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Rising ovarian cancer mortality in the elderly: a manifestation of differential survival.

Ovarian cancer mortality among the elderly in developed countries is increasing. Using published United States mortality data, annual age-specific ovarian cancer mortality rates from 1951 to 1989 were determined for the over-60 age groups and compared to corresponding annual age group population sizes. Rising ovarian cancer mortality rates among the elderly in the United States from 1951 to 1989 were increasingly dependent, with increasing age, upon increasing age group population size. These findings suggest that differential survival, and its effect upon the surviving gene pool in an aging population, may account for some of the observed increase in ovarian cancer mortality rates among recent successive elderly cohorts.

Age Distribution↗

Increasing lung cancer mortality rates in the elderly: a manifestation of differential survival.

Lung cancer mortality rates in the elderly are increasing. Using published United States mortality data, annual age-specific lung cancer mortality rates from 1968 to 1989 were determined for age groups over age 50 and compared to corresponding annual age group population sizes. Rising lung cancer mortality rates among the elderly in the United States from 1968 to 1989 were increasingly dependent, with increasing age, upon increasing age group population size. This finding suggests that differential survival, and its effect upon the surviving gene pool in an aging population, may account for observed increasing lung cancer mortality rates in recent successive elderly cohorts. That is, increasing lung cancer mortality rates in the elderly may reflect changes in the genetic susceptibility of the surviving population rather than changes in environmental exposures.

Age Factors↗

Analysis of the complete DNA sequence of the temperate bacteriophage TP901-1: evolution, structure, and genome organization of lactococcal bacteriophages.

A complete analysis of the entire genome of the temperate lactococcal bacteriophage TP901-1 has been performed and the function of 21 of 56 TP901-1-encoded ORFs has been assigned. This knowledge has been used to propose 10 functional modules each responsible for specific functions during bacteriophage TP901-1 proliferation. Short regions of microhomology in intergenic regions present in several lactococcal bacteriophages and chromosomal fragments of Lactococcus lactis are suggested to be points of exchange of genetic material through homologous recombination. Our results indicate that TP901-1 may have evolved by homologous recombination between the host chromosome and a mother phage and support the observation that phage remnants as well as prophages located in the Lactococcus chromosome contribute significantly to bacteriophage evolution. Some proteins encoded in the early transcribed region of the TP901-1 genome were more homologous to proteins encoded by phages infecting gram-positive hosts other than L. lactis. This protein homology argues for the occurrence of horizontal genetic exchange among these bacteriophages and indicates that they have access to a common gene pool.

Bacteriophages↗

H5N1 influenza viruses isolated from geese in Southeastern China: evidence for genetic reassortment and interspecies transmission to ducks.

The H5N1 viruses (H5N1/97) associated with the "bird-flu" incident in the Hong Kong SAR have not been isolated since the slaughter of poultry in December 1997 brought that outbreak to an end. Recent evidence points to this virus as having arisen through a reassortment of a number of precursor avian viruses and a virus related to Goose/Guangdong/1/96 (H5N1) (Gs/Gd/96) was the likely donor of the H5 hemagglutinin. We characterize the Goose/Guangdong/1/96-like viruses isolated from geese and ducks imported into Hong Kong in the year 2000. Antigenically and genetically, these recent H5N1 viruses fall into two groups, one mainly associated with geese, and the other, recently transmitted to ducks. Further, viruses isolated from a goose and a duck in December 2000 have acquired NS, PA, M, and PB2 genes from the aquatic avian influenza gene pool through reassortment. For pandemic preparedness, it is important to monitor whether these reassortant viruses have the capacity for interspecies transmission to terrestrial poultry or mammals.

Animals↗

Models for angiogenesis in gliomas.

