Thorium / Uranium Mixed Oxide Nanocrystals: Synthesis, Structural Characterization and Magnetic Properties

One of the primary aims of the actinide community within nanoscience is to develop a good understanding similar to what is currently the case for stable elements. As a consequence, efficient, reliable and versatile synthesis techniques dedicated to the formation of new actinide-based nano-objects (e.g., nanocrystals) are necessary. Hence, a “library” dedicated to the preparation of various actinidebased nanoscale building blocks is currently being developed. Nanoscale building blocks with tunable sizes, shapes and compositions are of prime importance. So far, the non-aqueous synthesis method in highly coordinating organic media is the only approach which has demonstrated the capability to provide size and shape control of actinide-based nanocrystals (both for thorium and uranium, and recently extended to neptunium and plutonium). In this paper, we demonstrate that the non-aqueous approach is also well adapted to control the chemical composition of the nanocrystals obtained when mixing two different actinides. Indeed, the controlled hot co-injection of thorium acetylacetonate and uranyl acetate (together with additional capping agents) into benzyl ether can be used to synthesize thorium/uranium mixed oxide nanocrystals covering the full compositional spectrum. Additionally, we found that both size and shape are modified as a function of the thorium:uranium ratio. Finally, the magnetic properties of the different thorium/uranium mixed oxide nanocrystals were investigated. Contrary to several reports, we did not observe any ferromagnetic behavior. As a consequence, ferromagnetism cannot be described as a universal feature of nanocrystals of non-magnetic oxides as recently claimed in the literature.JRC.E.5 - Nuclear chemistr

Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.

We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease

Ret receptor tyrosine kinase sustains proliferation and tissue maturation in intestinal epithelia.

Expression of the Ret receptor tyrosine kinase is a defining feature of enteric neurons. Its importance is underscored by the effects of its mutation in Hirschsprung disease, leading to absence of gut innervation and severe gastrointestinal symptoms. We report a new and physiologically significant site of Ret expression in the intestine: the intestinal epithelium. Experiments in Drosophila indicate that Ret is expressed both by enteric neurons and adult intestinal epithelial progenitors, which require Ret to sustain their proliferation. Mechanistically, Ret is engaged in a positive feedback loop with Wnt/Wingless signalling, modulated by Src and Fak kinases. We find that Ret is also expressed by the developing intestinal epithelium of mice, where its expression is maintained into the adult stage in a subset of enteroendocrine/enterochromaffin cells. Mouse organoid experiments point to an intrinsic role for Ret in promoting epithelial maturation and regulating Wnt signalling. Our findings reveal evolutionary conservation of the positive Ret/Wnt signalling feedback in both developmental and homoeostatic contexts. They also suggest an epithelial contribution to Ret loss-of-function disorders such as Hirschsprung disease

Sex differences in intestinal carbohydrate metabolism promote food intake and sperm maturation

Physiology and metabolism are often sexually dimorphic, but the underlying mechanisms remain incompletely understood. Here, we use the intestine of Drosophila melanogaster to investigate how gut-derived signals contribute to sex differences in whole-body physiology. We find that carbohydrate handling is male-biased in a specific portion of the intestine. In contrast to known sexual dimorphisms in invertebrates, the sex differences in intestinal carbohydrate metabolism are extrinsically controlled by the adjacent male gonad, which activates JAK-STAT signalling in enterocytes within this intestinal portion. Sex reversal experiments establish roles for this malebiased intestinal metabolic state in controlling food intake and sperm production through gutderived citrate. Our work uncovers a male gonad-gut axis coupling diet and sperm production, and reveals that metabolic communication across organs is physiologically significant. The instructive role of citrate in inter-organ communication may be significant in more biological contexts than previously recognised

Synthesis of transuranium-based nanocrystals via the thermal decomposition of actinyl nitrates

In this communication, we report on the use of easily accessible actinide precursors to synthesize actinide oxide nanocrystals. Uranyl and neptunyl nitrates have been successfully used as starting materials in the non-aqueous synthesis of AnO2 (An = U, Np) nanocrystals. This communication reports for the first time on the formation of transuranium-based nanocrystals.JRC.E.5 - Nuclear chemistr

Opposing Roles of apolipoprotein E in aging and neurodegeneration

Apolipoprotein E (APOE) effects on brain function remain controversial. Removal of APOE not only impairs cognitive functions but also reduces neuritic amyloid plaques in mouse models of Alzheimer’s disease (AD). Can APOE simultaneously protect and impair neural circuits? Here, we dissociated the role of APOE in AD versus aging to determine its effects on neuronal function and synaptic integrity. Using two-photon calcium imaging in awake mice to record visually evoked responses, we found that genetic removal of APOE improved neuronal responses in adult APP/PSEN1 mice (8–10 mo). These animals also exhibited fewer neuritic plaques with less surrounding synapse loss, fewer neuritic dystrophies, and reactive glia. Surprisingly, the lack of APOE in aged mice (18–20 mo), even in the absence of amyloid, disrupted visually evoked responses. These results suggest a dissociation in APOE’s role in AD versus aging: APOE may be neurotoxic during early stages of amyloid deposition, although being neuroprotective in latter stages of aging