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  • pharmacokinetics  (2,025)
  • Saccharomyces cerevisiae  (735)
  • evolution  (696)
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  • Springer Nature  (4)
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  • 1
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    Springer Nature | Springer International Publishing
    Publication Date: 2024-04-05
    Description: This open access book covers a century of research on wheat genetics and evolution, starting with the discovery in 1918 of the accurate number of chromosomes in wheat. We re-evaluate classical studies that are pillars of the current knowledge considering recent genomic data in the wheat group comprising 31 species from the genera Amblyopyrum, Aegilops, Triticum, and other more distant relatives. For these species, we describe morphology, ecogeographical distribution, phylogeny as well as cytogenetic and genomic features. For crops, we also address evolution under human selection, namely pre-domestication cultivation and domestication. We re-examine the genetic and archeological evidence of where, when, and how domestication occurred. We discuss unique aspects of genome evolution and maintenance under polyploidization, in natural and synthetic allopolyploids of the wheat group. Finally, we propose some thoughts on the future prospects of wheat improvement. As such, it can be of great interest to wheat researchers and breeders as well as to plant scientists and students interested in plant genetics, evolution, domestication, and polyploidy.
    Keywords: Wheat ; Triticeae ; cytogenetics ; polyploidy ; genomics ; phylogenetics ; domestication ; evolution ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences::PST Botany and plant sciences ; thema EDItEUR::T Technology, Engineering, Agriculture, Industrial processes::TV Agriculture and farming::TVB Agricultural science ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences::PSA Life sciences: general issues::PSAK Genetics (non-medical)
    Language: English
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  • 2
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    Springer Nature | Palgrave Macmillan
    Publication Date: 2024-04-05
    Description: This open access book offers a comprehensive overview of the history of genomics across three different species and four decades, from the 1980s to the recent past. It takes an inclusive approach in order to capture not only the international initiatives to map and sequence the genomes of various organisms, but also the work of smaller-scale institutions engaged in the mapping and sequencing of yeast, human and pig DNA. In doing so, the authors expand the historiographical lens of genomics from a focus on large-scale projects to other forms of organisation. They show how practices such as genome mapping, sequence assembly and annotation are as essential as DNA sequencing in the history of genomics, and argue that existing depictions of genomics are too closely associated with the Human Genome Project. Exploring the use of genomic tools by biochemists, cell biologists, and medical and agriculturally-oriented geneticists, this book portrays the history of genomics as inseparably entangled with the day-to-day practices and objectives of these communities. The authors also uncover often forgotten actors such as the European Commission, a crucial funder and forger of collaborative networks undertaking genomic projects. In examining historical trajectories across species, communities and projects, the book provides new insights on genomics, its dramatic expansion during the late twentieth-century and its developments in the twenty-first century. Offering the first extensive critical examination of the nature and historicity of reference genomes, this book demonstrates how their affordances and limitations are shaped by the involvement or absence of particular communities in their production. ;
    Keywords: Genome mapping ; Yeast ; Saccharomyces cerevisiae ; Human DNA ; Pig DNA ; Sus scrofa ; High throughput sequencing technology ; Whole-genome projects ; Sequence assembly ; Annotation ; European Commission ; thema EDItEUR::P Mathematics and Science::PD Science: general issues::PDX History of science ; thema EDItEUR::M Medicine and Nursing::MB Medicine: general issues::MBX History of medicine ; thema EDItEUR::N History and Archaeology::NH History::NHB General and world history ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences::PSV Zoology and animal sciences
    Language: English
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  • 3
    Publication Date: 2024-04-05
    Description: This book facilitates an integrative understanding of the development, genetics and evolution of butterfly wing patterns. To develop a deep and realistic understanding of the diversity and evolution of butterfly wing patterns, it is essential and necessary to approach the problem from various kinds of key research fields such as “evo-devo,” “eco-devo,” ”developmental genetics,” “ecology and adaptation,” “food plants,” and “theoretical modeling.” The past decade-and-a-half has seen a veritable revolution in our understanding of the development, genetics and evolution of butterfly wing patterns. In addition, studies of how environmental and climatic factors affect the expression of color patterns has led to increasingly deeper understanding of the pervasiveness and underlying mechanisms of phenotypic plasticity. In recognition of the great progress in research on the biology, an international meeting titled “Integrative Approach to Understanding the Diversity of Butterfly Wing Patterns (IABP-2016)” was held at Chubu University, Japan in August 2016. This book consists of selected contributions from the meeting. Authors include main active researchers of new findings of corresponding genes as well as world leaders in both experimental and theoretical approaches to wing color patterns. The book provides excellent case studies for graduate and undergraduate classes in evolution, genetics/genomics, developmental biology, ecology, biochemistry, and also theoretical biology, opening the door to a new era in the integrative approach to the analysis of biological problems.
    Keywords: QH540-549.5 ; ecology ; nymphalid ; genetics ; mimicry ; evolution ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences::PSA Life sciences: general issues::PSAF Ecological science, the Biosphere
    Language: English
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  • 4
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    Springer Nature
    Publication Date: 2024-04-05
    Description: nymphalid; ecology; evolution; genetics; mimicry
    Keywords: nymphalid ; ecology ; evolution ; genetics ; mimicry ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences::PSA Life sciences: general issues::PSAF Ecological science, the Biosphere
    Language: English
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  • 5
    Electronic Resource
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    Journal of ornithology 141 (2000), S. 263-274 
    ISSN: 1439-0361
    Keywords: Systematics ; evolution ; anagenesis ; genealogy ; reference system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Zusammenfassung Verglichen mit anderen Tiergruppen, scheint die artliche Bestandsaufnahme der rezenten Vögel nahezu abgeschlossen zu sein. Doch ist das System der Vögel weiterhin umstritten und mit vielen Neuerungen konfrontiert. Die Gründe dafür liegen hauptsächlich in neuen, vor allem molekularbiologischen Methoden und in den unerwartet reichen Fossilfunden der jüngsten Zeit. Als Beispiele werden Altgaumenvögel, Kranichvögel, Ibisse, Flamingos, Mausvögel, Hopfe und Sperlingsvögel kurz behandelt. Die hier erzielten Fortschritte lassen die Befürchtung Stresemanns, die Großsystematik der Vögel sei mit den vorhandenen Methoden phylogenetisch nicht interpretierbar, zunächst als unbergründet erscheinen. Doch erwachsen einer solchen Interpretation andere Hindernisse, deren Bedeutung bisher zu wenig beachtet wurde, nämlich Parallelentwicklungen, die viel verbreiteter sind als gemeinhin angenommen. Ihre Häufigkeit lässt sich sogar mit evolutionsbiologischen Argumenten begründen. Es ist deshalb nicht zu erwarten, dass die Diskussionen um das „richtige“ System bald verstummen. Um dennoch die Eindeutigkeit der Information in nicht-systematischen Veröffentlichungen zu wahren, wird empfohlen ein etabliertes Referenzsystem auf Zeit zu wählen.
    Notes: Summary Unlike in most animal classes the inventory of extant species of the class Aves seems to be almost complete. Nevertheless avian systematics is challenged by many novelties and seems far from being settled. This is caused mainly by the application of novel methods of molecular analysis to phylogenetic problems and by the unexpectedly rich fossil record collected within the last 10–20 years. Examples from the Palaeognathae, Gruiformes, Threskiornithidae, Phoenicopteridae, Coliiformes, Upupiformes and Passeriformes are briefly treated. The progress in the field seems to disprove Stresemann's pessimistic view that the phylogeny of higher categories (orders) cannot be reconstructed by the available methods. However, phylogenetic interpretations are impeded by obstacles not considered by Stresemann and highly underestimated in most cases, namely by multiple independent developments leading to identical features. Frequent parallel developments are to be expected for theoretical evolutionary reasons. The diagnosis of such homoplasies can be extremely difficult or even impossible. Therefore we cannot expect the discussion about the “best” system of birds to end in the near future. Considering this dynamic situation in systematics, it is recommended to maintain unambiguousness of information in not strictly systematic publications by refering to a well established system as a temporally limited reference.
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  • 6
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    Acta biotheoretica 48 (2000), S. 137-147 
    ISSN: 1572-8358
    Keywords: Sex ; sexual selection ; mate selection ; evolution ; ploidy ; assortative mating ; recombination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Using computer simulations I studied the simultaneous effect of variable environments, mutation rates, ploidy, number of loci subject to evolution and random and assortative mating on various reproductive systems. The simulations showed that mutants for sex and recombination are evolutionarily stable, displacing alleles for monosexuality in diploid populations mating assortatively under variable selection pressure. Assortative mating reduced excessive allelic variance induced by recombination and sex, especially among diploids. Results suggest a novel adaptive value for sex and recombination. They show that the adaptive value of diploidy and that of the segregation of sexes is different to that of sex and recombination. The results suggest that the emergence of sex had to be preceded by the emergence of diploid monosexual organisms and provide an explanation for the emergence and maintenance of sex among diploids and for the scarcity of sex among haploid organisms.
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  • 7
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    Entomologia experimentalis et applicata 97 (2000), S. 237-249 
    ISSN: 1570-7458
    Keywords: herbivores ; predators ; parasitoids ; mutualism ; induced defence ; behaviour ; ecology ; evolution ; sensory physiology ; plant fitness ; pathogens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Herbivorous and carnivorous arthropods use plant volatiles when foraging for food. In response to herbivory, plants emit a blend that may be quantitatively and qualitatively different from the blend emitted when intact. This induced volatile blend alters the interactions of the plant with its environment. We review recent developments regarding the induction mechanism as well as the ecological consequences in a multitrophic and evolutionary context. It has been well established that carnivores (predators and parasitoids) are attracted by the volatiles induced by their herbivorous victims. This concerns an active plant response. In the case of attraction of predators, this is likely to result in a fitness benefit to the plant, because through consumption a predator removes the herbivores from the plant. However, the benefit to the plant is less clear when parasitoids are attracted, because parasitisation does usually not result in an instantaneous or in a complete termination of consumption by the herbivore. Recently, empirical evidence has been obtained that shows that the plant's response can increase plant fitness, in terms of seed production, due to a reduced consumption rate of parasitized herbivores. However, apart from a benefit from attracting carnivores, the induced volatiles can have a serious cost because there is an increasing number of studies that show that herbivores can be attracted. However, this does not necessarily result in settlement of the herbivores on the emitting plant. The presence of cues from herbivores and/or carnivores that indicate that the plant is a competitor- and/or enemy-dense space, may lead to an avoidance response. Thus, the benefit of emission of induced volatiles is likely to depend on the prevailing faunal composition. Whether plants can adjust their response and influence the emission of the induced volatiles, taking the prevalent environmental conditions into account, is an interesting question that needs to be addressed. The induced volatiles may also affect interactions of the emitting plant with its neighbours, e.g., through altered competitive ability or by the neighbour exploiting the emitted information. Major questions to be addressed in this research field comprise mechanistic aspects, such as the identification of the minimally effective blend of volatiles that explains the attraction of carnivores to herbivore-infested plants, and evolutionary aspects such as the fitness consequences of induced volatiles. The elucidation of mechanistic aspects is important for addressing ecological and evolutionary questions. For instance, an important tool to address ecological and evolutionary aspects would be to have plant pairs that differ in only a single trait. Such plants are likely to become available in the near future as a result of mechanistic studies on signal-transduction pathways and an increased interest in molecular genetics.
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  • 8
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    Entomologia experimentalis et applicata 95 (2000), S. 141-149 
    ISSN: 1570-7458
    Keywords: ecology ; reproductive success ; fecundity ; intraspecific competition ; evolution ; pest outbreaks ; pest control ; chemical control ; economic threshold ; oilseed rape ; turnip rape
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Populations of the rapeseed pollen beetle Meligethes aeneus F. (Col., Nitidulidae) from areas with 0–16 years of history of intensive rapeseed growing were compared for key ecological characters. During the first 16 years of rapeseed cultivation the reproductive success of M. aeneus increased 200–300% over that of the beetles living on the natural host plants, cruciferous weeds. The increase was linear over time and statistically highly significant, and it did not appear to be related to food quality or to the size of the beetles. During the same period the tolerance to intraspecific competition decreased, possibly due to the relative absence of such competition on the new crop. Furthermore, the optimum population density for M. aeneus to maximize the size of its next generation on summer turnip rape was determined to be 0.5–1.0 beetles/plant, which is slightly below the economic threshold for chemical control (1 beetle/plant). Therefore the practical protection of the rapeseed yield also ensures the highest possible pest population size for the next year. These mechanisms may in part explain the particular noxiousness of the species as a pest all over Europe. In general these data show that after the introduction of a new crop plant into a region, significant changes during the recruitment process in a pestiferous insect may take place, contributing to the future pest status of the insect. It is suggested that such genetic and ecological changes in insects may be a more common mechanism than previously thought in initiating and sustaining pest outbreaks, and that conventional pest management methods may enhance that effect.
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  • 9
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    Journal of insect behavior 13 (2000), S. 71-86 
    ISSN: 1572-8889
    Keywords: copulatory courtship ; behavioral interactions ; songs ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract D. birchii and D. serrata, two endemic Australian Drosophila species, have a copulatory courtship. The males of these species begin to court the female after mounting her and often go on with the courtship after the copulation is over. In the present paper we have described behavioral interactions between the male and the female and analyzed acoustic signals produced by the flies during courtship. Species differences were more pronounced in female than in male behavior. Variation within the species was obvious in the relative proportions of time the flies spent in different behaviors. Even though courtship took place nearly solely during copulation, some remains of precopulatory courtship were observed in both species. It is suggested that copulatory courtship exhibited by D. birchii and D. serrata flies is a derived rather than a primitive character.
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  • 10
    ISSN: 1572-8773
    Keywords: major facilitator superfamily ; iron transport ; siderophores ; enterobactin ; Saccharomyces cerevisiae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract While in fungi iron transport via hydroxamate siderophores has been amply proven, iron transport via enterobactin is largely unknown. Enterobactin is a catecholate-type siderophore produced by several enterobacterial genera grown in severe iron deprivation. By using the KanMX disruption module in vector pUG6 in a fet3Δ background of Saccharomyces cerevisiae we were able to disrupt the gene YOL158c Sce of the major facilitator super family (MFS) which has been previously described as a gene encoding a membrane transporter of unknown function. Contrary to the parental strain, the disruptant was unable to utilize ferric enterobactin in growth promotion tests and in transport assays using 55Fe-enterobactin. All other siderophore transport properties remained unaffected. The results are evidence that in S. cerevisiae the YOL158c Sce gene of the major facilitator super family, now designated ENB1, encodes a transporter protein (Enb1p), which specifically recognizes and transports enterobactin.
