Chemical-Shift Perturbations Reflect Bile Acid Binding to Norovirus Coat Protein: Recognition Comes in Different Flavors

Bile acids have been reported as important cofactors promoting human and murine norovirus (NoV) infections in cell culture. The underlying mechanisms are not resolved. Through the use of chemical shift perturbation (CSP) NMR experiments, we identified a low-affinity bile acid binding site of a human GII.4 NoV strain. Long-timescale MD simulations reveal the formation of a ligand-accessible binding pocket of flexible shape, allowing the formation of stable viral coat protein–bile acid complexes in agreement with experimental CSP data. CSP NMR experiments also show that this mode of bile acid binding has a minor influence on the binding of histo-blood group antigens and vice versa. STD NMR experiments probing the binding of bile acids to virus-like particles of seven different strains suggest that low-affinity bile acid binding is a common feature of human NoV and should therefore be important for understanding the role of bile acids as cofactors in NoV infection.     

Olive oil consumption and reduced incidence of hypertension: The SUN study

Olive oil, a major component of the Mediterranean diet, has been associated in some small clinical trials and cross-sectional studies with a reduction in blood pressure. The objective of this study was to assess the association of olive oil consumption with the incidence of hypertension in an epidemiologic cohort, the Seguimiento Universidad de Navarra (SUN) study. The SUN Project is a prospective cohort study whose members are all university graduates. The recruitment and follow-up of participants is made using mailed questionnaires. Diet was assessed using a semiquantitative food frequency questionnaire previously validated in Spain, with 136 items. Outcomes of interest were newly diagnosed cases of hypertension, as reported by participants in the follow-up questionnaires. Logistic regression models were fit to assess the risk of hypertension associated with olive oil consumption. For the present analysis, we have taken in consideration the first 6,863 participants, with at least 2 yr of follow-up. After a median follow-up time of 28.5 mon, the cumulative incidence of hypereension was 4.7% in men and 1.7% in women. A lower risk of hypertension was observed among participants with a higher olive oil consumption at baseline, but the results were not statistically significant (P=0.13 for the linear trend test in the multivariate model). However, among men, the adjusted odds ratios (OR) (95% confidence intervals) of hypertension for the second to fifth quintiles of olive oil consumption, compared with the first quintile, were 0.55 (0.28–1.10), 0.75 (0.39–1.43), 0.32 (0.15–0.70), and 0.46 (0.23–0.94), respectively (P=0.02 for linear trend). No association was found between olive oil consumption and the risk of hypertension among women. In conclusion, in a Mediterranean population, we found olive oil consumption to be associated with a reduced risk of hypertension only among men. The lack of association observed among women might be attributed to the overall lower incidence of hypertension found among females and the resulting lower statistical power.     

A urine patch framework to simulate nitrogen leaching on New Zealand dairy farms

On New Zealand dairy farms, it is the nitrogen excreted directly onto pasture, particularly urine, that drives nitrogen (N) leaching from the farm. A new framework (UPF: Urine Patch Framework) is presented that post-processes the results of a whole farm model and runs a mechanistic soil model to simulate the urine patches. Two alternative methods to simulate the spatial distribution of urine patches were implemented and compared (Grid: spatially explicit, and Probabilistic: based on the probability of different temporal urination patterns). This paper describes the implementation of these two methods in connection with a Whole Farm Model; and compares the N leaching predictions with observed data. Two examples are provided, one analyzing the impact of urine patch overlap and another, the relative risk of N leaching at different times of urinary N deposition. The model showed good correlation and predictive ability between simulated annual N leaching results and observed data [R² = 94 %, mean relative prediction error (MRPE) = 10 % for Grid and R² = 72 %, MRPE = 20 % for Probabilistic]. The two methods produced similar results across an 8-year period for monthly and annual N leaching (R² = 96 %, MRPE = 10 % and R² = 86 %, MRPE = 8 %; respectively). Only 8 % of the paddock area was covered with multiple urinations during 1 year, but as much as 39 % of the total urine volume was deposited on overlapped patches. Systematically removing all urinary N for 1 month in either May or June reduced N leaching by approximately 20 %. Avoiding urinary N deposition during autumn or early winter could be highly effective in mitigating N leached during the following winter.     

