Secondary heterologous dengue infection risk: Disequilibrium between immune regulation and inflammation?

Increased serum levels of cytokines released by cells of the immune response have been detected in patients suffering from dengue disease. Likewise, secondary infections by a different dengue virus serotype result in a highest risk of development of the severe dengue disease. Both findings suggest that the memory immune response is one of the key players in the pathogenesis of this disease. Here we take advantage of the particular Cuban epidemiological situation in dengue to analyze a broad spectrum of cell-mediated immune response mediators at mRNA and protein level. Evidences for a regulatory immune pattern in homologous (TGF-β, IL-10) vs. pro-inflammatory pattern (IFN-γ, TNF-α) in heterologous dengue virus re-challenge were found, suggesting a possible association with the higher incidence of severe dengue cases in the latter case.     

Recognition of the neural chemoattractant Netrin-1 by integrins alpha6beta4 and alpha3beta1 regulates epithelial cell adhesion and migration

Netrins, axon guidance cues in the CNS, have also been detected in epithelial tissues. In this study, using the embryonic pancreas as a model system, we show that Netrin-1 is expressed in a discrete population of epithelial cells, localizes to basal membranes, and specifically associates with elements of the extracellular matrix. We demonstrate that alpha6beta4 integrin mediates pancreatic epithelial cell adhesion to Netrin-1, whereas recruitment of alpha6beta4 and alpha3beta1 regulate the migration of CK19+/PDX1+ putative pancreatic progenitors on Netrin-1. These results provide evidence for the activation of epithelial cell adhesion and migration by a neural chemoattractant, and identify Netrin-1/integrin interactions as adhesive/guidance cues for epithelial cells.     

Compensation in pre-synaptic dopaminergic function following nigrostriatal damage in primates

Clinical symptoms of Parkinson's disease only become evident after 70-80% reductions in striatal dopamine. To investigate the importance of pre-synaptic dopaminergic mechanisms in this compensation, we determined the effect of nigrostriatal damage on dopaminergic markers and function in primates. MPTP treatment resulted in a graded dopamine loss with moderate to severe declines in ventromedial striatum (approximately 60-95%) and the greatest reductions (approximately 95-99%) in dorsolateral striatum. A somewhat less severe pattern of loss was observed for striatal nicotinic receptor, tyrosine hydroxylase and vesicular monoamine transporter expression. Declines in striatal dopamine uptake and transporter sites were also less severe than the reduction in dopamine levels, with enhanced dopamine turnover in the dorsolateral striatum after lesioning. The greatest degree of adaptation occurred for nicotine-evoked [(3)H]dopamine release from striatal synaptosomes, which was relatively intact in ventromedial striatum after lesioning, despite > 50% declines in dopamine. This maintenance of evoked release was not due to compensatory alterations in nicotinic receptor characteristics. Rather, there appeared to be a generalized preservation of release processes in ventromedial striatum, with K(+)-evoked release also near control levels after lesioning. These combined compensatory mechanisms help explain the finding that Parkinson's disease symptomatology develops only with major losses of striatal dopamine.     

City refuse compost as a phosphorus source to overcome the P-fixation capacity of sesquioxide-rich soils

In sesquioxide-rich soils of tropical and subtropical areas and volcanic-ash soils with high levels of active Al(Fe), large amounts of phosphate fertilizers are needed to overcome their high P-fixation capacity (quenching strategy). A greenhouse pot experiment has been used to evaluate the effectiveness of city refuse compost (CRC) as a P-source for these variable-charge soils, compared to inorganic P. Mature CRC and K₂HPO₄ were applied at rates equivalent to 125, 250, 375, 500 and 625 kg P ha^–1 to a ferrallitic soils from Tenerife Island (Andeptic Paleudult) with a high content in active Al+Fe (4.82%) and a high P-fixation capacity (87%). Perennial ryegrass (Lolium perenne L.) was grown in pots and plants were harvested at regular intervals after seedling emergence. CRC increases plant P concentration and soil labile-P proportional to the applied rate. The best results were obtained from a compost application of 30 t ha^–1 equivalent-rate, after a residence time of at least three months. An important residual effect in the supply capacity of P in relation to the phosphate fertilizer was also observed. The relative agronomic effectiveness (RAE) in comparison to K₂HPO₄ was 66% after 6 months, considering P uptake + soil labile-P. The soil P-fixation capacity was significantly reduced from a compost application of 40 t ha^–1 equivalent-rate. Competition in adsorption between organic ligands and phosphate, in combination with net mineralization of organic P in compost, might account for the high RAE value obtained. The main conclusion is that the city refuse compost could be a suitable P-amendment for resquioxic soils due to its high RAE, and the residual effect on P-supply. ei]H. Lambers     

Structure–function relationships of the peptide Paulistine: A novel toxin from the venom of the social wasp Polybia paulista

Background

The peptide Paulistine was isolated from the venom of wasp Polybia paulista. This peptide exists under a natural equilibrium between the forms: oxidised — with an intra-molecular disulphide bridge; and reduced — in which the thiol groups of the cysteine residues do not form the disulphide bridge. The biological activities of both forms of the peptide are unknown up to now.