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  • 11
    ISSN: 1572-9028
    Keywords: rutile supported V2O5–WO3 catalyst ; evolution ; NO reduction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract This paper concerns the relation between surface structure of crystalline vanadia-like active species on vanadia–tungsta catalyst and their activity in the selective reduction of NO by ammonia to nitrogen. The investigations were performed for Ti–Sn-rutile-supported isopropoxy-derived catalyst. The SCR activity and surface species structure were determined for the freshly prepared catalyst, for the catalyst previously used in NO reduction by ammonia (320 ppm NO, 335 ppm NH3 and 2.35 vol% O2) at 573 K as well as for the catalyst previously annealed at 573 K in helium stream containing 2.35 vol% O2. The crystalline islands, exposing main V2O5 surface, with some tungsten atoms substituted for V-ones, were found, with XPS and FT Raman spectroscopy, to be present at the surface of the freshly prepared catalyst. A profound evolution of the active species during the catalyst use at 573 K was observed. Dissociative water adsorption on V5+OW6+ sites is discussed as mainly responsible for the catalyst activity at 473 K and that on both V5+OW6+ and V4+OW6+ sites as determining the activity at 523 K.
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  • 12
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    Foundations of science 5 (2000), S. 429-456 
    ISSN: 1572-8471
    Keywords: awareness ; reflexive awareness and consciousness ; evolution ; experience and pattern matching ; symbolic language
    Source: Springer Online Journal Archives 1860-2000
    Topics: Natural Sciences in General
    Notes: Abstract An evolutionary point of view is proposed to make more appropriate distinctions between experience, awareness and consciousness. Experience can be defined as a characteristic linked closely to specific pattern matching, a characteristic already apparent at the molecular level at least. Awareness can be regarded as the special experience of one or more central, final modules in the animal neuronal brain. Awareness is what experience is to animals. Finally, consciousness could be defined as reflexive awareness. The ability for reflexive awareness is distinctly different from animal and human awareness and depends upon the availability of a separate frame of reference, as provided by symbolic language. As such, words have made reflexive awareness – a specific and infrequent form of awareness – possible. Conciousness might be defined as the experience evoked by considering, i.e. thinking about experiences themselves. If there is a hard problem of explaining consciousness, than this actually must be considered as the hard problem already met when trying to explain basic experience, since its nature remains elusive.
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  • 13
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    Journal for general philosophy of science 31 (2000), S. 57-73 
    ISSN: 1572-8587
    Keywords: complex systems ; evolution ; nonlinearity ; pre-determination ; self-organization ; soft management ; structure-attractors ; synergetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Philosophy , Nature of Science, Research, Systems of Higher Education, Museum Science
    Notes: Abstract The philosophical consequences of synergetics, the interdisciplinary theory of evolution and self-organization of complex systems, are being drawn in the paper. The idea of discreteness of evolutionary paths is in the focus of attention. Although the future is open, and there are many alternative evolutionary paths for complex systems, not any arbitrary (either conceivable or desirable) evolutionary path is feasible in a given system. There are discrete spectra of possible evolutionary paths which are determined exclusively by inner properties of the corresponding systems. Synergetics allows us to reveal general laws of self-organization and, therefore, certain limits of arbitrariness of nature in choosing possible paths of evolution as well as in constructing of a complex evolutionary whole. A comparative analysis between the modern synergetic notions and a few ideas of the Western philosophy (F. Nietzsche, N. Hartmann, M. Heidegger) and of the Eastern teachings (Taoism, Buddhism) is made.
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  • 14
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    International journal of value-based management 13 (2000), S. 297-308 
    ISSN: 1572-8528
    Keywords: morality ; moral systems ; behavior ; evolution ; adaptation ; natural selection ; altruism ; reciprocal altruism ; fitness ; reciprocity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Economics
    Notes: Abstract The ethical and moral behavior of Homo sapiens is no longer the exclusive domain of religion and philosophy because we recognize that such behavior affects the reproductive success of individuals within the species. We are a social species and therefore our survival is influenced by our capacity for cooperation and our willingness to take risks for kin. Emotions, some of which are found in other species, help to mediate our altruistic behavior. The reproductive benefits of helping kin, especially offspring, are readily seen. Helping non-kin can be beneficial if individuals can differentiate between ‘reciprocators’ and ‘non-reciprocators’ and direct altruistic behavior toward reciprocators. Also, if third parties are favorably impressed by observing altruistic behavior, the rewards need not come from the recipient of the altruistic behavior.
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  • 15
    ISSN: 1572-9737
    Keywords: conservation genetics ; Equus ; evolution ; mitochondrial DNA control region ; mitochondrial 12S rRNA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The evolution, taxonomy and conservation of the genus Equuswere investigated by examining the mitochondrial DNA sequences of thecontrol region and 12S rRNA gene. The phylogenetic analysis of thesesequences provides further evidence that the deepest node in thephylogeny of the extant species is a divergence between twolineages; one leading to the ancestor of modern horses (E.ferus, domestic and przewalskii) and the other to thezebra and ass ancestor, with the later speciation events of the zebrasand asses occurring either as one or more rapid radiations, or withextensive secondary contact after speciation. Examination of the geneticdiversity within species suggested that two of the E. hemionussubspecies (E. h. onager and E. h. kulan) onlyrecently diverged, and perhaps, are insufficiently different to beclassified as separate subspecies. The genetic divergence betweendomestic and wild forms of E. ferus (horse) and E.africanus (African ass) was no greater than expected within anequid species. In E. burchelli (plains zebra) there was anindication of mtDNA divergence between populations increasing withdistance. The implications of these results for equid conservation arediscussed and recommendations are made for conservation action.
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  • 16
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    Journal of the history of biology 33 (2000), S. 457-491 
    ISSN: 1573-0387
    Keywords: J. B. S. Haldane ; biology ; politics ; genetics ; evolution ; population genetics ; physiology ; Darwinism ; experimental biology ; eugenics ; Britain ; Russia ; India ; Soviet ; Communism ; socialism ; philosophy ; vision ; literature ; popularization ; religion ; human experimentation ; bioethics ; Venus ; Mars ; science fiction ; technocracy ; futurology ; H. G. Wells ; Julian Huxley ; Olaf Stapledon ; C. S. Lewis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , History
    Notes: Abstract This paper seeks to reinterpret the life and work of J. B. S. Haldane by focusing on an illuminating but largely ignored essay he published in1927, “The Last Judgment” – the sequel to his better known work, Daedalus (1924). This astonishing essay expresses a vision of the human future over the next 40,000,000 years, one that revises and updates Wellsian futurism with the long range implications of the “new biology” for human destiny. That vision served as a kind of lifelong credo, one that infused and informed his diverse scientific work, political activities, and popular writing, and that gave unity and coherence to his remarkable career.
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  • 17
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    Journal of the history of biology 33 (2000), S. 221-246 
    ISSN: 1573-0387
    Keywords: August Weismann ; ciliates ; Clifford Dobell ; cytology ; death ; Emile Maupas ; evolution ; Herbert Spencer Jennings ; Otto Bütschli ; Paramecium ; rejuvenescence ; sex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , History
    Notes: Abstract In the period 1875–1920, a debate about the generality and applicability of evolutionary theory to all organisms was motivated by work on unicellular ciliates like Paramecium because of their peculiar nuclear dualism and life cycles. The French cytologist Emile Maupas and the German zoologist August Weismann argued in the 1880s about the evolutionary origins and functions of sex (which in the ciliates is not linked to reproduction), and death (which appeared to be the inevitable fate of lineages denied sexual conjugation), an argument rooted in the question of whether the ciliates and their processes where homologous to other cellular organisms. In the beginning of the twentieth century, this question of homology came to be less important as the ciliates were used by the British protozoologist Clifford Dobell and the American zoologist Herbert Spencer Jennings to study evolutionary processes in general rather than problems of development and cytology. For them, homology mattered less than analogy. This story illustrates two partially distinct problems in evolutionary biology: first, the question of whether all living things have common features and origins; and second, whether their history and current nature can be described by identical mechanisms. Where Maupas (contra Weismann) made the ciliates qualitatively the same as all other organisms in order to create a cohesive evolutionary theory for biology, Jennings and Dobell made them qualitatively different in order to achieve the same end.
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  • 18
    ISSN: 1432-0983
    Keywords: Key words Citrinin ; Pet mutants ; Mitochondrial biogenesis ; Vacuolar ATPase ; YKL118W disruption ; Saccharomyces cerevisiae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In countries with a hot climate the mycotoxin citrinin represents a serious problem in fungal food-poisoning. In humans the renal system is affected the most and the mitochondrial respiratory chain was identified as a possible sensitive target for this toxin. In addition, citrinin has an antifungal activity that also inhibits the growth of the yeast Saccharomyces cerevisiae. So far the precise mode of action and the subcellular targets for citrinin have not been identified. Therefore, we decided to use the model organism yeast for a genetic approach to identify genes that play a role in the sensitivity against this mycotoxin. A large collection of conditional respiratory deficient yeast mutants was screened for sensitivity against citrinin. One special pet-ts mutant was identified that exhibited a higher sensitivity against citrinin. The genetic system of yeast allowed the isolation of the respective wild-type gene. This yeast gene encodes the Vph2p subunit that is essential for the correct assembly of the vacuolar ATPase. Isolation of the mutated gene and gene-disruption experiments of VPH2 and the partially overlapping small YKL118W gene verified this finding. The wild-type VPH2 gene restores all defects of the mutants. In contrast to this, YKL118W gave no complementation and the null mutant showed no phenotype. Thereby the yeast vacuolar ATPase was found to be important for the toxic effect of citrinin in yeast cells. The consequences of this finding for the molecular mechanism of citrinin action and its relation to the mitochondrial respiratory chain are discussed.
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  • 19
    ISSN: 1432-0983
    Keywords: Key wordsPOL32 ; SRS2 ; DNA repair ; Saccharomyces cerevisiae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Pol32 is a subunit of Saccharomyces cerevisiae DNA polymerase δ required in DNA replication and repair. To gain insight into the function of Pol32 and to determine in which repair pathway POL32 may be involved, we extended the analysis of the pol32Δ mutant with respect to UV and methylation sensitivity, UV-induced mutagenesis; and we performed an epistasis analysis of UV sensitivity by combining the pol32Δ with mutations in several genes for postreplication repair (RAD6 group), nucleotide excision repair (RAD3 group) and recombinational repair (RAD52 group). These studies showed that pol32Δ is deficient in UV-induced mutagenesis and place POL32 in the error-prone RAD6/REV3 pathway. We also found that the increase in the CAN1 spontaneous forward mutation of different rad mutators relies entirely or partially on a functional POL32 gene. Moreover, in a two-hybrid screen, we observed that Pol32 interacts with Srs2, a DNA helicase required for DNA replication and mutagenesis. Simultaneous deletion of POL32 and SRS2 dramatically decreases cellular viability at 15 °C and greatly increases cellular sensitivity to hydroxyurea at the permissive temperature. Based on these findings, we propose that POL32 defines a link between the DNA polymerase and helicase activities, and plays a role in the mutagenic bypass repair pathway.
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  • 20
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    Current genetics 38 (2000), S. 264-270 
    ISSN: 1432-0983
    Keywords: Key words Endopolygalacturonase ; Saccharomyces cerevisiae ; Kluyveromyces marxianus ; Pectinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The gene encoding endopolygalacturonase (EC 3.2.1.15) has been cloned, sequenced and expressed from three strains of Saccharomyces cerevisiae (including non-secretors) and three strains of Kluyveromyces marxianus. Both control and coding regions showed small differences within each species, one including loss of a potential glycosylation site. Two non-secreting S. cerevisiae strains (FY1679 and var. uvarum) had non-transcribed copies of functional genes. Maximum enzyme activity was achieved with the S. cerevisiae FY1679 gene in an expressing vector, with an enzyme activity of 51 μmol of reducing sugar released from polygalacturonic acid μg protein−1 min−1, the highest so far reported for a yeast.
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  • 21
    ISSN: 1432-0983
    Keywords: Key words Translation release factors ; Chromosome stability ; Microtubules ; Saccharomyces cerevisiae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Chromosome stability in suppressor mutants for SUP35 and SUP45 genes coding for translation release factors was studied. We obtained spontaneous and UV-induced sup35 or sup45 mutants in a haploid strain disomic for chromosome III and tested the stability of an extra copy of this chromosome. The majority of the mutants showed increased chromosome instability. This phenotype was correlated with an increased sensitivity to the microtubule-poisoning drug benomyl which affects chromosome segregation at anaphase. Our data suggest that termination-translation factors eRF3 and eRF1 control chromosome transmission at mitotic anaphase in Saccharomyces cerevisiae.
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    Journal of thermal analysis and calorimetry 59 (2000), S. 643-648 
    ISSN: 1572-8943
    Keywords: drying ; intracellular water ; Saccharomyces cerevisiae ; TG
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The intracellular water content of a microorganism is an important parameter which is a determinant factor of its physiological properties. It is usually measured by complex and time consuming procedures. Thermogravimetry using infrared balance has been used for this purpose, through the identification of different drying steps occurring during the analysis. This work employs the same method with much smaller samples, using conventional thermogravimetric equipment in a simpler and faster way than other conventional procedures. Commercial yeast (Saccharomyces cerevisiae ) washed samples are analyzed in isothermal procedures which are run in about 30 min. The drying rate curve, when plotted as a function of the residual mass of the cells, allows the identification of the step where the intracellular water is lost and the determination of its content. The obtained values, on extracellular water free basis, are in the range of 65 to 69% and agree with those measured by other techniques.
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    The environmentalist 20 (2000), S. 257-271 
    ISSN: 1573-2991
    Keywords: evolution ; tides ; sea level ; time series
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract The increasing use of computers since the 1960s, has implied the digitization of observations in meteorology, oceanography and other observational sciences. Enough data has been accumulated to suggest that some patterns of evolution in the world may be discernable. The present article deals with what appears as changing tides around Canada.
