A comparative study of mutations in Escherichia coli and Salmonella typhimurium shows that codon conservation is strongly correlated with codon usage.

Escherichia coli and Salmonella typhimurium are closely related species of enteric bacteria, having diverged from 120 to 160 million years ago, according to the estimate of Ochman & Wilson (1987. J. Mol. Evol.26, 74-86). In order to study base substitution mutations in the genomes of these bacteria, we have compared pairs of genes for the same product in the two species, and have selected a sample in which the protein length is the same in both E. coli and S. typhimurium. From the alignment of these gene pairs, we observe that frequently used codons are more conserved than infrequently used codons, i.e., the apparent mutation rate is higher for rare codons than for popular codons.

Analysis of a copy number mutant of plasmid pSC101: co-maintenance of wild type and mutant plasmids.

We have isolated a high copy number mutant of plasmid pSC101 which is maintained at a level 4 times higher than that of the wild type. The mutation is a single base change that maps in codon 93 of the initiation protein RepA. We find that the mutation relaxes the autoregulation of the protein but increases its affinity for the repeated sequences in the origin. The wild type and the mutant repA genes are co-dominant and the mutated protein acts in trans even in the presence of the wild type protein. Co-maintenance of the two types of plasmids results in an intermediate copy number. Computer simulation indicates that simple models can explain the behaviour of the two plasmids.

Teenage depression: a cultural-interpersonal-intrapsychic perspective.

The "crossroads families" are caught between old value systems and American mainstream goals. Traditional family and sex-related roles and orientations conflict with those of the new social system. In turn, neither of the teenager's orientations--toward home or toward peer activity--is validated. In the clinical case presented, Anna, at adolescence, wants to relinquish many of her household chores and enter her social world more fully. She needs unconflictual support for such a move. If this does not take place, her autonomous movement represents an unconscious betrayal of her depleted and controlling mother as well as an abandonment of the parental coalition. This leaves her feeling resentful, guilty, and ultimately unlovable. Attitudes marked by helplessness and confusion are thus significant to the depressed affect that brings this teenager into family therapy. Teenagers of non-Hispanic background who enter family therapy reveal gross overlap with teenagers of the Hispanic "crossroads" family model. Here, the family gives mixed messages for homebound and intimate closeness as well as accomplishment in the societal mainstream. A primary difference between ethnic groups involves the freer expressions of anger and pain between husband and wife in the non-Hispanic families. This is not similar to the backgrounds of the more individuated Hispanic teenagers. While more open expressions of anger within the family do indicate higher levels of autonomy, the hostility that is expressed by the parents presents serious complications when this includes "triangulating" the child into the family tension. Here, as cited, the mother often uses her daughter as a confidant and ally at times of severe parental discord. This places additional strain on the child's conflict with separation. Importantly, the daughter experiences renewed rejection and betrayal when the mother "submits" to her spouse. These are significant family processes that heighten mixed messages around autonomy. Milagros, a depressed (more individuated) adolescent, is consistently entangled into her parent's abrasive relationship. Her interpersonal family struggles have become intrapsychic and, ultimately, transferential.

Codon usage in Homo sapiens: evidence for a coding pattern on the non-coding strand and evolutionary implications of dinucleotide discrimination.

This study reports the analysis of codon usage in 35 complete Homo sapiens genes. Both codon frequency and inter-codon interference exhibit patterns of evolutionary interest. There is a significant positive correlation between the frequency with which a given codon is used and the frequency with which its complement is used. Since the frequency of appearance of the complementary codon on the coding strand is equal to the frequency of appearance of the original codon on the non-coding strand, in the same phase, the non-coding strand is found to resemble the coding strand in triplet composition. The same effect has been observed in Escherichia coli. This preference for the use of certain complementary triplets as codons suggests that the evolution of the use of the genetic code depended to some extent upon the double-stranded nature of the coding material. In addition, the effect of discrimination against the use of two dinucleotides, CpG and UpA, is observed in codon usage and also in adjacent codon interference. Codons beginning with G, or A, are unlikely to be preceded by codons ending in C, or U, respectively. Consideration of codon assignment in the genetic code together with the observed CpG infrequency suggests that the evolution of the code may have been influenced by conditions in which the use of CpG dinucleotides was unfavorable. The infrequent use of UpA dinucleotides can be explained as the result of frameshift mutation during gene evolution.

Substance P neurons sprout in the cervical spinal cord of the wobbler mouse: a model for motoneuron disease.

