Side chain to main chain hydrogen bonds stabilize a polyglutamine helix in a transcription factor

Polyglutamine (polyQ) tracts are low-complexity regions and their expansion is linked to certain neurodegenerative diseases. Here the authors combine experimental and computational approaches to find that the length of the androgen receptor polyQ tract correlates with its helicity and show that the polyQ helical structure is stabilized by hydrogen bonds between the Gln side chains and main chain carbonyl groups

Study of an intrinsically safe infrastructure for training and research on nuclear technologies

Within European Partitioning & Transmutation research programs, infrastructures specifically dedicated to the study of fundamental reactor physics and engineering parameters of future fast-neutron-based reactors are very important, being some of these features not available in present zero-power prototypes. This presentation will illustrate the conceptual design of an Accelerator-Driven System with high safety standards, but ample flexibility for measurements. The design assumes as base option a 70MeV, 0.75mA proton cyclotron, as the one which will be installed at the INFN National Laboratory in Legnaro, Italy and a Beryllium target, with Helium gas as core coolant. Safety is guaranteed by limiting the thermal power to 200 kW, with a neutron multiplication coefficient around 0.94, loading the core with fuel containing Uranium enriched at 20% inserted in a solid-lead diffuser. The small decay heat can be passively removed by thermal radiation from the vessel. Such a system could be used to study, among others, some specific aspects of neutron diffusion in lead, beam-core coupling, target cooling and could serve as a training facility

Prelesional arterial endothelial phenotypes in hypercholesterolemia: universal ABCA1 upregulation contrasts with region-specific gene expression in vivo

Atherosclerosis originates as focal arterial lesions having a predictable distribution to regions of bifurcations, branches, and inner curvatures where blood flow characteristics are complex. Distinct endothelial phenotypes correlate with regional hemodynamics. We propose that systemic risk factors modify regional endothelial phenotype to influence focal susceptibility to atherosclerosis. Transcript profiles of freshly isolated endothelial cells from three atherosusceptible and three atheroprotected arterial regions in adult swine were analyzed to determine the initial prelesional effects of hypercholesterolemia on endothelial phenotypes in vivo. Cholesterol efflux transporter ATP-binding cassette transporter A1 (ABCA1) was upregulated at all sites in response to short-term high-fat diet. Proinflammatory and antioxidative endothelial gene expression profiles were induced in atherosusceptible and atheroprotected regions, respectively. However, markers for endoplasmic reticulum stress, a signature of susceptible endothelial phenotype, were not further enhanced by brief hypercholesterolemia. Both region-specific and ubiquitous (ABCA1) phenotype changes were identified as early prelesional responses of the endothelium to hypercholesterolemia

Radiopaque drug-eluting beads for transcatheter embolotherapy: Experimental study of drug penetration and coverage in swine

Purpose: To determine local doxorubicin levels surrounding radiopaque drug-eluting beads (DEBs) in normal swine liver and kidney following transcatheter arterial chemoembolization. The influence of bead size (70150 μm or 100300 μm) was compared with regard to tissue penetration and spatial distribution of the bead, as well as eventual drug coverage (ie, amount of tissue exposed to drug). Materials and Methods: Radiopaque DEBs were synthesized by suspension polymerization followed by incorporation of iodized oil and doxorubicin. Chemoembolization of swine liver and kidney was performed under fluoroscopic guidance. Three-dimensional tissue penetration of imageable DEBs was investigated ex vivo with microcomputed tomography (microCT). Drug penetration from the bead surface and drug coverage was evaluated with epifluorescence microscopy, and cellular localization of doxorubicin was evaluated with confocal microscopy. Necrosis was evaluated with hematoxylin and eosin staining. Results: MicroCT demonstrated that 70150-μm DEBs were present in more distal arteries and located in a more frequent and homogeneous spatial distribution. Tissue penetration of doxorubicin from the bead appeared similar (∼300 μm) for both DEBs, with a maximum tissue drug concentration at 1 hour coinciding with nuclear localization of doxorubicin. The greater spatial frequency of the 70150-μm DEBs resulted in approximately twofold improved drug coverage in kidney. Cellular death is predominantly observed around the DEBs beginning at 8 hours, but increased at 24 and 168 hours. Conclusions: Smaller DEBs penetrated further into targeted tissue (ie, macroscopic) with a higher spatial density, resulting in greater and more uniform drug coverage (ie, microscopic) in swine. © 2012 SIR

Development of Imageable Beads for Transcatheter Embolotherapy

Purpose: To develop and characterize radiopaque embolization microspheres capable of in vivo detection with intraprocedural fluoroscopy and computed tomography (CT) imaging and to evaluate their spatial distribution inside target tissues during and after transcatheter embolization. Materials and Methods: Polyvinyl alcohol hydrogel microspheres were loaded with Lipiodol and examined for iodine content, stability of loading, and conspicuity with fluoroscopy and CT in vitro. Transcatheter embolization of swine liver and kidney was performed with the radiopaque microspheres and spatial distribution was evaluated with intraprocedural fluoroscopy and CT. Ex vivo evaluation was performed with light microscopy and micro-CT. Results: In vitro analyses demonstrated that radiopaque microspheres could be loaded with sufficient iodine content to be detected with routine fluoroscopy and CT imaging and that such loading was relatively stable. Radiopaque microspheres were visible in vivo with fluoroscopy and CT during transcatheter embolization. CT imaging during embolization procedures demonstrated a dose-dependent relationship in the number and size of visualized embolized arteries. Imaging features of radiopaque microsphere distribution inside target tissues correlated well with ex vivo light microscopic and micro-CT evaluation of microsphere distribution. Conclusions: Radiopaque embolization microspheres are visualized during transcatheter embolization with routine intraprocedural fluoroscopy and CT. These radiopaque microspheres provided the three-dimensional spatial distribution of embolic material inside target organs during the procedure, and therefore can provide real-time intraprocedural feedback for the interventional radiologist. These microspheres may be useful for demonstrating the influence of material and technical variability in transcatheter embolization in addition to providing intraprocedural identification of tissue at risk of undertreatment. © 2010 SIR