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  • 24
    ISSN: 1573-4927
    Keywords: ancient endogenous provirus ; evolution ; retrotransposition
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    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract A new family of murine endogenous proviruses (VL6.0) is described here. The intact provirus is near 6 kb in length and shows a genomic organization of 5" LTR, gag, pol, env, and 3" LTR. The primer binding site (PBS) is that of a tRNAgly. The lack of functional open reading frames and occurrence of significant gaps in most, if not all, members of this group show it to be ancient. Our estimate of copy number per haploid genome is 30+. Members of this group have been isolated from Mus musculus domesticus, M. m. casteneus, M. m. hortulanus, M. caroli, and M. spretus. The occurrence of these sequences throughout such diverse members of the genus Mus may indicate that the date of the original infection predated the divergence of the extant Mus lineages at around 2.5 million years ago. Analysis of gap (deletion/insertion) patterns indicates that these sequences may have proliferated within the Mus genome by a mechanism of reverse transcriptase-mediated transposition. As yet, there are no closely related murine retroviruses described. The closest mammalian retrovirus based on sequence similarity is from the miniature swine (Sus scrofa).
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  • 25
    ISSN: 1573-4943
    Keywords: Homology modeling ; rotational energy barrier ; simulated annealing ; pyridoxal 5′-diphosphoadenosine ; pyridoxal 5′-triphosphoadenosine ; Saccharomyces cerevisiae ; phosphoenolpyruvate carboxykinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Molecular mechanics calculations have been employed to obtain models of the complexes between Saccharomyces cerevisiae phosphoenolpyruvate (PEP) kinase and the ATP analogs pyridoxal 5′-diphosphoadenosine (PLP-AMP) and pyridoxal 5′-triphosphoadenosine (PLP-ADP), using the crystalline coordinates of the ATP-pyruvate-Mn2+-Mg2+ complex of Escherichia coli PEP carboxykinase [Tari et al. (1997), Nature Struct. Biol. 4, 990–994]. In these models, the preferred conformation of the pyridoxyl moiety of PLP-ADP and PLP-AMP was established through rotational barrier and simulated annealing procedures. Distances from the carbonyl-C of each analog to ε-N of active-site lysyl residues were calculated for the most stable enzyme-analog complex conformation, and it was found that the closest ε-N is that from Lys290, thus predicting Schiff base formation between the corresponding carbonyl and amino groups. This prediction was experimentally verified through chemical modification of S. cerevisiae PEP carboxykinase with PLP-ADP and PLP-AMP. The results here described demonstrate the use of molecular modeling procedures when planning chemical modification of enzyme-active sites.
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    Molecular genetics and genomics 263 (2000), S. 81-89 
    ISSN: 1617-4623
    Keywords: Key words Flp recombinase ; Site-specific recombination ; Homologous recombination ; RAD52 ; Saccharomyces cerevisiae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Site-specific recombination within the Saccharomyces cerevisiae 2-micron DNA plasmid is catalyzed by the Flp recombinase at specific Flp Recognition Target (FRT) sites, which lie near the center of two precise 599-bp Inverted Repeats (IRs). However, the role of IR DNA sequences other than the FRT itself for the function of the Flp reaction in vivo is not known. In the present work we report that recombination efficiency differs depending on whether the FRT or the entire IR serves as the substrate for Flp. We also provide evidence for the involvement of the IR in RAD52-dependent homologous recombination. In contrast, the catalysis of site-specific recombination between two FRTs does not require the function of RAD52. The efficiency of Flp site-specific recombination between two IRs cloned in the same orientation is about one hundred times higher than that obtained when only the two FRTs are present. Moreover, we demonstrate that a single IR can activate RAD52-dependent homologous recombination between two flanking DNA regions, providing new insights into the role of the IR as a substrate for recombination and a new experimental tool with which to study the molecular mechanism of homologous recombination.
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  • 27
    ISSN: 1617-4623
    Keywords: Key wordsYarrowia lipolytica ; Saccharomyces cerevisiae ; Ambient pH signalling ; Signal transduction ; Transmembrane protein
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    Topics: Biology
    Notes: Abstract In Yarrowia lipolytica, the transcription factor Rim101p mediates both pH regulation and control of mating and sporulation. Like its homologues PacC of Aspergillus nidulans and Rim101p of Saccharomyces cerevisiae, YlRim101p is activated by proteolytic C-terminal processing, which occurs in response to a signal transduced by a pathway involving several PAL gene products. We report here the cloning and sequencing of two of these genes, PAL2 and PAL3. PAL2 encodes a putative 632-residue protein with six possible transmembrane segments, which differs from the transmembrane proteins Rim9p of S. cerevisiae and PalI of A. nidulans, but is homologous to A. nidulans PalH and to the product of the ORF YNL294c, a predicted polypeptide of unknown function in S. cerevisiae. PAL3 encodes an 881-residue polypeptide that is homologous to PalF of A. nidulans and to a newly identified putative polypeptide of S. cerevisiae. Both PAL2 and PAL3 are expressed constitutively, regardless of ambient pH. Mutations in these genes affect growth at alkaline pH and sporulation in both Y. lipolytica and in S. cerevisiae. They affect invasiveness of haploid strains in S. cerevisiae only, and conjugation in Y. lipolytica only. These results highlight the conservation of the Pal pathway initially described in A. nidulans.
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  • 28
    ISSN: 1617-4623
    Keywords: Key wordsGAL regulon ; Transcription ; Saccharomyces cerevisiae ; Galactose suppression
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    Topics: Biology
    Notes: Abstract A plasmid clone that suppresses galactose toxicity in a gal7 yeast strain has been isolated from a multicopy genomic DNA library. Molecular analysis revealed that the region responsible for the suppression of galactose toxicity corresponds to the ORF YPR030w, which was named MRG19. A CEN-based plasmid carrying the above ORF was unable to suppress the toxicity. Galactokinase activity was substantially reduced in cell extracts obtained from transformants bearing multiple copies of MRG19. Multiple copies of MRG19 were also able to suppress galactokinase expression driven by the CYC1 promoter but not the TEF1 promoter. Multiple copies of MRG19 could not suppress GAL1-driven galactokinase expression in a gal80 strain. However, MRG19-mediated suppression of CYC1-driven galactokinase expression was independent of GAL80 function. These results imply that multiple copies of MRG19 suppress galactokinase expression probably at the level of transcription. In agreement with this idea, multiple copies of MRG19 also suppress β-galactosidase expression driven by the GAL1 promoter in a GAL80-dependent manner. Disruption of MRG19 leads to an increase in the cell density at stationary phase in synthetic complete medium. MRG19 encodes a previously uncharacterised 124-kDa protein that shows no sequence homology to any known proteins.
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  • 29
    ISSN: 1618-2545
    Keywords: biogeography ; calmodulin ; DNA sequence ; elongation factor EF-1α ; evolution
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    Topics: Biology
    Notes: Abstract Phylogenetic relationships within theGibberella fujikuroi species complex were extended to newly discovered strains using nucleotide characters obtained by sequencing polymerase chain reaction (PCR) amplified DNA from 4 loci used in a previous study [nuclear large subunit 28S rDNA, nuclear ribosomal internal transcribed spacer (ITS) region, mitochondriaal small subunit (mtSSU) ribosomal DNA, and β-tubulin] together with two newly sampled protein-encoding nuclear genes, translation elongation factor EF-1α and calmodulin. Sequences from the ribosomal ITS region were analyzed separately and found to contain of two highly divergent, nonorthologous ITS2 types. Phylogenetic analysis of the individual and combined datasets identified 10 new phylogenetically distinct species distributed among the following three areas: 2 within Asia and 4 within both Africa and South America. Hypotheses of the monophyly ofFusarium subglutinans and its two formae speciales, f. sp.pini and f. sp.ananas, were strongly rejected by a likelihood analysis. Maximum parsimony results further indicate that the protein-encoding nuclear genes provide considerably more phylogenetic signal that the ribosomal genes sequenced. Relative apparent synapomorphy analysis was used to detect long-branch attraction taxa and to obtain a statistical measure of phylogenetic signal in the individual and combined datasets.
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  • 30
    ISSN: 1618-2545
    Keywords: Ascomycota ; evolution ; pyrenomycetes ; systematics
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    Topics: Biology
    Notes: Abstract To investigate the systematic position of the unitunicate pyremomycetePapulosa amerospora, we performed phylogenetic analyses of SSU rDNA sequences from 37 ascomycetes. Among these sequences were some new ones from taxa that might be related toPapulosa: Hyponectriaceae (Hyponectria buxi, Monographella nivalis), Phyllachorales (Phyllachora graminis), and Xylariales (Barrmaelia melanotes, Poronia punctata). Our results showed 100% bootstrap support for a clade of all unitunicate pyrenomycetes, the class Sordariomycetes. We also found strong support for recognizing the subclasses Hypocreomycetidae and Xylariomycetidae. The remaining taxa, belonging to subclass Sordariomycetidae, appeared as a polyphyletic group in one analysis, but was monophyletic when shorter SSU sequences were used.Barrmaelia melanotes, Poronia punctata, Hyponectria buxi, andMonographella nivalis are members of Xylariomycetidae, but we could not determine whetherMonographella should be included in Hyponectriaceae. The new family Papulosaceae is erected forPapulosa on molecular and morphological bases, but the exact systematic position ofPapulosa within subclass Sordariomycetidae is still uncertain, since the genus did not cluster consistently with any of the included taxa. Phyllachorales are not closely related to Diaporthales, as previously suggested.
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    Glycoconjugate journal 17 (2000), S. 465-483 
    ISSN: 1573-4986
    Keywords: N-acetylglucosaminyltransferases ; glycosylation ; glycoproteins ; Golgi complex ; evolution ; development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract This review covers discoveries made over the past 30–35 years that were important to our understanding of the synthetic pathway required for initiation of the antennae or branches on complex N-glycans and O-glycans. The review deals primarily with the author's contributions but the relevant work of other laboratories is also discussed. The focus of the review is almost entirely on the glycosyltransferases involved in the process. The following topics are discussed. (1) The localization of the synthesis of complex N-glycan antennae to the Golgi apparatus. (2) The “evolutionary boundary” at the stage in N-glycan processing where there is a change from oligomannose to complex N-glycans; this switch correlates with the appearance of multicellular organisms. (3) The discovery of the three enzymes which play a key role in this switch, N-acetylglucosaminyltransferases I and II and mannosidase II. (4) The “yellow brick road” which leads from oligomannose to highly branched complex N-glycans with emphasis on the enzymes involved in the process and the factors which control the routes of synthesis. (5) A short discussion of the characteristics of the enzymes involved and of the genes that encode them. (6) The role of complex N-glycans in mammalian and Caenorhabditis elegans development. (7) The crystal structure of N-acetylglucosaminyltransferase I. (8) The discovery of the enzymes which synthesize O-glycan cores 1, 2, 3 and 4 and their elongation.
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    Journal of bioeconomics 2 (2000), S. 9-23 
    ISSN: 1573-6989
    Keywords: evolution ; altruism ; morality ; utilitarianism ; Marxism ; Rawls ; fairness
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Economics
    Notes: Abstract Several evolutionary mechanisms have been identified in the literature that would generate altruism in humans. The most powerful (except for kin selection) and most controversial is group selection, as recently analyzed by Sober & D.S. Wilson. I do not take a stand on the issue of the existence of group selection. Instead, I examine the level of human altruism that could exist if group selection were an engine of human evolution. For the Sober & Wilson mechanism to work, groups practicing altruism must grow faster than other groups. I call altruistic behavior that would lead to faster growth ‘efficient altruism’. This often consists of cooperation in a prisoner's dilemma. ltruistic acts such as helping a temporarily hungry or injured person would qualify as efficient altruism. Efficient altruism would also require monitoring recipients to avoid shirking. Utilitarianism would be an ethical system consistent with efficient altruism, but Marxism or the Rawlsian system would not. Discussions of efficient altruism also help understand intuitions about fairness. We perceive those behaviors as ‘fair’ that are consistent with efficient altruism. It is important to understand that, even if humans are selected to be altruistic, the forms of altruism that might exist must be carefully considered and ircumscribed.
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    Biology and philosophy 15 (2000), S. 443-463 
    ISSN: 1572-8404
    Keywords: David Hull ; evolution ; selection
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    Topics: Biology , Philosophy
    Notes: Abstract One of the principal difficulties in assessing Science as aProcess (Hull 1988) is determining the relationship between the various elements of Hull's theory. In particular, it is hard to understand precisely how conceptual selection is related to Hull's account of the social dynamics of science. This essay aims to clarify the relation between these aspects of his theory by examining his discussion of the``demic structure'' of science. I conclude that the social account cando significant explanatory work independently of the selectionistaccount. Further, I maintain that Hull's treatment of the demicstructure of science points us toward an important set of issues insocial epistemology. If my reading of Science as a Process iscorrect, then most of Hull's critics (e.g., those who focus solelyon his account of conceptual selection) have ignored promisingaspects of his theory.
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    Biology and philosophy 15 (2000), S. 493-508 
    ISSN: 1572-8404
    Keywords: complexity ; entropy balance ; environment independence ; evolution ; information fundamental identity ; uncertainty
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Philosophy
    Notes: Abstract Some real objects show a very particular tendency: that of becomingindependent with regard to the uncertainty of their surroundings. This isachieved by the exchange of three quantities: matter, energy andinformation. A conceptual framework, based on both Non-equilibriumThermodynamic and the Mathematical Theory of Communication is proposedin order to review the concept of change in living individuals. Three mainsituations are discussed in this context: passive independence inconnection with resistant living forms (such as seeds, spores, hibernation,...), active independence in connection with the life span of aliving individual (whether an ant or an ant farm), and the newindependence in connection with the general debate of biological evolution.
