Immunometabolism and the modulation of immune responses and host defense: A role for methylglyoxal?

The immune system plays an essential role in protecting the body against pathogens. Immune cells are activated during infections, resulting in a metabolic shift from oxidative phosphorylation to glycolysis. During glycolysis, methylglyoxal (MGO) can be formed as a by-product. As a highly reactive dicarbonyl compound, MGO can rapidly react with proteins to form advanced glycation end products (AGEs). MGO and MGO-derived AGEs have been implicated in the development of insulin resistance, type 2 diabetes and its complications and several other age-related inflammatory diseases. MGO has been found in adipose tissue, atherosclerosis plaques and inflamed livers. Aside from the potential harmful role of MGO, there are studies showing beneficial effects of MGO as a defense mechanism during infections and diseases. In this review, we summarize anti-microbial effects of MGO and the link between MGO and immune cell activation, as potential mediator during host defense.     

Pseudomonas aeruginosa-induced production of free radicals by IFNgamma plus TNFalpha-activated human endothelial cells: mechanism of host defense or of bacterial pathogenesis?

We have previously shown that human umbilical vein endothelial cells (HUVEC) can be activated by IFNgamma plus TNFalpha to kill intracellular (IC) Pseudomonas aeruginosa through production of reactive oxygen intermediate, but the cumulative effects of cytokine activation and bacterial infection on host cells has not been extensively addressed. In this study we investigated the fate of IFNgamma plus TNFalpha-activated HUVEC that have harboured IC bacteria for up to 24 h. At 10 h, the endothelial cell killing of P. aeruginosa isolates exceeded 90%. IC bacteria enhanced the expression of inducible nitric oxide synthase (iNOS) and induced overproduction of NO and superoxide by infected HUVEC. P. aeruginosa IC infection also induced a slight decrease in the cellular level of reduced glutathione (GSH). Overproduction of NO correlated with a marked peroxidation of plasma membrane lipids and decline in HUVEC viability. Treatment of cells with the antioxidant alpha-lipoic acid significantly increased the survival of infected cells. Our data suggest that with the failure of adequate scavenger mechanisms, oxidant radicals overproduced in response to bacterial infection were highly toxic to host cells. Therefore, instead of contributing to defence against infectious agents, the upregulation of free radicals production by endothelial cells in response to cytokine activation would be detrimental to the host.     

Diversity of plant–animal interactions: Possibilities for a new plant defense indicator value?

The interactions between herbivores and plants are of general interest in ecology. Even though the extensive research carried out during the last decades has culminated in many theories, additional studies are necessary to validate these findings. In particular, the hypotheses dealing with the complex interrelations of plant defense mechanisms and herbivores continue to be debated.In this paper, we develop a new indicator value that quantifies the defense mechanisms of Central European woody plants against large mammalian herbivores. The indicator value is based on three plant-specific traits: chemical defense (toxic compounds, digestion inhibitors), mechanical defense and leaf size. Our validation of the newly established indicator shows that evergreen woody plants have a significantly higher indicator value than deciduous woody plants. Moreover, plant defense is correlated with growth height: woody plants growing in the browsing zone preferred by large mammalian herbivores have significantly higher levels of defense compared with woody plants capable of growth high above the reach of large herbivores.We conclude that the new plant defense indicator value is a valuable tool for the validation of existing hypotheses and habitat calibration on a statistical basis. The quantification of plant mechanisms of defense against large herbivores produces a significantly better understanding of the multifaceted nature of plant–animal interactions and should contribute positively to future studies.     

Protection of host anemones by snapping shrimps: a case for symbiotic mutualism?

The sea anemone Bartholomea annulata is an ecologically important member of Caribbean coral reefs which host a variety of symbiotic crustacean associates. Crustacean exosymbionts typically gain protection from predation by dwelling with anemones. Concurrently, some symbionts may provide protection to their host by defending against anemone predators such as the predatory fireworm, Hermodice carunculata, which can severely damage or completely devour prey anemones. Herein we show through both field and laboratory studies that anemones hosting the symbiotic alpheid shrimp Alpheus armatus are significantly less likely to sustain damage by H. carunculata than anemones without this shrimp. Our results suggest that the association between A. armatus and B. annulata, although complex because of the numerous symbionts involved, may be closer to mutualism on the symbiotic continuum.     

Quantitative genetics of Aedes aegypti vector competence for dengue viruses: towards a new paradigm?

Similar to many other host-pathogen interactions, the vector competence of Aedes aegypti for dengue viruses appears to be determined by genotype-by-genotype interactions, whereby the outcome of infection depends on the specific combination of mosquito and virus genotypes. This can complicate efforts to dissect the genetic basis of vector competence in nature because it obscures mapping between genotype and phenotype and brings into question the notion of universal mosquito resistance or susceptibility. Conversely, it offers novel opportunities to better define compatible vector-pathogen associations based on integration of both vector and pathogen genomics, which should eventually improve understanding of pathogen transmission dynamics and the risk of vector-borne disease emergence.     

Inhibition of keratinocyte apoptosis by IL-15: a new parameter in the pathogenesis of psoriasis?

