Perception of Cleft Palate Speech by Japanese Listeners-an Assessment of Palatalized Articulations.

To examine how people react to palatalized articulation, we used one cleft palate speech (CPS) sample of palatalized articulation that was purchased in Japan and one recorded sample of speech from a non-cleft palate individual. Study design The two speech samples were rated by 137 native listeners. Each participant rated the set of speech samples for 10 features using a 10-point scale.

TRPM2 activation by cyclic ADP-ribose at body temperature is involved in insulin secretion.

There are eight thermosensitive TRP (transient receptor potential) channels in mammals, and there might be other TRP channels sensitive to temperature stimuli. Here, we demonstrate that TRPM2 can be activated by exposure to warm temperatures (>35 degrees C) apparently via direct heat-evoked channel gating. beta-NAD(+)- or ADP-ribose-evoked TRPM2 activity is robustly potentiated at elevated temperatures.

Increased sensitivity of desensitized TRPV1 by PMA occurs through PKCepsilon-mediated phosphorylation at S800.

Important mechanisms that regulate inhibitory and facilitatory effects on TRPV1-mediated nociception are desensitization and phosphorylation, respectively. Using Ca2+-imaging, we have previously shown that desensitization of TRPV1 upon successive capsaicin applications was reversed by protein kinase C activation in dorsal root ganglion neurons and CHO cells. Here, using both Ca2+-imaging and patch-clamp methods, we show that PMA-induced activation of PKCepsilon is essential for increased sensitivity of desensitized TRPV1.

Structure and function of TRPV1.

Capsaicin, the main ingredient in hot chili peppers, elicits a sensation of burning pain by selectively activating sensory neurons that convey information about noxious stimuli to the central nervous system. The capsaicin receptor, transient receptor potential vanilloid 1 (TRPV1), is predicted to have six transmembrane (TM) domains and a short, pore-forming hydrophobic stretch between the fifth and sixth TM domains, and is activated not only by capsaicin but also by heat (>43 degrees C), acid and various lipids. Within the TPRV1 protein, many regions and amino acids involved in specific functions (multimerization, capsaicin action, proton action, heat activation, desensitization, permeability, phosphorylation and modulation by lipids) have been identified since the cloning in 1997.

Sensitization of TRPV1 by EP1 and IP reveals peripheral nociceptive mechanism of prostaglandins.

Prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2) are major inflammatory mediators that play important roles in pain sensation and hyperalgesia. The role of their receptors (EP and IP, respectively) in inflammation has been well documented, although the EP receptor subtypes involved in this process and the underlying cellular mechanisms remain to be elucidated. The capsaicin receptor TRPV1 is a nonselective cation channel expressed in sensory neurons and activated by various noxious stimuli.

Regulation mechanisms of vanilloid receptors.

The capsaicin receptor TRPV1 (also known as the vanilloid receptor VR1) is a non-selective cation channel and is activated not only by capsaicin but also by noxious heat or protons. Tissue damage associated with infection, inflammation or ischaemia, produces an array of chemical mediators that activate or sensitize nociceptor terminals. An important component of this pro-algeic response is ATP.

DIP (mDia interacting protein) is a key molecule regulating Rho and Rac in a Src-dependent manner.

Cell movement is driven by the coordinated regulation of cytoskeletal reorganization through Rho GTPases downstream of integrin and growth-factor receptor signaling. We have reported that mDia, a target protein of Rho, interacts with Src and DIP. Here we show that DIP binds to p190RhoGAP and Vav2, and that DIP is phosphorylated by Src and mediates the phosphorylation of p190RhoGAP and Vav2 upon EGF stimulation.

[Molecular mechanisms of nociception].

Capsaicin, the main ingredient in 'hot' chili peppers, elicits burning pain by activating nociceptors. The cloned capsaicin receptor (TRPV1) is a nonselective cation channel with six transmembrane domains, and is activated not only by capsaicin but also by noxious heat (> 43 degrees C) or protons (acidification), both of which cause pain in vivo. Furthermore, analyses of mice lacking VR1 showed that VR1 is essential for selective modalities of pain sensation and for tissue injury-induced thermal hyperalgesia.

Structural determinant of TRPV1 desensitization interacts with calmodulin.

The capsaicin receptor, TRPV1 (VR1), is a sensory neuron-specific ion channel that serves as a polymodal detector of pain-producing chemical and physical stimuli. Extracellular Ca2+-dependent desensitization of TRPV1 observed in patch-clamp experiments when using both heterologous expression systems and native sensory ganglia is thought to be one mechanism underlying the paradoxical effectiveness of capsaicin as an analgesic therapy. Here, we show that the Ca2+-binding protein calmodulin binds to a 35-aa segment in the C terminus of TRPV1, and that disruption of the calmodulin-binding segment prevents TRPV1 desensitization.

The Rho GTPase effector protein, mDia, inhibits the DNA binding ability of the transcription factor Pax6 and changes the pattern of neurite extension in cerebellar granule cells through its binding to Pax6.

mDia, one of the target proteins of the GTPase Rho, is known to be involved in cytoskeletal reorganization and cytokinesis. Here, we report that mDia enters the nucleus and binds to the transcription factor, Pax6. In cultured non-neuronal cells, overexpression of mDia with Pax6 causes redistribution of some Pax6 molecules from the nucleus to the cytosol and decreases Pax6 transcriptional activity.

Direct phosphorylation of capsaicin receptor VR1 by protein kinase Cepsilon and identification of two target serine residues.

The capsaicin receptor, VR1, is a sensory neuron-specific ion channel that serves as a polymodal detector of pain-producing chemical and physical stimuli. It has been reported that ATP, one of the inflammatory mediators, potentiates the VR1 currents evoked by capsaicin or protons and reduces the temperature threshold for activation of VR1 through metabotropic P2Y(1) receptors in a protein Kinase C (PKC)-dependent pathway, suggesting the phosphorylation of VR1 by PKC. In this study, direct phosphorylation of VR1 upon application of phorbol 12-myristate 13-acetate (PMA) was proven biochemically in cells expressing VR1.