Protection of DNA against low-energy electrons by amino acids: A first-principles molecular dynamics study

Using first-principles molecular dynamics simulations, we have investigated the notion that amino acids can play a protective role when DNA is exposed to excess electrons produced by ionizing radiation. In this study we focus on the interaction of glycine with the DNA nucleobase thymine. We studied thymine-glycine dimers and a condensed phase model consisting of one thymine molecule solvated in amorphous glycine. Our results show that the amino acid acts as a protective agent for the nucleobase in two ways. If the excess electron is initially captured by the thymine, then a proton is transferred in a barrier-less way from a neighboring hydrogen-bonded glycine. This stabilizes the excess electron by reducing the net partial charge on the thymine. In the second mechanism the excess electron is captured by a glycine, which acts as a electron scavenger that prevents electron localization in DNA. Both these mechanisms introduce obstacles to further reactions of the excess electron within a DNA strand, e.g. by raising the free energy barrier associated with strand breaks.

Flexible energetics of cheetah hunting strategies provide resistance against kleptoparasitism

Population viability is driven by individual survival, which in turn depends on individuals balancing energy budgets. As carnivores may function close to maximum sustained power outputs, decreased food availability or increased activity may render some populations energetically vulnerable. Prey theft may compromise energetic budgets of mesopredators, such as cheetahs and wild dogs, which are susceptible to competition from larger carnivores. We show that daily energy expenditure (DEE) of cheetahs was similar to size-based predictions and positively related to distance traveled. Theft at 25% only requires cheetahs to hunt for an extra 1.1 hour per day, increasing DEE by just 12%. Therefore, not all mesopredators are energetically constrained by direct competition. Other factors that increase DEE, such as those that increase travel, may be more
important for population viability.

A simple inhibition coefficient for quantifying potency of biocontrol agents against plant-pathogenic fungi

Microbial interactions depend on a range of biotic and environmental variables, and are both dynamic and unpredictable. For some purposes, and under defined conditions, it is nevertheless imperative to evaluate the inhibitory efficacy of microbes, such as those with potential as biocontrol agents. We selected six, phylogenetically diverse microbes to determine their ability to inhibit the ascomycete Fusarium
coeruleum, a soil-dwelling pathogen of potato tubers that causes the storage disease dry rot. Interaction assays, where colony development was quantified (for both fungal pathogen and potential control agents), were therefore carried out on solid media. The key parameters that contributed to, and were indicative of, inhibitory efficacy were identified as: fungal growth-rates (i) prior to contact with the biocontrol
agent and (ii) if/once contact with the biocontrol agent was established (i.e. in the zone of mixed
culture), and (iii) the ultimate distance traveled by the fungal mycelium. It was clear that there was no correlation between zones of fungal inhibition and the overall reduction in the extent of fungal colony development. An inhibition coefficient was devised which incorporated the potential contributions of distal inhibition of fungal growth-rate; prevention of mycelium development in the vicinity of the biocontrol
agent; and ability to inhibit plant-pathogen growth-rate in the zone of mixed culture (in a ratio of 2:2:1). The values derived were 84.2 for Bacillus subtilis (QST 713), 74.0 for Bacillus sp. (JC12GB42), 30.7 for Pichia anomala (J121), 19.3 for Pantoea agglomerans (JC12GB34), 13.9 for Pantoea sp. (S09:T:12), and
21.9 (indicating a promotion of fungal growth) for bacterial strain (JC12GB54). This inhibition coefficient, with a theoretical maximum of 100, was consistent with the extent of F. coeruleum-colony development (i.e. area, in cm2) and assays of these biocontrol agents carried out previously against Fusarium
spp., and other fungi. These findings are discussed in relation to the dynamics and inherent complexity of natural ecosystems, and the need to adapt models for use under specific sets of conditions.

Synergism between high-pressure processing and active packaging against Listeria monocytogenes in ready-to-eat chicken breast

The effects of high-pressure processing (HPP) in conjunction with an essential oil-based active packaging on the surface of ready-to-eat (RTE) chicken breast were investigated as post-processing listericidal treatment. Three different treatments were used, and all samples were vacuum packed: (i) HPP at 500. MPa for 1. min (control), (ii) active packaging based on coriander essential oil, and (iii) active packaging and HPP. When applied individually, active packaging and pressurisation delayed the growth of Listeria monocytogenes. The combination of HPP and active packaging resulted in a synergistic effect reducing the counts of the pathogen below the detection limit throughout 60. days storage at 4. °C. However, when these samples were stored at 8. °C, growth did occur, but again a delay in growth was observed. The effects on colour and lipid oxidation were also studied during storage and were not significantly affected by the treatments. Active packaging followed by in-package pressure treatment could be a useful approach to reduce the risk of L. monocytogenes in cooked chicken without impairing its quality. Industrial relevance: Ready-to-eat products are of great economic importance to the industry. However, they have been implicated in several outbreaks of listeriosis. Therefore, effective ways to reduce the risk from this pathogenic microorganism can be very attractive for manufacturers. This study showed that the use of active packaging followed by HPP can enhance the listericidal efficiency of the treatment while using lower pressure levels, and thus having limited effects on colour and lipid oxidation of RTE chicken breast.

