Free energy barrier for melittin reorientation from a membrane-bound state to a transmembrane state

An important step in a phospholipid membrane pore formation by melittin antimicrobial peptide is a reorientation of the peptide from a surface into a transmembrane conformation. In this work we perform umbrella sampling simulations to calculate the potential of mean force (PMF) for the reorientation of melittin from a surface-bound state to a transmembrane state and provide a molecular level insight into understanding peptide and lipid properties that influence the existence of the free energy barrier. The PMFs were calculated for a peptide to lipid (P/L) ratio of 1/128 and 4/128. We observe that the free energy barrier is reduced when the P/L ratio increased. In addition, we study the cooperative effect; specifically we investigate if the barrier is smaller for a second melittin reorientation, given that another neighboring melittin was already in the transmembrane state. We observe that indeed the barrier of the PMF curve is reduced in this case, thus confirming the presence of a cooperative effect

The -9/+9 polymorphism of the bradykinin receptor beta 2 Gene and athlete status: A study involving two European cohorts

Previous studies concerning the relevance of BDKRB2 gene polymorphisms revealed that the absence (-9 allele) of a nine-base-pair sequence in exon 1 of the BDKRB2 gene is correlated with higher skeletal muscle metabolic efficiency, glucose uptake during exercise, and endurance athletic performance. The aim of the study was to investigate the association between the BDKRB2 -9/+9 polymorphism and elite athletic status in two cohorts of eastern European athletes. We examined the genotype distribution of the BDKRB2 9/+9 polymorphic site in a group of Polish athletes and confirmed the results obtained in a replication study of Russian athletes. Three hundred and two Polish athletes and 684 unrelated sedentary controls, as well as 822 Russian athletes and 507 unrelated sedentary volunteers, were recruited for this study. All samples were genotyped for the -9/+9 polymorphism within exon 1 of the BDKRB2 gene using polymerase chain reaction. Significance was assessed by chi square analysis with Bonferroni's correction for multiple testing. We found no statistical difference in the -9/+9 genotype and allele frequencies in two groups of athletes divided into four subgroups: endurance, sprint-endurance, sprint-strength, and strength athletes, compared with controls. There were no significant differences in allele frequencies (p = 0.477) and genotype distribution (p = 0.278) in the initial and replication studies. Thus, no association was found between the BDKRB2 -9/+9 polymorphism and elite athletic status in two cohorts of eastern European athletes

Association of the MTHFR 1298A/C (rs1801131) polymorphism with speed and strength sports in Russian and Polish athletes

It has been suggested that DNA hypomethylation because of poorer effectiveness of the 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme induces muscular growth. We hypothesised that the common, functional 1298A>C polymorphism in the MTHFR gene is associated with athletic status. To test this hypothesis, we investigated the distribution of the 1298A>C variant in Polish (n = 302) and Russian (n = 842) athletes divided into four groups: endurance, strength-endurance, sprint-strength and strength-endurance, as well as in 1540 control participants. We found different genotypes (the AC heterozygote advantage) and allele distributions among sprint-strength athletes and strength athletes than the groups of sedentary controls for each nationality. In the combined study, the allelic frequencies for the 1298C variant were 35.6% in sprint-strength athletes (OR 1.18 [1.02-1.36], P = 0.024 vs. controls) and 38.6% in strength athletes (OR 1.34 [1.10-1.64], P = 0.003 vs. controls). The results of the initial and repetition studies as well as the combined analysis suggest that the functional 1298A>C polymorphism in the MTHFR gene is associated with athletic status. The presence of the C allele seems to be beneficial in sprint-strength and strength athletes. It needs to be established whether and to what extent this effect is mediated by alteration in DNA methylation status

Side Chain Hydrophobicity Modulates Therapeutic Activity and Membrane Selectivity of Antimicrobial Peptide Mastoparan-X