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    Biology and philosophy 15 (2000), S. 641-668 
    ISSN: 1572-8404
    Keywords: complexity ; evolution ; function ; modularity ; parts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Philosophy
    Notes: Abstract The functional complexity, or the number of functions, of organisms hasfigured prominently in certain theoretical and empirical work inevolutionary biology. Large-scale trends in functional complexity andcorrelations between functional complexity and other variables, such assize, have been proposed. However, the notion of number of functions hasalso been operationally intractable, in that no method has been developedfor counting functions in an organism in a systematic and reliable way.Thus, studies have had to rely on the largely unsupported assumption thatnumber of functions can be measured indirectly, by using number ofmorphological, physiological, and behavioral “parts” as a proxy. Here, amodel is developed that supports this assumption. Specifically, the modelpredicts that few parts will have many functions overlapping in them, andtherefore the variance in number of functions per part will be low. If so,then number of parts is expected to be well correlated with number offunctions, and we can use part counts as proxies for function counts incomparative studies of organisms, even when part counts are low. Alsodiscussed briefly is a strategy for identifying certain kinds of parts inorganisms in a systematic way.
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    Biology and philosophy 15 (2000), S. 713-732 
    ISSN: 1572-8404
    Keywords: Darwin ; error theory ; ethics ; evolution ; evolutionary ethics ; Mackie ; naturalistic fallacy ; Ruse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Philosophy
    Notes: Abstract Suppose that the human tendency to think of certain actions andomissions as morally required – a notion that surely lies at the heart of moral discourse – is a trait that has been naturallyselected for. Many have thought that from this premise we canjustify or vindicate moral concepts. I argue that this is mistaken, and defend Michael Ruse's view that the moreplausible implication is an error theory – the idea thatmorality is an illusion foisted upon us by evolution. Thenaturalistic fallacy is a red herring in this debate,since there is really nothing that counts as a ‘fallacy’ at all. If morality is an illusion, it appears to followthat we should, upon discovering this, abolish moraldiscourse on pain of irrationality. I argue that thisconclusion is too hasty, and that we may be able usefullyto employ a moral discourse, warts and all, withoutbelieving in it.
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  • 37
    ISSN: 1618-2545
    Keywords: Ascomycota ; evolution ; molecular clock ; plant pathogen ; powdery mildew
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Phylogenetic relationships of Erysiphales within Ascomycota were inferred from the newly determined sequences of the 18S rDNA and partial sequences of the 28S rDNA including the D1 and D2 regions of 10 Erysiphales taxa. Phylogenetic analyses revealed that the Erysiphales form a distinct clade among ascomycetous fungi suggesting that the Erysiphales diverged from a single ancestral taxon. The Myxotrichaceae of the Onygenales was distantly related to the other onygenalean families and was the sister group to the Erysiphales calde, with which it combined to form a clade. The Erysiphales/Myxotrichaceae clade was also closely related to some discomycetous fungi (Leotiales, Cyttariales and Thelebolaceae) including taxa that form cleistothecial ascomata. The present molecular analyses as well as previously reported morphological observations suggest the possible existence of a novel evolutionary pathway from cleistothecial discomycetous fungi to Erysiphales and Myxotrichaceae. However, since most of these fungi, except for the Erysiphales, are saprophytic on dung and/or plant materials, the questions of how and why an obligate biotroph like the Erysiphales radiated from the saprophytic fungi remain to be addressed. We also estimated the radiation time of the Erysiphales using the 18S rDNA sequences and the two molecular clockes that have been previously reported. The calculation showed that the Erysiphales split from the Myxotrichaceae 190–127 myr ago. Since the radiation time of the Erysiphales does not exceed 230 myr ago, even when allowance is made for the uncertainty of the molecular clocks, it is possible to consider that the Erysiphales evolved after the radiation of angiosperms. The results of our calculation also showed that the first radiation within the Erysiphales (138–92 myr ago) coincided with the date of a major diversification of angiosperms (130–90 myr ago). These results may support our early assumption that the radiation of the Erysiphales coincided with the evolution of angiosperm plants.
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    Investigational new drugs 18 (2000), S. 373-381 
    ISSN: 1573-0646
    Keywords: clinical pharmacology ; dihydropyrimdine dehydrogenase ; eniluracil ; oral 5-FU ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacological inactivation of dihydropyrimidine dehydrogenase (DPD)represents one strategy to improve 5-FU therapy, which historically hasbeen associated with unpredictable pharmacological behavior andtoxicity. This is principally due to high interpatientdifferences in the activity of DPD, the enzyme that mediates theinitial and rate-limiting step in 5-FU catabolism. Byinactivating DPD and suppressing the catabolism of 5-FU,eniluracil has dramatically altered the pharmacological profileof 5-FU. The maximum tolerated dose of oral 5-FU given with oraleniluracil (1.0 to 25 mg/m2) is substantially lower thanconventional 5-FU doses. In the presence of eniluracil,bioavailability of 5-FU has increased to approximately 100%, thehalf-life is prolonged to 4 to 6 hours, and systemic clearanceis reduced 〉 20-fold to values comparable the glomerularfiltration rate (46 to 58 mL/min/m2). Renal excretion(∼ 45% to 75%), instead of DPD-related catabolism, is theprincipal route of elimination of oral 5-FU given witheniluracil. Chronic daily administration of oral 5-FU 1.0mg/m2 twice daily with eniluracil 20 mg twice dailyproduces 5-FU steady-state concentrations (8–38 ng/mL) similarto those achieved with protracted intravenous administration onclinically relevant dose-schedules. On a daily × 5regimen, higher 5-FU AUC values are related to neutropenia,whereas elevated 5-FU AUC and steady-state concentrations arerelated to diarrhea when oral 5-FU is given daily with eniluracilon a chronic schedule. The pharmacokinetic behavior of oraleniluracil is similar to that for oral 5-FU. Administration ofeniluracil 10 to 20 mg twice daily completely inactivates DPDactivity both in peripheral blood mononuclear cells and incolorectal tumor tissue, and prolonged inhibition of DPD afterdiscontinuation of eniluracil treatment has been noted. In thepresence of eniluracil, oral administration of 5-FU is feasibleand variation in 5-FU exposure is reduced, with the anticipationof further reduction in variation as dosing guidelines based onrenal function are formulated.
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    Neural processing letters 11 (2000), S. 29-38 
    ISSN: 1573-773X
    Keywords: evolution ; online ; game ; neural ; network ; genetic ; real-time
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract In standard neuro-evolution, a population of networks is evolved in a task, and the network that best solves the task is found. This network is then fixed and used to solve future instances of the problem. Networks evolved in this way do not handle real-time interaction very well. It is hard to evolve a solution ahead of time that can cope effectively with all the possible environments that might arise in the future and with all the possible ways someone may interact with it. This paper proposes evolving feedforward neural networks online to create agents that improve their performance through real-time interaction. This approach is demonstrated in a game world where neural-network-controlled individuals play against humans. Through evolution, these individuals learn to react to varying opponents while appropriately taking into account conflicting goals. After initial evaluation offline, the population is allowed to evolve online, and its performance improves considerably. The population not only adapts to novel situations brought about by changing strategies in the opponent and the game layout, but it also improves its performance in situations that it has already seen in offline training. This paper will describe an implementation of online evolution and shows that it is a practical method that exceeds the performance of offline evolution alone.
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    Journal of mammalian evolution 7 (2000), S. 1-22 
    ISSN: 1573-7055
    Keywords: Dasyurus ; marsupials ; control region ; mtDNA ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract There has been a great deal of interest in determining phylogenetic relationships within the family Dasyuridae due to the widespread distribution, ecological diversity, and relative plesiomorphy of this taxon within the Australasian marsupial radiation. In the past, it has been extremely problematic to determine the phylogenetic relationships among species within Dasyurus, with numerous studies using both morphological and molecular characters providing different topologies. Here, the mitochondrial DNA (mtDNA) control region is used as a novel set of characters in an attempt to identify relationships among the six closely related extant species. Sequences were obtained from multiple individuals representing all extant species of quolls including, when possible, individuals from different geographical regions. Sequences were analyzed using both parsimony criteria and neighbor-joining methods. Results presented here concur with those of Krajewski et al. (1997) in (1) placing D. geoffroii in a highly supported clade with D. spartacus, (2) resolving a monophyletic group of D. albopunctatus + D. geoffroii + D. spartacus, and (3) placing D. hallucatus as the sister taxon to all other species of quolls. Results also show two highly supported and geographically distinct clades of D. maculatus (Tasmanian and mainland) that do not correspond to the currently used subspecific nomenclature. Preliminary results also indicate that there are different clades among geographic groups of D. hallucatus that warrant further investigation. The mtDNA control region is a highly variable locus and may be used in forensic tests for species identification in this genus.
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  • 41
    ISSN: 1573-6857
    Keywords: evolution ; Oryza ; retrotransposon ; rice ; wild species
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The Oryza officinalis complex is a genetically diverse, tertiary genepool of rice. We analyzed part of the primary structure of the integrase coding domain (ICD) of a gypsy-like retrotransposon from species of the O. officinalis species complex. PCR was performed with degenerate primers that hybridized to conserved sequences in the integrase genes of gypsy-type retrotransposons, using total DNA from different species of the O. officinalis complex as templates. Cloning and sequencing of the PCR products showed that the amplified fragments are highly homologous to each other (75–90%) and belong to one family of retrotransposons that is related to the previously studied RIRE-2 element from rice. Two main subfamilies of 292 and 351 bp were distinguished. Analysis of primary sequence data supports previous reports that sequence divergence during vertical transmission has been the major influence on the evolution of gypsy-type retrotransposons in Oryza species. Based on sequence data phylogenetic relationships among species of the O. officinalis complex were estimated. The data suggests that O. eichingeri is more closely related to the ancestral species of the complex.
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    International journal of primatology 21 (2000), S. 421-444 
    ISSN: 1573-8604
    Keywords: phylogenetics ; biogeography ; speciation ; Ateles ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We used the results of phylogenetic analyses of relationships among spider monkeys (Ateles) based on mitochondrial and nuclear DNA to investigate questions of their evolutionary origins and speciation mechanisms. We employed the concept of a local molecular clock to date nodes of interest (corresponding to hypothesized species and subspecies) in the various phylograms for comparison to hypothesized biogeographical events that might have affected speciation. We considered various mechanisms—Pleistocene refuge formation, riverine barriers, geological fluctuations, and ecological changes associated with these mechanisms—for their contribution to speciation in Ateles. Most speciation among the various species of Ateles occurred during the middle to late Pliocene, suggesting that Pleistocene refuge formation was not a key speciation mechanism. However, it is likely that the genetic structure of populations of Ateles was modified to some extent by refuge formation. Additionally, riverine barriers do not seem to interrupt gene flow significantly among Ateles. No river formed a barrier among species of Ateles, with the exception of the lower Amazon and possibly some of the black-water rivers draining the Guianan highlands. Large-scale geographic changes associated with the continued rise of the eastern and western cordilleras of the northern Andes and associated changes in habitat were the most important causes of speciation in Ateles. The various factors that modify genetic structure in Ateles are important to consider in order to protect endangered primate genera in the Neotropics.
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  • 43
    ISSN: 1573-8604
    Keywords: vocalization ; sexual advertisement ; predator advertisement ; taxonomy ; evolution ; mouse lemur ; primate ; Madagascar
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Advertisement calls are often important noninvasive tools for discriminating cryptic species and for assessing specific diversity and speciation patterns in nature. We investigated the contribution of these calls to uncover specific diversity in nocturnal Malagasy lemurs. We compared sexual advertisement and predator advertisement calls of two mouse lemur species, western gray and eastern rufous mouse lemurs (Microcebus murinus and M. rufus, respectively) living in two contrasting habitats (dry deciduous vs. rain forest), and analyzed them statistically. Both species emitted several highly variable whistle calls in the context of predator-avoidance. Intrapopulation variation was high and overlapped interspecific variation. Sexual advertisement calls, given in the mating context, displayed a totally distinct, species-specific acoustic structure. Whereas gray mouse lemurs produced rapidly multifrequency modulated, long trill calls, rufous mouse lemurs gave slowly frequency-modulated short chirp calls. Our results suggest specific status for gray and rufous mouse lemurs and indicate the importance of predation and social needs in shaping vocal communication.
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  • 44
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    Evolutionary ecology 14 (2000), S. 665-692 
    ISSN: 1573-8477
    Keywords: disease ; evolution ; frequency-dependent selection ; genetic diversity ; life history ; lifespan ; polymorphism ; reproduction rate ; resistance ; specificity ; virulence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Pathogens and parasites can be strong agents of selection, and often exhibit some degree of genetic specificity for individual host strains. Here we show that this host–pathogen specificity can affect the evolution of host life history traits. All else equal, evolution should select for genes that increase individuals' reproduction rates or lifespans (and thus total reproduction per individual). Using a simple host–pathogen model, we show that when the genetic specificity of pathogen infection is low, host strains with higher reproduction rates or longer lifespans drive slower-reproducing or shorter-lived host strains to extinction, as one would expect. However, when pathogens exhibit specificity for host strains with different life history traits, the evolutionary advantages of these traits can be greatly diminished by pathogen-mediated selection. Given sufficient host–pathogen specificity, pathogen-mediated selection can maintain polymorphism in host traits that are correlated with pathogen resistance traits, despite large intrinsic fitness differences among host strains. These results have two important implications. First, selection on host life history traits will be weaker than expected, whenever host fitness is significantly affected by genotype-specific pathogen attack. Second, where polymorphism in host traits is maintained by pathogen-mediated selection, preserving the genetic diversity of host species may require preserving their pathogens as well.
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  • 45
    ISSN: 1573-904X
    Keywords: allometric scaling ; interspecies scaling ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To evaluate (1) allometric scaling of systemic clearance (CL)using unbound drug concentration, (2) the potential usage of brainweight (BRW) correction in allometric scaling of both CL and oralclearance (CL/F). Methods. Human clearance was predicted allometrically (CLu = a ·Wbiv) using unbound plasma concentration for eight Parke-Daviscompounds and 29 drugs from literature sources. When the exponent bivwas higher than 0.85, BRW was incorporated into the allometricrelationship (CLu*BRW = a · Wbiv). This approach was also applied tothe prediction of CLu/F for 10 Parke-Davis compounds. Human oralt1/2, Cmax, AUC, and bioavailability were estimated based onallometrically predicted pharmacokinetic (PK) parameters. Results. Human CL and CL/F were more accurately estimated usingunbound drug concentration and the prediction was further improvedwhen BRW was incorporated into the allometric relationship. ForParke-Davis compounds, the predicted human CL and CL/F werewithin 50-200% and 50-220% of the actual values, respectively. Theestimated human oral t1/2, Cmax, and AUC were within 82-220%,56-240%, and 73-190% of the actual values for all 7 compounds,suggesting that human oral PK parameters of those drugs could bereasonably predicted from animal data. Conclusions. Results from the retrospective analysis indicate thatallometric scaling of free concentration could be applied to orallyadministered drugs to gain knowledge of drug disposition in man, and to helpdecision-making at early stages of drug development.
