Inhibition of the unique repolarisation K+ channel current IKur by verapamil in human atrial myocytes

Abstract no. CVS-03published_or_final_versio

CRTC1 transcriptional coactivator is required for hepatitis B virus gene expression and replication

This journal suppl. entitled: Metabolism, Diet and Disease 2014: Cancer and metabolismConference Theme: Cancer and metabolismPoster Presentation: P31BACKGROUND: Chronic hepatitis B virus (HBV) infection occurs in over 400 million people worldwide, 15-40% of whom will terminally develop severe liver diseases including hepatocellular carcinoma. Although development of HCC is a multi-step process, high HBV DNA level is a major risk factor for disease progression. Transcription of HBV from the cccDNA template is essential for its replication and requires CREB transcription factor, a master regulator of cell metabolism. However, transcriptional coactivators that facilitate CREB-dependent activation of HBV transcription remain to be identified and characterized …published_or_final_versio

Experimental Investigation of a Broadband High-Temperature Superconducting Terahertz Mixer Operating at Temperatures Between 40 and 77 K

© 2017, Springer Science+Business Media, LLC. This paper presents a systematic investigation of a broadband thin-film antenna-coupled high-temperature superconducting (HTS) terahertz (THz) harmonic mixer at relatively high operating temperature from 40 to 77 K. The mixer device chip was fabricated using the CSIRO established step-edge YBa2Cu3O7-x (YBCO) Josephson junction technology, packaged in a well-designed module and cooled in a temperature adjustable cryocooler. Detailed experimental characterizations were carried out for the broadband HTS mixer at both the 200 and 600 GHz bands in harmonic mixing mode. The DC current-voltage characteristics (IVCs), bias current condition, local oscillator (LO) power requirement, frequency response, as well as conversion efficiency under different bath temperatures were thoroughly investigated for demonstrating the frequency down-conversion performance

Ubiquitination and proteosome-dependent degradation of the activated form of human liver-enriched transcription factor CREB-H regulated by protein kinase A

Poster Presentation - Theme 1: Cell biologyCREB-H is a membrane-bound bZIP transcription factor which is mainly expressed in liver and small intestine. CREB-H plays important roles in the regulation of lipid metabolism, iron metabolism, gluconeogenesis and acute phase response. CREB-H is proteolytically activated by regulated intramembrane proteolysis to generate a C-terminal truncated form known as ...postprin

HTS step-edge Josephson junction terahertz harmonic mixer

© 2016 Federal Australian Crown copyright. A high-temperature superconducting (HTS) terahertz (THz) frequency down-converter or mixer based on a thin-film ring-slot antenna coupled YBa2Cu3O7-x (YBCO)/MgO step-edge Josephson junction is reported. The frequency down-conversion was achieved using higher order harmonics of an applied lower frequency (19-40 GHz) local oscillator signal in the Josephson junction mixing with a THz signal of over 600 GHz, producing a 1-3 GHz intermediate frequency signal. Up to 31st order of harmonic mixing was obtained and the mixer operated stably at temperatures up to 77 K. The design details of the antenna, HTS Josephson junction mixer, the matching and isolation circuits, and the DC and RF performance evaluation are described in this paper

Refractive index in holographic superconductors

With the probe limit, we investigate the behavior of the electric permittivity and effective magnetic permeability and related optical properties in the s-wave holographic superconductors. In particular, our result shows that unlike the strong coupled systems which admit a gravity dual of charged black holes in the bulk, the electric permittivity and effective magnetic permeability are unable to conspire to bring about the negative Depine-Lakhtakia index at low frequencies, which implies that the negative phase velocity does not appear in the holographic superconductors under such a situation.Comment: JHEP style, 1+15 pages, 11 figures, version to appear in JHE

Differential Effects of Tyrosine Kinase Inhibitors on Volume-sensitive Chloride Current in Human Atrial Myocytes: Evidence for Dual Regulation by Src and EGFR Kinases

