The glycoprotein P0 in peripheral gliogenesis

Recent data show that during development protein zero, P0, the most abundant peripheral nerve myelin protein, is detecable long before myelination. In particular, the expression of P0 in a fraction of migrating neural crest reveals progenitor cell heterogeneity in the developing PNS. Here we review the regulation and potential function of P0 during peripheral gliogenesis.     

A polymorphism but no mutations in the GADD45 gene in breast cancers

The p53 gene product is part of a pathway regulating growth arrest at the G₁ checkpoint of the cell cycle. Mutation of other components of this pathway, including the products of the ataxia telangiectasia (AT), GADD45, mdm2, and p21^WAF1/CIP1 genes may have effects comparable to mutations in the p53 gene. The GADD45 gene is induced by ionizing radiation and several DNA-damaging xenobiotics. Induction requires the binding of wild-type p53 to an evoulutionarily highly conserved putative intronic p53 binding site in intron 3 of GADD45. We recently analyzed the entire coding region of the p53 gene in primary breast cancers of Midwestern white women and found 21 mutations among 53 tumors (39,6%). We now have shown by direct sequencing that there are no mutations in the intronic p53 binding site of the GADD45 gene in any of the 53 primary breast cancers and no mutations in the entire coding region of the GADD45 gene in a subset of 26 consecutive tumors (12 with p53 mutation and 14 without p53 mutation). The only sequence variation detected was a common polymorphism in intron 3. The absence of mutations in the GADD45 gene, including the putative p53-binding intronic site, suggests that this gene is not a frequent target of mutations in breast cancer. Although mutations of the p53 gene have been studied in a wide spectrum of human cancers, GADD45 has not been examined in any tumor or cell line to the best of our knowledge. Our results raise the possibility that mutation of the GADD45 gene alone is not functionally equivalent to loss of wild-type p53 activity. Received: 14 September 1995     

Missense mutations and evolutionary conservation of amino acids: evidence that many of the amino acids in factor IX function as "spacer" elements.

We report 31 point mutations in the factor IX gene and explore the relationship between the level of evolutionary conservation of an amino acid and the probability of a mutation causing hemophilia B. From our total sample of 125 hemophiliacs and from those reported by others, we identify 95 independent missense mutations, 94 of which occur at amino acids that are evolutionarily conserved in the available mammalian factor IX sequences. The likelihood of a missense mutation causing hemophilia B depends on whether the residue is also conserved in the factor IX-related proteases: factor VII, factor X, and protein C. Most of the possible missense mutations in generically conserved residues (i.e., those conserved in factor IX and in all the related proteases) should cause disease. In contrast, missense mutations in factor IX-specific residues (i.e., those conserved in human, cow, dog, and mouse factor IX but not in the related proteases) are sixfold less likely to cause disease. Missense mutations at nonconserved residues are 33-fold less likely to cause disease. At least three models are compatible with these observations. A comparison of sequence alignments from four and nine species of factor IX and an examination of the missense mutations occurring at CpG residues suggest a model in which most residues fall on opposite ends of a spectrum. In about 40% of residues, virtually any missense mutation in a minority of the residues will cause disease, while virtually no missense mutations will cause disease in most of the remaining residues. Thus, many of the residues in factor IX are spacers; that is, the main chains are presumably necessary to keep other amino acid interactions in register, but the nature of the side chain is unimportant.     

Dominance,age, and reproductive success in free-ranging female hanuman langurs (Presbytis entellus)

Correlations among female age, dominance, and reproduction were investigated for a 12-year period in free-ranging, provisioned Hanuman langurs (Presbytis entellus), living in one-male groups near Jodhpur in Rajasthan, India. Of 2940 displacement episodes, 27% occurred over natural food, 26% over provisioned food, 8% over grooming, 23% over position and shade, and 16% for other reasons. It was possible to reconstruct a displacement hierarchy that was linear and stable over short periods but fluctuated according to the age composition of the troop, resulting in an age inversed dominance structure. Females occupied top ranks as soon as they experienced menarche (around 2.4 years of age) and gradually declined thereafter, with postmenopausal females (≥30 years) being the lowest ranking individuals. Old females tended to be peripheral, while young females were highly social and active. Fertility peaked at about 7 years and gradually decreased thereafter, but infant mortality was much higher in young females than in old ones. During years when females gave birth, their ranks, especially those of old females, were higher than the average expectation for their age class, which suggests that females compete more vigorously if they have an infant. Reproductive success (i.e., infant survival to ≥2 years) declined significantly from high-over middle-to low-ranking females but did not differ for the three age classes investigated, because the higher fecundity of young females was balanced by better rearing success of older females. These results are discussed in light of the controversy over whether the langur social system is strongly influenced by kin selection (Hrdy and Hrdy, 1976; Dolhinow et al., 1979).     

