REGULATION OF L-TYPE VOLTAGE-DEPENDNET CALCIUM CHANNELS BY THE REM GTPASE

The Rem, Rem2, Rad, and Gem/Kir GTPases, comprise a novel subfamily of the small Ras-related GTP-binding proteins known as the RGK GTPases, and have been shown to function as potent negative regulators of high voltage-activated (HVA) Ca2+ channels upon overexpression. HVA Ca2+ channels modulate Ca2+ influx in response to membrane depolarization to regulate a wide variety of cellular functions and they minimally consist of a pore-forming α1 subunit, an intracellular β subunit, and a transmembrane complex α2/δ subunit. While the mechanisms underlying RGK-mediated Ca2+ channel regulation remain poorly defined, it appears that both membrane localization and the binding of accessory Ca2+ channel β subunits (CaVβ) are required for suppression of Ca2+ channel currents. We identified a direct interaction between Rem and the L-type Cavα1 C-terminus (CCT), but not the CCT from CaV3.2 T-type channels. Deletion mapping studies suggest that the conserved CB-IQ domain is required for Rem:CCT association, a region known to contribute to both Ca2+-dependent channel inactivation and facilitation through interactions of Ca2+-bound calmodulin (CaM) with the proximal CCT. Furthermore, both Rem2 and Rad GTPases display similar patterns of CCT binding, suggesting that CCT represents a common binding partner for all RGK proteins. While previous studies have found that association of the Rem C-terminus with the plasma membrane is required for channel inhibition, it is not required for CaVβ- subunit binding. However, Rem:CCT association is well correlated with the plasma membrane localization of Rem and more importantly, Rem-mediated channel inhibition upon overexpression. Moreover, co-expression of the proximal CB-IQ containing region of CCT (residues 1507-1669) in HIT-T15 cells partially relieves Rem blockade of ionic current. Interestingly, Ca2+/CaM disrupts Rem:CCT association in vitro. Moreover, CaM overexpression partially relieves Rem-mediated L-type Ca2+ channel inhibition and Rem overexpression alters the kinetics of calcium-dependent inactivation. Together, these data suggest that the association of Rem with the CCT represents a crucial molecular determinant for Rem-mediated L-type Ca2+ channel regulation and provides new insights into this novel channel regulatory process. These studies also suggest that instead of acting as complete Ca2+ channel blockers, RGK proteins may function as endogenous regulators for the channel inactivation machinery

On Observability Analysis in Multiagent Systems

peer reviewedIn multiagent systems (MASs), agents’ observation upon system behaviours may improve the overall team performance, but may also leak sensitive information to an observer. A quantified observability analysis can thus be useful to assist decision-making in MASs by operators seeking to optimise the relationship between performance effectiveness and information exposure through observations in practice. This paper presents a novel approach to quantitatively analysing the observability properties in MASs. The concept of opacity is applied to formally express the characterisation of observability in MASs modelled as partially observable multiagent systems. We propose a temporal logic oPATL to reason about agents’ observability with quantitative goals, which capture the probability of information transparency of system behaviours to an observer, and develop verification techniques for quantitatively analysing such properties. We implement the approach as an extension of the PRISM model checker, and illustrate its applicability via several examples

A systematic density-based clustering method using anchor points

National Research Foundation (NRF) Singapore under its AI Singapore Programme; Singapore Ministry of Health under its National Innovation Challenge on Active and Confident Agein

