Molecular Sensors and Modulators of Thermoreception

Peer reviewedPostprin

The Basal Thermal Sensitivity of the TRPV1 Ion Channel Is Determined by PKCβII

Copyright © 2014 the authors 0270-6474/14/348246-13$15.00/0.Peer reviewedPublisher PD

Efficient randomized-adaptive designs

Response-adaptive randomization has recently attracted a lot of attention in the literature. In this paper, we propose a new and simple family of response-adaptive randomization procedures that attain the Cramer--Rao lower bounds on the allocation variances for any allocation proportions, including optimal allocation proportions. The allocation probability functions of proposed procedures are discontinuous. The existing large sample theory for adaptive designs relies on Taylor expansions of the allocation probability functions, which do not apply to nondifferentiable cases. In the present paper, we study stopping times of stochastic processes to establish the asymptotic efficiency results. Furthermore, we demonstrate our proposal through examples, simulations and a discussion on the relationship with earlier works, including Efron's biased coin design.Comment: Published in at http://dx.doi.org/10.1214/08-AOS655 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Direct Gα q Gating Is the Sole Mechanism for TRPM8 Inhibition Caused by Bradykinin Receptor Activation

Activation of Gα q-coupled receptors by inflammatory mediators inhibits cold-sensing TRPM8 channels, aggravating pain and inflammation. Both Gα q and the downstream hydrolysis of phosphatidylinositol 4, 5-bisphosphate (PIP 2) inhibit TRPM8. Here, I demonstrate that direct Gα q gating is essential for both the basal cold sensitivity of TRPM8 and TRPM8 inhibition elicited by bradykinin in sensory neurons. The action of Gα q depends on binding to three arginine residues in the N terminus of TRPM8. Neutralization of these residues markedly increased sensitivity of the channel to agonist and membrane voltage and completely abolished TRPM8 inhibition by both Gα q and bradykinin while sparing the channel sensitivity to PIP 2. Interestingly, the bradykinin receptor B2R also binds to TRPM8, rendering TRPM8 insensitive to PIP 2 depletion. Furthermore, TRPM8-Gα q binding impaired Gα q coupling and signaling to PLCβ-PIP 2. The crosstalk in the TRPM8-Gα q-B2R complex thus determines Gα q gating rather than PIP 2 as a sole means of TRPM8 inhibition by bradykinin. TRPM8 channels are inhibited by receptors coupled to Gα q, contributing to pain and inflammation. Zhang reveals Gα q gating sites on TRPM8 and shows that bradykinin receptor solely uses Gα q gating sites for TRPM8 inhibition upon activation, while depriving the channel of sensitivity to PIP 2

Advances in Optofluidics

Optofluidics a niche research field that integrates optics with microfluidics. It started with elegant demonstrations of the passive interaction of light and liquid media such as liquid waveguides and liquid tunable lenses. Recently, the optofluidics continues the advance in liquid-based optical devices/systems. In addition, it has expanded rapidly into many other fields that involve lightwave (or photon) and liquid media. This Special Issue invites review articles (only review articles) that update the latest progress of the optofluidics in various aspects, such as new functional devices, new integrated systems, new fabrication techniques, new applications, etc. It covers, but is not limited to, topics such as micro-optics in liquid media, optofluidic sensors, integrated micro-optical systems, displays, optofluidics-on-fibers, optofluidic manipulation, energy and environmental applciations, and so on

Ca2+ regulation of TRP ion channels

Ca2+ signaling influences nearly every aspect of cellular life. Transient receptor potential (TRP) ion channels have emerged as cellular sensors for thermal, chemical and mechanical stimuli and are major contributors to Ca2+ signaling, playing an important role in diverse physiological and pathological processes. Notably, TRP ion channels are also one of the major downstream targets of Ca2+ signaling initiated either from TRP channels themselves or from various other sources, such as G-protein coupled receptors, giving rise to feedback regulation. TRP channels therefore function like integrators of Ca2+ signaling. A growing body of research has demonstrated different modes of Ca2+-dependent regulation of TRP ion channels and the underlying mechanisms. However, the precise actions of Ca2+ in the modulation of TRP ion channels remain elusive. Advances in Ca2+ regulation of TRP channels are critical to our understanding of the diversified functions of TRP channels and complex Ca2+ signaling