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  • 46
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; recombinant human interleukin-11 ; absorption ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
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  • 47
    ISSN: 1573-904X
    Keywords: (R,S)-Ifosfamide ; R2-, R3-, S2-, S3-DCE-IFF ; iterative-two stage analysis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To describe the pharmacokinetics of R- andS-Ifosfamide (IFF), and their respective 2 and 3 N-dechloroethylated (DCE)metabolites (R2-, R3-, S2, S3-DCE-IFF) in cancer patients. Methods. (R,S)-IFF was administered (1.5 g/m2)daily for 5 days in 13 cancer patients. Plasma and urine samples were collectedand analyzed using an enantioselective GC-MS method. An average of 97observations per patient were simultaneously fitted using apharmacokinetic-metabolism (PK-MB) model. A population PK analysis was performedusing an iterative 2-stage method (IT2S). Results. Auto-induction of IFF metabolism was observed over the 5day period. Increases were seen in IFF clearance (R: 4 vs 7 L/h; S: 5vs 10 L/h), and in the formation of DCE (R: 7 vs 9%; S: 14 vs 19%)and active metabolites (4-OHM-IFF; R: 71 vs 77%; S: 67 vs 71%). Anovel finding of this analysis was that the renal excretion of the DCEmetabolites was also induced. Conclusions. This population PK-MB model for (R,S)-IFF may beuseful in the optimization of patient care, and gives new insight intothe metabolism of (R,S)-IFF.
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  • 48
    ISSN: 1573-904X
    Keywords: stealth and remote loading proliposome ; doxorubicin ; pharmacokinetics ; acute toxicity ; anticancer effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The aim of the study was to prepare stealth and remoteloading proliposome (SRP-L) to carry doxorubicin (DXR) and evaluatethe pharmacokinetics, acute toxicity, and anticancer effect of DXRcarried with SRP-L. Methods. SRP-L was transparent solution. When SRP-L was injectedinto 0.9% NaCl aqueous solution containing DXR, liposomes formedand automatically loaded DXR (SRP-L-DXR). The long circulation ofSRP-L-DXR was evaluated using the pharmacokinetics ofSRP-L-DXR, cardiolipin liposomal DXR (CL-DXR) and free DXR (F-DXR).The acute toxicity and anticancer effect of SRP-L-DXR were evaluatedin C57BL/6 mice and murine hystocytoma M5076 tumor model. Results. The average diameter of SRP-L-DXR in pure water was112.9 ± 8.6 (nm) and the encapsulation efficiency of SRP-L-DXRwas 96.5 ± 0.2% in pure water, 95.5 ± 0.1% in 5% glucose and 98.01± 0.6% in 0.9% NaCl. The plasma concentration of SRP-L-DXR wasmuch higher than those of F-DXR and CL-DXR. Compared with thatof F-DXR, the SRP-L-DXR had lower acute toxicity and its anticancereffects depended upon the therapeutic treatment. Conclusions. A novel proliposome (SRP-L) was developed, whichcould automatically load DXR and form SRP-L-DXR with excellentcharacteristics. SRP-L-DXR had lower acute toxicity but was notalways more effective for the treatment of the ascitic M5076 thanF-DXR.
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  • 49
    ISSN: 1573-904X
    Keywords: morphine ; nociceptive effect ; electrical stimulation vocalisation method ; microdialysis ; retrodialysis by drug ; pharmacokinetics ; pharmacodynamics ; modelling ; blood-brain barrier transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To quantify the contribution of distributional processes across the blood-brain barrier (BBB) to the delay in antinociceptive effect of morphine in rats. Methods. Unbound morphine concentrations were monitored in venous blood and in brain extracellular fluid (ECF) using microdialysis (MD) and in arterial blood by regular sampling. Retrodialysis by drug was used for in vivo calibration of the MD probes. Morphine was infused (10 or 40 mg/kg) over 10 min intravenously. Nociception, measured by the electrical stimulation vocalisation method, and blood gas status were determined. Results. The half-life of unbound morphine in striatum was 44 min compared to 30 min in venous and arterial blood (p 〈 0.05). The BBB equilibration of morphine, expressed as the ratio of areas under the curve between striatum and venous blood, was less than unity (0.28 ± 0.09 and 0.22 ± 0.17 for 10 and 40 mg/kg), respectively, indicating active efflux of morphine across the BBB. The concentration-effect relationship exhibited a clear hysterisis with an effect delay half-life of 32 and 5 min based on arterial blood and brain ECF concentrations, respectively. Conclusions. Eighty five percent of the effect delay was caused by morphine transport across the BBB, indicating possible involvement of rate limiting mechanisms at the receptor level or distributional phenomena for the remaining effect delay of 5 min.
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  • 50
    ISSN: 1573-904X
    Keywords: bioequivalence ; dose proportionality ; mixed effects model ; pharmacokinetics ; power model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The aim of this work was a pragmatic, statistically sound and clinically relevant approach to dose-proportionality analyses that is compatible with common study designs. Methods. Statistical estimation is used to derive a (1-α)% confidence interval (CI) for the ratio of dose-normalized, geometric mean values (Rdnm) of a pharmacokinetic variable (PK). An acceptance interval for Rdnm defining the clinically relevant, dose-proportional region is established a priori. Proportionality is declared if the CI for Rdnm is completely contained within the critical region. The approach is illustrated with mixed-effects models based on a power function of the form PK = β0 • Doseβ1; however, the logic holds for other functional forms. Results. It was observed that the dose-proportional region delineated by a power model depends only on the dose ratio. Furthermore, a dose ratio (ρ1) can be calculated such that the CI lies entirely within the pre-specified critical region. A larger ratio (ρ2) may exist such that the CI lies completely outside that region. The approach supports inferences about the PK response that are not constrained to the exact dose levels studied. Conclusion. The proposed method enhances the information from a clinical dose-proportionality study and helps to standardize decision rules.
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  • 51
    ISSN: 1573-904X
    Keywords: SK&F 107647 ; peptide ; pharmacokinetics ; hematore gulatory ; adenocarcinoma ; cytokines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To describe the pharmacokinetics of SK&F 107647, a synthetichematoregulatory peptide, in healthy volunteers and in patientswith adenocarcinoma.Methods. SK&F 107647 pharmacokinetics were evaluated in 2dose-escalation studies. Volunteers received SK&F 107647 as single15-minute iv infusion doses of 1, 10, 100, 500, and 1000 μg/kg. Cancerpatients received 2-hour iv infusions of 0.001, 0.01, 0.1 and 1μg/kg once daily for 10 days. Drug concentrations were quantified in plasmaand urine of healthy volunteers and on days 1 and 10 in plasma ofcancer patients receiving the two top dose levels.Results. In volunteers, mean clearance (CL) ranged from 76.7 to 101ml/hour/kg; mean volume of distribution at steady-state (Vss)rangedfrom 175 to 268 ml/kg. Most of the administered dose was renallyexcreted as intact peptide within 24 hours postinfusion. In patients,mean CL was 57.6 ml/hour/kg, mean Vss ranged from 128 to 150ml/kg and terminal half-life from 2.1 to 3.4 hours. There was littleaccumulation of drug. In both studies, linear pharmacokinetics wasobserved. Clearance approached normal glomerular filtration rate(GFR) in volunteers and correlated with creatinine clearance incancer patients.Conclusions. SK&F 107647 exhibits linear pharmacokinetics, a smallVss, and clearance, primarily renal, approaching normal GFR.
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  • 52
    ISSN: 1573-904X
    Keywords: glycyrrhizic acid ; modeling ; enterohepatic cycling ; PBPK ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To analyze the role of the kinetics of glycyrrhizic acid (GD) in its toxicity. A physiologically-based pharmacokinetic (PBPK) model that has been developed for humans. Methods. The kinetics of GD, which is absorbed as glycyrrhetic acid (GA), were described by a human PBPK model, which is based on a rat model. After rat to human extrapolation, the model was validated on plasma concentration data after ingestion of GA and GD solutions or licorice confectionery, and an additional data derived from the literature. Observed interindividual variability in kinetics was quantified by deriving an optimal set of parameters for each individual. Results. The a-priori defined model successfully forecasted GA kinetics in humans, which is characterized by a second absorption peak in the terminal elimination phase. This peak is subscribed to enterohepatic cycling of GA metabolites. The optimized model explained most of the interindividual variance, observed in the clinical study, and adequately described data from the literature. Conclusions. Preclinical information on GD kinetics could be incorporated in the human PBPK model. Model simulations demonstrate that especially in subjects with prolonged gastrointestinal residence times, GA may accumulate after repeated licorice consumption, thus increasing the health risk of this specific subgroup of individuals.
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  • 53
    ISSN: 1573-904X
    Keywords: luteinising hormone-releasing hormone (LH-RH) antagonist ; cetrorelix ; pharmacokinetics ; population PK/PD-modeling ; testosterone ; rat ; dog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Population models for thepharmacokinetic-pharmacodynamic relationship for cetrorelix (CET), a luteinising hormone-releasinghormone (LH-RH) antagonist, and the pharmacodynamic response ontestosterone production were investigated in rats and dogs. Methods. The plasma concentrations of CET and testosterone weredetermined after intravenous and subcutaneous injections. Thepopulation PK/PD-models were developed using P-PHARM software. Results. Absolute bioavailability of cetrorelix was 100% in rats and97% in dogs. In rats, the pharmacokinetics was explained by atwo-compartment model with saturable absorption, while athree-compartment model was used in dogs. Testosterone suppression in both specieswas described by a sigmoid Emax model with maximum effect (Emax)considered as total hormonal suppression. The duration of testosteronesuppression in rats was longer at higher doses. The populationelimination half-lifes after iv-dose were 3.0 h in rats and 9.3 h in dogs.Population mean estimates of IC50 were 1.39 and 1.24 ng/ml in ratsand dogs, respectively. Conclusions. A population pharmacokinetic model was developed toexplain the dissolution rate limited absorption from the injection site.The suppression of testosterone could be described by an indirectinhibitory sigmoid Emax model. In both species 1-2 ng/ml CET inplasma was necessary to suppress testosterone production.
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  • 54
    ISSN: 1573-904X
    Keywords: methylphenidate ; average bioequivalence ; individual bioequivalence ; human ; pharmacokinetics ; replicated design
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To determine the relative bioavailability of two marketed,immediate-release methylphenidate tablets. The study used a replicatedstudy design to characterize intrasubject variability, and determinebioequivalence using both average and individual bioequivalencecriteria. Methods. A replicated crossover design was employed using 20subjects. Each subject received a single 20 mg dose of the reference tableton two occasions and two doses of the test tablet on two occasions.Blood samples were obtained for 10 hr after dosing, and plasma wasassayed for methylphenidate by GC/MS. Results. The test product was more rapidly dissolved in vitro and morerapidly absorbed in vivo than the reference product. The mean Cmaxand AUC(0 − ∞) differed by 11% and 9%, respectively. Using anaverage bioequivalence criterion, the 90% confidence limits for theLn-transformed Cmax and AUC(0 − ∞), comparing the two replicatesof the test to the reference product, fell within the acceptable range of80–125%. Using an individual bioequivalence criterion the test productfailed to demonstrate equivalence in Cmax to the reference product. Conclusions. The test and reference tablets were bioequivalent usingan average bioequivalence criterion. The intrasubject variability of thegeneric product was greater and the subject-by-formulation interactionvariance was borderline high. For these reasons, the test tablets werenot individually bioequivalent to the reference tablets.
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  • 55
    ISSN: 1573-904X
    Keywords: 1,4-dihydropyridine calcium channel antagonist ; (+)-[3H]PN 200-110 ; senescence-accelerated prone mouse ; brain concentration ; pharmacokinetics ; in vivo receptor binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To characterize the in vivo specific binding andpharmacokinetics of a 1,4-dihydropyridine (DHP) calcium channel antagonist, PN200-110, in the senescent brain, using senescence-accelerated pronemice (SAMP8) and senescence-resistant mice (SAMR1). Methods. Blood, brain, and heart samples were taken periodically fromSAMR1 and SAMP8 following intravenous injection of (+)-[3H]PN200-110, and the concentration of (+)-[3H]PN 200-110 in the plasmaand tissues was determined. In addition, the in vivo specific bindingof (+)-[3H]PN 200-110 in the brains of SAMR1 and SAMP8 wasmeasured periodically after intravenous injection of the radioligand. Results. There was very little significant difference between SAMR1and SAMP8 in terms of the half-life (t1/2), total body clearance (CLtot),steady-state volume of distribution (Vdss), and AUC for the plasmaconcentration of (+)-[3H]PN 200-110 after intravenous injection ofthe radioligand. The brain concentration (AUCbrain) for (+)-[3H]PN200-110 and the brain/plasma AUC ratio (AUCbrain/AUCplasma) weresignificantly lower in SAMP8 than in SAMR1, and the heartconcentration (AUCheart) and the heart/plasma AUC ratio (AUCheart/AUCplasma)were similar in both strains. Also, the brain/plasma unbound AUCratio (AUCbrain/AUCplasma-free) for (+)-[3H]PN 200-110 wassignificantly lower in SAMP8 than in SAMR1. The in vivo specific binding(AUCspecific binding, maximal number of binding sites: Bmax) of(+)-[3H]PN 200-110 was significantly lower in brain particulate fractionsof SAMP8 than SAMR1. Conclusions. The concentration and in vivo specific binding of(+)-[3H]PN 200-110 was significantly reduced in the senescent brain. Thesimultaneous analysis of the concentrations of centrally acting drugsand the in vivo specific binding in the brain in relation to theirpharmacokinetics may be valuable in evaluating their CNS effects.