The discovery of new anti-infective compounds is stagnating and multi-resistant bacteria continue to emerge, threatening to end the "antibiotic era". Antimicrobial peptides (AMPs) and lipo-peptides such as daptomycin offer themselves as a new potential class of antibiotics; however, further optimization is needed if AMPs are to find broad use as antibiotics. In the present work, eight analogues of mastoparan-X (MPX) were investigated, having side chain modifications in position 1, 8 and 14 to modulate peptide hydrophobicity. The self-association properties of the peptides were characterized, and the peptide-membrane interactions in model membranes were compared with the bactericidal and haemolytic properties. Alanine substitution at position 1 and 14 resulted in higher target selectivity (red blood cells versus bacteria), but also decreased bactericidal potency. For these analogues, the gain in target selectivity correlated to biophysical parameters showing an increased effective charge and reduction in the partitioning coefficient for membrane insertion. Introduction of an unnatural amino acid, with an octyl side chain by amino acid substitution, at positions 1, 8 and 14 resulted in increased bactericidal potency at the expense of radically reduced membrane target selectivity. Overall, optimized membrane selectivity or bactericidal potency was achieved by changes in side chain hydrophobicity of MPX. However, enhanced potency was achieved at the expense of selectivity and vice versa in all cases

Panethnic Differences in Blood Pressure in Europe: A Systematic Review and Meta-Analysis

BACKGROUND: People of Sub Saharan Africa (SSA) and South Asians(SA) ethnic minorities living in Europe have higher risk of stroke than native Europeans(EU). Study objective is to provide an assessment of gender specific absolute differences in office systolic(SBP) and diastolic(DBP) blood pressure(BP) levels between SSA, SA, and EU. METHODS AND FINDINGS: We performed a systematic review and meta-analysis of observational studies conducted in Europe that examined BP in non-selected adult SSA, SA and EU subjects. Medline, PubMed, Embase, Web of Science, and Scopus were searched from their inception through January 31st 2015, for relevant articles. Outcome measures were mean SBP and DBP differences between minorities and EU, using a random effects model and tested for heterogeneity. Twenty-one studies involving 9,070 SSA, 18,421 SA, and 130,380 EU were included. Compared with EU, SSA had higher values of both SBP (3.38 mmHg, 95% CI 1.28 to 5.48 mmHg; and 6.00 mmHg, 95% CI 2.22 to 9.78 in men and women respectively) and DBP (3.29 mmHg, 95% CI 1.80 to 4.78; 5.35 mmHg, 95% CI 3.04 to 7.66). SA had lower SBP than EU(-4.57 mmHg, 95% CI -6.20 to -2.93; -2.97 mmHg, 95% CI -5.45 to -0.49) but similar DBP values. Meta-analysis by subgroup showed that SA originating from countries where Islam is the main religion had lower SBP and DBP values than EU. In multivariate meta-regression analyses, SBP difference between minorities and EU populations, was influenced by panethnicity and diabetes prevalence. CONCLUSIONS: 1) The higher BP in SSA is maintained over decades, suggesting limited efficacy of prevention strategies in such group in Europe;2) The lower BP in Muslim populations suggests that yet untapped lifestyle and behavioral habits may reveal advantages towards the development of hypertension;3) The additive effect of diabetes, emphasizes the need of new strategies for the control of hypertension in groups at high prevalence of diabetes

Perevarimost' smesejj s raznym kolichestvom pshenichnojj solomy obrabotannojj edkim natriem opredelena na bychkakh

Feed mixtures containing different amounts of untreated and NaOH - treated wheat strau were fed to young bulls. The wheat strau was treated with 4.5 kg NaOH on 100 kg straw (dry matter basis). For the feed mixtures containing up to 40% (5, 20, 40%) untreated and NaOH - treated straw coefficients of digestibility were not significantly different. The feed mixtures containing above 40% NaOH - treated straw (50%) showed the improvement of digestibility by 4 to 7 units.На основе опытов проведённых на бычках (220 - 25О кг) установлено переваримость смесей с применением соломы обработанной едким натрием (4,5 кг. NаОН на 100 кг соломы) и не обработанной. Установлено, что переваримость питательных веществ из смесей с учётом соломы обработанной едким натрием и не обработанной натриевой щелочью похожа, при условии, что количество соломы в смеси не превышает 40%. Установлено более высокие коэффициенты переваримости для смесей, в которых количество соломы обработанно едким натрием было выше чем 40%