Wnt-beta-catenin signaling initiates taste papilla development

Fungiform taste papillae form a regular array on the dorsal tongue. Taste buds arise from papilla epithelium and, unusually for epithelial derivatives, synapse with neurons, release neurotransmitters and generate receptor and action potentials. Despite the importance of taste as one of our five senses, genetic analyses of taste papilla and bud development are lacking. We demonstrate that Wnt-beta-catenin signaling is activated in developing fungiform placodes and taste bud cells. A dominant stabilizing mutation of epithelial beta-catenin causes massive overproduction of enlarged fungiform papillae and taste buds. Likewise, genetic deletion of epithelial beta-catenin or inhibition of Wnt-beta-catenin signaling by ectopic dickkopf1 (Dkk1) blocks initiation of fungiform papilla morphogenesis. Ectopic papillae are innervated in the stabilizing beta-catenin mutant, whereas ectopic Dkk1 causes absence of lingual epithelial innervation. Thus, Wnt-beta-catenin signaling is critical for fungiform papilla and taste bud development. Altered regulation of this pathway may underlie evolutionary changes in taste papilla patterning.     

Chronobiology of sleep in humans

Periodic circadian (24-h) cycles play an important role in daily hormonal and behavioural rhythms. Usually our sleep/wake cycle, temperature and melatonin rhythms are internally synchronized with a stable phase relationship. When there is a desynchrony between the sleep/wake cycle and circadian rhythm, sleep disorders such as advanced and delayed sleep phase syndrome can arise as well as transient chronobiologic disturbances, for example from jet lag and shift work. Appropriately timed bright light is effective in re-timing the circadian rhythm and sleep pattern to a more desired time, ameliorating these disturbances. Other less potent retiming effects may also be obtained from the judicious use of melatonin and exercise.     

Oberflächenspannung und Schallgeschwindigkeit

Summary The preceding empirical relation was found between the surface tension of liquids, the specific weight of liquids, and the velocity of sound:=6.3 · 10^{–4 3/2}. In place of the vèocity of sound can be used, with suitable changes in the equation, the compressibility or, in the case of solid substances, the elasticity of the material in question. The range of validity of this relation is so large that it is possible by means of it to calculate the surface tension of solid substances and of gases.     

Darstellbarkeit doppelbrechender Lipoidtropfen aus dem Urin und pathogenetische Auffassungen der Lipoidurie

Summary (1) No double refractile Iipoid droplets can be obtained by alcohol ether extraction from urine or from urinary protein as it is possible from blood serum.(2) The conclusion is drawn that the double refractile lipoids droplets in urinary sediment do not pass through the glomeruli and therefore are not reabsorbed by the tubuli, but that they come from the own lipoproteins of the epithelial cells of renal tubuli and pass into urine by dissolution and desquamation of these cells.     

La formule chromosomique chez cinq espèces de Chiroptères

Summary Five species ofChiroptera were studied and the following numbers were found:Rhinolophus hipposideros Bechst.N=27;Barbastella barbastellus Schr.N=16;Plecotus auritus L.N=16;Myotis myotis Bork.N=21;Miniopterus schreibersii Kuhl,N=23. Centric fusions occur in the chromosomal evolution ofChiroptera. Sex-chromosomes ofX-Y type.     

Pyruvate dehydrogenase kinase regulatory mechanisms and inhibition in treating diabetes, heart ischemia, and cancer

The fraction of pyruvate dehydrogenase complex (PDC) in the active form is reduced by the activities of dedicated PD kinase isozymes (PDK1, PDK2, PDK3 and PDK4). Via binding to the inner lipoyl domain (L2) of the dihydrolipoyl acetyltransferase (E2 60mer), PDK rapidly access their E2-bound PD substrate. The E2-enhanced activity of the widely distributed PDK2 is limited by dissociation of ADP from its C-terminal catalytic domain, and this is further slowed by pyruvate binding to the N-terminal regulatory (R) domain. Via the reverse of the PDC reaction, NADH and acetyl-CoA reductively acetylate lipoyl group of L2, which binds to the R domain and stimulates PDK2 activity by speeding up ADP dissociation. Activation of PDC by synthetic PDK inhibitors binding at the pyruvate or lipoyl binding sites decreased damage during heart ischemia and lowered blood glucose in insulin-resistant animals. PDC activation also triggers apoptosis in cancer cells that selectively convert glucose to lactate. Received 25 August 2006; received after revision 20 November 2006; accepted 20 December 2006