Clinical research: a globalized network.

Clinical research has become increasingly globalized, but the extent of globalization has not been assessed. To describe the globalization of clinical research, we used all (n = 13,208) multinational trials registered at ClinicalTrials.gov to analyzed geographic connections among individual countries.

Heterogeneity in low voltage-activated Ca2+ channel-evoked Ca2+ responses within neurons of the thalamic paraventricular nucleus.

Low voltage-activated Ca2+ channels (LVA or T-type Ca2+ channels) are crucial to burst firing and oscillations in thalamocortical relay cells and are exhibited by neurons in the paraventricular nucleus of thalamus (PVT), a dorsal midline nucleus deemed important in the neural representation of motivational behaviours. We used a functional approach (whole-cell patch-clamp electrophysiology combined with confocal laser scanning microscopy) to analyse the spatial distribution of LVA Ca2+ channel-evoked Ca2+ transients in PVT neurons. We observed that the magnitude of LVA Ca2+ channel-evoked Ca2+ transients was significantly greater in proximal dendrites (located up to 20 microm from the soma) than in the soma.

Low voltage-activated Ca2+ channels are coupled to Ca2+-induced Ca2+ release in rat thalamic midline neurons.

High voltage-activated Ca2+ channels are coupled to the release of Ca2+ from intracellular stores. Here we present evidence that, in the paraventricular thalamic nucleus and other midline thalamic nuclei, activation of low voltage-activated (LVA) Ca2+ channels stimulates Ca2+-induced Ca2+ release (CICR) from intracellular stores. Voltage-clamp activation of LVA Ca2+ channels in fluo-4 AM-loaded neurons induced an initial transient increase in intracellular Ca2+ concentrations ([Ca2+]i) (mean increase, 19.

Acid-sensitive two-pore domain potassium (K2P) channels in mouse taste buds.

Sour (acid) taste is postulated to result from intracellular acidification that modulates one or more acid-sensitive ion channels in taste receptor cells. The identity of such channel(s) remains uncertain. Potassium channels, by regulating the excitability of taste cells, are candidates for acid transducers.

Acid-sensing ion channel-2 is not necessary for sour taste in mice.

The acid-sensitive cation channel acid-sensing ion channel-2 (ASIC2) is widely believed to be a receptor for acid (sour) taste in mammals on the basis of its physiological properties and expression in rat taste bud cells. Using reverse transcriptase-PCR, we detected expression of ASIC1 and ASIC3, but not ASIC4, in mouse and rat taste buds and nonsensory lingual epithelium. Surprisingly, we did not detect mRNA for ASIC2 in mouse taste buds, although we readily observed its expression in rat taste buds.

Expression of gonadotropin-releasing hormone and gonadotropin-releasing hormone receptor in sheep spinal cord.

Consistent with its neuroendocrine role, gonadotropin-releasing hormone (GnRH) is located principally within the hypothalamus, although extra-hypothalamic expression has been reported. The present study characterized the expression of GnRH and GnRH receptor (GnRH-R) in sheep spinal cord using real-time PCR and immunocytochemistry. Both GnRH and GnRH-R mRNA were detected in sheep spinal cord.