The mechanisms of humic substances self-assembly with biological molecules: The case study of the prion protein

Humic substances (HS) are the largest constituent of soil organic matter and are considered as a key component of the terrestrial ecosystem. HS may facilitate the transport of organic and inorganic molecules, as well as the sorption interactions with environmentally relevant proteins such as prions. Prions enter the environment through shedding from live hosts, facilitating a sustained incidence of animal prion diseases such as Chronic Wasting Disease and scrapie in cervid and ovine populations, respectively. Changes in prion structure upon environmental exposure may be significant as they can affect prion infectivity and disease pathology. Despite its relevance, the mechanisms of prion interaction with HS are still not completely understood. The goal of this work is to advance a structural-level picture of the encapsulation of recombinant, non-infectious, prion protein (PrP) into different natural HS. We observed that PrP precipitation upon addition of HS is mainly driven by a mechanism of “salting-out” whereby PrP molecules are rapidly removed from the solution and aggregate in insoluble adducts with humic molecules. Importantly, this process does not alter the protein folding since insoluble PrP retains its α-helical content when in complex with HS. The observed ability of HS to promote PrP insolubilization without altering its secondary structure may have potential relevance in the context of “prion ecology”. These results suggest that soil organic matter interacts with prions possibly without altering the protein structures. This may facilitate prions preservation from biotic and abiotic degradation leading to their accumulation in the environment

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .)

Oligomerization of Humic Phenolic Monomers by Oxidative Coupling under Biomimetic Catalysis

Three humic phenolic monomers, catechol (CAT), caffeic acid (CAFF), and p-coumaric acid (COUM), were subjected to oxidative coupling catalyzed by biomimetic watersoluble iron-porphyrin (Fe(TDCPPS)Cl) in either separate or mixed solution, and the reaction products were characterized by gas chromatography-mass spectrometry (GC-MS) and electrospray-mass spectrometry (ESIMS). The GC-MS analysis proved the formation of C-C and C-O dimers, whereas the ESI-MS/MS analysis also suggested trimerization for all the monomers and tetramerization for CAT. On the basis of mass spectra, molecular structures were assigned to the observed oligomers. In the phenolic separate solutions, dimers represented about 65%, 44%, and 30% of reaction products for CAT, CAFF, and COUM, respectively, whereas trimers were from 4 to 5%. A relevant part of the products were unidentified oligomers and several degradation compounds, mostly aromatic aldehydes and alcohols and aromatic or aliphatic carboxylic acids. When all three humic phenolic monomers underwent the catalyzed coupling reaction in one mixed solution, 14% of the reaction products were identified as C-C dimers of CAT. Although no other C-O dimers of CAT, nor any dimers of COUM and CAFF, could be identified, some other structurally unknown oligomers were present among the reaction products of the mixed solution. However, no oligomers larger than tetramers were formed in either separate or mixed solutions. This work indicates the essential role of biomimetic metal-porphyrins in catalyzing the oxidative coupling of humic phenolic monomers in aqueous media, thereby promoting the polymerization of natural organic matter

Agritourism Farms - Evaluation of Their Websites Quality and Web 2.0

Based on surveys carried out in 2009 and 2012 it can be suggested that the web presentations of agritourism farms are virtually unchanged. The quality of the web pages for the same farms is statistically higher only for the criterion of “Content – structure” of websites. It can be assumed that in 2012 farmers devoted more attention to the structure of information that is presented on their own websites. Farms that have their own domain name show statistically significantly higher quality websites. Generally, it can be said that the website presentations of agritourism farms do not use the new approaches to the internet technologies as much as they could. For this reason, an approach has been proposed for upgrading the www presentations of lesser quality by means of the WCMS WordPress. It is recommended to use the Web 2.0 technologies, e.g. integrate through the mashup technologies the associated information sources into the websites (links to social networks and weather forecasts or the RSS sources in a given region). This paper was elaborated within the framework of the solution VZ MSM 6046070906 „Economics sources of Czech agriculture and their efficient use in the context of m ultifunctional agri-food systems“

Voltammetric Determination of 5‐Aminoquinoline at Carbon Film Electrode and Carbon and Gold Screen Printed Electrodes – A Comparative Study

Aminoquinolines are widely used as antimalarial drugs and thus there is an ever increasing demand for their determination. In this paper, non-traditional carbon film electrode developed in our laboratory (CFE) with easily replaceable carbon film was used for the determination of 5-aminoquinoline (5-AQ) and compared with well-established commercially available carbon screen printed electrode (CSPE) and gold screen printed electrode (AuSPE). Electrochemical behavior of 5-AQ was characterized by cyclic and differential pulse voltammetry. Differences in electrochemical behavior of 5-AQ at different electrodes were evaluated. Determination of 5-AQ was carried out by differential pulse, square wave, and direct current voltammetry. Practical applicability of the method was verified by direct determination of 5-AQ in model samples of drinking and river water. Achieved limits of quantitation were in submicromolar concentrations. It was found out that novel CFE in terms of overall performance is in most aspects superior to routinely used commercially available CSPE and AuSPE