Glycans from Fasciola hepatica Modulate the Host Immune Response and TLR-Induced Maturation of Dendritic Cells

Helminths express various carbohydrate-containing glycoconjugates on their surface, and they release glycan-rich excretion/secretion products that can be very important in their life cycles, infection and pathology. Recent evidence suggests that parasite glycoconjugates could play a role in the evasion of the immune response, leading to a modified Th2-polarized immune response that favors parasite survival in the host. Nevertheless, there is limited information about the nature or function of glycans produced by the trematode Fasciola hepatica, the causative agent of fasciolosis. In this paper, we investigate whether glycosylated molecules from F. hepatica participate in the modulation of host immunity. We also focus on dendritic cells, since they are an important target of immune-modulation by helminths, affecting their activity or function. Our results indicate that glycans from F. hepatica promote the production of IL-4 and IL-10, suppressing IFNγ production. During infection, this parasite is able to induce a semi-mature phenotype of DCs expressing low levels of MHCII and secrete IL-10. Furthermore, we show that parasite glycoconjugates mediate the modulation of LPS-induced maturation of DCs since their oxidation restores the capacity of LPS-treated DCs to secrete high levels of the pro-inflammatory cytokines IL-6 and IL-12/23p40 and low levels of the anti-inflammatory cytokine IL-10. Inhibition assays using carbohydrates suggest that the immune-modulation is mediated, at least in part, by the recognition of a mannose specific-CLR that signals by recruiting the phosphatase Php2. The results presented here contribute to the understanding of the role of parasite glycosylated molecules in the modulation of the host immunity and might be useful in the design of vaccines against fasciolosis.     

Spatial modeling of techno‐economic potential of biojet fuel production in Brazil

It is expected that Brazil could play an important role in biojet fuel (BJF) production in the future due to the long experience in biofuel production and the good agro‐ecological conditions. However, it is difficult to quantify the techno‐economic potential of BJF because of the high spatiotemporal variability of available land, biomass yield, and infrastructure as well as the technological developments in BJF production pathways. The objective of this research is to assess the recent and future techno‐economic potential of BJF production in Brazil and to identify location‐specific optimal combinations of biomass crops and technological conversion pathways. In total, 13 production routes (supply chains) are assessed through the combination of various biomass crops and BJF technologies. We consider temporal land use data to identify potential land availability for biomass production. With the spatial distribution of the land availability and potential yield of biomass crops, biomass production potential and costs are calculated. The BJF production cost is calculated by taking into account the development in the technological pathways and in plant scales. We estimate the techno‐economic potential by determining the minimum BJF total costs and comparing this with the range of fossil jet fuel prices. The techno‐economic potential of BJF production ranges from 0 to 6.4 EJ in 2015 and between 1.2 and 7.8 EJ in 2030, depending on the reference fossil jet fuel price, which varies from 19 to 65 US$/GJ across the airports. The techno‐economic potential consists of a diverse set of production routes. The Northeast and Southeast region of Brazil present the highest potentials with several viable production routes, whereas the remaining regions only have a few promising production routes. The maximum techno‐economic potential of BJF in Brazil could meet almost half of the projected global jet fuel demand toward 2030.     

Cytokines involved in the immunosuppressor period in experimental fasciolosis in rats

The aim of this study was to evaluate the kinetics of the cytokines interferon-gamma, interleukin-2, interleukin-10 and interleukin-4 produced by spleen mononuclear cells stimulated by Con A during an experimental infection in rats with Fasciola hepatica. The proliferative response to Con A of Spm cells from rats infected with F. hepatica was significantly decreased on day 7 post-infection (P<0.006) and simultaneously an increase of interferon-gamma, interleukin-10 and interleukin-4 production along with a decrease of interleukin-2 by spleen mononuclear cells were observed. Interleukin-4 and interleukin-10 were involved in ablating cellular proliferation in vitro, as the addition of neutralising antibodies to either cytokine reversed the proliferative block. The addition of exogenous recombinant interleukin-2 also restored the proliferative response by spleen mononuclear cells obtained 7 days after infection from infected rats. At the same time, we found an increase in interleukin-10 production by peritoneal cells (in close contact with the flukes) and decreased nitric oxide levels. In addition, histological studies on the liver on day 7 after infection showed the presence of parasite inside migratory tunnels in the parenchyma, and polymorphonuclear leukocytes, predominantly eosinophils, around the parasite. The transient suppression in proliferative response mediated by cytokines interleukin-4 and interleukin-10 in the spleen, and diminution of nitric oxide production in the peritoneum could be mechanisms to evade the protective immune response during the first stages of liver penetration by the parasite.     

A first molecular phylogenetic analysis of Passiflora (Passifloraceae)

Passiflora, a genus with more than 400 species, exhibits a high diversity of floral and vegetative structures and a complex taxonomy, which includes 23 subgenera and many sections and series. To better understand Passiflora's variability and interspecific relationships, the phylogeny of 61 species, classified in 11 of 23 suggested subgenera, was investigated. Three molecular markers were used, the nuclear ribosomal internal transcribed spacers (nrITS), the plastid trnL-trnF spacer regions (～1000 bp), and the rps4 plastid gene (～570 bp). Three major clades were highly supported, independent of the marker and phylogenetic method used; one included the subgenera Distephana, Dysosmia, Dysosmioides, Passiflora, and Tacsonioides, a second, the subgenera Adopogyne, Decaloba, Murucuja, and Pseudomurucuja, and a third, the subgenus Astrophea. We call these the Passiflora, Decaloba, and Astrophea clades, respectively. The position of subgenus Deidamioides is undefined. The monophyly of Passiflora could not be statistically corroborated, and the relationships among the major clades and of these clades with the related genera remain unresolved. Our results indicate that a reevaluation of the monophyly of Passiflora and its infrageneric classification is necessary.     