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  • 56
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    Pharmaceutical research 17 (2000), S. 903-905 
    ISSN: 1573-904X
    Keywords: P-glycoprotein ; hepatic metabolism ; pharmacokinetics ; first-pass metabolism ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
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  • 57
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    Pharmaceutical research 17 (2000), S. 127-134 
    ISSN: 1573-904X
    Keywords: in-situ head perfusion ; pharmacokinetics ; red blood cells ; water
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To develop a viable, single pass rat head perfusion modeluseful for pharmacokinetic studies. Methods. A viable rat head preparation, perfused with MOPS-bufferedRinger's solution, was developed. Radiolabelled markers (red bloodcells, water and sucrose) were injected in a bolus into the internalcarotid artery and collected from the posterior facial vein over 28minutes. The double inverse Gaussian function was used to estimatethe statistical moments of the markers. Results. The viability of the perfusion was up to one hour, with optimalperfusate being 2% bovine serum albumin at 37°C, pH 7.4. Thedistribution volumes for red blood cells, sucrose and water (from all studies,n = 18) were 1.0 ± 0.3ml, 6.4 ± 4.2ml and 18.3 ± 11.9ml, respectively.A high normalised variance for red blood cells (3.1 ± 2.0) suggestsa marked vascular heterogeneity. A higher normalised variance forwater (6.4 ± 3.3) is consistent with additional diffusive/permeabilitylimitations. Conclusions. Analysis of the physiological parameters derived fromthe moments suggested that the kinetics of the markers were consistentwith distribution throughout the head (weight 25g) rather than justthe brain (weight 2g). This model should assist in studying solutepharmacokinetics in the head.
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  • 58
    ISSN: 1573-904X
    Keywords: α1-acid glycoprotein ; protein binding ; dissociation rate ; species difference ; physiological model ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The extremely low clearance and small distribution volumeof UCN-01 in humans could be partly due to the high degree of bindingto hAGP (1,2). The quantitative effects of hAGP on the pharmacokineticsof UCN-01 at several levels of hAGP and UCN-01 were estimatedin rats given an infusion of hAGP to mimic the clinical situation anda physiological model for analysis was developed. Methods. The plasma concentrations of UCN-01 (72.5–7250 nmol/kgiv) in rats given an infusion of hAGP, 15 or 150 nmol/h/kg, weremeasured by HPLC. Pharmacokinetic analysis under conditionsassuming rapid equilibrium of protein binding and incorporating thedissociation rate was conducted. Results. The Vdss and CLtot of UCN-01 (725 nmol/kg iv) in ratsgiven an infusion of hAGP, 150 nmol/h/kg, fell to about 1/250 and 1/700that in control rats. The Vdss and CLtot following 72.5–7250nmol/kg UCN-01 to rats given 150 nmol/h/kg hAGP were 63.9–688ml/kg and 3.18–32.9 ml/h/kg, respectively, indicating non-linearitydue to saturation of UCN-01 binding. The CLtot estimated by thephysiological model assuming rapid equilibrium of UCN-01 bindingto hAGP, was six times higher than the observed value while the CLtotestimated by the model incorporating koff, measured using DCC, wascomparable with the observed value. Conclusions. These results suggest that the slow dissociation ofUCN-01 from hAGP limits its disposition and elimination.
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  • 59
    ISSN: 1573-904X
    Keywords: IVIVC ; racemate ; enantiomers ; metoprolol ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To investigate the ability of an IVIVC developedwith a racemate drug as well as each enantiomer in predicting the invivo enantiomer drug performance. Methods. Dissolution of metoprolol extended releasetablets with different release characteristics (e.g., fast (F),moderate (M), and slow (S)) was performed using USP ApparatusI, pH 1.2, 50 rpm. Metoprolol racemate tablets (S, M, and F, 100 mg) and 50mg oral solution were administered to healthy volunteers, blood samples werecollected over 24 (solution) and 48 (tablet) hours and assayed. IVIVC modelsdeveloped were: (1) Racemate-fraction of drug dissolved (FRD) vsRacemate-fraction of drug absorbed (FRA), (2) R-FRD vs R-FRA, and (3) S-FRDvs S-FRA for combinations of formulations (S/M/F, S/M, S/F, and M/F).Enantiomer Cmax and AUC prediction errors (PEs) were estimated for modelevaluation after convolution of in vivo release rates. Results. The R-IVIVC and S-IVIVC accurately predicted theR- and S-metoprolol pharmacokinetic profiles, respectively. The averagedprediciton errors (PE) for the enantiomer Cmax and AUC were less than10% for S/M/F, M/F, and S/F IVIVC models. Racemate-IVIVC (M/F) wasable to predict S-enantiomer with an average %PE of 2.52 for S-Cmaxand 4.3 for S-AUC. However, the racemate-IVIVC was unable to predict theR-enantiomer pharmacokinetic profile. Conclusions. Metoprolol racemate data cannot be used toaccurately predict R-enantiomer drug concentrations. However, the racematedata was predictive of the active stereoisomer.
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  • 60
    ISSN: 1615-6110
    Keywords: Cladistics ; evolution ; Illiciales ; Illicium ; ITS ; star anise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Sequences of the internal transcribed spacers (ITS) of nuclear ribosomal DNA were determined for 15 species ofIllicium (Illiciaceae) to examine phylogenetic relationships. The ITS trees show a major dichotomy between the two North American species (I. floridanum andI. parviflorum) and the remaining east Asian species. This suggests that the existing division between two sections (sect.Illicium and sect.Cymbostemon) ofIllicium based on tepal characters in unnatural. The ITS phylogeny shows congruence with palynology: of the species examined, the three species (I. angustisepalum, I. anisatum andI. fargesii) from sect.Illicium that possess trizonocolpate pollen consistently form a clade, although nesting within a clade consisting of the species of sect.Cymbostemon, which generally have trisyncolpate pollen. The low ITS sequence divergence and the close relationship among east Asian species suggest a recent diversification of this group of species or an unusual slowdown of sequence mutations.
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  • 61
    ISSN: 1615-6110
    Keywords: In situ hybridization ; evolution ; NOR ; rDNA ; Muscari
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In the subgenusLeopoldia of the genusMuscari, M. comosum is an exceptional species because it presents the most asymmetrical karyotype of the group and because its only active NOR is located in the fifth chromosome pair, while in the other species it is located in the first or second chromosome pairs (all the species have 2n = 18 chromosomes). SinceM. comosum has a derived karyotype different from those of the other species of the group, the resulting question is whether, in the first and second chromosome pair of this species, ribosomal cistrons persist. Observations after fluorescence in situ hybridization (FISH) using rDNA probes indicate that there are indeed ribosomal loci in the first and second chromosome pairs of this species, although these loci are inactive with respect to nucleolus organization. The location of rDNA regions in another three species of the same genus (M. atlanticum, M. dionysicum andM. matritensis) provides a basis for examining the significance of these findings in relation to the evolution of the ribosomal loci in this genus. Our observations indicate that in the genusMuscari, the largest sites for rRNA genes are not necessarily active, and, therefore, the activation of these regions is not related to the number of copies but to a specific regulation mechanism.
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  • 62
    ISSN: 1617-4623
    Keywords: Key words Autonomously replicating sequence (ARS) ; Anti-bent DNA ; DNA structure ; Replication origin ; Saccharomyces cerevisiae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In order to better understand the involvement of the DNA molecule in the replication initiation process we have characterized the structure of the DNA at Autonomously Replicating Sequences (ARSs) in Saccharomyces cerevisiae. Using a new method for anti-bent DNA analysis, which allowed us to take into account the bending contribution of each successive base plate, we have investigated the higher-order structural organization of the DNA in the region which immediately surrounds the ARS consensus sequence (ACS). We have identified left- and right-handed anti-bent DNAs which flank this consensus sequence. The data show that this organization correlates with an active ACS. Analysis of the minimum nucleotide sequence providing ARS function to plasmids reveals an example where the critical nucleotides are restricted to the ACS and the right-handed anti-bent DNA domain, although most of the origins considered contained both left- and right-handed anti-bent DNAs. Moreover, mutational analysis shows that the right-handed form is necessary in order to sustain a specific DNA conformation which is correlated with the level of plasmid maintenance. A model for the role of these individual structural components of the yeast replication origin is presented. We discuss the possible role of the right-handed anti-bent DNA domain, in conjunction with the ACS, in the process of replication initiation, and potentialities offered by the combination of left- and right-handed structural components in origin function.
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  • 63
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    Molecular genetics and genomics 263 (2000), S. 877-888 
    ISSN: 1617-4623
    Keywords: Key words Staurosporine ; Vacuolar-type proton pumping ATPase ; Vacuolar protein sorting ; ATP-binding cassette transporter ; Saccharomyces cerevisiae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Mutations at several loci affect the sensitivity of the yeast Saccharomyces cerevisiae to staurosporine. We report here the characterization of novel staurosporine- and temperature-sensitive mutants (stt). Cloning and integration mapping showed that the genes STT2/STT6, STT5, STT7, STT8 and STT9 are allelic to VPS18, ERG10, GPI1, VPS34 and VPS11, respectively. The products of ERG10 and GPI1, respectively, catalyze mevalonate and glycosyl phosphatidylinositol anchor synthesis, while VPS18 and VPS11 genes belong to the class C VPS (Vacuolar Protein Sorting) genes, and the VPS34 gene is classified as a class D VPS. Therefore, staurosporine sensitivity is affected by ergosterol and glycolipid biosynthesis and by vacuolar functions. We found that other vps mutants belonging to classes C and D exhibit staurosporine sensitivity, and that they show calcium sensitivity and fail to grow on glycerol as the sole carbon source; both of the last two characteristics are shared by vacuolar H+-ATPase mutants (vma). As vma mutants were also found to show staurosporine-sensitive growth, staurosporine sensitivity is likely to be affected by acidification of the vacuole. Moreover, wild type yeast cells are more sensitive to staurosporine in alkaline media than in acidic media, suggesting that staurosporine is exported from the cytosol by H+/drug antiporters. Pleiotropic drug resistance (PDR) genes also provide some resistance to staurosporine, because Δpdr5, Δsnq2 and Δyor1 strains are more sensitive to staurosporine than the wild-type strain. This suggests that staurosporine is also exported by the ATP-binding cassette (ABC) transporters on the plasma membrane. vma mutants and vps mutants of classes C and D vps are sensitive to hygromycin B and vanadate, while ABC transporter-depleted mutants do not show such sensitivity, indicating that two systems differ in their ability to protect the cell against different types of drug.
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    Journal of economics 71 (2000), S. 1-30 
    ISSN: 1617-7134
    Keywords: evolution ; local interaction ; cooperation ; prisoner's dilemma ; Markov processes ; C78
    Source: Springer Online Journal Archives 1860-2000
    Topics: Economics
    Notes: Abstract We study local interaction within a population located on a connected graph. Subjects engage in several bilateral interactions during each round in a generalized Prisoners' Dilemma (PD). In each round of play one randomly selected player gets the possibility to update the action he plays in this PD. All individuals use the update rule “Win Cooperate, Lose Defect,” a multi-player variant of Tit-for-Tat. Theoretical results on the set of stable states of the associated dynamics are provided for the cases with and without rare mutations. Simulations provide insight into the probability distribution over these stable states. In both cases a rather high probability is assigned to stable states with a moderate level of cooperation implying that dominated strategies are used. Furthermore, the probability of reaching the stable state with Nash equilibrium play is small.
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  • 65
    ISSN: 1617-4623
    Keywords: Key words DNA repair ; Helix-hairpin-Helix motif ; Methylmethane sulfonate (MMS) ; Saccharomyces cerevisiae ; UV radiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The gene MUS81 (Methyl methansulfonate, UV sensitive) was identified as clone 81 in a two-hybrid screen using the Saccharomyces cerevisiae Rad54 protein as a bait. It encodes a novel protein with a predicted molecular mass of 72,316 (632 amino acids) and contains two helix-hairpin-helix motifs, which are found in many proteins involved in DNA metabolism in bacteria, yeast, and mammals. Mus81p also shares homology with motifs found in the XPF endonuclease superfamily. Deletion of MUS81 caused a recessive methyl methansulfonate- and UV-sensitive phenotype. However, mus81Δ cells were not significantly more sensitive than wild-type to γ-radiation or double-strand breaks induced by HO endonuclease. Double mutant analysis suggests that Rad54p and Mus81p act in one pathway for the repair of, or tolerance to, UV-induced DNA damage. A complex containing Mus81p and Rad54p was identified in immunoprecipitation experiments. Deletion of MUS81 virtually eliminated sporulation in one strain background and reduced sporulation and spore viability in another. Potential homologs of Mus81p have been identified in Schizosaccharomyces pombe, Caenorhabditis elegans and Arabidopsis thaliana. We hypothesize that Mus81p plays a role in the recognition and/or processing of certain types of DNA damage (caused by UV and MMS) during repair or tolerance processes involving the recombinational repair pathway.
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  • 66
    ISSN: 1573-5028
    Keywords: evolution ; C4 plant ; maize ; ribulose-bisphosphate carboxylase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The small subunit of ribulose-bisphosphate carboxylase (Rubisco), encoded by rbcS, is essential for photosynthesis in both C3 and C4 plants, even though the cell specificity of rbcS expression is different between C3 and C4 plants. The C3 rbcS is specifically expressed in mesophyll cells, while the C4 rbcS is expressed in bundle sheath cells, and not mesophyll cells. Two chimeric genes were constructed consisting of the structural gene encoding β-glucuronidase (GUS) controlled by the two promoters from maize (C4) and rice (C3) rbcS genes. These constructs were introduced into a C4 plant, maize. Both chimeric genes were specifically expressed in photosynthetic organs, such as leaf blade, but not in non-photosynthetic organs. The expressions of the genes were also regulated by light. However, the rice promoter drove the GUS activity mainly in mesophyll cells and relatively low in bundle sheath cells, while the maize rbcS promoter induced the activity specifically in bundle sheath cells. These results suggest that the rice promoter contains some cis-acting elements responding in an organ-pecific and light-inducible regulation manner in maize but does not contain element(s) for bundle sheath cell-specific expression, while the maize promoter does contain such element(s). Based on this result, we discuss the similarities and differences between the rice (C3) and maize (C4) rbcS promoter in terms of the evolution of the C4 photosynthetic gene.