The mutant mouse, wobbler, possesses a recessively inherited degeneration of motoneurons and other ventral horn cells in the cervical spinal cord, and therefore it has been proposed as an animal model of human motoneuron disease. Affected mice have been identified by behavioral tests that also determined the extent of the motor deficit. The results from these tests were combined and used to define distinct stages of the disease process that could then be correlated histochemically with the amount of acetylcholinesterase (AChE) staining in the cervical spinal cord. AChE is used as a marker for cholinergic neurons and is known to hydrolyze the neuropeptide modulator substance P (SP). SP, a peptide neuromodulator of primary afferent transmission in the dorsal horn, excites motoneurons in the ventral horn, and may possess secondary functions in neuronal maintenance. Therefore, the levels of immunoreactive (IR) SP and AChE were examined in an attempt to determine the possible interaction between these factors in motoneuron degeneration. By enzyme histochemistry, the cervical spinal cord, taken from wobbler mice at behaviorally identified stages of the motor deficit, exhibited decreased levels of AChE throughout the ventral horn. The decrease detected in the AChe staining intensity was linear and correlated with the decrease in the number of AChE-positive cells in the ventral cervical spinal cord, as the motor deficit progressed. Presumably, the continual decrease in AChE staining represents the degeneration of cholinergic perikarya and neuronal processes in the ventral horn as the motoneuron disease proceeds. At two well-established stages of the motor deficit, the amount of immunoreactive SP increased in the ventral horn compared with the control mice. The elevated levels of immunoreactive SP suggest sprouting may have occurred preceding, or in response to, the motoneuron degeneration. Several additional hypotheses are discussed in respect to phenomena that might contribute to the increase of immunoreactive SP in the degenerating ventral horn of the wobbler mouse.

Evidence for a coding pattern on the non-coding strand of the E. coli genome.

Analysis of codon usage frequency for the combined coding sequences of 52 E. coli genes, taken from the European Molecular Biology Laboratory Nucleotide Sequence Data Library, Release 2, shows that there is a significant positive correlation between the frequency with which a given codon appears on the coding strand and the frequency with which it appears, in phase, on the non-coding strand.

Design and methodology of the Zagreb preliminary study: response rates at the study stages.

A procedure for recruitment of a trial cohort from a demographically defined population is described. Provision was made by means of a prescreening survey to determine demographic and attitudinal characteristics in the group invited to screening before the invitation was extended, thus providing information on non-participants as well as participants. Men who satisfied the criteria for borderline levels of one or more of the three risk factors on at least two of possible three occasions were invited to participate in a radomized multifactor treatment trial either being treated by medication for the appropriate risk factor [or factors], or observed during the same intervals in the same fashion as those treated. During follow-up attempts were made to measure adherence to the prescribed medication.

Effect of repetitive health examinations on blood sugar levels: the Zagreb preliminary study.

In this study recruitment rates of subjects with borderline glucose tolerance were investigated (using the specific procedure described below) and were shown to be 1.8% of the population approached and 2.5% of the population screened. 75 g glucose load yielded higher numbers of subjects with borderline glucose tolerance levels at screening than a 50 g glucose load. However, the numbers of the people finally recruited into the cohort by confirmatory screening were the same when only the 50 g load was used at confirmatory screenings. Subjects recruited in this way remained in the study for 24 months. Repeated health checks had an effect of lowering concentrations of blood glucose after an oral load in treated and control groups, and in those with borderline and those with normal blood glucose values at the initial screening. It is concluded that the process of screening and observation itself has an effect upon glucose tolerance, independent of formal 'treatment'.

Repetitive health examinations as an intervention measure.

A cohort of 107 men aged 51-53 years with borderline levels of blood pressure, serum cholesterol, or glucose tolerance was recruited from a general population in central Zagreb, Yugoslavia, and randomized into two groups; one was treated with drugs and the other observed in a similar fashion but not treated. Ninety-five men appeared regularly for the check-ups over a 2-year period. Levels of systolic blood pressure, cholesterol, and glucose showed a substantial decrease over a period of 2 years in both treated and control groups. The possible effect of repeated check-ups and their implications are discussed.

The genetic code and error transmission.

The amino acid substitutions resulting from single-base substitution in the natural genetic code have been compared with those resulting from single-base substitutions in computer-generated random codes. Considering the amino acid properties of molecular weight, polar requirement, number of dissociating groups, pK(1)', isoelectric point, and alpha-helix forming ability, it is concluded that, for the natural code, single-base substitution in the first position of the codon tends to result in the substitution of an amino acid more similar to the original amino acid than would be expected from a random code. In the natural code, the second position of the codon plays the largest role in determining the properties of the amino acid.