The Co-Au interface in bimetallic nanoparticles: a high resolution STEM study

We report the formation of Au/Co nanoparticles and their characterization by aberration (Cs) corrected scanning transmission electron microscopy (STEM). The nanoparticles were synthesized by inert gas condensation, forming initially core-shell and bimetallic crystals. However, after thermal treatment at normal atmospheric conditions, the Co nanoparticles changed their morphology into a fine layer forming a perfect interface with the gold. The ordering of the zone rich in Co presents a fcc arrangement matching the gold lattice. The atomic analysis on the interface and the comparison of the STEM images with numerical simulations corroborated the atomic substitution of gold by cobalt.     

Phosphated crosslinked pectin as a potential excipient for specific drug delivery: preparation and physicochemical characterization

Pectin was chemically modified with different amounts of trisodium trimetaphosphate (STMP) in aqueous solution (pH = 12), thereby giving a material with reduced water solubility. The physiochemical characterization of this new material was carried out through Fourier transform infrared and thermogravimetric analyses. Phosphated pectin (Pect‐STMP) together with prebiotic (oligosaccharide) were incorporated into an aqueous dispersion of polymethacrylate (Eudragit^® RS 30 D) in order to obtain free films using a casting process (50 °C) on a Teflon plate. The free films were evaluated using water vapour transmission, average swelling index in simulated gastric fluid (SGF) and simulated intestinal fluid, scanning electron microscopy and a diffusion study with theophylline in buffer solution with and without pectinolytic enzyme. The results suggest that the new material can be used in the coating process for oral solid‐reservoir systems, to prevent the premature release of drugs in SGF (pH = 1.2). Furthermore, the presence of both Pect‐STMP and oligosaccharide favours the specific degradation of the pellicle by the action of the enzymes produced by colonic microflora. The material obtained in this work has the potential to be applied in devices for drug delivery in the colon, making possible modified release of drugs. Nevertheless, subsequent colon‐specific experiments in vivo need to be carried out in order to confirm the possible application of this new material. Copyright © 2009 Society of Chemical Industry     

Influence of chemical structure of hardener on mechanical and adhesive properties of epoxy polymers

The mechanical and adhesive properties of epoxy formulations based on diglycidyl ether of bisphenol A cured with various aliphatic amines were evaluated in the glass state. Impact and uniaxial compression tests were used to determine the impact energy, elastic modulus and yield stress, respectively. The adhesion tests were carried out in steel–steel joints using single‐lap shear, T‐peel, and impact adhesive joints geometry. The better mechanical and adhesive behavior of the networks is obtained when exists high flexibility of chain between crosslink and/or high elastic modulus. The 1‐(2‐aminoethyl)piperazine epoxy network presents the best adhesive properties, high flexibility, and the largest impact energy. However, it possesses low elastic modulus and yield stress. Also, exhibits increases in peel strength and impact energy while reductions in lap shear strength. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Resistance of metallic substrates protected by an organic coating containing glass flakes

The resistance against corrosion of an epoxy-polyamine-based coating immersed in a 3 wt.% sodium chloride solution was investigated by electrochemical impedance spectroscopy (EIS). The organic coating contained glass flakes as pigment in order to enhance its barrier characteristics. The data show that this coating is more strongly adhered and exhibits higher protection characteristics when applied onto carbon steel substrates than on galvanized steel. Though the capacitance of the coating (C_C) does not show any appreciable variation with immersion time, the resistance (R_PO) of the film is observed to increase with time upon immersion. The analysis of the data sustains that the organic film behaves as a porous, non-barrier coating. Two time constants are observed even at earlier exposures, and the improved corrosion resistance developed after the coating system was exposed to the test electrolyte is considered to originate from the precipitation of corrosion products within the pores in the film.     

New Anacardic Acid‐Inspired Benzamides: Histone Lysine Acetyltransferase Activators

A series of N‐(4‐cyano‐3‐trifluoromethyl‐phenyl)‐2‐ethoxy‐6‐alkyl (and alkenyl) benzamides related to the anacardic acid derivative CTPB have been prepared from 2,6‐dihydroxybenzoic acid with a Suzuki coupling and addition of the anion of 4‐cyano‐3‐trifluoromethylphenylamine to a benzodioxinone as the key steps. In U937 cells, these analogues, in particular 7 c , 7 d , 7 f and 7 j , induced cell‐cycle arrest in the G1 phase, caused apoptosis in about 20 % of the cells, and increased the acetylation levels of H3. These activities correlate with the enzymatic activation of histone lysine acetyltransferases (KATs): CBP and PCAF.