Collagen gene construction and evolution

Summary Collagen genes appear to have been assembled by the tandem repetition of homologous primary (9 base pair), secondary (54 base pair), and tertiary (702 base pair) modules. In vertebrate interstitial collagen genes many of the secondary modules are separated by introns, but in invertebrate collagen genes the non-coding sequences lie near the ends of supposed tertiary modules and are therefore about 702 (54×13) base pairs apart. The genes for vertebrate interstitial collagens (types I–III) seem to have been constructed by the tandem repetition of five tertiary modules, three of which were subsequently shortened by internal deletions. This shortening of the gene resulted in the non-integral relationship between the period of the fibrils and the length of the molecules of vertebrate collagens, and was therefore responsible for the mechanical properties of the completed product. Comparisons of the amino acid sequences of various collagens indicate that the main types of collagen evolved about 800–900 million years ago, a date that agrees well with the fossil record of primitive Metazoa.     

Naloxone influences ultrasonic calling in young mice

The ultrasonic calls produced by three day old mice when separated from the nest mother and siblings increase in number when naloxone is injected.     

Reverse transformation of Chinese hamster ovary cells by methyl xanthines : Structure-function relationships

Using a number of drugs that increase cellular cAMP levels, alterations in the amount of cell surface fibronectin and other transformation parameters were studied in Chinese hamster ovary (CHO) cells. The drugs include db-cAMP, different methylxanthines (theophylline, aminophylline, methyl isobutyl xanthine (MIX), caffeine and theobromine), papaverine and cholera toxin. Methylxanthines that have a methyl group at the seventh position lack reverse transforming potential; those that lack a methyl group at the seventh position induced reverse transformation in CHO cells, causing an increase in surface fibronectin, cell substratum adhesive strength and anchorage dependence for growth. Further, as methyl xanthines are substituted in other positions different from the seventh position, the more efficient they become in restoring normal phenotypic properties; the later agents also induced low saturation density via a cytostatic state causing accumulation of cells in the S and G2 phases of the cycle in contrast to the G1 arrest of normal cells at low saturation density. db-cAMP and cholera toxin induced cell elongation but like caffeine and theobromine, did not induce surface fibronectin. The non-methylxanthine phosphodiesterase inhibitor papaverine induced neither cell elongation nor surface fibronectin but produced a cytostatic effect similar to aminophylline and MIX. These studies suggest that the reverse transformation properties fall into two groups: (a) Differentiation-related properties including cell morphology, parallel alignment and surface matrix fibronectin, etc.; (b) cell cycle-related properties-low saturation density, cell arrest at G1 phase and anchorage-dependent growth. Phosphodiesterase inhibitors reversibly eliminate indefinite division potential of CHO cells by inducing a cytostatic situation and not by inducing a G1-specific arrest.     

Adrenergic Regulation of the Reduction in Acetyl Coenzyme A: Arylamine 7V-Acetyltransferase Activity in the Rat Pineal

Abstract: Pharmacologically active agents were employed to study the mechanisms that control the reduction in levels of acetyl-coA: arylamine N-acetyltransferase activity (NAT) (EC 2.3.1.5) in the rat pineal. Pretreatment of rats with phenoxybenzamine or phentolamine prevented the rapid light-mediated decrease in NAT activity, although pretreatment with yohimbine or atropine did not alter this effect of light. Administration of mecamylamine resulted in a rapid reduction in enzyme activity prior to light exposure. When clonidine was administered intraperitoneally to animals with elevated NAT levels, there was a rapid decrease in enzyme activity, mimicking the effects of light. However, intraperitoneal injections of norepinephrine, methoxamine and phenylephrine into similar groups of animals had no significant effect on enzyme acitivity. When clonidine and norepinephrine were administered intraventricularly, there was a rapid reduction in enzyme activity. On the other hand, intraventricular administration of phenylephrine did not result in reduced enzyme activity. Pretreatment of animals with phenoxybenzamine failed to block the reduction in NAT activity precipitated by low doses of clonidine. This clonidine-mediated reduction in enzyme activity was, however, blocked by yohimbine. When animals were simultaneously exposed to light and administered clonidine, the rapid reduction in NAT activity was affected only when animals were pretreated with both yohimbine and phenoxybenzamine. In contrast to the decrease in pineal NAT activity observed in in vivo preparations, incubation of pineals with clonidine in an organ culture system produced a moderate, but consistent, rise in enzyme activity. These results suggest that stimulation of a receptor with α-adrenergic characteristics mediates the reduction in NAT activity produced by light. Stimulation of yet a second adrenergic-like receptor appears to mediate a reduction in pineal NAT activity precipitated by clonidine. Our evidence suggests that one or both of these receptors are located within the central nervous system.     

Developmental delays in exploration and locomotor activity in male rats exposed to low level lead

Delays in the development of exploratory and locomotor behavior in neonatal male rats (up to 21 days of age) are shown to accrue as a consequence of low level lead exposure. Cross fostering experiments indicate that these delays are primarily due to prenatal exposure. These Pb induced behavioral modifications appear to be associated with the delays in synaptogenesis and biochemical development of the cerebral cortex reported previously (4, 18). A new behavioral bioassay for detecting delays in brain development is described.