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  • 67
    ISSN: 1573-5036
    Keywords: evolution ; glutamine synthetase ; sequences ; subunit composition ; Trientalis europaea
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Ion-exchange chromatography of extracts from Trientalis europaea L. leaf tissue have been shown to contain two distinct isoforms of glutamine synthetase (GS). However, analysis by Western blotting has shown that the first peak to elute contains a mixture of large and small GS subunits, whilst the second peak is comprised entirely of a smaller subunit. This is contrary to the widespread assumptions concerning plant GS biochemistry. Isolation of intact chloroplasts and subsequent extraction of GS, followed by ion-exchange chromatography, has shown that the first peak to elute contains a large subunit, and the second chloroplastic peak is composed entirely of the small subunit. This smaller subunit may be present due to it being encoded by a separate chloroplastic GS gene, or it may be present as a product of post-translational modification. DNA sequencing has been used to try and determine which of these may be occurring. The three partial DNA sequences (505 nucleotides) we have obtained from T. europaea have been compared with 64 other sequences available on the NCBI database, which have mainly been obtained from crop species. Neighbour joining and parsimony analysis (1000 bootstrap) has shown support (∼30%) for the separation of plant GS from all other phyla. Within the plant phylum, there is total support for the separation of chloroplastic and cytosolic GS (100%), whilst the cytosolic sequences divide further into monocot and dicot species (77% support by NJ). Further subgroups of plants from the same families is also suggested. This is consistent with previous work containing fewer, but longer (∼1000 nucleotides) GS sequences. The addition of GS sequences obtained from wild plant species, such as T. europaea, to the large amount of information already available on the database, will permit a better understanding of the evolution of this important enzyme.
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  • 68
    ISSN: 1573-5079
    Keywords: anatomy ; C3 and C4 photosynthesis ; Chenopodiaceae ; cotyledon ; deserts ; evolution ; leaf ; Salsola
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Most species of the genus Salsola (Chenopodiaceae) that have been examined exhibit C4 photosynthesis in leaves. Four Salsola species from Central Asia were investigated in this study to determine the structural and functional relationships in photosynthesis of cotyledons compared to leaves, using anatomical (Kranz versus non-Kranz anatomy, chloroplast ultrastructure) and biochemical (activities of photosynthetic enzymes of the C3 and C4 pathways, 14C labeling of primary photosynthesis products and 13C/12C carbon isotope fractionation) criteria. The species included S. paulsenii from section Salsola, S. richteri from section Coccosalsola, S. laricina from section Caroxylon, and S. gemmascens from section Malpigipila. The results show that all four species have a C4 type of photosynthesis in leaves with a Salsoloid type Kranz anatomy, whereas both C3 and C4 types of photosynthesis were found in cotyledons. S. paulsenii and S. richteri have NADP- (NADP-ME) C4 type biochemistry with Salsoloid Kranz anatomy in both leaves and cotyledons. In S. laricina, both cotyledons and leaves have NAD-malic enzyme (NAD-ME) C4 type photosynthesis; however, while the leaves have Salsoloid type Kranz anatomy, cotyledons have Atriplicoid type Kranz anatomy. In S. gemmascens, cotyledons exhibit C3 type photosynthesis, while leaves perform NAD-ME type photosynthesis. Since the four species studied belong to different Salsola sections, this suggests that differences in photosynthetic types of leaves and cotyledons may be used as a basis or studies of the origin and evolution of C4 photosynthesis in the family Chenopodiaceae.
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    Genetic resources and crop evolution 47 (2000), S. 385-393 
    ISSN: 1573-5109
    Keywords: Citrullus lanatus ; cluster analysis ; evolution ; morphology ; watermelon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Morphological data recorded from field trials using Citrullus lanatus germplasm collected in Namibia were used to analyse and compare the various morphotypes of this species. The experiment comprised wild types and local landraces as well as commercial cultivars. Cluster analysis supported the indigenous classification system used in Namibia, in which Citrullus types are distinguished based on gross morphology, ecology and usage and grouped into seed, cooking and fresh-eating (watermelon) types. Commercial watermelon cultivars formed a distinct cluster. Wide variation was found within the local types whereas the genetic basis of the commercial type appears to be narrow. The commercial cultivars were most closely related to local watermelon types and more distantly related to the wild types, whereas the cooking melons form an intermediate group.
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  • 70
    ISSN: 1573-5117
    Keywords: reflecting organ ; upper lip ; Myodocopa ; chemical cues ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Multifunctions of the upper lip in a bioluminescent myodocopid Vargula hilgendorfii were studied by video observation and histological method. The localization of luciferin and luciferase gland cells within the upper lip was partly successful. Two long protrusions of the upper lip, both of V. hilgendorfii and a non-luminescent species of the same family, immediately anterior to the mouth, were found to show very flexible movement especially while eating, as if smearing on the food surface a secretion from the protrusions (glands), which may support the hypothesized secretion of digestive enzymes from the upper lip. This hypothesis is further supported by the new finding of a pair of ducts which connect the basal part of the upper lip with the posterior digestive duct (stomach). Comparative studies of V. hilgendorfii with several sympatric non-luminescent species of the same family have also revealed that it has a characteristic reflecting organ immediately posterior to the anus. It is a conical small protrusion, as if dangling from the ventral edge of the abdomen at the apex of the cone. It is observable only in live specimens, when the furca, which is located outwardly to the organ, is sufficiently transparent. When illuminated, the reflecting organ reflects the distinct light. The diameter of the mirror (chemical composition provisionally analyzed) is about 6–8% of the carapace length. The organ develops from the very first stage of its ontogeny without reference to sex, which suggests that the function may be related to intraspecific signaling or predatory deterrence.
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    Hydrobiologia 419 (2000), S. 31-63 
    ISSN: 1573-5117
    Keywords: morphology ; ontogeny ; Ostracoda ; evolution ; fifth limb ; crustacean phylogeny
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The chaetotaxy (shape, structure and distribution of setae) of appendages and valve allometry during the post embryonic ontogeny of the cyprididine ostracod Eucypris virens are described. It is shown that the basic ontogenetic development of E. virens is very similar to that of other species of the family Cyprididae. During ontogeny, the chaetotaxy shows continual development on all podomeres of the limbs with the exception of the last podomere on the antennulae. The long setae on the exopodite and protopodite of the antennae have a natatory function until the actual natatory setae develop in later instars. Aesthetascs (presumed chemoreceptors) ya and y3 are the first to develop and may have an important function in the first instars. Cyprididae require a pediform limb in the posterior of the body presumably to help them to attach to substrates and this is reflected by the pediform nature of one limb at all times throughout all instars. This study has also shown that the fifth limb is most probably of thoracic origin and hence ostracods have only one pair of maxillae.
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    Hydrobiologia 419 (2000), S. 7-11 
    ISSN: 1573-5117
    Keywords: morphology ; palaeontology ; ecology ; genetics ; Ostracoda ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Morphology, palaeontology, genetics and ecology are the main scientific domains contributing theories, concepts and new data to evolutionary biology. Ostracods are potentially very good model organisms for evolutionary studies because they combine an excellent fossil record with a wide extant distribution and, therefore, allow studies on both patterns and processes leading to extant diversity. This preface provides an overview of the 15 contributions to the present volume and concludes that this set of papers supports the claim that ostracod studies are situated in all main evolutionary domains.
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  • 73
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    Hydrobiologia 417 (2000), S. 91-99 
    ISSN: 1573-5117
    Keywords: evolution ; phylogeny ; larval characters ; morphology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The plesiomorphic mode of crustacean development is widely accepted to be via a larva called the nauplius. Extant taxa like the Cephalocarida, Branchiopoda, Ostracoda, Mystacocarida, Copepoda, Cirripedia, Ascothoracida, Facetotecta, Euphausiacea and Penaeidea hatch from an egg as a free-living nauplius. Other crustaceans show an embryonic phase of development suggestive of a naupliar organization. Several features of the nauplius larva have been proposed as diagnostic characters for the Crustacea: a median (nauplius) eye; at least three pairs of head appendages (antennules, antennae, mandibles); a posteriorly directed fold (the labrum) extending over the mouth and a cephalic (nauplius) shield. The relationship between trilobite protaspis with at least four appendages and the crustacean nauplius remains unclear, but reports of a copepod orthonauplius with four appendages are rejected. Swimming is suggested to represent the underived mode of locomotion for the crustacean nauplius, and that naupliar swimming directly results in naupliar feeding which also is underived.
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  • 74
    ISSN: 1573-5117
    Keywords: population genetics ; evolution ; allozymes ; DNA ; marine genetics ; Acanthaster planci
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The basic assumptions that widespread marine species should show little spatial variation in genetic structure, given their high potential for dispersal on ocean currents, is being questioned. This has taken some time because there are few studies of widespread marine species over oceanic scales, few data sets that have the high density of sampling required for the detection of fine population structure, and there is little incentive to look further if initial analyses suggest the expected result. The interpretation of the population genetic structure of crown-of-thorns starfish (Acanthaster planci) has been found to vary considerably depending on the sample set included in the analyses and on the method of analysis used. Scatter plots of genetic distance or θ, and spatial autocorrelation approaches gave markedly different results ranging from no structure to isolation by distance. Only visual examination of maps of patterns of variation in allele variation first detected that crown-of-thorns starfish occupy large regions with little between population differentiation, but between which there are markedly higher levels of differentiation. These findings highlight the care required in interpreting population structure, particularly where there are few sample points. Many marine species may have population structures where sharp genetic disjunctions, not associated with any obvious environmental boundaries, separate regions of relative genetic homogeneity. Such population structures are very different from those traditionally assumed and are not yet understood. Further advances in understanding the genetic structure of marine species will demand an iterative approach where a greater number of samples are collected over particular regions identified by earlier interpretations.
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    Hydrobiologia 420 (2000), S. 15-27 
    ISSN: 1573-5117
    Keywords: phylogeny ; evolution ; allozymes ; rDNA ; DNA sequence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The first application of molecular systematics to sponges was in the 1980s, using allozyme divergence to dis-criminate between conspecific and congeneric sponge populations. Since this time, a fairly large database has been accumulated and, although the first findings seemed to indicate that sponge species were genetically more divergent than those of other marine invertebrates, a recent review of the available dataset indicates that levels of interspecific gene identities in most sponges fall within the normal range found between species of other invertebrates. Nevertheless, some sponge genera have species that are extremely divergent from each other, suggesting a possible polyphyly of these genera. In the 1990s, molecular studies comparing sequences of ribosomal RNA have been used to reappraise the phylogenetic relationships among sponge genera, families, orders and classes. Both the 18S small subunit and the 28S large subunit rRNA genes have been sequenced (41 complete or partial and 75 partial sequences, respectively). Sequences of 18S rRNA show good support for Porifera being true Metazoa, but they are not informative for resolving relationships among genera, families or orders. 28S rRNA domains D1 and D2 appear to be more informative for the terminal nodes and provide resolution for internal topologies in sufficiently closely related species, but the deep nodes between orders or classes cannot be resolved using this molecule. Recently, a more conserved gene, Hsp70, has been used to try to resolve the relationships in the deep nodes. Metazoan monophyly is very well supported. Nevertheless, the divergence between the three classes of Porifera, as well as the divergence between Porifera, Cnidaria and Ctenophora, is not resolved. Research is in progress using other genes such as those of the homeodomain, the tyrosine kinase domain, and those coding for the aggregation factor. For the moment the dataset for these genes is too restricted to resolve the phylogenetic relationships of these phyla. However, whichever the genes, the phylogenies obtained suggest that Porifera could be paraphyletic and that the phylogenetic relationships of most of the families and orders of the Demospongiae have to be reassessed. The Calcarea and Hexactinellida are still to be studied at the molecular level.
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  • 76
    ISSN: 1573-5133
    Keywords: Cyprinidae ; piscivores ; prey fish ; small barbs ; species flock ; evolution ; speciation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The endemic cyprinid species flock in Lake Tana consists of 15 species of large hexaploid barbs, eight of which are piscivorous. Previously, it was assumed that all piscivores preyed on the same small barb species, Barbus trispilopleura. In this paper we present a description of morphology and ecology of a new abundant small barb species, Barbus tanapelagius sp. nova (holotype RMNH 33731) from Lake Tana, Ethiopia, which appears to be the major prey species for the large pelagic piscivorous barbs. B. tanapelagius differs clearly in morphology from the other 3 small, diploid Barbus species known from Lake Tana, B. trispilopleura Boulenger, 1902, B. humilis Boulenger, 1902 and B. pleurogramma Boulenger, 1902. Conspicuous differences are its elongated body, large eye diameter, prominent and hooked lower jaw contour and colouration. Preliminary data suggest that B. tanapelagius also differs ecologically from the other small Barbus spp. by its pelagic, strictly zooplanktivorous feeding and its occurrence mainly in the deeper, offshore waters. The other small Barbus species are most probably largely benthic feeders and dominant in the shallow inshore waters. Previous views about the evolution of the present 8 endemic piscivorous large barb species therefore require reconsideration, as the present paper shows a more complex scenario including several prey species.
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    Hydrobiologia 420 (2000), S. 55-62 
    ISSN: 1573-5117
    Keywords: chromosomes ; evolution ; nucleolar organizer region
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The number of cytogenetic studies of marine fish has increased in recent years. Fish groups, such as Perciformes, which comprises many of the extant marine teleosts of economic importance, show little divergence in chromosome number and most species display a diploid number of 48 acrocentric chromosomes. In the Serranidae, Sparidae, Sciaenidae (Perciformes) and Mugilidae (Mugiliformes) small chromosome variations are restricted to subtle heterochromatin or nucleolar organizer region (NOR) modifications. There appears to exist a strict relationship between both absence of geographic barriers throughout the marine environment and high mobility of these animals (eggs, larvae, or adults), with a rarity of chromosome rearrangement at the macrostructural level. Moreover, a cellular homeostasis might also be important to karyotype maintenance among these fishes, limiting changes in the chromosome complement to cryptic chromosome rearrangements. Other groups, such as Blenniidae, Gobiidae and Scorpaenidae, for instance, show more extensive chromosome diversity, which is probably related to limited mobility. Numerical and structural chromosome polymorphisms and several sexual chromosome systems are recurrent among these fishes. A wide karyotypic diversification also characterizes the Tetraodontiformes, an interesting fish group with peculiar morphological, physiological and ecological characteristics.