FXYD3: A Promising Biomarker for Urothelial Carcinoma

Objective Urothelial carcinoma (UC) of the kidney is a relatively rare but aggressive form of kidney cancer. Differential diagnosis of renal UC from renal cell carcinoma (RCC) can be difficult, but is critical for correct patient management. We aimed to use global gene expression profiling to identify genes specifically expressed in urothelial carcinoma (UC) of the kidney, with purpose of finding new biomarkers for differential diagnosis of UC of both upper and lower tract from normal tissues. Materials and Methods Microarray gene expression profiling was performed on a variety of human kidney tumor samples, including clear cell, papillary, chromophobe, oncocytoma, renal UC and normal kidney controls. Differentially expressed mRNAs in various kidney tumor subtypes were thus identified. Protein expression in human UC tumor samples from both upper and lower urinary tract was evaluated by immunohistochemistry. Results FXYD3 (MAT-8) mRNA was specifically expressed in UC of the kidney and not in normal kidney tissue or in any RCC tumor subtypes. FXYD3 mRNA levels displayed equal or better prediction rate for the detection of renal UC than the mRNA levels of selected known UC markers as p63, vimentin, S100P, KRT20 and KRT7. Finally, immunohistochemical staining of clinical UC samples showed that FXYD3 protein is overexpressed in majority of UC of the upper genitourinary tract (encompassing the kidney, ~90%) and in majority of high grade bladder UC (~84%, it's < 40% in low grade tumors, P < 0.001) compared to normal kidney and bladder tissues. Conclusion FXYD3 may be a promising novel biomarker for the differential diagnosis of renal UC and a promising prognosis marker of UC from bladder. Because it was identified genome-widely, FXYD3 may have important biological ramifications for the genetic study of UC

On the Origin of the Strong Optical Variability of Emission-line Galaxies

Emission-line galaxies (ELGs) are crucial in understanding the formation and evolution of galaxies, while little is known about their variability. Here we report the study on the optical variability of a sample of ELGs selected in the COSMOS field, which has narrow-band observations in two epochs separated by $\gtrsim$ 12 years. This sample was observed with Suprime-Cam (SC) and Hyper Suprime-Cam (HSC) on the $Subaru$ telescope in NB816 and $i'/i$ bands, respectively. After carefully removing the wing effect of a narrow-band filter, we check the optical variability in a sample of 181 spectroscopically confirmed ELGs. We find that 0 (0/68) Ha emitters, 11.9% (5/42) [OIII] emitters, and 0 (0/71) [OII] emitters show significant variability ($|\Delta m_{NB}| \geq 3\,\sigma_{\Delta m_{NB,AGN}} = 0.20\, mag$) in the two-epoch narrow-band observations. We investigate the presence of active galactic nucleus (AGN) in this variable ELG (var-ELG) sample with three methods, including X-ray luminosity, mid-infrared activity, and radio-excess. We find zero bright AGN in this var-ELG sample, but cannot rule out the contribution from faint AGN. We find that SNe could also dominate the variability of the var-ELG sample. The merger morphology shown in the HST/F814W images of all the var-ELG sample is in agreement with the enhancement of star formation, i.e., the SNe activity.Comment: 20 pages, 10 figures, accepted for publication in The Astrophysical Journa

On Quantified Observability Analysis in Multi-Agent Systems

Postprin

Layered sphere-shaped TiO2 capped with gold nanoparticles on structural defects and their catalysis of formaldehyde oxidation

We describe here a one-step method for the synthesis of Au/TiO2 nanosphere materials, which were formed by layered deposition of multiple anatase TiO2 nanosheets. The Au nanoparticles were stabilized by structural defects in each TiO2 nanosheet, including crystal steps and edges, thereby fixing the Au-TiO2 perimeter interface. Reactant transfer occurred along the gaps between these TiO2 nanosheet layers and in contact with catalytically active sites at the Au-TiO2 interface. The doped Au induced the formation of oxygen vacancies in the Au-TiO2 interface. Such vacancies are essential for generating active oxygen species (*O-) on the TiO2 surface and Ti3+ ions in bulk TiO2. These ions can then form Ti3+-O-Ti4+ species, which are known to enhance the catalytic activity of formaldehyde (HCHO) oxidation. These studies on structural and oxygen vacancy defects in Au/TiO2 samples provide a theoretical foundation for the catalytic mechanism of HCHO oxidation on oxide-supported Au materials. (C) 2015 The Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V