Determination of glucose exchange rates and permeability of erythrocyte membrane in preeclampsia and subsequent oxidative stress-related protein damage using dynamic-<Superscript>19</Superscript>F-NMR

The cause of the pregnancy condition preeclampsia (PE) is thought to be endothelial dysfunction caused by oxidative stress. As abnormal glucose tolerance has also been associated with PE, we use a fluorinated-mimic of this metabolite to establish whether any oxidative damage to lipids and proteins in the erythrocyte membrane has increased cell membrane permeability. Data were acquired using ¹⁹F Dynamic-NMR (DNMR) to measure exchange of 3-fluoro-3-deoxyglucose (3-FDG) across the membrane of erythrocytes from 10 pregnant women (5 healthy control women, and 5 from women suffering from PE). Magnetisation transfer was measured using the 1D selective inversion and 2D EXSY pulse sequences, over a range of time delays. Integrated intensities from these experiments were used in matrix diagonalisation to estimate the values of the rate constants of exchange and membrane permeability. No significant differences were observed for the rate of exchange of 3-FDG and membrane permeability between healthy pregnant women and those suffering from PE, leading us to conclude that no oxidative damage had occurred at this carrier-protein site in the membrane.     

The total burden of rare,non-synonymous exome genetic variants is not associated with childhood or late-life cognitive ability

Human cognitive ability shows consistent, positive associations with fitness components across the life-course. Underlying genetic variation should therefore be depleted by selection, which is not observed. Genetic variation in general cognitive ability (intelligence) could be maintained by a mutation–selection balance, with rare variants contributing to its genetic architecture. This study examines the association between the total number of rare stop-gain/loss, splice and missense exonic variants and cognitive ability in childhood and old age in the same individuals. Exome array data were obtained in the Lothian Birth Cohorts of 1921 and 1936 (combined N = 1596). General cognitive ability was assessed at age 11 years and in late life (79 and 70 years, respectively) and was modelled against the total number of stop-gain/loss, splice, and missense exonic variants, with minor allele frequency less than or equal to 0.01, using linear regression adjusted for age and sex. In both cohorts and in both the childhood and late-life models, there were no significant associations between rare variant burden in the exome and cognitive ability that survived correction for multiple testing. Contrary to our a priori hypothesis, we observed no evidence for an association between the total number of rare exonic variants and either childhood cognitive ability or late-life cognitive ability.     

Small reactive carbonyl compounds as tissue lipid oxidation products; and the mechanisms of their formation thereby

Small reactive carbonyl compounds (RCCs) such as formaldehyde, acetaldehyde, acrolein, crotonaldehyde, glyoxal, methylglyoxal, glycolaldehyde, glycidaldehyde, and 2-butene-1,4-dial are involved in carbonyl and oxidative stress-related physiological disorders. While some evidence indicates that lipid oxidation could be an important source of these compounds in vivo, this has sometimes been doubted because the mechanisms of their formation thereby are poorly understood. Here, representative literature supporting the significant formation of these compounds during lipid oxidation under physiologically relevant conditions are highlighted, and the strengths and weaknesses of previously proposed mechanisms of their formation thereby are considered. In addition, based on the current understanding of lipid oxidation chemistry, some new pathways of their formation are suggested. The suggested pathways also generate 4-hydroxy-2-butenal, a precursor of the carcinogen furan, whose endogenous formation in tissues has hitherto not been seriously considered.     

Factors influencing the fecundity of Moniliformis moniliformis (Acanthocephala): constant diet and varied dose

Aspects of the reproductive performance of Moniliformis moniliformis were investigated in rats allowed to feed ad libitum on a purified diet containing 1% (w/w) fructose as an energy source for the worms. The rats were infected with either 10, 20, 40 or 80 cystacanths each with the intention of investigating density-dependent effects on worm fecundity. The establishment of the worms in the gut was independent of dose, but survival, growth and reproductive performance generally were shown to be related to the infective dose given to the rats. The effects could not be related to the absolute numbers of worms present in the small intestine at post-mortem examination. In general, some unidentified regulatory process appeared to operate to create severe density-dependence in survival so that surviving parasites were not present in numbers expected to generate competition. Attainment of sexual maturity, growth and the production of mature eggs by worms from rats given doses of 80 cystacanths each were delayed compared with worms from rats given the other doses, but eventually the performance of the high-dose worms caught up. Worms attached more anteriorly in the small intestine grew bigger and produced more mature eggs. Possible mechanisms responsible for the observed effects are discussed.