Keratinocytes (KC) are important source of and targets for several cytokines. Although KC express IL-15 mRNA, the functional effects of IL-15 on these epithelial cells remain to be dissected. Investigating primary human foreskin KC and HaCaT cells, we show here by semiquantitative RT-PCR and flow cytometric analysis that both translate IL-15 and IL-15R mRNA and express IL-15 and IL-15Ralpha protein on the cell surface, suggesting that human KC can employ IL-15 for juxtacrine signaling. While IL-15 exerted no significant effect on KC proliferation and IL-6 or IL-8 secretion, IL-15 inhibited both anti-Fas and methylcellulose-induced KC apoptosis in vitro. This is in line with the recognized potent anti-apoptotic effects of IL-15. IL-2, whose receptor shares two components with the IL-15R, failed to inhibit KC apoptosis. Together with the role of IL-15 in sustaining chronic immune reactions, this invited the question of whether a reduction of KC apoptosis by IL-15 may be involved in the pathogenesis of psoriasis, a chronic hyperproliferative inflammatory skin disease characterized by abnormally low KC apoptosis in the epidermis. Remarkably, compared with nonlesional psoriatic skin and skin of healthy volunteers, lesional psoriatic epidermis showed high IL-15 protein expression in the epidermis and enhanced binding activity for IL-15. Therefore, antagonizing the inhibitory effects of IL-15 on KC apoptosis deserves exploration as a novel therapeutic strategy in psoriasis management.     

Characterization of H9 subtype influenza viruses from the ducks of southern China: a candidate for the next influenza pandemic in humans?

A current view of the emergence of pandemic influenza viruses envisages a gene flow from the aquatic avian reservoir to humans via reassortment in pigs, the hypothetical "mixing vessel." Understanding arising from recent H5N1 influenza outbreaks in Hong Kong since 1997 and the isolation of avian H9N2 virus from humans raises alternative options for the emergence of a new pandemic virus. Here we report that H9N2 influenza viruses established in terrestrial poultry in southern China are transmitted back to domestic ducks, in which the viruses generate multiple reassortants. These novel H9N2 viruses are double or even triple reassortants that have amino acid signatures in their hemagglutinin, indicating their potential to directly infect humans. Some of them contain gene segments that are closely related to those of A/Hong Kong/156/97 (H5N1/97, H5N1) or A/Quail/Hong Kong/G1/97 (G1-like, H9N2). More importantly, some of their internal genes are closely related to those of novel H5N1 viruses isolated during the outbreak in Hong Kong in 2001. This study reveals a two-way transmission of influenza virus between terrestrial and aquatic birds that facilitates the generation of novel reassortant H9N2 influenza viruses. Such reassortants may directly or indirectly play a role in the emergence of the next pandemic virus.     

Biodiesel-TBL+: A new hierarchical sustainability assessment framework of PC&I for biodiesel production – Part I

Sustainability assessment of biodiesel production is a topic of increasing importance due to the interest of governments to define sovereignty strategies and diversification of their energy matrix, and to set up the impact of biofuels production. In this context, this work aims to propose a hierarchical structure of sustainability assessment that integrates dimensions of sustainable development with principles, criteria and indicators (PC&I). The method employed to define the hierarchical structure was a comprehensive literature review, based on information search strategy and classification. About 400 documents were reviewed and 103 documents were ultimately selected, including laws, policy documents, certificates, directives and other normative documents and papers published in peer-reviewed journals. The first result of the analysis was the need to strengthen identification of the sustainable development assessment, adding the political and technological dimensions to the three traditional dimensions, social, economic and environmental, studied in this kind of evaluation. The second result was the proposal of a hierarchical framework for the sustainability assessment of biodiesel production, organized in four levels: the first level comprises the five dimensions associated with sustainable development evaluation, the second includes 13 principles, the third contains 40 criteria and the fourth level corresponds to a set of indicators that describes each criterion. Outcomes of this work provide a foundation for further discussion of sustainability assessments for biodiesel production and its potential application in specific contexts.     

Manipulation of host behaviour by parasites: a weakening paradigm?

New scientific paradigms often generate an early wave of enthusiasm among researchers and a barrage of studies seeking to validate or refute the newly proposed idea. All else being equal, the strength and direction of the empirical evidence being published should not change over time, allowing one to assess the generality of the paradigm based on the gradual accumulation of evidence. Here, I examine the relationship between the magnitude of published quantitative estimates of parasite-induced changes in host behaviour and year of publication from the time the adaptive host manipulation hypothesis was first proposed. Two independent data sets were used, both originally gathered for other purposes. First, across 137 comparisons between the behaviour of infected and uninfected hosts, the estimated relative influence of parasites correlated negatively with year of publication. This effect was contingent upon the transmission mode of the parasites studied. The negative relationship was very strong among studies of parasites which benefit from host manipulation (transmission to the next host occurs by predation on an infected intermediate host), i.e. among studies which were explicit tests of the adaptive manipulation hypothesis. There was no correlation with year of publication among studies on other types of parasites which do not seem to receive benefits from host manipulation. Second, among 14 estimates of the relative, parasite-mediated increase in transmission rate (i.e. increases in predation rates by definitive hosts on intermediate hosts), the estimated influence of parasites again correlated negatively with year of publication. These results have several possible explanations, but tend to suggest biases with regard to what results are published through time as accepted paradigms changed.     

