Myeloperoxidase-dependent Lipid Peroxidation Promotes the Oxidative Modification of Cytosolic Proteins in Phagocytic Neutrophils

Phagocytic neutrophils generate reactive oxygen species to kill microbes. Oxidant generation occurs within an intracellular phagosome, but diffusible species can react with the neutrophil and surrounding tissue. To investigate the extent of oxidative modification, we assessed the carbonylation of cytosolic proteins in phagocytic neutrophils. A 4-fold increase in protein carbonylation was measured within 15 min of initiating phagocytosis. Carbonylation was dependent on NADPH oxidase and myeloperoxidase activity and was inhibited by butylated hydroxytoluene and Trolox, indicating a role for myeloperoxidase-dependent lipid peroxidation. Proteomic analysis of target proteins revealed significant carbonylation of the S100A9 subunit of calprotectin, a truncated form of Hsp70, actin, and hemoglobin from contaminating erythrocytes. The addition of the reactive aldehyde 4-hydroxynonenal (HNE) caused carbonylation, and HNE-glutathione adducts were detected in the cytosol of phagocytic neutrophils. The post-translational modification of neutrophil proteins will influence the functioning and fate of these immune cells in the period following phagocytic activation, and provides a marker of neutrophil activation during infection and inflammation.     

Morphological and genetic differentiation in populations of the dispersal‐limited coco de mer (Lodoicea maldivica): implications for management and conservation

Aims Developing plant conservation strategies requires knowledge of ecological and genetic processes underlying population dynamics. We aimed to quantify morphological and genetic differentiation among remnant populations of the iconic coco‐de‐mer palm Lodoicea maldivica. We hypothesized that limited gene flow among widely spaced populations would result in high genetic variation and large phenotypic differences among populations. Location Islands of Praslin and Curieuse (CU), Seychelles, Indian Ocean. Methods We conducted an extensive population survey and recorded morphological parameters for 447 Lodoicea in the main populations at Vallée de Mai (VM) and Fond Ferdinand (FF) on Praslin, and on CU. We collected leaf material from 180 trees in these populations for DNA genotyping using amplified fragment length polymorphisms. Results A total of 16,766 Lodoicea trees were recorded in the three populations (72.6% of Lodoicea on both islands). Lodoicea trees at VM and FF showed similar morphology, but differed in most parameters from those at CU, which were shorter, grew more slowly and produced fewer seeds. Mean overall genetic diversity was 0.337, and percentage of polymorphic loci was 91.1. Genetic diversity of the CU population was lower than that at VM and FF. There was weak genetic differentiation between CU and Praslin populations, but 99% of all genetic diversity was within populations. Main conclusions Trees on CU differed in growth and morphology from those of the two Praslin populations. These phenotypic differences, however, were not mirrored in the genetic structure of the populations. All populations were relatively genetically diverse with remarkably little differentiation among populations. This suggests that the capacity of Lodoicea to dominate across a range of habitats may be because of high phenotypic plasticity. High genetic connectivity may be maintained through long‐distance wind pollination. Given the uncertainty about the extent of underlying adaptive variation, we recommend that restoration projects avoid transferring seeds between island populations.     

Cytokine gene polymorphisms and atopic disease in two European cohorts. (ECRHS-Basel and SAPALDIA)

Background

Avoidance of allergens is still recommended as the first and best way to prevent allergic illnesses and their comorbid diseases. Despite a variety of attempts there has been very limited success in the area of environmental control of allergic disease. Our objective was to identify a non-invasive, non-pharmacological method to reduce indoor allergen loads in atopic persons' homes and public environments. We employed a novel in vivo approach to examine the possibility of using aluminum sulfate to control environmental allergens.

Methods

Fifty skin test reactive patients were simultaneously skin tested with conventional test materials and the actions of the protein/glycoprotein modifier, aluminum sulfate. Common allergens, dog, cat, dust mite, Alternaria, and cockroach were used in the study.

Results

Skin test reactivity was significantly reduced by the modifier aluminum sulfate. Our studies demonstrate that the effects of histamine were not affected by the presence of aluminum sulfate. In fact, skin test reactivity was reduced independent of whether aluminum sulfate was present in the allergen test material or removed prior to testing, indicating that the allergens had in some way been inactivated.

Conclusion

Aluminum sulfate was found to reduce the in vivo allergic reaction cascade induced by skin testing with common allergens. The exact mechanism is not clear but appears to involve the alteration of IgE-binding epitopes on the allergen. Our results indicate that it may be possible to diminish the allergenicity of an environment by application of the active agent aluminum sulfate, thus producing environmental control without complete removal of the allergen.     

