Warmth suppresses and desensitizes damage-sensing ion channel TRPA1

<p>Abstract</p> <p>Background</p> <p>Acute or chronic tissue damage induces an inflammatory response accompanied by pain and alterations in local tissue temperature. Recent studies revealed that the transient receptor potential A1 (TRPA1) channel is activated by a wide variety of substances that are released following tissue damage to evoke nociception and neurogenic inflammation. Although the effects of a noxious range of cold temperatures on TRPA1 have been rigorously studied, it is not known how agonist-induced activation of TRPA1 is regulated by temperature over an innocuous range centred on the normal skin surface temperature. This study investigated the effect of temperature on agonist-induced currents in human embryonic kidney (HEK) 293 cells transfected with rat or human TRPA1 and in rat sensory neurons.</p> <p>Results</p> <p>Agonist-induced TRPA1 currents in HEK293 cells were strongly suppressed by warm temperatures, and almost abolished at 39°C. Such inhibition occurred when TRPA1 was activated by either electrophilic or non-electrophilic agonists. Warming not only decreased the apparent affinity of TRPA1 for mustard oil (MO), but also greatly enhanced the desensitization and tachyphylaxis of TRPA1. Warming also attenuated MO-induced ionic currents in sensory neurons. These results suggest that the extent of agonist-induced activity of TRPA1 may depend on surrounding tissue temperature, and local hyperthermia during acute inflammation could be an endogenous negative regulatory mechanism to attenuate persistent pain at the site of injury.</p> <p>Conclusion</p> <p>These results indicate that warmth suppresses and desensitizes damage-sensing ion channel TRPA1. Such warmth-induced suppression of TRPA1 may also explain, at least in part, the mechanistic basis of heat therapy that has been widely used as a supplemental anti-nociceptive approach.</p

Intraperitoneal administration of telomerase-specific oncolytic adenovirus sensitizes ovarian cancer cells to cisplatin and affects survival in a xenograft model with peritoneal dissemination

Despite tremendous development in chemotherapy for ovarian cancer over the past few decades, the prognosis of advanced cases with massive peritoneal dissemination is still unsatisfactory, and novel treatment modalities that can combine with chemotherapy are urgently needed. We recently developed virotherapy for solid tumors using telomerase-specific replication-selective adenoviruses (Telomelysin: OBP-301), in which the human telomerase reverse transcriptase (hTERT) gene promoter has been inserted to direct tumor-specific E1 gene expression. In this study, we investigated the anti-tumor effects of OBP-301, combined with cisplatin (CDDP), on ovarian cancer cells. In vitro treatment of SKOV3 cells with OBP-301 at a multiplicity of infection (MOI) of 0.01–100 induced significant cell death in a dose-dependent manner, with moderate cytotoxicity at an MOI of 1–10 and maximal cytotoxicity at an MOI of 100. In contrast, OBP-301 treatment of normal human cells showed no significant cell death at an MOI of 1–10 and exhibited modest cytotoxicity at an MOI of 100. The effects of low-dose CDDP at 0.5–1 μM, which induced only 20% cell death, were significantly augmented by combination with OBP-301 at an MOI of 1–10, finally achieving 40% cell death. Such enhancement of CDDP sensitivity was also observed in CDDP-resistant ovarian cancer cells. The combinatorial effects were further tested using a xenograft mouse model of SKOV3 with peritoneal dissemination. After intraperitoneal administration of OBP-301, we confirmed that injected OBP-301 fused with the green fluorescent protein (GFP) gene (OBP-401) was preferentially localized to peritoneal disseminations, as determined by fluorescence imaging. Treatment of mice with CDDP at low dose (0.5 mg kg–1) had modest effects, showing a 10% decrease in disseminations, whereas combination with intraperitoneal administration of OBP-301 at an MOI of 10 led to enhanced effects, achieving an approximately 80% decrease in disseminations. Kaplan–Meier analysis showed improved overall survival of mice treated with CDDP plus OBP-301 compared with CDDP alone. These findings support the therapeutic potential of intraperitoneal administration of OBP-301 to sensitize ovarian cancer cells to CDDP

Wearable thermoelectrics for personalized thermoregulation.

Thermoregulation has substantial implications for energy consumption and human comfort and health. However, cooling technology has remained largely unchanged for more than a century and still relies on cooling the entire space regardless of the number of occupants. Personalized thermoregulation by thermoelectric devices (TEDs) can markedly reduce the cooling volume and meet individual cooling needs but has yet to be realized because of the lack of flexible TEDs with sustainable high cooling performance. Here, we demonstrate a wearable TED that can deliver more than 10°C cooling effect with a high coefficient of performance (COP &gt; 1.5). Our TED is the first to achieve long-term active cooling with high flexibility, due to a novel design of double elastomer layers and high-ZT rigid TE pillars. Thermoregulation based on these devices may enable a shift from centralized cooling toward personalized cooling with the benefits of substantially lower energy consumption and improved human comfort

Study of carbon dust formation and their structure using inductively coupled plasmas under high atomic hydrogen irradiation

金沢大学理工研究域電子情報学系Experiments on erosion and dust formation on graphite materials have been performed using high power induction plasmas containing high atomic hydrogen flux (∼1024 m-2 s-1). Chemical sputtering by atomic hydrogen irradiation with incident energy below 1 eV eroded the graphite targets significantly, and the sputtering yield was roughly estimated to be 0.002-0.005, which is as high as that obtained by ion beam and fusion plasma experiments. The transport of the released hydrocarbon along the gas flow, interacting with low temperature plasmas, results in carbon dust formation on the eroded graphite target and also on the silicon and graphite samples located at the remote position. The dust size and density observed on the samples decreases with distance from the graphite target. The dust shape strongly depends on the target surface temperature, and the graphite dust turns into polyhedral particle like diamond when the surface temperature rises to 1100 K. © 2009 Elsevier B.V. All rights reserved

Active front-end rectifier modelling using dynamic phasors for more-electric aircraft applications

The More-Electric Aircraft (MEA) has become a dominant trend for next-generation aircraft. The Electrical Power System (EPS) on-board may take many forms: AC, DC, hybrid, frequency-wild, variable voltage, together with the possibility of novel connectivity topologies. To address the stability, availability and capability issues as well as to assess the performance of the power quality and transient behaviour, extensive simulation work is required to develop the EPS architectures. The paper develops a fast-simulation model of active front-end rectifiers based on the dynamic phasor concept. The model is suitable for accelerated simulation studies of EPS under normal, unbalanced and line fault conditions. The performance and effectiveness of the developed model have been demonstrated by comparison against time-domain models in three-phase and synchronous space-vector representations. The experimental verification of the dynamic phasor model is also reported. The prime purpose of the model is for the simulation studies of MEA power architectures at system level; however it can be directly applied for simulation study of any other EPS interfacing with active front-end rectifiers

Outstanding Reviewers for: Organic & Biomolecular Chemistry in 2017

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