Combined effect of low-power laser irradiation and anthraquinone anticancer drug aclarubicin on survival of immortalized cells: Comparison with mitoxantrone

The photodynamic response of the anthraquinone anticancer drug aclarubicin (ACL) was investigated in vitro and compared with that of mitoxantrone (MTX). Cultured immortalized rodent B14 and NIH 3T3 cells were used in the experiments as a model for cells with neoplastic phenotype. Long-term cytotoxicity and inhibition of cell proliferation assayed by the clonal growth and MTT-tetrazolium methods were estimated to compare the efficacy of aclarubicin and mitoxantrone in photosensitizing cells and their death after non-thermal exposure to monochromatic laser light. Green He-Ne (543.5 nm) or red semiconductor (670 nm) low-power laser (LPL) irradiations were applied. Different dose-responses of both cell lines to aclarubicin and mitoxantrone were found so that the cytotoxicity of MTX was considerably greater than the cytotoxicity of ACL. Phototherapy response (P < 0.0001) was observed only for B14 cells after sensitisation with aclarubicin. Under the same conditions no significant effect of red light irradiation (semiconductor 670 nm laser) on survival of both cell lines treated with mitoxantrone was found.     

The structural basis of cooperative regulation at an alternate genetic switch

Bacteriophage lambda is a paradigm for understanding the role of cooperativity in gene regulation. Comparison of the regulatory regions of lambda and the unrelated temperate bacteriophage 186 provides insight into alternate ways to assemble functional genetic switches. The structure of the C-terminal domain of the 186 repressor, determined at 2.7 A resolution, reveals an unusual heptamer of dimers, consistent with presented genetic studies. In addition, the structure of a cooperativity mutant of the full-length 186 repressor, identified by genetic screens, was solved to 1.95 A resolution. These structures provide a molecular basis for understanding lysogenic regulation in 186. Whereas the overall fold of the 186 and lambda repressor monomers is remarkably similar, the way the two repressors cooperatively assemble is quite different and explains in part the differences in their regulatory activity.     

The N-terminal domains of TRF1 and TRF2 regulate their ability to condense telomeric DNA

TRF1 and TRF2 are key proteins in human telomeres, which, despite their similarities, have different behaviors upon DNA binding. Previous work has shown that unlike TRF1, TRF2 condenses telomeric, thus creating consequential negative torsion on the adjacent DNA, a property that is thought to lead to the stimulation of single-strand invasion and was proposed to favor telomeric DNA looping. In this report, we show that these activities, originating from the central TRFH domain of TRF2, are also displayed by the TRFH domain of TRF1 but are repressed in the full-length protein by the presence of an acidic domain at the N-terminus. Strikingly, a similar repression is observed on TRF2 through the binding of a TERRA-like RNA molecule to the N-terminus of TRF2. Phylogenetic and biochemical studies suggest that the N-terminal domains of TRF proteins originate from a gradual extension of the coding sequences of a duplicated ancestral gene with a consequential progressive alteration of the biochemical properties of these proteins. Overall, these data suggest that the N-termini of TRF1 and TRF2 have evolved to finely regulate their ability to condense DNA.     

Meta-analysis suggests choosy females get sexy sons more than "good genes"

Female preferences for specific male phenotypes have been documented across a wide range of animal taxa, including numerous species where males contribute only gametes to offspring production. Yet, selective pressures maintaining such preferences are among the major unknowns of evolutionary biology. Theoretical studies suggest that preferences can evolve if they confer genetic benefits in terms of increased attractiveness of sons ("Fisherian" models) or overall fitness of offspring ("good genes" models). These two types of models predict, respectively, that male attractiveness is heritable and genetically correlated with fitness. In this meta-analysis, we draw general conclusions from over two decades worth of empirical studies testing these predictions (90 studies on 55 species in total). We found evidence for heritability of male attractiveness. However, attractiveness showed no association with traits directly associated with fitness (life-history traits). Interestingly, it did show a positive correlation with physiological traits, which include immunocompetence and condition. In conclusion, our results support "Fisherian" models of preference evolution, while providing equivocal evidence for "good genes." We pinpoint research directions that should stimulate progress in our understanding of the evolution of female choice.     

Predicting cyanobacterial dynamics in the face of global change: the importance of scale and environmental context

There is growing concern that harmful cyanobacterial blooms are increasing in frequency and occurrence around the world. Although nutrient enrichment is commonly identified as a key predictor of cyanobacterial abundance and dominance in freshwaters, several studies have shown that variables related to climate change can also play an important role. Based on our analysis of the literature, we hypothesized that temperature or water‐column stability will be the primary drivers of cyanobacterial abundance in stratified lakes whereas nutrients will be the stronger predictors in frequently mixing water bodies. To test this hypothesis, as well as quantify the drivers of cyanobacteria over different scales and identify interactions between nutrients and climate‐related variables, we applied linear and nonlinear mixed‐effect modeling techniques to seasonal time‐series data from multiple lakes. We first compared time series of cyanobacterial dominance to a published lake survey and found that the models were similar. Using time‐series data of cyanobacterial biomass, we identified important interactions among nutrients and climate‐related variables; dimictic basin experienced a heightened susceptibility to cyanobacterial blooms under stratified eutrophic conditions, whereas polymictic basins were less sensitive to changes in temperature or stratification. Overall, our results show that due to predictable interactions among nutrients and temperature, polymictic and dimictic lakes are expected to respond differently to future climate warming and eutrophication.     