Measurements of immune responses for establishing correlates of vaccine protection against HIV

Well-defined correlates of protective immunity are an essential component of rational vaccine development. Despite years of basic science and three HIV vaccine efficacy trials, correlates of immunological protection from HIV infection remain undefined. In December 2010, a meeting of scientists engaged in basic and translational work toward developing HIV-1 vaccines was convened. The goal of this meeting was to discuss current opportunities and optimal approaches for defining correlates of protection, both for ongoing and future HIV-1 vaccine candidates; specific efforts were made to engage young scientists. We discuss here the highlights from the meeting regarding the progress made and the way forward for a protective HIV-1 vaccine.

Antimicrobial Efficacy of an Innovative Emulsion of Medium Chain Triglycerides against Canine and Feline Periodontopathogens

OBJECTIVES: To test the in vitro antimicrobial efficacy of a non-toxic emulsion of free fatty acids against clinically relevant canine and feline periodontopathogens 
METHODS: Antimicrobial kill kinetics were established utilising an alamarBlue® viability assay against 10 species of canine and feline periodontopathogens in the biofilm mode of growth at a concentration of 0·125% v/v medium chain triglyceride (ML:8) emulsion. The results were compared with 0·12% v/v chlorhexidine digluconate and a xylitol-containing dental formulation. Mammalian cellular cytotoxicity was also investigated for both the ML:8 emulsion and chlorhexidine digluconate (0·25 to 0·0625% v/v) using in vitro tissue culture techniques.
RESULTS: No statistically significant difference was observed in the antimicrobial activity of the ML:8 emulsion and chlorhexidine digluconate; a high percentage kill rate (>70%) was achieved within 5 minutes of exposure and was maintained at subsequent time points. A statistically significant improvement in antibiofilm activity was observed with the ML:8 emulsion compared with the xylitol-containing formulation. The ML:8 emulsion possessed a significantly lower (P<0·001) toxicity profile compared with the chlorhexidine digluconate in mammalian cellular cytotoxicity assays.
CLINICAL SIGNIFICANCE: The ML:8 emulsion exhibited significant potential as a putative effective antimi-crobial alternative to chlorhexidine- and xylitol- based products for the reduction of canine and feline periodontopathogens.

Antimicrobial and immunomodulatory properties of PGLa-AM1, CPF-AM1, and magainin-AM1: Potent activity against oral pathogens

Cationic amphipathic α-helical peptides are intensively studied classes of host defence peptides (HDPs). Three peptides, peptide glycine-leucine-amide (PGLa-AM1), caerulein-precursor fragment (CPF-AM1) and magainin-AM1, originally isolated from norepinephrine-stimulated skin secretions of the African volcano frog Xenopus amieti (Pipidae), were studied for their antimicrobial and immunomodulatory activities against oral and respiratory pathogens. Minimal effective concentrations (MECs), determined by radial diffusion assay, were generally lower than minimal inhibitory concentrations (MICs) determined by microbroth dilution. PGLa-AM1 and CPF-AM1 were particularly active against Streptococcus mutans and all three peptides were effective against Fusobacterium nucleatum, whereas Enterococcus faecalis and Candida albicans proved to be relatively resistant micro-organisms. A type strain of Pseudomonas aeruginosa was shown to be more susceptible than the clinical isolate studied. PGLa-AM1 displayed the greatest propensity to bind lipopolysaccharide (LPS) from Escherichia coli, P. aeruginosa and Porphyromonas gingivalis. All three peptides showed less binding to P. gingivalis LPS than to LPS from the other species studied. Oral fibroblast viability was unaffected by 50. μM peptide treatments. Production of the pro-inflammatory cytokine IL-8 by oral fibroblasts was significantly increased following treatment with 1 or 10. μM magainin-AM1 but not following treatment with PGLa-AM1 or CPF-AM1. In conclusion, as well as possessing potent antimicrobial actions, the X. amieti peptides bound to LPS from three human pathogens and had no effect on oral fibroblast viability. CPF-AM1 and PGLa-AM1 show promise as templates for the design of novel analogues for the treatment of oral and dental diseases associated with bacteria or fungi.

Study on risk assessment and management and prevention of conflicts of interest in the prevention and fight against betting-related match fixing in the EU 28: Final Report

This report concerns the provisions and practices on betting-related match fixing in sports
within the 28 Member States. Carried out in late 2013/early 2014, respondents in each Member
State reported on that state’s gambling-related provisions in respect of football and tennis and
(in each country) a third sport determined on the basis of either its popularity (in terms of
participation or television viewing) or the existence of betting-related “scandals” in that sport
within that particular jurisdiction. Those reports helped the authors to compare the Member
States’ regulatory and self-regulatory frameworks relating to risk assessment and conflict of
interest management, with a view to indicating areas of best practice, identifying particularly
good legislative frameworks and highlighting areas where change was either desirable or
necessary. While some individual Member States have legislation which might provide
templates that others could adapt for their own use, the authors were not convinced that “more
law”, whether at the national or European level, was desirable. Rather, more effective
cooperation among the stakeholders was identified as being more likely to provide tangible
benefits than would new legal frameworks.