Cardiorespiratory optimization during improvised singing and toning.

We evaluated the effect of different forms of singing on cardiorespiratory physiology, and we aimed at disentangling the role of breathing from that of vocal production. Cardiorespiratory recordings were obtained from 20 healthy adults at rest and during: a) singing of familiar slow songs as in the standard form of Western culture; b) improvised vocalization of free vowel sounds, known as toning. To disentangle the role of breathing from that of vocal production, we compared the vocal conditions with matched breathing-only conditions. Toning significantly improved heart rate variability, ventilatory efficiency and slowed respiration to almost exactly six breaths per minute (p < 0.001), a pattern that is known to optimize cardiovascular function and that coincides with the period of endogenous circulatory rhythms. Singing songs also positively impacted cardiorespiratory function, although to a lesser extent. The breathing pattern imposed upon participants in the absence of vocal production was sufficient to generate the physiological benefits. The effects of toning are similar to what has been previously described as a result of engaging in formal breathing exercises. Toning and singing may offer an engaging and cost effective tool to trigger beneficial respiratory patterns and the related cardiovascular benefits.

The role of plasma membrane STIM1 and Ca(2+)entry in platelet aggregation. STIM1 binds to novel proteins in human platelets.

Ca(2+) elevation is essential to platelet activation. STIM1 senses Ca(2+) in the endoplasmic reticulum and activates Orai channels allowing store-operated Ca(2+) entry (SOCE). STIM1 has also been reported to be present in the plasma membrane (PM) with its N-terminal region exposed to the outside medium but its role is not fully understood. We have examined the effects of the antibody GOK/STIM1, which recognises the N-terminal region of STIM1, on SOCE, agonist-stimulated Ca(2+) entry, surface exposure, in vitro thrombus formation and aggregation in human platelets. We also determined novel binding partners of STIM1 using proteomics. The dialysed GOK/STIM1 antibody failed to reduced thapsigargin- and agonist-mediated Ca(2+) entry in Fura2-labelled cells. Using flow cytometry we detect a portion of STIM1 to be surface-exposed. The dialysed GOK/STIM1 antibody reduced thrombus formation by whole blood on collagen-coated capillaries under flow and platelet aggregation induced by collagen. In immunoprecipitation experiments followed by proteomic analysis, STIM1 was found to extract a number of proteins including myosin, DOCK10, thrombospondin-1 and actin. These studies suggest that PM STIM1 may facilitate platelet activation by collagen through novel interactions at the plasma membrane while the essential Ca(2+)-sensing role of STIM1 is served by the protein in the ER.

Isolation of ORCTL3 in a novel genetic screen for tumor-specific apoptosis inducers.

We have established a systematic high-throughput screen for genes that cause cell death specifically in transformed tumor cells. In a first round of screening, cDNAs that induce apoptosis in a transformed human cell line are detected. Positive genes are subsequently tested in a synthetic lethal screen in normal cells versus their isogenic counterparts that have been transformed by a particular oncogene. In this way, the organic cation transporter-like 3 (ORCTL3) gene was found to be inactive in normal rat kidney (NRK) cells, but to induce apoptosis in NRK cells transformed by oncogenic H-ras. ORCTL3 also causes cell death in v-src-transformed cells and in various human tumor cell lines but not in normal cells or untransformed cell lines. Although ORCTL3 is a member of the organic cation transporter gene family, our data indicate that this gene induces apoptosis independently of its putative transporter activity. Rather, various lines of evidence suggest that ORCTL3 brings about apoptosis by an endoplasmic reticulum stress-mediated mechanism. Finally, we detected ORCTL3 to be downregulated in human kidney tumors.