Transcriptomic Analysis Highlights Time-specific Embryonic Adaptation of Mice to the Lack of PrP

The physiological function of the PrP remains largely elusive. Its invalidation does not affect mouse survival and induces subtle phenotypes. To potentially assess this conundrum, we first comparatively analyzed the adult brain transcriptome of wild-type mice with that of transgenic mice invalidated at this locus either at the zygotic (Zürich PrP0/0 mice) or adult stages (NFH-Cre-Lox mice). Only subtle differences could be evidenced in the adult brains following microarray and QPCR analyses. When performed at an early adult stage, neuronal Prnp disruption appeared to sequentially induce an oxidative stress response and a nervous system remodeling, but it involved a limited number of only slightly modified genes. In sharp contrast, analysis at early embryonic stages, 7.5 and 8.5 dpc, just after the suspected normal time set of the Prnp locus activation, led to a transient perturbation of the transcriptome involving a larger number of genes and pointing to potential pathways related to the PrP physiological function. Overall, our data suggests an early adaptation of the mouse to the potentially detrimental lack of PrP during embryogenesis while its presence is less influential or redundant at later developmental stages

Antifouling activity of macroalgal extracts on Fragilaria pinnata (Bacillariophyceae): a comparison with Diuron

International audienc

A review of economic evaluations of behavior change interventions: setting an agenda for research methods and practice

BACKGROUND: The objective of this study was to review methodological economic evaluations of lifestyle behavior change interventions (LBCIs) examine how they address methodological challenges for public health evaluation identified in the literature. METHODS: Pubmed and the NHS evaluation database were searched for published studies in six key areas behavior change: smoking, physical activity, dietary behavior, (illegal) use, alcohol use and sexual behavior. From included studies (n = 142), extracted data on general study characteristics, characteristics of the methodological quality and handling of methodological challenges. Economic evaluation evidence for LBCIs showed a number of weaknesses: study design and characteristics of evaluated interventions were not reported; methodological quality showed several shortcomings and addressing methodological challenges remained limited. CONCLUSIONS: findings of this review we propose an agenda for improving future support decision-making. Recommendations for practice include improving of essential study details and increasing adherence with good practice Recommendations for research methods focus on mapping out complex causal for modeling, developing measures to capture broader domains of community outcomes, testing methods for considering equity, identifying non-health sector costs and advancing methods for evidence synthesis

Amelioration of premature aging in mtDNA mutator mouse by exercise: the interplay of oxidative stress, PGC-1α, p53, and DNA damage. A hypothesis.

The mtDNA mutator mouse lacks the proofreading capacity of the sole mtDNA polymerase, leading to accumulation of somatic mtDNA mutations, and a profound premature aging phenotype including elevated oxidative stress and apoptosis, and reduced mitochondrial function. We have previously reported that endurance exercise alleviates the aging phenotype in the mutator mice, reduces oxidative stress, and enhances mitochondrial biogenesis. Here we summarize our findings, with the emphasis on the central role of p53 in these adaptations. We demonstrate that mtDNA in sedentary and exercised PolG mice carry similar amounts of mutations in muscle, but in addition to that sedentary mice have more non-mutational damage, which is mitigated by exercise. It follows therefore that the profound alleviation of the mtDNA mutator phenotype in muscle by exercise may not require a reduction in mtDNA mutational load, but rather a decrease of mtDNA damage and/or oxidative stress. We further hypothesize that the observed 'alleviation without a reduction of mutational load' implies that the oxidative stress in PolG muscle is maintained, at least in part, by the 'malicious cycle', a hypothetical positive feedback potentially driven by the 'transcriptional mutagenesis', that is the conversion of chemically modified nucleotides into mutant RNA bases by the mitochondrial RNA polymerase