beta 1 Integrin-dependent cell adhesion to EMILIN-1 is mediated by the gC1q domain

EMILIN-1 (Elastin Microfibril Interface Located ProteIN), the prototype of the EMILIN family, consists of a cysteine-rich domain (EMI domain) at the N terminus, an extended region with a high potential coiled-coil structure, a short collagenous stalk, and a self-interacting globular gC1q-l domain. EMILIN-1 is an adhesive extracellular matrix constituent associated with elastic fibers, detected also in the proximity of cell surfaces. To localize the cell attachment site(s), monoclonal antibodies (mAbs) against EMILIN-1 or the gC1q-1 domain were used to inhibit cell attachment to EMILIN-1. Thus, one mAb mapping to the gC1q-1 domain caused complete inhibition of cell attachment. EMILIN-1 and gC1q-1 displayed a comparable dose-dependent ability to promote cell adhesion. Adhesion kinetics was similar to that of fibronectin (FN), reaching the maximum level of attachment at 20 min, but in the absence of cations adhesion was negligible. The relative adhesion strength to detach 50% of the cells was similar for EMILIN-1 and gC1q-1 (250-270 x g) but lower than that for FN (>500). Cell adhesion to EMILIN-1 or gC1q-1 was completely blocked by a function-blocking beta(1) integrin subunit mAb. In contrast, adhesion to the complement C1q component was totally unaffected. Among the various function-blocking mAbs against the alpha integrin subunits only the anti-alpha(4) fully abrogated cell adhesion to gC1q-1 and up to 70% to EMILIN-1. Furthermore, only K562 cells transfected with the alpha(4) integrin chain, but not wild type K562, were able to adhere to EMILIN-1 and were specifically inhibited by anti-alpha(4) function-blocking mAb. Finally, cells attached to EMILIN-1 or gC1q-1, compared with cells plated on FN or vitronectin, which appeared well spread out on the substrate with prominent stress fibers and focal contacts, were much smaller with wide ruffles and a different organization status of the actin cytoskeleton along the cell periphery. This pattern was in accord with the ability of EMILIN-1 to promote cell movement.     

Glucose-induced pathways for actin tyrosine dephosphorylation during Dictyostelium spore germination

In the presence of germination signals, dormant spores of Dictyostelium discoideum rapidly germinate to start a new life cycle. Previously we have shown that half of the actin molecules in spores are maintained in a tyrosine-phosphorylated state, and a decline of the actin phosphorylation levels is a prerequisite for spore swelling. In this study, we have established d-glucose as a trigger molecule for the actin dephosphorylation. Present in a nutrient germination medium, d-glucose both may act as a trigger molecule and/or may serve as a substrate within a pathway for actin dephosphorylation depending upon spore age. However, the glucose-induced actin dephosphorylation was insufficient for spores to swell. Other factors in the nutrient medium were required for complete germination of young spores aged 1 to 5 days. In contrast, dispersion in nonnutrient buffer was necessary and sufficient for a decline of actin phosphorylation levels and even the emergence of amoebae in older spores (6 days and beyond). Moreover, the dephosphorylation pathway in the older spores was independent of energy production. We propose that the diversification of the actin dephosphorylation pathway may enable spores to increase their probability of germination upon spore aging.     

Floodplain lake fish assemblages in the Amazon River: directions in conservation biology

The Neotropical region is renowned for its high biodiversity, and the Amazon River basin contains the highest number of fish species of any river system in the world. In recent years, habitat fragmentation and exploitation of biotic resources have threatened biological integrity and provoked to need for sustainable management and conservation of the Amazon River system. We studied 36 floodplain lakes along 2000 km of the Amazon River. The fish assemblages associated with flood forests are moderately diverse, with low species dominance and reduced populations. To detect nestedness of fish assemblage composition in floodplain lakes, a nested subset analysis was performed on species presence–absence. The incidence matrix (species × lakes) was maximally packed using the Nestedness Temperature Calculator software. The results of ranking lakes and species allow us to establish targets for conservation. Such strategy for sustainable management should be focused on maintaining the Amazonian biodiversity.     

Mechanisms of interleukin-6 protection against ischemia-reperfusion injury in rat liver

Numerous animal studies simulating liver injury have demonstrated that interleukin-6 (IL-6) exerts a protective effect. This study was designed to further analyze the molecular mechanisms underlying the protective role of IL-6 in a rat model of liver ischemia/reperfusion injury. We show that IL-6: (i) at high doses reduces cell damage which occurs in ischemic-reperfused liver, while at low doses displays only a limited protective capacity, (ii) anticipates and enhances hepatocyte compensatory proliferation seen in ischemic-reperfused liver also at a low, more pharmacologically acceptable dose, (iii) sustains the acute phase response which is dampened in ischemic-reperfused liver, (iv) strengthens the heat shock-stress response shown by ischemic-reperfused liver and (v) overcomes the dysfunctions of the unfolding protein response found in ischemic-reperfused liver. We also show that IL-6-enhanced STAT3 activation probably plays a crucial role in the potentiation of the different protective pathways activated in ischemic-reperfused liver. Our data confirm that IL-6 is a potential therapeutic in liver injury of different etiologies and reveal novel mechanisms by which IL-6 sustains liver function after ischemia/reperfusion injury.