High temperature sensitivity is intrinsic to voltage-gated potassium channels.

Temperature-sensitive transient receptor potential (TRP) ion channels are members of the large tetrameric cation channels superfamily but are considered to be uniquely sensitive to heat, which has been presumed to be due to the existence of an unidentified temperature-sensing domain. Here we report that the homologous voltage-gated potassium (Kv) channels also exhibit high temperature sensitivity comparable to that of TRPV1, which is detectable under specific conditions when the voltage sensor is functionally decoupled from the activation gate through either intrinsic mechanisms or mutations. Interestingly, mutations could tune Shaker channel to be either heat-activated or heat-deactivated. Therefore, high temperature sensitivity is intrinsic to both TRP and Kv channels. Our findings suggest important physiological roles of heat-induced variation in Kv channel activities. Mechanistically our findings indicate that temperature-sensing TRP channels may not contain a specialized heat-sensor domain; instead, non-obligatory allosteric gating permits the intrinsic heat sensitivity to drive channel activation, allowing temperature-sensitive TRP channels to function as polymodal nociceptors

Understand spiciness: mechanism of TRPV1 channel activation by capsaicin.

Capsaicin in chili peppers bestows the sensation of spiciness. Since the discovery of its receptor, transient receptor potential vanilloid 1 (TRPV1) ion channel, how capsaicin activates this channel has been under extensive investigation using a variety of experimental techniques including mutagenesis, patch-clamp recording, crystallography, cryo-electron microscopy, computational docking and molecular dynamic simulation. A framework of how capsaicin binds and activates TRPV1 has started to merge: capsaicin binds to a pocket formed by the channel's transmembrane segments, where it takes a "tail-up, head-down" configuration. Binding is mediated by both hydrogen bonds and van der Waals interactions. Upon binding, capsaicin stabilizes the open state of TRPV1 by "pull-and-contact" with the S4-S5 linker. Understanding the ligand-host interaction will greatly facilitate pharmaceutical efforts to develop novel analgesics targeting TRPV1

Integrating semi-supervised label propagation and random forests for multi-atlas based hippocampus segmentation

A novel multi-atlas based image segmentation method is proposed by integrating a semi-supervised label propagation method and a supervised random forests method in a pattern recognition based label fusion framework. The semi-supervised label propagation method takes into consideration local and global image appearance of images to be segmented and segments the images by propagating reliable segmentation results obtained by the supervised random forests method. Particularly, the random forests method is used to train a regression model based on image patches of atlas images for each voxel of the images to be segmented. The regression model is used to obtain reliable segmentation results to guide the label propagation for the segmentation. The proposed method has been compared with state-of-the-art multi-atlas based image segmentation methods for segmenting the hippocampus in MR images. The experiment results have demonstrated that our method obtained superior segmentation performance.Comment: Accepted paper in IEEE International Symposium on Biomedical Imaging (ISBI), 201