Unusual growth pattern in the Frasnian alveolitids (Tabulata) from the Holy Cross Mountains (Poland)

Abstract: Growth periodicity is a phenomenon occurring in fossil and modern corals. The most apparent feature is growth banding, and environmental changes are broadly accepted as controls on this phenomenon. If environment controls the growth, then all corallites within a colony should repeat the same growth pattern, as individuals are clones and must have shared the same environment. A study on several species of Alveolitidae (Anthozoa, Tabulata) from the Late Devonian (Early Frasnian) of the Holy Cross Mountains (Poland) shows that the growth pattern varies between neighbouring individuals within the same corallum. This contradicts observations of closely related Favositida as demonstrated on Pachyfavosites sp. from the Givetian of Avesnois, France, where neighbouring individuals repeat the same pattern. Therefore, environmental control on growth rhythm in Alveolitidae can be excluded; the causes of differences between individuals remain unknown.     

Importance of demography and dispersal for the resilience and restoration of a critically endangered tropical conifer Araucaria nemorosa

Aims In situ species survival involves persistence at current sites and/or colonization of new locations. Determining the likelihood of these events requires an understanding of population dynamics and dispersal. We address these issues in populations of a critically endangered tropical conifer Araucaria nemorosa and provide conservation recommendations. Location Port Boise, island of Grand Terre, New Caledonia, Pacific Ocean. Methods We characterize the demographic structure of six populations of A. nemorosa based upon size class frequencies and relative basal area compared to competing angiosperm trees. Using genotype data from 280 adult individuals at seven microsatellite loci, we indirectly estimate dispersal distances and project a maximal dispersal envelope around the extant populations. Results Our survey detected marked differences in demographic parameters including the proportion of basal area occupied by A. nemorosa versus angiosperm trees (ranging from 25% to 77%), the size class frequency distributions of A. nemorosa and seedling densities (ranging from 500 to 37300 seedlings ha^?1) among some populations. Wright’s genetic neighbourhood ranged from 22 to 876 trees, and historic gene dispersal ranged from 10.8 to 82.4 m, indicating that most seed dispersal is <100 m. Main conclusions This study indicates that the risk of recruitment failure in remnant populations of Araucaria nemorosa is low in most of the stands but is high in the inland population Forêt Nord. In situ natural regeneration appears to be constrained in this population, most likely as a consequence of competitive exclusion. Our results also suggest that the majority of seed dispersal is too short to allow A. nemorosa to disperse to new more hospitable sites within an ecologically relevant time‐scale. Our findings have implications not only for this emblematic tree species but also for a wide range of fragmented and degraded plant species populations with limited dispersal that are vulnerable to competitive exclusion.     

Drivers of vegetative dormancy across herbaceous perennial plant species

Vegetative dormancy, that is the temporary absence of aboveground growth for ≥ 1 year, is paradoxical, because plants cannot photosynthesise or flower during dormant periods. We test ecological and evolutionary hypotheses for its widespread persistence. We show that dormancy has evolved numerous times. Most species displaying dormancy exhibit life‐history costs of sprouting, and of dormancy. Short‐lived and mycoheterotrophic species have higher proportions of dormant plants than long‐lived species and species with other nutritional modes. Foliage loss is associated with higher future dormancy levels, suggesting that carbon limitation promotes dormancy. Maximum dormancy duration is shorter under higher precipitation and at higher latitudes, the latter suggesting an important role for competition or herbivory. Study length affects estimates of some demographic parameters. Our results identify life historical and environmental drivers of dormancy. We also highlight the evolutionary importance of the little understood costs of sprouting and growth, latitudinal stress gradients and mixed nutritional modes.     

Myricitrin as a substrate and inhibitor of myeloperoxidase: implications for the pharmacological effects of flavonoids

Flavonoids are increasingly being ingested by the general population as chemotherapeutic and anti-inflammatory agents. They are potentially toxic because of their conversion to free radicals and reactive quinones by peroxidases. Little detailed information is available on how flavonoids interact with myeloperoxidase, which is the predominant peroxidase present at sites of inflammation. This enzyme uses hydrogen peroxide to oxidize chloride to hypochlorous acid, as well as to produce an array of reactive free radicals from organic substrates. We investigated how the flavonoid myricitrin is oxidized by myeloperoxidase and how it affects the activities of this enzyme. Myricitrin was readily oxidized by myeloperoxidase in the presence of hydrogen peroxide. Its main oxidation product was a dimer that underwent further oxidation. In the presence of glutathione, myricitrin was oxidized to a hydroquinone that was conjugated to glutathione. When myeloperoxidase oxidized myricitrin and related flavonoids it became irreversibly inactivated. The number of hydroxyl groups in the B ring of the flavonoids and the presence of a free hydroxyl m-phenol group in the A ring were important for the inhibitory effects. Less enzyme inactivation occurred in the presence of chloride. Neutrophils also oxidized myricitrin to dimers in a reaction that was partially dependent on myeloperoxidase. Myricitrin did not affect the production of hypochlorous acid by neutrophils. We conclude that myricitrin will be oxidized by neutrophils at sites of inflammation to produce reactive free radicals and quinones. It is unlikely to affect hypochlorous acid production by neutrophils.