During the last decades a lot of attention has been focussed on mechanisms of glioma vascularization, particularly in terms of investigating vascular growth factors and receptors. Recently, these efforts resulted in various approaches for antiangiogenic treatment strategies using in vitro cell culture systems as well as experimental orthotopic and non-orthotopic brain tumors. These basic science and preclinical trials need an assortment of models, which should allow investigating a variety of questions. Several objectives concerning basic endothelial cell (EC) characteristics can adequately be studied in vitro using EC monolayer assays. Three-dimensional spheroid techniques respect the more complex cell-cell and cell-environment interplay within a 3-dimensional culture. Recent advances in molecular genetic techniques offer a wide access to the genome of EC. Using these micro array or chip methods differences between micro- and macromolecular EC as well as variations within the gene pool of different organ specific EC can be assessed. To optimize the imitation of the crucial interaction of human gliomas with host endothelial cells, immunological cells and extracellular matrix, animal models are mandatory. An essential rule is to utilize an orthotopic model, since tumor-host-interaction is organ specific. To avoid alloimmunogenic responses, it is desirable to use weak or non-immunogenic glioma grafts, which is best accomplished in a syngeneic model. However, since rat gliomas poorly resemble human glioma growth patterns, human glioma xenografting into immunocompromized animals should be considered. In vivo-monitoring techniques like videoscopy via a cranial window or magnetic resonance imaging (MRI) allow for functional studies and improve the validity of the model employed. Finally, it is essentially to recognize the limitations of each model considered and to select that model which seems to be most appropriate for the objectives to be investigated.

Animals↗

Genotypic characteristics of cyclic parthenogens and their obligately asexual derivatives.

Among extant taxa it appears that cyclic parthenogenesis has evolved on fewer than ten occasions. Evidence suggests that these groups are all derived from bisexual ancestors with genetic systems possessing specific preadaptations for the breeding system shift. Its apparently independent origin in two cecidomyiid lineages suggests that, when such preadaptations exist, the adoption of cyclic parthenogenesis may be a highly probable event. The genetic consequences of this transition are not dramatic; the genotypic characteristics of most cyclic parthenogens are similar to those of bisexuals. Specifically, genotypic frequencies at polymorphic loci are generally in Hardy-Weinberg equilibrium and linkage disequilibrium between variants at different loci is rare. Levels of variation in local populations of cyclic parthenogens are lower than those typical of sexual outcrossers, but the lack of variation appears to be a consequence of founder effects, as regional gene pool diversity is not similarly impoverished. An unusual genotypic structure occasionally develops in populations from habitats in which sustained parthenogenetic reproduction is possible and sexual recruitment is low. Under these circumstances low fitness genotypes are winnowed from the population by natural selection. The truncation of genotypic diversity often produces Hardy-Weinberg deviations and linkage disequilibrium. The depletion of clonal diversity rarely leads to the domination of a habitat by a single clone; an array of ecologically diversified clonal variants remains. The level of clonal variation in such populations is occasionally augmented by sexual recruitment, but the persistence of clonal diversity in local populations of obligate parthenogens makes it clear that clonal coexistence is not a consequence of such recruitment. Cyclic parthenogens have made the transition to obligate asexuality with high frequency, but there is little evidence to support the argument (Williams, 1975) that such shifts result from the relaxation of the short-term selection pressures supposedly necessary to sustain the sexual phase of the life cycle. Maynard Smith (1978) has recognized that in groups such as the aphids, which have never evolved the ability to produce their diapausing eggs asexually, sexuality may simply be retained as a consequence of its role in the formation of these eggs. However, he accepted that short-term selection was required to maintain sexuality in groups such as the cladocerans in which asexual forms have demonstrated their ability to retain life cycle complexity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Sequence conservation among the glucose transporter from the cyanobacterium Synechocystis sp. PCC 6803 and mammalian glucose transporters.

Synechocystis sp. PCC 6803 is capable of facultative photoheterotrophy with glucose as the sole carbon source. Eight mutants that were unable to take up glucose were transformed with plasmids from pooled gene banks of wild-type Synechocystis DNA prepared in an Escherichia coli vector that does not replicate in Synechocystis. One mutant (EG216) could be complemented with all gene banks to restore ability for photoheterotrophic growth. One of the gene banks was fractionated into single clones and plasmid DNA from each clone used to complement EG216. This yielded a 1.5 kb DNA fragment that was sequenced. It contained one complete open reading frame (gtr) whose putative gene product displayed high sequence conservation with the xylose transporter of E. coli and the mammalian glucose transporters. Further, the isolated gtr gene interrupted in vitro by a kanamycin resistance cassette could be used to construct mutants from wild-type Synechocystis sp. PCC 6803 that lacked a functional glucose transporter, thus confirming the identity of the gtr gene with the glucose transporter gene. This is the first prokaryotic glucose transporter known to share a sequence relationship with mammalian glucose transporters and the first sugar transporter from a cyanobacterium characterized at the sequence level.

