Browsing by Author "Nguyen, A"

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    Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake
    (American Association for the Advancement of Science (AAAS), 2023-11-10) Ferrari, A; Whang, E; Xiao, X; Kennelly, JP; Romartinez-Alonso, B; Mack, JJ; Weston, T; Chen, K; Kim, Y; Tol, MJ; Bideyan, L; Nguyen, A; Gao, YJ; Cui, LJ; Bedard, AH; Sandhu, J; Lee, SD; Fairall, L; Williams, KJ; Song, WX; Munguia, P; Russell, RA; Martin, MG; Jung, ME; Jiang, H; Schwabe, JWR; Young, SG; Tontonoz, P
    Intestinal absorption is an important contributor to systemic cholesterol homeostasis. Niemann-Pick C1 Like 1 (NPC1L1) assists in the initial step of dietary cholesterol uptake, but how cholesterol moves downstream of NPC1L1 is unknown. We show that Aster-B and Aster-C are critical for nonvesicular cholesterol movement in enterocytes. Loss of NPC1L1 diminishes accessible plasma membrane (PM) cholesterol and abolishes Aster recruitment to the intestinal brush border. Enterocytes lacking Asters accumulate PM cholesterol and show endoplasmic reticulum cholesterol depletion. Aster-deficient mice have impaired cholesterol absorption and are protected against diet-induced hypercholesterolemia. Finally, the Aster pathway can be targeted with a small-molecule inhibitor to manipulate cholesterol uptake. These findings identify the Aster pathway as a physiologically important and pharmacologically tractable node in dietary lipid absorption. © 2023 The Authors, exclusive licensee American Association for the Advancement of Science.
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    Test-retest reliability and inter scanner variability of 11C-raclopride striatal binding potentials between two INVEON PET/CT imaging systems for naïve Sprague Dawley rats
    (Wiley, 2014-04-16) Callaghan, PD; Zahra, D; Wimberley, CA; Arthur, A; Rahardjo, GL; Hamze, H; Davis, E; Nguyen, A; Boisson, F; Perkins, G; Pascali, G; Reilhac, A; Grégoire, MC
    Background: 11C-raclopride is a routine tracer for quantification of dopamine D2 receptors in neurological and psychiatric disease. D2 imaging in key longitudinal models has significant utility of understanding mechanisms and therapeutic interventions. Aims: Optimisation of preclinical imaging and data analysis protocols for 11C-raclopride in rat brain. Methods: a) Test-retest reliability: Naïve male Sprague Dawley rats (n = 6) underwent test-retest assessment of binding potential variability, with two scans, 1 week apart. Rats were anaesthetised (1–5% isoflurane) and received 11C-raclopride (>0.1 nmol, 20–40 MBq) during 1 hour image acquisition (Siemens Inveon PET/CT), followed by a 10 minute CT scan. b) Assessment of the intersystem variability of the INVEON scanners (n = 12). Test-retest experiments were performed on a second INVEON system. c) Assessment of inter system variability with arterial blood sampling (n = 5). Acquisitions were performed (as above) with prior femoral artery cannulation: 23 blood samples (∼30 ul) were collected during PET acquisition, and plasma metabolite corrected input functions generated. PET list mode data were histogrammed (23 frames) and reconstructed with 2D filtered backprojection algorithm. The impact of some post-reconstruction image processing techniques, such iterative deconvolution of the image and data denoising techniques, onto the accuracy and reliability of the computed parameter of interest were also investigated. Binding potential parametric maps were calculated from the dynamic PET data (using either a standard reference tissue modelling using the cerebellum TAC (test-retest), and or a 2 compartment kinetic modelling with input function). Preliminary results: Significant improvements were seen for tissue activity data after denoising /iterative deconvolution (see figure). Analysis of binding potential data are currently in progress. Conclusion: Assessment of within and intersystem variability will aid the appropriate statistical design of future longitudinal 11C-raclopride imaging studies. Improvements from post-reconstruction image processing techniques show significant benefits. © 1999-2022 John Wiley & Sons, Inc.
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    Top-down patterning of topological surface and edge states using a focused ion beam
    (Springer Nature, 2023-03-27) Bake, A; Zhang, Q; Ho, CS; Causer, GL; Zhao, WY; Yue, ZJ; Nguyen, A; Akhgar, G; Karel, J; Mitchell, DRG; Pastuovic, Z; Lewis, RA; Cole, JH; Nancarrow, M; Wang, XL; Cortie, DL
    The conducting boundary states of topological insulators appear at an interface where the characteristic invariant ℤ2 switches from 1 to 0. These states offer prospects for quantum electronics; however, a method is needed to spatially-control ℤ2 to pattern conducting channels. It is shown that modifying Sb2Te3 single-crystal surfaces with an ion beam switches the topological insulator into an amorphous state exhibiting negligible bulk and surface conductivity. This is attributed to a transition from ℤ2 = 1 → ℤ2 = 0 at a threshold disorder strength. This observation is supported by density functional theory and model Hamiltonian calculations. Here we show that this ion-beam treatment allows for inverse lithography to pattern arrays of topological surfaces, edges and corners which are the building blocks of topological electronics. Open Access This article is licensed under a Creative Commons Attribution 4.0 © Crown Copyright 2023
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    Transport measurements in porous Bi2Te3 thin films
    (American Physical Society, 2022-03-16) Akhgar, G; Nguyen, A; Cortie, DL; Bake, A; Zhao, WY; Liu, C; Fuhrer, MS; Culcer, D; Hamilton, AR; Edmonds, MT; Karel, J
    Recent theoretical work has predicted the existence of disordered topological insulators , however, minimal experimental work has been conducted on disordered TIs. Here we used molecular-beam epitaxy (MBE) to grow Bi2Te3 thin films that were comprised of nanocrystals embedded in an amorphous matrix. Further disorder was introduced through Ne ion irradiation which produced porosity in the films. In this talk we will present magnetoresistance measurements on porous Bi2Te3, where weak anti-localisation (WAL) was observed. The magnetoresistance curves were fitted using a Dirac Fermion model specifically derived to model weak antilocalization in TIs. Our results also show that the temperature dependence of the phase coherence length in porous Bi2Te3, with an increased surface to volume ratio, exhibits 2D-like transport.