Cadherin 23 is a component of the tip link in hair-cell stereocilia

Mechanoelectrical transduction, the conversion of mechanical force into electrochemical signals, underlies a range of sensory phenomena, including touch, hearing and balance. Hair cells of the vertebrate inner ear are specialized mechanosensors that transduce mechanical forces arising from sound waves and head movement to provide our senses of hearing and balance; however, the mechanotransduction channel of hair cells and the molecules that regulate channel activity have remained elusive. One molecule that might participate in mechanoelectrical transduction is cadherin 23 (CDH23), as mutations in its gene cause deafness and age-related hearing loss. Furthermore, CDH23 is large enough to be the tip link, the extracellular filament proposed to gate the mechanotransduction channel. Here we show that antibodies against CDH23 label the tip link, and that CDH23 has biochemical properties similar to those of the tip link. Moreover, CDH23 forms a complex with myosin-1c, the only known component of the mechanotransduction apparatus, suggesting that CDH23 and myosin-1c cooperate to regulate the activity of mechanically gated ion channels in hair cells.     

Accelerator mass spectrometry radiocarbon ages of amino acid extracts from Californian palaeoindian skeletons

A decade ago, aspartic acid racemization ages were determined for some skeletal remains found in California, near La Jolla, Del Mar and Sunnyvale, suggesting that people were present in North America during the Upper Pleistocene. These ages were obtained from the aspartic acid racemization rate, which was calibrated using a radiocarbon date of 17,150 +/- 1,470 yr BP determined for a skeleton found in Laguna Beach, California. These studies generated an intense controversy not only about the antiquity of human beings in the New World but also about the validity of racemization-based ages, and prompted efforts to date the finds by other means. Here we have used accelerator mass spectrometry (AMS) to determine the radiocarbon ages of the amino acid extracts used in the original racemization studies. Our studies indicate that some of the controversial Californian skeletons, which had been assigned to the Upper Pleistocene, are in fact Holocene.     

Proviral sequences of baboon endogenous type C RNA virus in DNA of human leukaemic tissues.

Hybridisation of RNA from a baboon endogenous type C RNA virus to DNA from tissues of leukaemic patients indicates that a virus of this type is horizontally transmitted among humans. DNA from several patients with leukaemia hybridised 70% of the hybridisable RNA from baboon endogenous type C RNA virus (BaEV) and yielded hybrids of high tm, whereas DNA from normal human tissues hybridised only 23% of the BaEV RNA, and the tm of these hybrids was lower.     

The effect of ion pair formation on the antimuscarinic activity of methantheline

Summary The quaternary ammonium compound, methantheline, was found to antagonize acetylcholine induced contractions in isolated guinea pig ileum by a mechanism which did not conform to the criteria for either competitive or non-competitive inhibition. Enhancement of the lipid solubility of methantheline by formation of an ion pair with trichloracetate failed to influence its cholinergic inhibitory activity. The results suggest that in the guinea pig ileum a) an intracellular site of action does not exist for methantheline and b) the membrane receptors for methantheline most likely are located in an aqueous environment.     

Interactions ofΔ 11-tetrahydrocannabinol with cannabinol and cannabidiol following oral administration in man. Assay of cannabinol and cannabidiol by mass fragmentographywith cannabinol and cannabidiol following oral administration in man. Assay of cannabinol and cannabidiol by mass fragmentography

Summary Oral administration to man of 20 mg ¹1-tetrahydrocannabinol (THC) together with placebo or 40 mg cannabinol (CBN) or 40 mg cannabidiol (CBD) gave evidence of a possible limited interaction of THC with CBN but not with CBD as indicated by average plasma THC levels. Peak CBD and CBN concentrations were similar to that of THC, viz. about 5–8 ng/ml.Supported by the Swedish Medical Research Council and grant MH-00424 from the Veterans Administration.     

The effect of ion pair formation on the antimuscarinic activity of methantheline.

The quaternary ammonium compound, methantheline, was found to antagonize acetylcholine induced contractions in isolated guinea pig ileum by a mechanism which did not conform to the criteria for either competitive or non-competitive inhibition. Enhancement of the lipid solubility of methantheline by formation of an ion pair with trichloracetate failed to influence its cholinergic inhibitory activity. The results suggest that in the guinea pig ileum a) an intracellular site of action does not exist for methantheline and b) the membrane receptors for methantheline most likely are located in an aqueous environment.