Amino Acid Sequence↗

Recurrent mutations in the factor IX gene: founder effect or repeat de novo events. Investigation of the German haemophilia B population and review of de novo mutations.

The investigation of 114 unrelated patients, representing about half the sample of the German haemophilia B population, enabled us to delineate the causative mutation in 103 (90.4%) haemophilic factor IX genes. Of these 103 cases 84 (81.6%) turned out to be unique molecular events, the remainder being repeats. Haplotype analysis revealed that the great majority, if not all, of these recurrent observations occurred independently. This conclusion is supported by our finding that three de novo mutations could be demonstrated at two sites of frequent mutation. A further 20 de novo events could be established in an unselected sample of 37 families with sporadic haemophilia B and 37 families with a history of the disease. Altogether, the germ line of origin could be determined in 21 of these 23 cases, thereby indicating a ratio of male to female mutation rates close to 2. On the basis of the data available, it is becoming clear that rearrangements in the factor IX gene (35.4% of de novo cases) are responsible for haemophilia B at a higher frequency than has been observed today (12.3%). More than two-thirds of the de novo cases cause the severe form of the disease, thereby reflecting the deficit of these haemophilic genes in the actual gene pool because of excess mortality in the past. In addition 40% (12/30) of the de novo single-base mutations were transitions at CpG dinucleotides. Compared with the expected at-random frequency, this observation indicates an 83-fold enhancement of mutation at CpG.

DNA Mutational Analysis↗

Genetics of diabetes in Nauru: effects of foreign admixture, HLA antigens and the insulin-gene-linked polymorphism.

Genetic factors play a major role in predisposition to diabetes in the Micronesian population of Nauru. In people aged 60 years and older, 83% of full-blooded Nauruans were diabetic compared with 17% of those with ancestral foreign admixture, as detected by HLA typing. HLA distributions also showed a small increased risk for early onset of diabetes (less than 46 years) associated with HLA-Bw22 (Bw56). Variation in the restriction fragment length of DNA near the insulin gene was found, but was not associated with diabetes. The distribution in fragment lengths, previously reported in Caucasoids, was observed in healthy Polynesians, Melanesians and Micronesians.

Adult↗

Molecular characterisation of inter- and intra-specific somatic hybrids of potato using randomly amplified polymorphic DNA (RAPD) markers.

Protoplast fusion allows the transfer of both mono- and polygenic traits between species that are sexually incompatible. This approach has particular relevance for potato, and somatic hybridisation has been used to introduce a range of disease resistance genes from sexually incompatible wild species into the cultivated potato gene pool. In addition, protoplast fusion allows the resynthesis of tetraploid genotypes from preselected diploid or dihaploid donor parents. A limiting factor for the efficient exploitation of this technology in potato breeding is the difficulty of unequivocally identifying nuclear hybrids (heterokaryons). In order to facilitate the identification of hybrids at an early stage following fusion, Randomly Amplified Polymorphic DNA markers (RAPDs) have been used to characterise molecularly both inter- and intra-specific somatic hybrids of potato. RAPD markers detect naturally occurring polymorphism in the donor genotypes and utilise short oligonucleotide primers of arbitrary nucleotide sequence in combination with the polymerase chain reaction (PCR). The exploitation of RAPDs in the characterisation of both somatic and sexual hybrids is discussed.

Base Sequence↗

Two distinct P element subfamilies in the genome of Drosophila bifasciata.

The genome of Drosophila bifasciata harbours two distinct subfamilies of P-homologous sequences, designated M-type and O-type elements based on similarities to P element sequences from other species. Both subfamilies have some general features in common: they are of similar length (M-type: 2935 bp, O-type: 2986 bp), are flanked by direct repeats of 8 bp (the presumptive target sequence), contain terminal inverted repeats, and have a coding region consisting of four exons. The splice sites are at homologous positions and the exons have the coding capacity for proteins of 753 amino acids (M-type) and 757 amino acids (O-type). It seems likely that both types of element represent functional transposons. The nucleotide divergence of the two P element subfamilies is high (31%). The main structural difference is observed in the terminal inverted repeats. Whereas the termini of M-type elements consists of 31 bp inverted repeats, the inverted repeats of the O-type elements are interrupted by non-complementary stretches of DNA, 12 bp at the 5' end and 14 bp at the 3' end. This peculiarity is shared by all members of the O-type subfamily. Comparison with other P element sequences indicates incongruities between the phylogenies of the species and the P transposons. M-type and O-type elements apparently have no common origin in the D. bifasciata lineage. The M-type sequence seems to be most closely related to the P element from Scaptomyza pallida and thus could be considered as a more recent invader of the D. bifasciata gene pool. The origin of the O-type elements cannot be unequivocally deduced from the present data.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Genetic variation in two widespread species of salamanders, Taricha granulosa and Taricha torosa.