Major radiation of cheilostome bryozoans: Triggered by the evolution of a new larval type?

A macroevolutionary model is developed to account for the “adaptive radiation”; of cheilostome bryozoans that commenced in the Cenomanian after a long phase of low diversity. Living cheilostome species possess one of two types of larvae; planktotrophic (cyphonautes) larvae of relatively long duration, and brooded non‐planktotrophic (coronate) larvae of short duration. Planktotrophic larvae characterize the paraphyletic “malacostegans”; from which “advanced”; cheilostomes with non‐planktotrophic larvae are thought to have evolved monophyletically. Research on other marine invertebrates suggests that gene flow within and between populations is likely to be poorer in species having non‐planktotrophic larvae, and hence the frequency of allopatric and quasi‐sympatric speciation may be greater. Skeletal evidence of larval brooding in the cheilostomes first appears in the late Albian, immediately before their adaptive radiation, and the evolution of non‐planktotrophy with associated increase in speciation rate is proposed to have triggered this radiation.     

Induction of phlorotannin production in a brown alga: defense or resource dynamics?

Increase of phenolic secondary metabolites, phlorotannins, in brown algae due to gastropod grazing has been interpreted as an anti-herbivore adaptation. Here we tested whether such a response could be due to changes in truly available resources for the alga, not by the grazing activity of snails as such. We allowed two species of snails, Theodoxus fluviatilis and Physa fontinalis to graze on Fucus vesiculosus . These species feed on epibiota and particulate matter on the thallus but do not eat the thallus of F. vesiculosus . We further simulated snail grazing by nutrient enhancement, removal of epibiota and by a combination of the two. Manipulations of nutrient and light availability revealed the crucial role of epibiota in mediating resource availability for F. vesiculosus . Nutrient enhancement alone increased epibiota and decreased phlorotannins. Cleaning the thallus resulted in increased growth, and together with nutrient enhancement also in a trade-off with phlorotannins. Presence of T. fluviatilis on the thallus induced phlorotannin production, a response differing from the simulations of snail grazing. However, we suggest that the increase in phlorotannins may not be an induced defense but rather a consequence of a specific way of resource manipulation by this snail species. T. fluviatilis removes hyaline hairs that facilitate nutrient uptake. P. fontinalis did not remove hyaline hairs and the response of the alga to its grazing was similar to the treatment where we mechanically removed epibiota suggesting that cleaning of the thallus is the major mechanism how this snail species affects F. vesiculosus . Genetic variation in phlorotannin concentrations highly exceeded the induced responses of simulated or real snail grazing. This casts doubt for the efficiency of induced phlorotannin production to act as a defense, but is not contradictory with the interpretation of phlorotannins responding to variation in resource availability.     

Saccharomyces cerevisiae: a potential host for carboxylic acid production from lignocellulosic feedstock?

Carboxylic acids are important bulk chemicals that can be used as building blocks for the production of polymers, as acidulants, preservatives and flavour compound or as precursors for the synthesis of pharmaceuticals. Today, their production mainly takes place through catalytic processing of petroleum-based precursors. An appealing alternative would be to produce these compounds from renewable resources, using tailor-made microorganisms. Saccharomyces cerevisiae has already demonstrated its value for bioethanol production from renewable resources. In this review, we discuss Saccharomyces cerevisiae engineering potential, current strategies for carboxylic acid production as well as the specific challenges linked to the use of lignocellulosic biomass as carbon source.     

A new bioprocess for the production of prebiotic lactosucrose by an immobilized β-galactosidase

A new bioprocess for the synthesis of lactosucrose was studied using a covalently immobilized β-galactosidase on macrospheres of chitosan. The effects of temperature and pH on the production of lactosucrose and other oligosaccharides were evaluated. At 30 °C and pH 7.0, the maximum concentration of lactosucrose reached to 79 g L⁻¹. The change of the reaction conditions allowed to modify the qualitative profile of the final products without quantitative change in the total of oligosaccharides produced. At pH 7 and 30 °C, products profile was 79 g L⁻¹ of lactosucrose, 37 g L⁻¹ of galactooligosaccharides and 250 g L⁻¹ of total oligosaccharides, while at pH 5 and 64 °C the concentrations for the same compounds were 40, 62 and 250 g L⁻¹, respectively. The immobilization increased the thermal stability up to 260-fold. Using 300 g L⁻¹ of sucrose and 300 g L⁻¹ of lactose, and 8.5 mg of chitosan mL⁻¹, 30 cycles of reuse were performed and the biocatalyst kept the maximal lactosucrose synthesis. These results fulfill some important aspects for the enzyme immobilization and oligosaccharides synthesis: the simplicity of the protocols, the high operational stability of the enzyme and the possibility of driving the final products.