Young transgenic hMTH1 mice are protected against dietary fat‐induced metabolic stress—implications for enhanced longevity

hMTH1 protects against mutation during oxidative stress. It degrades 8‐oxodGTP to exclude potentially mutagenic oxidized guanine from DNA. hMTH1 expression is linked to ageing. Its downregulation in cultured cells accelerates RAS‐induced senescence, and its overexpression in hMTH1‐Tg mice extends lifespan. In this study, we analysed the effects of a brief (5 weeks) high‐fat diet challenge (HFD) in young (2 months old) and adult (7 months old) wild‐type (WT) and hMTH1‐Tg mice. We report that at 2 months, hMTH1 overexpression ameliorated HFD‐induced weight gain, changes in liver metabolism related to mitochondrial dysfunction and oxidative stress. It prevented DNA damage as quantified by a comet assay. At 7 months old, these HFD‐induced effects were less severe and hMTH1‐Tg and WT mice responded similarly. hMTH1 overexpression conferred lifelong protection against micronucleus induction, however. Since the canonical activity of hMTH1 is mutation prevention, we conclude that hMTH1 protects young mice against HFD by reducing genome instability during the early period of rapid growth and maximal gene expression. hMTH1 protection is redundant in the largely non‐growing, differentiated tissues of adult mice. In hMTH1‐Tg mice, expression of a less heavily mutated genome throughout life provides a plausible explanation for their extended longevity.     

Preferring thin people does not imply derogating fat people. A rasch analysis of the implicit weight attitude

Objective:

The meaning of the implicit weight attitude in individuals of different weight by distinguishing the contribution of positive and negative associations to the overall measure was investigated.

Design and Methods:

The implicit weight attitude was assessed using the Implicit Association Test. A Rasch model was used to identify which stimuli most affected the implicit measure. Explicit attitudes were assessed with a thin‐fat preference scale, and thermometer scales for both thin and fat people. The sample consists of 510 individuals categorized according to their BMI.

Results and Conclusion:

A significant implicit preference for thin relative to fat people was observed in all weight groups. In normal weight and obese individuals, the preference was mostly affected by positive stimuli (more easily associated with thin than with fat people). In underweight individuals, the preference was mostly guided by positive (more easily associated with thin than with fat people) and negative (more easily associated with fat than with thin people) stimuli. In overweight individuals, all stimuli contributed to the preference in a similar way. In all weight groups, the implicit weight attitude correlated with the explicit preference and/or the thin thermometer, whereas it never correlated with the fat thermometer. A pro‐thin bias was observed in normal weight and obese individuals, whereas both a pro‐thin and an anti‐fat bias were observed in underweight individuals. A clear preference for thin people relative to fat people was observed in overweight individuals. Therefore, uncritically interpreting the implicit preference for thin people as a sign of derogating fat people might be misleading.     

Use of conditional distributions in the analysis of ion channel recordings

A method to test the Markov nature of ion channel gating is proposed. It makes use of singly and doubly conditional distributions. The application of this method to recordings from single BK channels provides evidence that at least two states of the underlying kinetic scheme are left at a constant rate. Moreover, the probabilities, when leaving a state, of reaching another given state are shown to be constant for all the states of the system. Offprint requests to: D. Petracchi     

On the frequency of telomeric chromosomal changes induced by culture conditions suitable for fragile X expression

Summary Under culture conditions suitable for the expression of the fragile site Xq27, nonspecific telomeric structural changes similar to the specific fra(X) formation occurred apparently on every chromosome arm. Significant differences between individuals seem to exist. The total frequency of nonspecific terminal lesions not located on the long arm of the X chromosome was 0.22±0.17 per cell in 37 cultures examined. If telomeric lesions on Xq occur in more than 0.7% of the cells from a single culture in males and more than 1.5% of the cells from single culture in females, then this probably indicates a specific fra(X) expression. Lower percentages may be the result of nonspecific telomeric structural changes in Xq. These are expected to occur in the normal X as well and may, therefore, give rise to false positive diagnoses in the detection of hemi-, hetero-, and perhaps also homozygous fra(X) carriers.     

Coupled and uncoupled Markov systems: a possible way to distinguish between them

The conditional distributions of openings and closings are computed for Markov schemes with two open and two closed states and with different pathways connecting the open and closed aggregates. The computation is performed for uncoupled schemes by directly applying the probability laws and by using a convolution algorithm for coupled schemes. The results show that, for coupled schemes, conditional distributions can be nonmonotonic functions of the dwell time duration. Simulations, illustrating how the difference between coupled and uncoupled models can be detected, are also reported.     

The self-inhibited leaky integrator: Transfer functions and steady state relations

We analyse a model for neural activity including forgetting and self-inhibition processes. The analysis concerns the static and dynamic performances. The theoretical predictions are compared with previously published experimental data on the neural encoding in the ommatidia of the Limulus lateral eye. We conclude that the analysed model could reproduce the experimental behaviour, but different models cannot be excluded. Moreover an independent normalisation factor has to be assumed to account for the experimental gains.     

Spike amplitude modulation at high stimulation frequencies

Summary A technique of mathematical analysis has been developed for studying spike amplitude variations, during natural sinusoidal stimulation. This technique is suitable even when stimulation frequency is of the same order as, or higher than, the cell firing rate.We used this technique for the cat's retinal ganglion cells. The results agree with the previous ones (Gestri et al., 1967) at low stimulation frequencies and show that the spike amplitude modulation occur even at high frequencies, the phase shift between spike amplitude and firing probability being a function of the stimulation frequency.     

Impact of long-term cropping of glyphosate-resistant transgenic soybean [<Emphasis Type="Italic">Glycine max</Emphasis> (L.) Merr.] on soil microbiome

The transgenic soybean [Glycine max (L.) Merrill] occupies about 80 % of the global area cropped with this legume, the majority comprising the glyphosate-resistant trait (Roundup Ready^®, GR or RR). However, concerns about possible impacts of transgenic crops on soil microbial communities are often raised. We investigated soil chemical, physical and microbiological properties, and grain yields in long-term field trials involving conventional and nearly isogenic RR transgenic genotypes. The trials were performed at two locations in Brazil, with different edaphoclimatic conditions. Large differences in physical, chemical and classic microbiological parameters (microbial biomass of C and N, basal respiration), as well as in grain production were observed between the sites. Some phyla (Proteobacteria, Actinobacteria, Acidobacteria), classes (Alphaproteobacteria, Actinomycetales, Solibacteres) and orders (Rhizobiales, Burkholderiales, Myxococcales, Pseudomonadales), as well as some functional subsystems (clustering-based subsystems, carbohydrates, amino acids and protein metabolism) were, in general, abundant in all treatments. However, bioindicators related to superior soil fertility and physical properties at Londrina were identified, among them a higher ratio of Proteobacteria:Acidobacteria. Regarding the transgene, the metagenomics showed differences in microbial taxonomic and functional abundances, but lower in magnitude than differences observed between the sites. Besides the site-specific differences, Proteobacteria, Firmicutes and Chlorophyta were higher in the transgenic treatment, as well as sequences related to protein metabolism, cell division and cycle. Although confirming effects of the transgenic trait on soil microbiome, no differences were recorded in grain yields, probably due to the buffering capacity associated with the high taxonomic and functional microbial diversity observed in all treatments.