Two species of the genus Taricha are widely distributed. T. granulosa ranges from southern Alaska to central California. T. torosa is comprised of two described subspecies, T. t. torosa, which occupies much of the coast ranges of California, and T. t. sierrae, which inhabits the western slopes of the Sierra Nevada Mountains. A starch gel electrophoretic survey for genetic variation at 34 loci in four population samples of T. granulosa and at 40 loci in five population samples of T. torosa reveals differences among these taxa both in amounts of intrapopulational variability and in patterns of geographic variation. Average observed heterozygosity is 9.6% +/- 0.3% in T. granulosa, 3.3% +/- 0.5% in T. t. torosa, and 7.2% +/- 1.2% in T. t. sierrae. Average numbers of alleles per lon T. t. sierrae, and lowest in T. t. torosa. Oregon and California granulosa are genetically nearly as different as the subspecies of torosa, but geographic variation is continuous in the former. T. torosa on the other hand is comprised of three distinct gene pools--T. t. sierrae and northern and southern races of T. t. torosa. Strikingly different amounts of intrapopulational genetic variation and patterns of geographic variation may be explained by steady-state species differences, but historical causes may also exist.

Animals↗

Arrangement of genes TRP1 and TRP3 of Saccharomyces cerevisiae strains.

The tryptophan biosynthetic genes TRP1 and TRP3 and partly also TRP2 and TRP4 have been compared by the technique of Southern hybridization and enzyme measurements in twelve wild isolates of Saccharomyces cerevisiae from natural sources of different continents, in the commonly used laboratory strain S. cerevisiae X2180-1A and in a Kluyveromyces marxianus strain. We could classify these strains into four groups, which did not correlate with their geographical distribution. In no case are the TRP3 and TRP1 genes fused as has been found in other ascomycetes. Two strains were found which, in contrast to strain X2180-1A, show derepression of gene TRP1. Two examples are discussed to demonstrate the usefulness of Southern hybridizations for the identification of closely related strains.

DNA Restriction Enzymes↗

Biochemical resolution of European and African isolates of Trichinella nelsoni Britov and Boev, 1972.

Isoenzyme analysis was used to characterize 47 isolates of Trichinella nelsoni from Europe (EUR) and two from Kenya and Tanzania (AFR). In all, 27 isoenzymes showed polymorphism within the species. The EUR parasites, isolated from domestic, synanthropic, sylvatic animals and man, showed isoenzymatic profiles different from those exhibited by AFR parasites isolated from sylvatic animals. The EUR parasites showed polymorphism due to three isoenzymes, i.e. ME, MPI and PGM. Euclidean distance and a dendrogram were used to evaluate the relationships among isolates. The Euclidean values showed that EUR and AFR genotypes are distant from each other and from the reference strains T. spiralis s.str. and T. pseudospiralis. The genetic data indicate the absence of gene flow between AFR and EUR isolates. The biochemical results suggest the presence of genetic heterogeneity in T. nelsoni and support the existence of a zoogeographical segregation of the two gene pools. The authors propose that as operational labels, code T3 be assigned to EUR isolates and code T7, to AFR isolates.

Animals↗

Response of Drosophila persimilis to phototactic and geotactic selection.

The initial experimental population of Drosophila persimilis was photopositive and slightly geonegative. In this respect, the initial population of D. persimilis differed from the experimental population of D. pseudoobscura, described by others, which was close to photo- and geotactic neutrality. In D. persimilis as in D. pseudoobscura, photo- and geotactic selection was efficient in both positive and negative directions. In D. persimilis, unlike in D. pseudoobscura, the responses to geotactic and phototactic selection were clearly asymmetrical. As a result of such responses, selection practically eliminated interspecific difference in geotaxis and almost eliminated interspecific difference in phototaxis. The realized heritabilities of photo- and geotaxis over the first ten generations of selection in D. persimilis are between 6 and 7 percent. Practically, these heritabilities in D. persimilis have the same value, whereas in D. pseudoobscura the heritabilities are clearly different. These findings suggest that D. persimilis differs considerably from D. pseudoobscura in the composition of the genes determining photo- and geotactic behavior, most probably reflecting adaptations of these sibling species to different ecological niches. However, both species are capable of reacting quickly to external stresses by reorganizing their gene pools and by correspondingly changing their behavior.

