Thrombin inhibitors with lipid peroxidation and lipoxygenase inhibitory activities

Vascular oxidative stress, endothelial injury, and thrombosis are intertwined processes that display a synergistic pathological effect in many cardiovascular diseases. Antithrombotic therapy with anticoagulant and/or antiplatelet agents, combined with interventions against vascular oxidative stress and/or inflammation, both boosting endothelial antithrombotic potential, could display a synergistic action in the treatment of thrombosis. Of the compounds 10a-h and 11a-d, shown to possess thrombin inhibitory activity, 11a-d were found to display radical scavenging activity, 10a, 10d, and 10f were demonstrated to inhibit lipid peroxidation of linoleic acid, and 10b and 10h inhibited soybean lipoxygenase. The observed combination of thrombin inhibition with lipid peroxidation and/or lipoxygenase inhibitory activity makes compounds 10 and 11 interesting candidates for further investigations towards multiple antithrombotic drugs.     

Reconstructing a puzzle: existence of cyanophages containing both photosystem‐I and photosystem‐II gene suites inferred from oceanic metagenomic datasets

Cyanobacteria play a key role in marine photosynthesis, which contributes to the global carbon cycle and to the world oxygen supply. Genes encoding the photosystem‐II (PSII) reaction centre are found in many cyanophage genomes, and it was suggested that the horizontal transfer of these genes might be involved in increasing phage fitness. Recently, evidence for the existence of phages carrying Photosystem‐I (PSI) genes was also reported. Here, using a combination of different marine metagenomic datasets and a unique crossing of the datasets, we now describe the finding of phages that, as in plants and cyanobacteria, contain both PSII and PSI genes. In addition, these phages also contain NADH dehydrogenase genes. The presence of modified PSII and PSI genes in the same viral entities in combination with electron transfer proteins like NAD(P)H dehydrogenase (NDH‐1) strongly points to a role in perturbation of the cyanobacterial host photosynthetic electron flow. We therefore suggest that, depending on the physiological condition of the infected cyanobacterial host, the viruses may use different options to maximize survival. The modified PSI may alternate between functioning with PSII in linear electron transfer and contributing to the production of both NADPH and ATP or functioning independently of PSII in cyclic mode via the NDH‐1 complex and thus producing only ATP.     

Egg size and offspring quality: a meta‐analysis in birds

Parents affect offspring fitness by propagule size and quality, selection of oviposition site, quality of incubation, feeding of dependent young, and their defence against predators and parasites. Despite many case studies on each of these topics, this knowledge has not been rigorously integrated into individual parental care traits for any taxon. Consequently, we lack a comprehensive, quantitative assessment of how parental care modifies offspring phenotypes. This meta‐analysis of 283 studies with 1805 correlations between egg size and offspring quality in birds is intended to fill this gap. The large sample size enabled testing of how the magnitude of the relationship between egg size and offspring quality depends on a number of variables. Egg size was positively related to nearly all studied offspring traits across all stages of the offspring life cycle. Not surprisingly, the relationship was strongest at hatching but persisted until the post‐fledging stage. Morphological traits were the most closely related to egg size but significant relationships were also found with hatching success, chick survival, and growth rate. Non‐significant effect sizes were found for egg fertility, chick immunity, behaviour, and life‐history or sexual traits. Effect size did not depend on whether chicks were raised by their natural parents or were cross‐fostered to other territories. Effect size did not depend on species‐specific traits such as developmental mode, clutch size, and relative size of the egg, but was larger if tested in captive compared to wild populations and between rather than within broods. In sum, published studies support the view that egg size affects juvenile survival. There are very few studies that tested the relationship between egg size and the fecundity component of offspring fitness, and no studies on offspring survival as adults or on global fitness. More data are also needed for the relationships between egg size and offspring behavioural and physiological traits. It remains to be established whether the relationship between egg size and offspring performance depends on the quality of the offspring environment. Positive effect sizes found in this study are likely to be driven by a causal effect of egg size on offspring quality. However, more studies that control for potential confounding effects of parental post‐hatching care, genes, and egg composition are needed to establish firmly this causal link.     