To determine whether protein tyrosine kinase (PTK) modulates volume-sensitive chloride current (I Cl.vol) in human atrial myocytes and to identify the PTKs involved, we studied the effects of broad-spectrum and selective PTK inhibitors and the protein tyrosine phosphatase (PTP) inhibitor orthovanadate (VO 4 -3). I Cl.vol evoked by hyposmotic bath solution (0.6-times isosmotic, 0.6T) was enhanced by genistein, a broad-spectrum PTK inhibitor, in a concentration-dependent manner (EC 50 = 22.4 μM); 100 μM genistein stimulated I Cl.vol by 122.4 ± 10.6%. The genistein-stimulated current was inhibited by DIDS (4,4′-diisothiocyanostilbene-2,2′-disulfonic acid, 150 μM) and tamoxifen (20 μM), blockers of I Cl.vol. Moreover, the current augmented by genistein was volume dependent; it was abolished by hyperosmotic shrinkage in 1.4T, and genistein did not activate Cl - current in 1T. In contrast to the stimulatory effects of genistein, 100 μM tyrphostin A23 (AG 18) and A25 (AG 82) inhibited I Cl.vol by 38.2 ± 4.9% and 40.9 ± 3.4%, respectively. The inactive analogs, daidzein and tyrphostin A63 (AG 43), did not alter I Cl.vol. In addition, the PTP inhibitor VO 4 -3 (1 mM) reduced I Cl.vol by 53.5 ± 4.5% (IC 50 = 249.6 μM). Pretreatment with VO 4 -3 antagonized genistein-induced augmentation and A23- or A25-induced suppression of I Cl.vol. Furthermore, the selective Src-family PTK inhibitor PP2 (5 μM) stimulated I Cl.vol, mimicking genistein, whereas the selective EGFR (ErbB-1) kinase inhibitor tyrphostin B56 (AG 556, 25 μM) reduced I Cl.vol, mimicking A23 and A25. The effects of both PP2 and B56 also were substantially antagonized by pretreatment with VO 4 -3. The results suggest that I Cl.vol is regulated in part by the balance between PTK and PTP activity. Regulation is complex, however. Src and EGFR kinases, distinct soluble and receptor-mediated PTK families, have opposing effects on I Cl.vol, and multiple target proteins are likely to be involved.published_or_final_versio

β-TrCP-mediated ubiquitination and degradation of liver-enriched transcription factor CREB-H

CREB-H is an endoplasmic reticulum-resident bZIP transcription factor which critically regulates lipid homeostasis and gluconeogenesis in the liver. CREB-H is proteolytically activated by regulated intramembrane proteolysis to generate a C-terminally truncated form known as CREB-H-ΔTC, which translocates to the nucleus to activate target gene expression. CREB-H-ΔTC is a fast turnover protein but the mechanism governing its destruction was not well understood. In this study, we report on β-TrCP-dependent ubiquitination and proteasomal degradation of CREB-H-ΔTC. The degradation of CREB-H-ΔTC was mediated by lysine 48-linked polyubiquitination and could be inhibited by proteasome inhibitor. CREB-H-ΔTC physically interacted with β-TrCP, a substrate recognition subunit of the SCFβ-TrCP E3 ubiquitin ligase. Forced expression of β-TrCP increased the polyubiquitination and decreased the stability of CREB-H-ΔTC, whereas knockdown of β-TrCP had the opposite effect. An evolutionarily conserved sequence, SDSGIS, was identified in CREB-H-ΔTC, which functioned as the β-TrCP-binding motif. CREB-H-ΔTC lacking this motif was stabilized and resistant to β-TrCP-induced polyubiquitination. This motif was a phosphodegron and its phosphorylation was required for β-TrCP recognition. Furthermore, two inhibitory phosphorylation sites close to the phosphodegron were identified. Taken together, our work revealed a new intracellular signaling pathway that controls ubiquitination and degradation of the active form of CREB-H transcription factor.published_or_final_versio

Harmonic Mixing Using a HTS Step-Edge Josephson Junction at 0.6 THz Frequency

© 2002-2011 IEEE. A high-temperature superconducting (HTS) terahertz (THz) heterodyne mixer based on a thin-film antenna-coupled YBa 2Cu3O7-x step-edge Josephson junction is presented. The frequency down-conversion from 0.6 THz to an intermediate frequency (IF) of 2 GHz was achieved using high-order harmonic mixing of a local oscillator (LO), thus removing the need to use a second THz source as the LO pumping source. The DC and RF characteristics of the harmonic mixer as well as the relationship of the IF output power versus the harmonic number were experimentally studied and compared with simulated results. Most of our measurements were made at 40 K, but we also observed stable harmonic mixing at 77 K which we believe has not been reported previously in HTS junction mixers