Treating hepatic steatosis and fibrosis by modulating mitochondrial pyruvate metabolism

A hepatic comorbidity of metabolic syndrome, known as nonalcoholic fatty liver disease (NAFLD), is increasing in prevalence in conjunction with the pandemics of obesity and diabetes. The spectrum of NAFLD ranges from simple hepatic fat accumulation to a more severe disease termed nonalcoholic steatohepatitis (NASH), involving inflammation, hepatocyte death, and fibrosis. Importantly, NASH is linked to a much higher risk of cirrhosis, liver failure, and hepatocellular carcinoma, as well as an increased risk for nonhepatic malignancies and cardiovascular disease. Interest in the understanding of the disease processes and search for treatments for the spectrum of NAFLD-NASH has increased exponentially, but there are no approved pharmacologic therapies. In this review, we discuss the existing literature supporting insulin-sensitizing thiazolidinedione compounds as potential drug candidates for the treatment of NASH. In addition, we put these results into new context by summarizing recent studies suggesting these compounds alter mitochondrial metabolism by binding and inhibiting the mitochondrial pyruvate carrier. Keywords: Nonalcoholic Steatohepatitis, Mitochondria, Pyruvate, Thiazolidinedion

Isolation & Characterization of Bacteria in the Built Environment: Measuring The Effect of Pharmaceuticals on Growth

This work reports the isolation and characterization of bacteria from the built environment at Gettysburg College in Gettysburg, PA. Surfaces of a water fountain on campus were swabbed and serially streaked to isolate multiple bacteria on R2A agar. Following multiple rounds of growth, the unknown microbial candidates were narrowed to two visibly­distinct organisms. Morphological characterization and phylogenetic identification based on 16S rDNA sequencing revealed that the isolates were Chryseobactierum hispalense and Microbacterium maritypicum. We report synergistic biofilm formation between Chryseobactierum hispalense and Microbacterium maritypicum. The contamination of drinking water with varying levels of personal care products and pharmaceuticals (PCPPs) is well documented. Additionally, these environmental pollutants and their derivatives affect aquatic life, as illustrated with effect of the antidepressant fluoxetine on mudsnails. To determine if previously reported contaminants affect freshwater bacteria, we assessed both planktonic growth and biofilm formation following exposure to nalidixic acid (non­fluorinated quinolone antibiotic), diphenhydramine (over­the­counter drug Benadryl), and fluoxetine (Prozac)

Evidence for an anomalous current phase relation in topological insulator Josephson junctions

Josephson junctions with topological insulator weak links can host low energy Andreev bound states giving rise to a current phase relation that deviates from sinusoidal behaviour. Of particular interest are zero energy Majorana bound states that form at a phase difference of $\pi$. Here we report on interferometry studies of Josephson junctions and superconducting quantum interference devices (SQUIDs) incorporating topological insulator weak links. We find that the nodes in single junction diffraction patterns and SQUID oscillations are lifted and independent of chemical potential. At high temperatures, the SQUID oscillations revert to conventional behaviour, ruling out asymmetry. The node lifting of the SQUID oscillations is consistent with low energy Andreev bound states exhibiting a nonsinusoidal current phase relation, coexisting with states possessing a conventional sinusoidal current phase relation. However, the finite nodal currents in the single junction diffraction pattern suggest an anomalous contribution to the supercurrent possibly carried by Majorana bound states, although we also consider the possibility of inhomogeneity.Comment: 6 pages, 4 figure

Phase Coherence and Andreev Reflection in Topological Insulator Devices

Topological insulators (TIs) have attracted immense interest because they host helical surface states. Protected by time-reversal symmetry, they are robust to non-magnetic disorder. When superconductivity is induced in these helical states, they are predicted to emulate p-wave pairing symmetry, with Majorana states bound to vortices. Majorana bound states possess non-Abelian exchange statistics which can be probed through interferometry. Here, we take a significant step towards Majorana interferometry by observing pronounced Fabry-Perot oscillations in a TI sandwiched between a superconducting and normal lead. For energies below the superconducting gap, we observe a doubling in the frequency of the oscillations, arising from the additional phase accumulated from Andreev reflection. When a magnetic field is applied perpendicular to the TI surface, a number of very sharp and gate-tunable conductance peaks appear at or near zero energy, which has consequences for interpreting spectroscopic probes of Majorana fermions. Our results demonstrate that TIs are a promising platform for exploring phase-coherent transport in a solid-state system.Comment: 9 pages, 7 figure

Dynamical Gate Tunable Supercurrents in Topological Josephson Junctions

Josephson junctions made of closely-spaced conventional superconductors on the surface of 3D topological insulators have been proposed to host Andreev bound states (ABSs) which can include Majorana fermions. Here, we present an extensive study of the supercurrent carried by low energy ABSs in Nb/Bi$_2$Se$_3$/Nb Josephson junctions in various SQUIDs as we modulate the carrier density in the Bi$_2$Se$_3$ barriers through electrostatic top gates. As previously reported, we find a precipitous drop in the Josephson current at a critical value of the voltage applied to the top gate. This drop has been attributed to a transition where the topologically trivial 2DEG at the surface is nearly depleted, causing a shift in the spatial location and change in nature of the helical surface states. We present measurements that support this picture by revealing qualitative changes in the temperature and magnetic field dependence of the critical current across this transition. In particular, we observe pronounced fluctuations in the critical current near total depletion of the 2DEG that demonstrate the dynamical nature of the supercurrent transport through topological low energy ABSs.Comment: 6 pages, 6 figure

Here Comes Tootsi

https://digitalcommons.library.umaine.edu/mmb-vp/1452/thumbnail.jp

Around The Map

https://digitalcommons.library.umaine.edu/mmb-ps/1370/thumbnail.jp

My Waltz Queen: Waltz Song

https://digitalcommons.library.umaine.edu/mmb-vp/2249/thumbnail.jp

Robust Fabry-Perot interference in dual-gated Bi2_2Se3_3 devices

We study Fabry-Perot interference in hybrid devices, each consisting of a mesoscopic superconducting disk deposited on the surface of a three-dimensional topological insulator. Such structures are hypothesized to contain protected zero modes known as Majorana fermions bound to vortices. The interference manifests as periodic conductance oscillations of magnitude $\sim 0.1$ $e^2/h$. These oscillations show no strong dependence on bulk carrier density or sample thickness, suggesting that they result from phase coherent transport in surface states. However, the Fabry-Perot interference can be tuned by both top and back gates, implying strong electrostatic coupling between the top and bottom surfaces of topological insulator.Comment: 5 pages, 3 figures. Accepted by Appl. Phys. Let