The influence of time,soil characteristics,and land‐use history on soil phosphorus legacies: a global meta‐analysis

Agriculturally driven changes in soil phosphorus (P) are known to have persistent effects on local ecosystem structure and function, but regional patterns of soil P recovery following cessation of agriculture are less well understood. We synthesized data from 94 published studies to assess evidence of these land‐use legacies throughout the world by comparing soil labile and total P content in abandoned agricultural areas to that of reference ecosystems or sites remaining in agriculture. Our meta‐analysis shows that soil P content was typically elevated after abandonment compared to reference levels, but reduced compared to soils that remained under agriculture. There were more pronounced differences in the legacies of past agriculture on soil P across regions than between the types of land use practiced prior to abandonment (cropland, pasture, or forage grassland). However, consistent patterns of soil P enrichment or depletion according to soil order and types of post‐agricultural vegetation suggest that these factors may mediate agricultural legacies on soil P. We also used mixed effects models to examine the role of multiple variables on soil P recovery following agriculture. Time since cessation of agriculture was highly influential on soil P legacies, with clear reductions in the degree of labile and total P enrichment relative to reference ecosystems over time. Soil characteristics (clay content and pH) were strongly related to changes in labile P compared to reference sites, but these were relatively unimportant for total P. The duration of past agricultural use and climate were weakly related to changes in total P only. Our finding of reductions in the degree of soil P alteration over time relative to reference conditions reveals the potential to mitigate these land‐use legacies in some soils. Better ability to predict dynamics of soil nutrient recovery after termination of agricultural use is essential to ecosystem management following land‐use change.     

Job strain and tobacco smoking: an individual-participant data meta-analysis of 166,130 adults in 15 European studies

Background

Tobacco smoking is a major contributor to the public health burden and healthcare costs worldwide, but the determinants of smoking behaviours are poorly understood. We conducted a large individual-participant meta-analysis to examine the extent to which work-related stress, operationalised as job strain, is associated with tobacco smoking in working adults.

Methodology and Principal Findings

We analysed cross-sectional data from 15 European studies comprising 166 130 participants. Longitudinal data from six studies were used. Job strain and smoking were self-reported. Smoking was harmonised into three categories never, ex- and current. We modelled the cross-sectional associations using logistic regression and the results pooled in random effects meta-analyses. Mixed effects logistic regression was used to examine longitudinal associations. Of the 166 130 participants, 17% reported job strain, 42% were never smokers, 33% ex-smokers and 25% current smokers. In the analyses of the cross-sectional data, current smokers had higher odds of job strain than never-smokers (age, sex and socioeconomic position-adjusted odds ratio: 1.11, 95% confidence interval: 1.03, 1.18). Current smokers with job strain smoked, on average, three cigarettes per week more than current smokers without job strain. In the analyses of longitudinal data (1 to 9 years of follow-up), there was no clear evidence for longitudinal associations between job strain and taking up or quitting smoking.

Conclusions

Our findings show that smokers are slightly more likely than non-smokers to report work-related stress. In addition, smokers who reported work stress smoked, on average, slightly more cigarettes than stress-free smokers.     

Resistance of human leukocytes to vesicular stomatitis virus infection as one of the innate antiviral immune activities; participation of cell subpopulations

Among reactions of innate immunity, resistance of human peripheral blood leukocytes (PBL) to viral infection seems important. The purpose of our study was to find, which of the subpopulations of PBL is the most responsible for the innate antiviral immunity of these cells. The innate immunity was measured by using the direct method of infection of leukocytes with vesicular stomatitis virus (VSV). The lack of VSV replication by infected leukocytes (0-1 log TCID50) was taken as an indicator for complete immunity; a low level of VSV (2-3 log) for partial immunity; and high VSV titer (more than 4 log) for no immunity. The resistance/innate immunity of whole PBL and subpopulations such as: adherent cells, fractions enriched in lymphocytes T, and lymphocytes B (separated on column with nylon wool), NK(+) and NK(-) (separated by microbeads activated cell sorting MACS) differ from each other. All fractions express higher resistance/innate immunity than the whole PBL. NK(+) cells were found the most resistant fraction of PBL to VSV infection. The results indicate that among the leukocytes in PBL the regulation mechanisms of innate immunity exist. The study on the mechanism of innate immunity regulation as well as the role of NK in innate immunity of PBL must be continued.     

Synthesis of pyrrolizidine alkaloids via 1,3-dipolar cycloaddition involving cyclic nitrones and unsaturated lactones

The 1,3-dipolar cycloaddition of cyclic nitrone derived from tartaric acid and (S)-5-hydroxymethyl-2(5H)-furanone leads to a single adduct which was transformed into 2,6-dihydroxyhastanecine via reaction sequence involving reduction of the lactone moiety, glycolic cleavage of the terminal diol, and the N-O hydrogenolysis followed by the intramolecular alkylation of the nitrogen atom.