Methods

Both forms of Paulistine were synthesised and the thiol groups of the reduced form were protected with the acetamidemethyl group [Acm-Paulistine] to prevent re-oxidation. The structure/activity relationships of the two forms were investigated, taking into account the importance of the disulphide bridge.

Results

Paulistine has a more compact structure, while Acm-Paulistine has a more expanded conformation. Bioassays reported that Paulistine caused hyperalgesia by interacting with the receptors of lipid mediators involved in the cyclooxygenase type II pathway, while Acm-Paullistine also caused hyperalgesia, but mediated by receptors involved in the participation of prostanoids in the cyclooxygenase type II pathway.

Conclusion

The acetamidemethylation of the thiol groups of cysteine residues caused small structural changes, which in turn may have affected some physicochemical properties of the Paulistine. Thus, the dissociation of the hyperalgesy from the edematogenic effect when the actions of Paulistine and Acm-Paulistine are compared to each other may be resulting from the influence of the introduction of Acm-group in the structure of Paulistine.

General significance

The peptides Paulistine and Acm-Paulistine may be used as interesting tools to investigate the mechanisms of pain and inflammation in future studies.     

Molecular Dynamics Simulations of Phospholipid Bilayers

Abstract

Molecular dynamics (MD) simulations at 37°C have been performed on three phospholipid bilayer systems composed of the lipids DLPE, DOPE, and DOPC. The model used included 24 explicit lipid molecules and explicit waters of solvation in the polar head group regions, together with constant-pressure periodic boundary conditions in three dimensions. Using this model, a MD simulation samples part of an infinite planar lipid bilayer. The lipid dynamics and packing behavior were characterized. Furthermore, using the results of the simulations, a number of diverse properties including bilayer structural parameters, hydrocarbon chain order parameters, dihedral conformations, electron density profile, hydration per lipid, and water distribution along the bilayer normal were calculated. Many of these properties are available for the three lipid systems chosen, making them well suited for evaluating the model and protocols used in these simulations by direct comparisons with experimental data. The calculated MD behavior, chain disorder, and lipid packing parameter, i.e. the ratio of the effective areas of hydrocarbon tails and head group per lipid (a_t/a_h), correctly predict the aggregation preferences of the three lipids observed experimentally at 37°C, namely: a gel bilayer for DLPE, a hexagonal tube for DOPE, and a liquid crystalline bilayer for DOPC. In addition, the model and conditions used in the MD simulations led to good agreement of the calculated properties of the bilayers with available experimental results, demonstrating the reliability of the simulations. The effects of the cis unsaturation in the hydrocarbon chains of DOPE and DOPC, compared to the fully saturated one in DLPE, as well as the effects of the different polar head groups of PC and PE with the same unsaturated chains on the lipid packing and bilayer structure have been investigated. The results of these studies indicate the ability of MD methods to provide molecular-level insights into the structure and dynamics of lipid assemblies.     

Sense-overlapping lncRNA as a decoy of translational repressor protein for dimorphic gene expression

Long noncoding RNAs (lncRNAs) are vastly transcribed and extensively studied but lncRNAs overlapping with the sense orientation of mRNA have been poorly studied. We analyzed the lncRNA DAPALR overlapping with the 5´ UTR of the Doublesex1 (Dsx1), the male determining gene in Daphnia magna. By affinity purification, we identified an RNA binding protein, Shep as a DAPALR binding protein. Shep also binds to Dsx1 5´ UTR by recognizing the overlapping sequence and suppresses translation of the mRNA. In vitro and in vivo analyses indicated that DAPALR increased Dsx1 translation efficiency by sequestration of Shep. This regulation was impaired when the Shep binding site in DAPALR was deleted. These results suggest that Shep suppresses the unintentional translation of Dsx1 by setting a threshold; and when the sense lncRNA DAPALR is expressed, DAPALR cancels the suppression caused by Shep. This mechanism may be important to show dimorphic gene expressions such as sex determination and it may account for the binary expression in various developmental processes.     

Enzymatic synthesis of biodiesel from palm oil assisted by microwave irradiation

Optimal conditions for enzymatic synthesis of biodiesel from palm oil and ethanol were determined with lipase from Pseudomonas fluorescens immobilized on epoxy polysiloxane–polyvinyl alcohol hybrid composite under a microwave heating system. The main goal was to reduce the reaction time preliminarily established by a process of conventional heating. A full factorial design assessed the influence of ethanol-to-palm oil (8:1–16:1) molar ratio and temperature (43–57 °C) on the transesterification yield. Microwave irradiations varying from 8 to 15 W were set up according to reaction temperature. Under optimal conditions (8:1 ethanol-to-oil molar ratio at 43 °C), 97.56 % of the fatty acids present in the palm oil were converted into ethyl esters in a 12-h reaction, corresponding to a productivity of 64.2 mg ethyl esters g^?1 h^?1. This represents a sixfold increase from the process carried out under conventional heating, thus proving to be a potential tool for enhancing biochemical modification of oils and fats. In general, advantages of the new process include: (1) microwaves speed up the enzyme-catalyzed reactions; (2) there are no destructive effects on the enzyme properties, such as stability and substrate specificity, and (3) the microwave assistance allows the entire reaction volume to be heated uniformly. These bring benefits of a low energy demand and a faster conversion of palm oil into biodiesel.