Performance differences among ex situ native-provenance collections of Pinus radiata D. Don. 1: potential for infusion into breeding populations in Australia and New Zealand

Growth and form traits from a series of three provenance trials of Pinus radiata D. Don planted in New Zealand and Australia were analysed at age 9 years from planting. The trials included selections from three mainland California natural populations—A?o Nuevo, Monterey and Cambria. Monterey and Cambria performed better than A?o Nuevo at two New Zealand sites, but Monterey and A?o Nuevo were almost identical in growth, whereas Cambria grew less vigorously at the Australian site. We detected significant provenance differences for diameter at breast height (DBH) growth and stem straightness across countries (p < 0.001). Estimated heritability for DBH ranged from 0.19 to 0.26 within sites, while heritability estimates for stem straightness and branching frequency ranged from 0.10 to 0.24. Estimated type B genetic correlations for DBH were always higher between the two trials in New Zealand trials than between pairs of trials in New Zealand and the Australian site. The genetic coefficient of variation (CV_A) for DBH was around 8–10% compared to ca. 5% for the current breeding population. These results suggested that there is appreciable genetic variation in the native populations, and infusion of these materials would increase the genetic variation in current breeding populations. Ten unrelated parents ranked above control seedlots from the older open-pollinated seed orchard stock for DBH growth and would be potential candidates for infusion. The promising performance of the Cambria material is an important result because the genetic base of the present Australian and New Zealand plantations is principally derived from A?o Nuevo and Monterey.     

Morphing of the phylogeographic lineages of the Balkan alpine newts (Ichthyosaura alpestris, Caudata, Salamandridae): in situ morphological diversification

Numerous alpine newt (Ichthyosaura alpestris) populations from the Balkans, representing all the previously established phylogeographic lineages, were studied for variations in various morphological characteristics (body size and shape, skull qualitative traits and number of trunk vertebrae). Here, we present a decoupling of morphological and mtDNA phylogeographic substructuring in the alpine newt on the Balkan Peninsula. In sharp contrast to other European newts (Triturus spp., Lissotriton spp.), the vast majority of morphological variation in the alpine newt is concentrated at the population level indicating an in situ morphological diversification. We found that the rate of morphological change is similar to the rate of mtDNA change. We hypothesize that the alpine newts are characterized by non-adaptive morphological evolution.     

A successful crayfish invader is capable of facultative parthenogenesis: a novel reproductive mode in decapod crustaceans

Biological invasions are impacting biota worldwide, and explaining why some taxa tend to become invasive is of major scientific interest. North American crayfish species, particularly of the family Cambaridae, are prominent invaders in freshwaters, defying the "tens rule" which states that only a minority of species introduced to new regions become established, and only a minority of those become invasive and pests. So far, success of cambarid invaders has largely been attributed to rapid maturation, high reproductive output, aggressiveness, and tolerance to pollution. We provide experimental evidence that females of one cambarid species particularly widespread in Europe, the spiny-cheek crayfish Orconectes limosus, are capable of facultative parthenogenesis. Such reproductive mode has never before been recognized in decapods, the most diverse crustacean order. As shown by analysis of seven microsatellite loci, crayfish females kept physically separated from males produced genetically homogeneous offspring identical with maternal individuals; this suggests they reproduced by apomixis, unlike those females which mated with males and had a diverse offspring. Further research is needed to clarify what environmental conditions are necessary for a switch to parthenogenesis in O. limosus, and what role it plays in natural crayfish populations. However, if such reproductive plasticity is present in other cambarid crayfish species, it may contribute to the overwhelming invasive success of this group.     

Regulation of neutrophil senescence by microRNAs

Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease.