Increasing the amphiphilicity of an estradiol based steroid structure by Barbier-allylation--ring-closing metathesis--dihydroxylation sequence

Polyhydroxylated steroids, such as brassinosteroids, phytoecdysteroids and steroid saponins, are structurally attractive compounds possessing a number of interesting biological properties. Accordingly, development of synthetic procedures to build steroid based structures mimicking the naturally occurring hydrophilic steroids is of topical interest. In the present work, a D-secoestrone derivative was modified further by Barbier-allylation - ring-closing metathesis - dihydroxylation sequence with the aim to prepare steroid based structures with limited hydrophilicity. A straightforward synthesis route was developed with the isolated yield for each step ranging from good to excellent. All compounds prepared were fully characterized by NMR spectroscopic techniques and completely assigned (1)H and (13)C spectra are reported herein. Finally, the effects of the synthesized amphiphilic steroid derivatives on the proliferation of cancer cells are reported and discussed.     

Structure and mechanism of the tripartite CusCBA heavy-metal efflux complex

Gram-negative bacteria frequently expel toxic chemicals through tripartite efflux pumps that span both the inner and outer membranes. The three parts are the inner membrane, substrate-binding transporter (or pump); a periplasmic membrane fusion protein (MFP, or adaptor); and an outer membrane-anchored channel. The fusion protein connects the transporter to the channel within the periplasmic space. One such efflux system CusCBA is responsible for extruding biocidal Cu(I) and Ag(I) ions. We previously described the crystal structures of both the inner membrane transporter CusA and the MFP CusB of Escherichia coli. We also determined the co-crystal structure of the CusBA adaptor-transporter efflux complex, showing that the transporter CusA, which is present as a trimer, interacts with six CusB protomers and that the periplasmic domain of CusA is involved in these interactions. Here, we summarize the structural information of these efflux proteins, and present the accumulated evidence that this efflux system uses methionine residues to bind and export Cu(I) and Ag(I). Genetic and structural analyses suggest that the CusA pump is capable of picking up the metal ions from both the periplasm and the cytoplasm. We propose a stepwise shuttle mechanism for this pump to export metal ions from the cell.     

Associations of maximal strength and muscular endurance test scores with cardiorespiratory fitness and body composition

The purpose of the present study was to assess the relationships between maximal strength and muscular endurance test scores additionally to previously widely studied measures of body composition and maximal aerobic capacity. 846 young men (25.5 ± 5.0 yrs) participated in the study. Maximal strength was measured using isometric bench press, leg extension and grip strength. Muscular endurance tests consisted of push-ups, sit-ups and repeated squats. An indirect graded cycle ergometer test was used to estimate maximal aerobic capacity (V(O2)max). Body composition was determined with bioelectrical impedance. Moreover, waist circumference (WC) and height were measured and body mass index (BMI) calculated. Maximal bench press was positively correlated with push-ups (r = 0.61, p < 0.001), grip strength (r = 0.34, p < 0.001) and sit-ups (r = 0.37, p < 0.001) while maximal leg extension force revealed only a weak positive correlation with repeated squats (r = 0.23, p < 0.001). However, moderate correlation between repeated squats and V(O2)max was found (r = 0.55, p < 0.001) In addition, BM and body fat correlated negatively with muscular endurance (r = -0.25 - -0.47, p < 0.001), while FFM and maximal isometric strength correlated positively (r = 0.36-0.44, p < 0.001). In conclusion, muscular endurance test scores were related to maximal aerobic capacity and body fat content, while fat free mass was associated with maximal strength test scores and thus is a major determinant for maximal strength. A contributive role of maximal strength to muscular endurance tests could be identified for the upper, but not the lower extremities. These findings suggest that push-up test is not only indicative of body fat content and maximal aerobic capacity but also maximal strength of upper body, whereas repeated squat test is mainly indicative of body fat content and maximal aerobic capacity, but not maximal strength of lower extremities.     

Biotic interactions hold the key to understanding metacommunity organisation

Biotic interactions are fundamental drivers governing biodiversity locally, yet their effects on geographical variation in community composition (i.e. incidence-based) and community structure (i.e. abundance-based) at regional scales remain controversial. Ecologists have only recently started to integrate different types of biotic interactions into community assembly in a spatial context, a theme that merits further empirical quantification. Here, we applied partial correlation networks to infer the strength of spatial dependencies between pairs of organismal groups and mapped the imprints of biotic interactions on the assembly of pond metacommunities. To do this, we used a comprehensive empirical dataset from Mediterranean landscapes and adopted the perspective that community assembly is best represented as a network of interacting organismal groups. Our results revealed that the co-variation among the beta diversities of multiple organismal groups is primarily driven by biotic interactions and, to a lesser extent, by the abiotic environment. These results suggest that ignoring biotic interactions may undermine our understanding of assembly mechanisms in spatially extensive areas and decrease the accuracy and performance of predictive models. We further found strong spatial dependencies in our analyses which can be interpreted as functional relationships among several pairs of organismal groups (e.g. macrophytes–macroinvertebrates, fish–zooplankton). Perhaps more importantly, our results support the notion that biotic interactions make crucial contributions to the species sorting paradigm of metacommunity theory and raise the question of whether these biologically-driven signals have been equally underappreciated in other aquatic and terrestrial ecosystems. Although more research is still required to empirically capture the importance of biotic interactions across ecosystems and at different spatial resolutions and extents, our findings may allow decision makers to better foresee the main consequences of human-driven impacts on inland waters, particularly those associated with the addition or removal of key species.     

Immunocompetence and resource holding potential in the damselfly, Calopteryx virgo L

It is generally believed that resource holding potential reliablyreflects male quality, but empirical evidence showing this isscarce. Here we show that the outcome of male-male competitionmay predict male immunocompetence in the territorial damselfly,Calopteryx virgo (Odonata: Calopterygidae). We staged contestsbetween 27 pairs of males and found that winners of the contestsshowed higher immunocompetence, measured as encapsulation response,compared with that of losers. Furthermore, the winners had largerfat reserves. We also collected 29 males that had not been usedin staged contests, and found that in these males encapsulationresponse correlated positively with an individual's fat reserves.Both immunocompetence and resource holding potential seem todepend on energy reserves, suggesting a trade-off between parasiteresistance and energetically costly territorial behavior. Theresults suggest that the outcome of male-male contest can beused to predict male quality in terms of immune defense.     

Untangling the assembly of littoral macroinvertebrate communities through measures of functional and phylogenetic alpha diversity

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Deleterious action of FA metabolites on ATP synthesis: possible link between lipotoxicity, mitochondrial dysfunction, and insulin resistance

Insulin resistance is a characteristic feature of type 2 diabetes and obesity. Insulin-resistant individuals manifest multiple disturbances in free fatty acid (FFA) metabolism and have excessive lipid accumulation in insulin target tissues. Although much evidence supports a causal role for altered FFA metabolism in the development of insulin resistance, i.e., "lipotoxicity", the intracellular mechanisms by which elevated plasma FFA levels cause insulin resistance have yet to be completely elucidated. Recent studies have implicated a possible role for mitochondrial dysfunction in the pathogenesis of insulin resistance in skeletal muscle. We examined the effect of FFA metabolites [palmitoyl carnitine (PC), palmitoyl-coenzyme A (CoA), and oleoyl-CoA] on ATP synthesis in mitochondria isolated from mouse and human skeletal muscle. At concentrations ranging from 0.5 to 2 microM, these FFA metabolites stimulated ATP synthesis; however, above 5 microM, there was a dose-response inhibition of ATP synthesis. Furthermore, 10 microM PC inhibits ATP synthesis from pyruvate. Elevated PC concentrations (> or =10 microM) inhibit electron transport chain activity and decrease the mitochondrial inner membrane potential. These acquired mitochondrial defects, caused by a physiological increase in the concentration of FFA metabolites, provide a mechanistic link between lipotoxicity, mitochondrial dysfunction, and muscle insulin resistance.     

Preservation of yeast cell morphology for scanning electron microscopy using 3.28-micro m IR laser irradiation

As an alternative to conventional fixation procedures for scanning electron microscopy (SEM) analysis, yeast cells (Saccharomyces cerevisiae) were irradiated in ambient air, with an intense 3.28-micro m IR laser pulse. The morphology of the irradiated cells was well preserved, while nonirradiated control cells were severely shriveled.