Spatial navigation deficits — overlooked cognitive marker for preclinical Alzheimer disease?

Detection of incipient Alzheimer disease (AD) pathophysiology is critical to identify preclinical individuals and target potentially disease-modifying therapies towards them. Current neuroimaging and biomarker research is strongly focused in this direction, with the aim of establishing AD fingerprints to identify individuals at high risk of developing this disease. By contrast, cognitive fingerprints for incipient AD are virtually non-existent as diagnostics and outcomes measures are still focused on episodic memory deficits as the gold standard for AD, despite their low sensitivity and specificity for identifying at-risk individuals. This Review highlights a novel feature of cognitive evaluation for incipient AD by focusing on spatial navigation and orientation deficits, which are increasingly shown to be present in at-risk individuals. Importantly, the navigation system in the brain overlaps substantially with the regions affected by AD in both animal models and humans. Notably, spatial navigation has fewer verbal, cultural and educational biases than current cognitive tests and could enable a more uniform, global approach towards cognitive fingerprints of AD and better cognitive treatment outcome measures in future multicentre trials. The current Review appraises the available evidence for spatial navigation and/or orientation deficits in preclinical, prodromal and confirmed AD and identifies research gaps and future research priorities

The epigenetic landscape of renal cancer

This is an accepted manuscript of an article published by Nature in Nature Reviews: Nephrology on 28/11/2016, available online: https://doi.org/10.1038/nrneph.2016.168 The accepted version of the publication may differ from the final published version.The majority of kidney cancers are associated with mutations in the von Hippel-Lindau gene and a small proportion are associated with infrequent mutations in other well characterized tumour-suppressor genes. In the past 15 years, efforts to uncover other key genes involved in renal cancer have identified many genes that are dysregulated or silenced via epigenetic mechanisms, mainly through methylation of promoter CpG islands or dysregulation of specific microRNAs. In addition, the advent of next-generation sequencing has led to the identification of several novel genes that are mutated in renal cancer, such as PBRM1, BAP1 and SETD2, which are all involved in histone modification and nucleosome and chromatin remodelling. In this Review, we discuss how altered DNA methylation, microRNA dysregulation and mutations in histone-modifying enzymes disrupt cellular pathways in renal cancers

Evolution of the design and fabrication of astrophysics targets for Turbulent Dynamo (TDYNO) experiments on OMEGA

lthough the overall function of a campaign’s primary target design may remain unchanged, the components and structure often evolve from one shot day to the next to better meet experimental goals. The target fabrication engineer’s involvement in this evolution can be important for advising modifications in order to improve and simplify assembly at the same time. Highly complex targets are constructed by General Atomics (GA) for astrophysics experiments conducted by the University of Chicago at the OMEGA laser facility. Several novel target components are fabricated, precision-assembled, and extensively measured in support of this campaign, and have evolved over the last three years to improve both the science and assembly. Examples include unique laser machined polyimide grids to enhance plasma mixing at target center, precision micromachined cylindrical shields that also act as component spacers, drawn glass target supports to suspend physics packages at critical distances, and tilted pinholes for collimated proton radiography. Target component fabrication and evolution details for this turbulent dynamics (TDYNO) campaign are presented, along with precision-assembly techniques, metrology methods, and considerations for future TDYNO experiments on OMEGA.</p

Evolution of the design and fabrication of astrophysics targets for Turbulent Dynamo (TDYNO) experiments on OMEGA

lthough the overall function of a campaign’s primary target design may remain unchanged, the components and structure often evolve from one shot day to the next to better meet experimental goals. The target fabrication engineer’s involvement in this evolution can be important for advising modifications in order to improve and simplify assembly at the same time. Highly complex targets are constructed by General Atomics (GA) for astrophysics experiments conducted by the University of Chicago at the OMEGA laser facility. Several novel target components are fabricated, precision-assembled, and extensively measured in support of this campaign, and have evolved over the last three years to improve both the science and assembly. Examples include unique laser machined polyimide grids to enhance plasma mixing at target center, precision micromachined cylindrical shields that also act as component spacers, drawn glass target supports to suspend physics packages at critical distances, and tilted pinholes for collimated proton radiography. Target component fabrication and evolution details for this turbulent dynamics (TDYNO) campaign are presented, along with precision-assembly techniques, metrology methods, and considerations for future TDYNO experiments on OMEGA.</p