The risk of developing neurodegenerative diseases increases with age. Although many of the molecular pathways regulating proteotoxic stress and longevity are well characterized, their contribution to disease susceptibility remains unclear. In this study, we describe a new Caenorhabditis elegans model of Machado-Joseph disease pathogenesis. Pan-neuronal expression of mutant ATXN3 leads to a polyQ-length dependent, neuron subtype-specific aggregation and neuronal dysfunction. Analysis of different neurons revealed a pattern of dorsal nerve cord and sensory neuron susceptibility to mutant ataxin-3 that was distinct from the aggregation and toxicity profiles of polyQ-alone proteins. This reveals that the sequences flanking the polyQ-stretch in ATXN3 have a dominant influence on cell-intrinsic neuronal factors that modulate polyQ-mediated pathogenesis. Aging influences the ATXN3 phenotypes which can be suppressed by the downregulation of the insulin/insulin growth factor-1-like signaling pathway and activation of heat shock factor-1.

A novel automatic 3D+time left ventricle (LV) segmentation framework is proposed for cardiac magnetic resonance (CMR) datasets. The proposed framework consists of three conceptual blocks to delineate both endo and epicardial contours throughout the cardiac cycle: (1) an automatic 2D mid-ventricular initialization and segmentation; (2) an automatic stack initialization followed by a 3D segmentation at the end-diastolic phase; and (3) a tracking procedure. Hereto, we propose to adapt the recent B-spline Explicit Active Surfaces (BEAS) framework to the properties of CMR images by integrating dedicated energy terms. Moreover, we extend the coupled BEAS formalism towards its application in 3D MR data by adapting it to a cylindrical space suited to deal with the topology of the image data. Furthermore, a fast stack initialization method is presented for efficient initialization and to enforce consistent cylindrical topology. Finally, we make use of an anatomically constrained optical flow method for temporal tracking of the LV surface. The proposed framework has been validated on 45 CMR datasets taken from the 2009 MICCAI LV segmentation challenge. Results show the robustness, efficiency and competitiveness of the proposed method both in terms of accuracy and computational load.

The most accurate results were achieved with two configurations: (1) the optical intraoral system with powder and (2) the open technique with splinted squared transfer copings, using polyether as impression material.