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

The Population Structure of Acinetobacter baumannii: Expanding Multiresistant Clones from an Ancestral Susceptible Genetic Pool

Outbreaks of hospital infections caused by multidrug resistant Acinetobacter baumannii strains are of increasing concern worldwide. Although it has been reported that particular outbreak strains are geographically widespread, little is known about the diversity and phylogenetic relatedness of A. baumannii clonal groups. Sequencing of internal portions of seven housekeeping genes (total 2,976 nt) was performed in 154 A. baumannii strains covering the breadth of known diversity and including representatives of previously recognized international clones, and in 19 representatives of other Acinetobacter species. Restricted amounts of diversity and a star-like phylogeny reveal that A. baumannii is a genetically compact species that suffered a severe bottleneck in the recent past, possibly linked to a restricted ecological niche. A. baumannii is neatly demarcated from its closest relative (genomic species 13TU) and other Acinetobacter species. Multilocus sequence typing analysis demonstrated that the previously recognized international clones I to III correspond to three clonal complexes, each made of a central, predominant genotype and few single locus variants, a hallmark of recent clonal expansion. Whereas antimicrobial resistance was almost universal among isolates of these and a novel international clone (ST15), isolates of the other genotypes were mostly susceptible. This dichotomy indicates that antimicrobial resistance is a major selective advantage that drives the ongoing rapid clonal expansion of these highly problematic agents of nosocomial infections

Three pillars of sustainability: in search of conceptual origins

The three-pillar conception of (social, economic and environmental) sustainability, commonly represented by three intersecting circles with overall sustainability at the centre, has become ubiquitous. With a view of identifying the genesis and theoretical foundations of this conception, this paper reviews and discusses relevant historical sustainability literature. From this we find that there is no single point of origin of this three-pillar conception, but rather a gradual emergence from various critiques in the early academic literature of the economic status quo from both social and ecological perspectives on the one hand, and the quest to reconcile economic growth as a solution to social and ecological problems on the part of the United Nations on the other. The popular three circles diagram appears to have been first presented by Barbier (Environ Conserv 14:101, doi: 10.1017/s0376892900011449, 1987), albeit purposed towards developing nations with foci which differ from modern interpretations. The conceptualisation of three pillars seems to predate this, however. Nowhere have we found a theoretically rigorous description of the three pillars. This is thought to be in part due to the nature of the sustainability discourse arising from broadly different schools of thought historically. The absence of such a theoretically solid conception frustrates approaches towards a theoretically rigorous operationalisation of ‘sustainability’