC) concentration (min:<0.1 microg equivalent MC-LR L(-1); max: 7.4 microg equivalent MC-LR L(-1)) could be explained by changes in the P. agardhii biomass. The highest toxin content was observed when P. agardhii biomass was the lowest, which suggests changes in the proportion of microcystin-producing and -nonproducing subpopulations and/or the physiological status of cells.