Adaptation, Biological↗

Deduced amino acid sequences at the fusion protein cleavage site of Newcastle disease viruses showing variation in antigenicity and pathogenicity.

The amino acid sequence at the F2/F1 cleavage site of the F0 fusion protein of 17 strains of Newcastle disease virus (NDV) was deduced from sequencing a 32 nucleotide area of the genome by reverse transcription and polymerase chain reaction (PCR) techniques. With the addition of sequences at the same area previously published for 9 other viruses comparisons were made of a total of 26 NDV strains and isolates (11 of low virulence, 15 of high virulence or mesogenic) covering ten antigenic groups determined by reactions with monoclonal antibodies. All the virulent viruses and the mesogenic strain Komarov showed the amino acid sequence 112R/K-R-Q-K/R-R116 for the C-terminus of the F2 protein and phenylalanine (F) at the N-terminus of the F1 protein, residue 117. The mesogenic isolate of the antigenic variant NDV responsible for the recent panzootic in racing pigeons, often termed "pigeon paramyxovirus type 1", examined in this study had the sequence 112G-R-Q-K-R-F117. The deduced amino acid sequence in the corresponding region of all viruses of low virulence was 112G/E-K/R-Q-G/E-R-L117. The virulent virus, PMV-1/chicken/Ireland/34/90 (34/90), which had a close antigenic relationship to a group of avirulent viruses, three of which were examined in the present study as representatives of the monoclonal antibody group H, showed between 4-6 nucleotide differences from these viruses in the 32 nucleotide region studied. These resulted in differences in the deduced amino acid sequence at residue 112 E-->K, 115 E-->K and 117-->F, giving 34/90 a typical virulent virus motif at the cleavage site. Despite the extremely small portion of the genome studied there were several areas which appeared characteristic for 34/90 and the three group H viruses of low virulence, which suggests that they may have arisen from the same gene pool.

Amino Acid Sequence↗

Influenza virus subtypes in aquatic birds of eastern Germany.

We report the findings of a 12-year surveillance study (1977-89) of avian influenza A viruses in eastern Germany. Viruses were isolated directly from feral ducks (n = 236) and other wild birds (n = 89); from domestic ducks (n = 735) living on a single farm; and from white Pekin ducks (n = 193) used as sentinels for populations of wild aquatic birds; mainly sea birds. The efficiency of virus isolation was 9.9% overall, with considerable variability noted among species: 8.7% in wild ducks, 0.9% in other feral birds and 38% in Pekin ducks. Use of sentinel ducks in wild pelagic bird colonies improved virus detection rates fivefold, suggesting that this approach is advantageous in ecological studies. Among the 40 different combinations of hemagglutinin (HA) and neuraminidase (NA) subtypes we identified, H6N1 predominated (23.6% for all avian species), followed by H4N6 (11%). Among individual species, the frequency profiles favored H2N3 (20.8%) and H4N6 (20.3%) in feral ducks; H7N7 (22.3%), H4N6 (24.4%) and H2N3 (10.4%) in Pekin ducks used as sentinels; and H6N1 (34.8%) and H6N6 (15.1%) in domestic ducks maintained on a single farm. By relying on sentinel birds for serological assays, it was possible to trace an "influenza season" in feral swan populations, beginning in August and continuing through the winter months. Comparison of subtype distribution of influenza viruses for Europe and North America showed significant differences. This supports the fact of two geographically distinct gene pools of influenza viruses in birds connected with their distinct flyways of each hemisphere. The high frequency of isolation of H2 influenza viruses is of considerable interest to those interested in the recycling of this subtype in humans. Similarly the frequent isolation of H7N7 influenza viruses raises concern about reservoirs of potentially pathogenic influenza virus for domestic poultry. Our results confirm the existence of a vast reservoir of influenza A viruses in European aquatic birds, which possesses sufficient diversity to account for strains that infect lower animals and humans.

Animals↗