Mouse ornithine decarboxylase is stable in Trypanosoma brucei.

The cDNA encoding mouse ornithine decarboxylase (ODC) was incorporated into a transforming vector pTSA-NEO2 carrying a procyclic acidic repetitive protein promoter and a neomycin phosphotransferase gene. The plasmid thus constructed, pMOD300, was introduced into the procyclic forms of Trypanosoma brucei via electroporation, and the transformants, selected under G418, expressed an ODC activity 100 times above the background level. Contrary to the commonly observed short half-life of mouse ODC in mammalian cells, however, the mouse ODC activity expressed in T. brucei remained stable for at least 6 h when protein synthesis was inhibited by cycloheximide. Pulse labelings and chase experiments with the irreversible ODC inhibitor [3,4-3H]difluoromethylornithine followed by gel electrophoresis, or with L-[35S] methionine followed by immunoprecipitation and gel electrophoresis indicated that the stable mouse ODC expressed in T. brucei has the same subunit molecular weight as the native enzyme. By an in vitro assay of protein stability in rabbit reticulocyte lysates (Loetscher, P., Pratt, G., and Rechsteiner, M. (1991) J. Biol. Chem. 266, 11213-11220), the native mouse ODC and the enzyme expressed in T. brucei had the same degree of instability. Thus, the mouse ODC expressed in T. brucei is probably identical to the native mouse ODC. Its remarkable stability in T. brucei must be due to the absence in trypanosomes of the proteolytic machinery present in mammalian cells responsible for rapid degradation of mouse ODC.     

Bioactivity of chitinolytic actinomycetes of marine origin

Summary Of 116 chitinolytic actinomycetes, previously isolated from marine sediments, 85 were found to possess antimicrobial activity. A high correlation was noted between chitinolysis and bioactivity. A majority of them suppressed the growth of Gram-positive bacteria but only a few inhibitedGram-negative strains and almost one-half of them exhibited antimyccotic activity. Several of the last group yielded polyenes of which heptaenes were the most commonly occurring ones. Other strains synthesized detectable amounts of \-lactam antibiotics. It is suggested that chitinolysis may serve as an indicator of potential bioactivity among marine actinomycetes. Offprint requests to: M. A. Pisano     

Convergent succession of phytoplankton in microcosms with different inoculum species composition

Summary Different initial mixtures of phyto-and zooplankton from different lakes were grown under identical chemical and physical conditions in medium size (8-and 12–1) laboratory microcosm cultures until convergence of phytoplankton species composition was attained. Five such experiments with four (four experiments) or three (one experiment) microcosm cultures were run. Three experiments were performed with weak stirring which permitted sedimentary elimination of the diatoms. Two experiments were conducted with stronger stirring to prevent sedimentation. In the three sedimentation intensive experiments, the final phytoplankton community was composed of the filamentous chlorophyte Mougeotia thylespora together with a smaller biomass of nanoplanktic algae. In the two sedimentation free experiments the final phytoplankton community consisted of pennate diatoms. Both dissolved nutrient concentrations and the chemical composition of biomass suggested strong nutrient limitation of algal growth rates in the final phase of the experiments. The zooplankton communities at the end of the experiments were composed of species that were apparently unable to ingest the large, dominant algae and that presumably fed on the nanoplanktic undergrowth and the bacteria. There was a distinct sequence of events in all experiments: first, the large zooplankton species (Daphnia and Copepoda) were replaced by smaller ones (Chydorus, Bosmina, rotifers); second, all cultures within one experiment developed the same nutritional status (limitation by the same nutrient); and third, the taxonomic composition of phytoplankton of the different cultures within one experiment converged. The last took 7–9 weeks, with is about 2–3 times as long as the time needed in a phytoplankton competition experiment to reach the final outcome.     

Changes in relative mobility of pancreatic amylase variants in isoelectric focusing

Using isoelectric focusing with one ampholytic solution, double- and single-banded amylase phenotypes were found in a sample of rhesus monkeys,Macaca mulatta. When applying different ampholytic solutions, these variants were shown to change their position relative to each other. Single-banded phenotypes showed either a position corresponding to one of the bands of the double-banded phenotype or to an intermediate one. Family studies, however, suggested that the differences between the observed patterns were not caused by genetic differences. This discloses a problem with respect to the interpretation of electrophoretic data, i.e. bands with different positions produced by isoelectric focusing may not necessarily represent genetic differences.