A tetravalent dengue nanoparticle stimulates antibody production in mice

<p>Abstract</p> <p>Background</p> <p>Dengue is a major public health problem worldwide, especially in the tropical and subtropical regions of the world. Infection with a single <it>Dengue virus </it>(DENV) serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients experiencing secondary infection with a different serotype progresses to the severe form of the disease, dengue hemorrhagic fever/dengue shock syndrome. Currently, there are no licensed vaccines or antiviral drugs to prevent or treat dengue infections. Biodegradable nanoparticles coated with proteins represent a promising method for in vivo delivery of vaccines.</p> <p>Findings</p> <p>Here, we used a murine model to evaluate the IgG production after administration of inactivated DENV corresponding to all four serotypes adsorbed to bovine serum albumin nanoparticles. This formulation induced a production of anti-DENV IgG antibodies (p < 0.001). However, plaque reduction neutralization assays with the four DENV serotypes revealed that these antibodies have no neutralizing activity in the dilutions tested.</p> <p>Conclusions</p> <p>Our results show that while the nanoparticle system induces humoral responses against DENV, further investigation with different DENV antigens will be required to improve immunogenicity, epitope specicity, and functional activity to make this platform a viable option for DENV vaccines.</p

Biolixiviation of secondary copper sulphates by Acidithiobacillus ferrooxidans.

Neste trabalho, foi investigada a biolixivia??o de sulfetos secund?rios de cobre com Acidithiobacillus ferrooxidans. O efeito dos par?metros pH, concentra??o dos c?tions Fe2+, Al3+ e Mg2+, sob a extra??o de cobre foram avaliados. Os experimentos em frascos agitados mostraram elevadas recupera??es de cobre pr?ximas a 75%. A cin?tica de extra??o do metal foi afetada pelo pH e concentra??o de Fe2+ e os valores ideais foram 1,6-1,8 e 5-10 g.L-1, respectivamente. A adi??o de fontes externas de alum?nio (at? 5 g.L-1) favoreceu a biolixivia??o devido ? complexa??o do ?on fluoreto liberado durante a dissolu??o do mineral.This work investigated the bioleaching of secondary copper ores (chalcocite and bornite) by a mesophile culture comprised mostly of Acidithiobacillus ferrooxidans. O efeito dos par?metros pH, concentra??o dos c?tions Fe2+, Al3+ e Mg2+, sob a. Experiments were performed in Erlenmeyer flasks (250 mL) containing 100 mL of a 5% (w/v) pulp stirred at 150 min-1. The effects of pH, Fe2+, Al3+ and Mg2+ concentrations on copper extraction were determined. The leaching kinetics from the marginal ore was slightly affected by both pH and ferrous iron concentrations and the largest leaching rates were observed at pH 1,6-1,8 and 5-10 g.L-1 Fe2+. Aluminum concentrations (up to 5 g.L-1) improved the copper extraction kinetics as fluoride ions were complexed by the element and the final copper extraction reached 75%

Regulation of Amyloid ? oligomer binding to neurons and neurotoxicity by the complex prion protein/mGluR5.

The prion protein (PrPC) has been suggested to operate as a scaffold/ receptor protein in neurons, participating in both physiological and pathological associated events. PrPC, laminin, and metabotropic glutamate receptor 5 (mGluR5) form a protein complex on the plasma membrane that can trigger signaling pathways involved in neuronal differentiation. PrPC and mGluR5 are co-receptors also for -amyloid oligomers(A Os)andhavebeenshowntomodulate toxicity and neuronal death in Alzheimer?s disease. In the present work, we addressed the potential crosstalk between these two signaling pathways, laminin-PrPC-mGluR5 or A O-PrPC- mGluR5, as well as their interplay. Herein, we demonstrated that an existing complex containing PrPC-mGluR5 has an important role in A Obinding and activity in neurons. A peptide mimicking the binding site of laminin onto PrPC (Ln- 1) binds to PrPC and induces intracellular Ca2 increase in neurons via the complex PrPC-mGluR5. Ln- 1 promotes internalization of PrPC and mGluR5 and transiently decreases A O biding to neurons; however, the peptide does not impactA Otoxicity.GiventhatmGluR5 is critical for toxic signaling by A Os and in prion diseases, we tested whether mGlur5 knock-out mice would be susceptible to prion infection. Our results show mild, but significant, effects on disease progression, without affecting survival of mice after infection. These results suggest that PrPC-mGluR5 form a functional response unit by which multiple ligands can trigger signaling. We propose that trafficking of PrPC-mGluR5 may modulate signaling intensity by different PrPC ligands

Cardanol-derived AChE inhibitors: Towards the development of dual binding derivatives for Alzheimer's disease

Cardanol is a phenolic lipid component of cashew nut shell liquid (CNSL), obtained as the byproduct of cashew nut food processing. Being a waste product, it has attracted much attention as a precursor for the production of high-value chemicals, including drugs. On the basis of these findings and in connection with our previous studies on cardanol derivatives as acetylcholinesterase (AChE) inhibitors, we designed a novel series of analogues by including a protonable amino moiety belonging to different systems. Properly addressed docking studies suggested that the proposed structural modifications would allow the new molecules to interact with both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE, thus being able to act as dual binding inhibitors. To disclose whether the new molecules showed the desired profile, they were first tested for their cholinesterase inhibitory activity towards EeAChE and eqBuChE. Compound 26, bearing an N-ethyl-N-(2-methoxybenzyl)amine moiety, showed the highest inhibitory activity against EeAChE, with a promising IC50 of 6.6 \u3bcM, and a similar inhibition profile of the human isoform (IC50 = 5.7 \u3bcM). As another positive feature, most of the derivatives did not show appreciable toxicity against HT-29 cells, up to a concentration of 100 \u3bcM, which indicates drug-conform behavior. Also, compound 26 is capable of crossing the blood-brain barrier (BBB), as predicted by a PAMPA-BBB assay. Collectively, the data suggest that the approach to obtain potential anti-Alzheimer drugs from CNSL is worth of further pursuit and development

Measurement of charged particle spectra in minimum-bias events from proton-proton collisions at root s =13 TeV

Pseudorapidity, transverse momentum, and multiplicity distributions are measured in the pseudorapidity range vertical bar eta vertical bar 0.5 GeV in proton-proton collisions at a center-of-mass energy of root s = 13 TeV. Measurements are presented in three different event categories. The most inclusive of the categories corresponds to an inelastic pp data set, while the other two categories are exclusive subsets of the inelastic sample that are either enhanced or depleted in single diffractive dissociation events. The measurements are compared to predictions from Monte Carlo event generators used to describe high-energy hadronic interactions in collider and cosmic-ray physics.Peer reviewe

Management of coronary disease in patients with advanced kidney disease

BACKGROUND Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease. METHODS We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P=0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P=0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P=0.03). CONCLUSIONS Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction