Relevance of the lariat model to the splicing of the H-2 gene family

We examined the splicing of the H-2 gene family, taking the H-2Kd as a prototype, in the framework of the lariat model. We mainly investigated the mechanism described by Konarska et al. [Nature (Lond.) 313, 552-557 (1985)] who propose a direct interaction between the 5' splicing site and the branching region. We also checked each of the H-2 introns for the presence of patterns resembling the published consensus for the branching region. The known splicing events in the H-2 gene family are not always consistent with the current models, and our results indicate that slightly different mechanisms govern the splicing of different introns. A tentative explanation of the alternative splicing of the first and last intron, previously described, is given. The removal of the large third intron is not easily rationalized unless new rules for an additional multistep processing are postulated.     

Objective comparison of exon and intron sequences by means of 2-dimensional data analysis methods

Here we advocate the use of 2-dimensional data representation in the context of the informational approach of sequence analysis (Claverie & Bougueleret (1986) Nucleic Acids Research 14, 179-196) by applying these methods to the problem of intron/exon discrimination. Two main findings are reported: i) oligonucleotide patterns complementary to the Ul small nuclear RNA are specifically avoided in exon sequences, ii) vertebrate intron sequences, to the exclusion of other eukaryotic phyla, are characterized by a peculiar distribution of CpG containing patterns.     

Effect on prostatic growth of 2-difluoromethylornithine, an effective inhibitor of ornithine decarboxylase.

2-Difluoromethylornithine (DFMO), an enzyme-activated irreversible inhibitor of ornithine decarboxylase, causes marked changes in the polyamine metabolism of ventral prostate when given to adult rats in drinking water (20 g/l) for 3 consecutive days. A 90% inhibition of ornithine decarboxylase activity is accompanied by approx. 80% decreases of the concentrations of putrescine and spermidine and by a 36% decrease in spermine. Concomitantly, S-adenosylmethionine decarboxylase activity increases 7-fold and the concentration of decarboxylated S-adenosylmethionine 450-fold. When DFMO is given to immature rats for 12 consecutive days the above described changes are accompanied by a marked reduction in the age-dependent increases of the wet weight and RNA and DNA contents of the ventral prostate. In adult rats DFMO decreases the weight and RNA content of the ventral prostate within 4 days by 32% and 24% respectively and maintains them constant for the next 19 days. After 23 days of treatment, the prostatic weight is 46% of that of control animals of the same age, whereas the weights of other organs are only slightly decreased. Cytological studies carried out at this time show that DFMO reduces the size of both prostatic acini and the epithelial cells lining the acini.     

Mutations of Chinese Hamster Somatic Cells from 2-Deoxygalactose Sensitivity to Resistance

In Chinese hamster somatic cells, the spontaneous change of phenotype from 2-deoxygalactose sensitivity to resistance was studied using fluctuation test experiments à la Luria and Delbrück (1943) for four Chinese hamster cell strains derived from V79. The results are consistent with true mutational events. The mutation rates are in the range of 1 to 3.5 X 10(-5) per cell per generation. The relationship between the 2-deoxyglactose resistance and the galactokinase markers is discussed.     

Acetylcholine receptors are not functionally independent.

Analysis of current recordings from acetylcholine-activated channels has largely rested so far on the hypothesis of independence, which states that the opening of one channel does not influence that of its neighbors. We have submitted this assumption to several tests, using as experimental material single channel currents from rat myotubes. We found that, even though the distribution of multiple channel openings may be approximated by the Poisson law, openings are strongly coupled. This conclusion is derived from the analysis of two-time properties associated with patch-clamp data. We show how these properties, which contain more detailed information than the stationary probabilities, can be calculated in practice and why a Poisson analysis is misleading in the present case. The implications of our findings are finally discussed in terms of channel structure and function.     

Protective effects of zinc on cadmium toxicity in rodents

A study of acute and subacute toxicity of cadmium ions [Cd(II)] was carried out on male Swiss mice and Sprague-Dawley rats with and without previous administration of zinc chloride. The LD₅₀ of Cd(II) as cadmium sulfate (ip) was lower in animals previously given 10 mg/kg of zinc(II) chloride (sc). Factors such as animal weight variations, biochemical parameters, and accumulation patterns of Cd(II) and Zn(II) were taken into consideration when the subacute toxicity was evaluated. Alteration of the activities of glutamic pyruvic transaminase (GPT) and of glutamic oxaloacetic transaminase (GOT) was observed in short-term-exposure (<6 h) cases. These alterations reverted to normal after 1 wk. The activity of alkaline phosphatase (ALP) and the concentrations of cholesterol and triglycerides in serum are also changed, especially so in the groups given CdSO₄ alone. In the experimental groups treated with ZnCl₂ prior to administration of cadmium, proteinuria was detected 5 wk after the treatment. Also at 5 wk, both Zn-treated and nontreated groups showed an abnormally low liver mass with respect to total body mass. Both Cd and Zn are retained preferentially in the liver but show also in the kidneys. If CdSO₄ and ZnCl₂ are given simultaneously, especially after 1 wk of treatment, Cd is accumulated in greater amounts in these organs when compared to the groups given only cadmium sulfate.