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    Environmental biology of fishes 57 (2000), S. 443-449 
    ISSN: 1573-5133
    Keywords: parental care ; feeding behaviour ; evolution ; trade-off ; individual differences ; fish
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The function of the fin digging behaviour in increasing food availability for the offspring was analysed in the convict cichlid, Cichlasoma (Archocentrus) nigrofasciatum. Consistent individual differences in the frequency of fin digging were found in the parental fish. Examination of the gastrointestinal tract of young revealed that higher frequency of parental fin digging was associated with higher consumption of large and more profitable prey (Diptera larvae), which inhabited deep horizons of the bottom substrate and possibly were difficult to access without parental assistance. Thus, parental fin digging was initially associated with a significant increase of the offspring growth rate. However, at later brood intervals, when parental care ceased, the young of the high-digging parents were characterised by a poorer consumption of small larvae that were most accessible for them without parental aid and represented an increasingly more important component of their ration than large larvae. Offspring of the low-digging parents, on the other hand, presumably as a result of their individual experience, showed a considerably better consumption of small larvae, increasing their growth rate. As a consequence, prior parental fin digging did not affect the offspring body size after independence. Thus, there exist pronounced individual differences and alternative parental styles in the convict cichlid.
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    Plant molecular biology 42 (2000), S. 151-166 
    ISSN: 1573-5028
    Keywords: evolution ; homeodomain protein ; knox gene ; meristem
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Knotted-like homeobox (knox) genes constitute a gene family in plants. Class I knox genes are expressed in shoot apical meristems, and (with notable exceptions) not in lateral organ primordia. Class II genes have more diverse expression patterns. Loss and gain of function mutations indicate that knox genes are important regulators of meristem function. Gene duplication has contributed to the evolution of families of homeodomain proteins in metazoans. We believe that similar mechanisms have contributed to the diversity of knox gene function in plants. Knox genes may have contributed to the evolution of compound leaves in tomato and could be involved in the evolution of morphological traits in other species. Alterations in cis-regulatory regions in some knox genes correlate with novel patterns of gene expression and distinctive morphologies. Preliminary data from the analysis of class I knox gene expression illustrates the evolution of complex patterns of knox expression is likely to have occurred through loss and gain of domains of gene expression.
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  • 80
    ISSN: 1573-5028
    Keywords: angiosperm ; development ; evolution ; fern ; gymnosperm ; MADS-box gene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Evolutionary developmental genetics (evodevotics) is a novel scientific endeavor which assumes that changes in developmental control genes are a major aspect of evolutionary changes in morphology. Understanding the phylogeny of developmental control genes may thus help us to understand the evolution of plant and animal form. The principles of evodevotics are exemplified by outlining the role of MADS-box genes in the evolution of plant reproductive structures. In extant eudicotyledonous flowering plants, MADS-box genes act as homeotic selector genes determining floral organ identity and as floral meristem identity genes. By reviewing current knowledge about MADS-box genes in ferns, gymnosperms and different types of angiosperms, we demonstrate that the phylogeny of MADS-box genes was strongly correlated with the origin and evolution of plant reproductive structures such as ovules and flowers. It seems likely, therefore, that changes in MADS-box gene structure, expression and function have been a major cause for innovations in reproductive development during land plant evolution, such as seed, flower and fruit formation.
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    Plant molecular biology 42 (2000), S. 181-194 
    ISSN: 1573-5028
    Keywords: actinorhiza ; endomycorrhizae ; evolution ; Frankia ; haemoglobins ; nod factors ; nodulation ; phylogeny ; rhizobia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In this review we will first describe the different steps leading to nodule formation, and these will be compared with processes of non-symbiotic plant development and growth. In general, aspects of both actinorhizal as well as rhizobial symbiosis are described, but in several cases, the emphasis will be on the Rhizobium-legume symbiosis because more knowledge of this system is available. Subsequently, the phylogeny of nodulating plants is described and a comparison is made between several aspects of legume and actinorhizal nodulation. At the end of this paper the relationship between nodule symbiosis and endomycorrhizal symbiosis is described, and it is discussed to what extent the development of root nodules involves unique properties, or whether processes and genes have been recruited from common plant development and the endomycorrhizal symbiosis.
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    Fish physiology and biochemistry 23 (2000), S. 225-232 
    ISSN: 1573-5168
    Keywords: methylisoborneol ; catfish ; cytochrome P450 ; biotransformation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 2-Methylisoborneol (MIB) and structurally related terpenoid compounds are responsible for millions of dollars of lost revenue to catfish farmers. In an attempt to determine enzymatic pathways of biotransformation and elimination of MIB, the in vitro metabolism of MIB was examined in the Ulvade strain of channel catfish (Ictalurus punctatus). Although cytochrome P450 (CYP) activities were observed and correlated with expression of specific isoforms (i.e. steroid hydroxylation and CYP3A expression), no metabolites of MIB were observed. To determine whether extrahepatic biotransformation may be occurring the in vivo metabolism and disposition of 14C-MIB was examined in Uvalde, USDA-103 channel catfish, and a channel catfish X blue catfish (Ictalurus furcatus) hybrid species. Confirming in vitro hepatic studies, no metabolites were observed in plasma from animals treated with an intra-arterial dose of 14C-MIB. 14C-MIB elimination was predicted using a two compartment model in each strain of fish. There was no significant difference in terminal half-lives between strains but possible differences in total body clearance and apparent volumes of distribution which may be related to higher lipid content in the hybrids. Results of these studies indicate biotransformation has no involvement in MIB elimination and that other physiological processes may play a more significant role in MIB disposition within Ictalurid fish species.
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    Journal of bioenergetics and biomembranes 32 (2000), S. 227-236 
    ISSN: 1573-6881
    Keywords: NDP kinase ; subunit interaction ; quaternary structure ; evolution ; mixed oligomers ; Dictyostelium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Physics
    Notes: Abstract Nucleoside (NDP) diphosphate kinases are oligomeric enzymes. Most are hexameric, but somebacterial enzymes are tetrameric. Hexamers and tetramers are constructed by assemblingidentical dimers. The hexameric structure is important for protein stability, as demonstratedby studies with natural mutants (the Killer-of-prune mutant ofDrosophila NDP kinase andthe S120G mutant of the human NDP kinase A in neuroblastomas) and with mutants obtainedby site-directed mutagenesis. It is also essential for enzymic activity. The function of the tetrameric structure is unclear.
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  • 84
    ISSN: 1573-6849
    Keywords: evolution ; genome ; Gossypium ; polyploidization ; repetitive element ; retrotransposon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Retrotransposons constitute a ubiquitous and dynamic component of plant genomes. Intragenomic and intergenomic comparisons of related genomes offer potential insights into retrotransposon behavior and genomic effects. Here, we have used fluorescent in-situ hybridization to determine the chromosomal distributions of a Ty1-copia-like retrotransposon in the cotton AD-genome tetraploid Gossypium hirsutum and closely related putative A- and D-genome diploid ancestors. Retrotransposon clone A108 hybridized to all G. hirsutum chromosomes, approximately equal in intensity in the A- and D-subgenomes. Similar results were obtained by hybridization of A108 to the A-genome diploid G. arboreum, whereas no signal was detected on chromosomes of the D-genome diploid G. raimondii. The significance and potential causes of these observations are discussed.
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  • 85
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    Genetica 109 (2000), S. 105-111 
    ISSN: 1573-6857
    Keywords: Drosophila ; evolution ; heterochromatin ; Y chromosome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Y chromosome evolution is characterized by the expansion of genetic inertness along the Y chromosome and changes in the chromosome structure, especially the tendency of becoming heterochromatic. It is generally assumed that the sex chromosome pair has developed from a pair of homologues. In an evolutionary process the proto-Y-chromosome, with a very short differential segment, develops in its final stage into a completely heterochromatic and to a great extends genetically eroded Y chromosome. The constraints evolving the Y chromosome have been the objects of speculation since the discovery of sex chromosomes. Several models have been suggested. We use the exceptional situation of the in Drosophila mirandato analyze the molecular process in progress involved in Y chromosome evolution. We suggest that the first steps in the switch from a euchromatic proto-Y-chromosome into a completely heterochromatic Y chromosome are driven by the accumulation of transposable elements, especially retrotransposons inserted along the evolving nonrecombining part of the Y chromosome. In this evolutionary process trapping and accumulation of retrotransposons on the proto-Y-chromosome should lead to conformational changes that are responsible for successive silencing of euchromatic genes, both intact or already mutated ones and eventually transform functionally euchromatic domains into genetically inert heterochromatin. Accumulation of further mutations, deletions, and duplications followed by the evolution and expansion of tandem repetitive sequence motifs of high copy number (satellite sequences) together with a few vital genes for male fertility will then represent the final state of the degenerated Y chromosome.
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  • 86
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    Journal of bioenergetics and biomembranes 32 (2000), S. 391-400 
    ISSN: 1573-6881
    Keywords: ATP synthase ; F1-ATPase ; Saccharomyces cerevisiae ; petite mutants ; epistasis ; mitochondrion ; pet mutants
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Physics
    Notes: Abstract The mitochondrial ATP synthase is a molecular motor that drives the phosphorylation ofADP to ATP. The yeast mitochondrial ATP synthase is composed of at least 19 differentpeptides, which comprise the F1 catalytic domain, the F0 proton pore, and two stalks, oneof which is thought to act as a stator to link and hold F1 to F0, and the other as a rotor.Genetic studies using yeast Saccharomyces cerevisiae have suggested the hypothesis thatthe yeast mitochondrial ATP synthase can be assembled in the absence of 1, and even 2, ofthe polypeptides that are thought to comprise the rotor. However, the enzyme complexassembled in the absence of the rotor is thought to be uncoupled, allowing protons to freelyflow through F0 into the mitochondrial matrix. Left uncontrolled, this is a lethal process andthe cell must eliminate this leak if it is to survive. In yeast, the cell is thought to lose ordelete its mitochondrial DNA (the petite mutation) thereby eliminating the genes encodingessential components of F0. Recent biochemical studies in yeast, and prior studies in E. coli,have provided support for the assembly of a partial ATP synthase in which the ATP synthaseis no longer coupled to proton translocation.
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  • 87
    ISSN: 1573-6849
    Keywords: cat ; chromosome painting ; comparative mapping ; dog ; evolution ; human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Domestic cats and dogs are important companion animals and model animals in biomedical research. The cat has a highly conserved karyotype, closely resembling the ancestral karyotype of mammals, while the dog has one of the most extensively rearranged mammalian karyotypes investigated so far. We have constructed the first detailed comparative chromosome map of the domestic dog and cat by reciprocal chromosome painting. Dog paints specific for the 38 autosomes and the X chromosomes delineated 68 conserved chromosomal segments in the cat, while reverse painting of cat probes onto red fox and dog chromosomes revealed 65 conserved segments. Most conserved segments on cat chromosomes also show a high degree of conservation in G-banding patterns compared with their canine counterparts. At least 47 chromosomal fissions (breaks), 25 fusions and one inversion are needed to convert the cat karyotype to that of the dog, confirming that extensive chromosome rearrangements differentiate the karyotypes of the cat and dog. Comparative analysis of the distribution patterns of conserved segments defined by dog paints on cat and human chromosomes has refined the human/cat comparative genome map and, most importantly, has revealed 15 cryptic inversions in seven large chromosomal regions of conserved synteny between humans and cats.
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  • 88
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    Journal of chemical ecology 26 (2000), S. 1773-1794 
    ISSN: 1573-1561
    Keywords: Grasshoppers ; polyphagy ; graminivory ; evolution ; secondary compound ; peritrophic envelope ; midgut ceca ; learning
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Modern grasshoppers probably evolved from polyphagous ancestors endowed with the ability to tolerate many plant secondary compounds. This tolerance involves various behavioral and anatomical adaptations. Polyphagous grasshoppers have a relatively low level of sensitivity to the taste of many secondary compounds, and, if they do respond to the taste, have the capacity to habituate. This gives time for the induction of detoxifying enzymes so that unpalatable but potentially nutritious plants may be eaten safely. Associative learning involving secondary compounds may be important in food aversion learning, enabling the insects to avoid foods that have inappropriate nutrients, for example. Learning is also involved when grasshoppers develop associations between the taste of chemicals in the surface waxes of plants and internal leaf chemistry, enabling them to make faster decisions about the acceptability of a plant. Anatomically, the midgut ceca of polyphagous grasshoppers have well-developed posterior arms, and it is possible that these are especially important in detoxification, while some species, in addition, have a specialized pocket region in which macromolecules accumulate to be eliminated from the body when the lining of peritrophic envelope is drawn out. Polyphagous species also have thick peritrophic envelopes to which various phenolics become adsorbed. Finally, the midgut environment contains surfactants that reduce tannin–protein complexing except at very high tannin concentrations. Some polyphagous species can utilize secondary compounds as defensive substances or, in one case, in cuticular sclerotization. Grass feeding has evolved on numerous occasions from these polyphagous ancestors, and it has been associated with a loss of many of the characters providing protection from secondary compounds.
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  • 89
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    Origins of life and evolution of the biospheres 30 (2000), S. 459-466 
    ISSN: 1573-0875
    Keywords: biogenesis ; biological ; coevolution ; evolution ; models ; origin of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Geosciences
    Notes: Abstract What was the first living molecule – RNA or protein?This question embodies the major disagreement instudies on the origin of life. The fact that incontemporary cells RNA polymerase is a protein andpeptidyl transferase consists of RNA suggests theexistence of a mutual catalytic dependence betweenthese two kinds of biopolymers. I suggest that thisdependence is a `frozen accident', a remnant from thefirst living system. This system is proposed to be acombination of an RNA molecule capable of catalyzingamino acid polymerization and the resulting proteinfunctioning as an RNA-dependent RNA polymerase. Thespecificity of the protein synthesis is thought to beachieved by the composition of the surrounding mediumand the specificity of the RNA synthesis – by Watson– Crick base pairing. Despite its apparent simplicity,the system possesses a great potential to evolve intoa primitive ribosome and further to life, as it isseen today. This model provides a possible explanationfor the origin of the interaction between nucleicacids and protein. Based on the suggested system, Ipropose a new definition of life as a system ofnucleic acid and protein polymerases with a constantsupply of monomers, energy and protection.
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  • 90
    ISSN: 1572-9699
    Keywords: electron microscopy ; killer effect ; Saccharomyces cerevisiae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A mesophilic wine yeast, Saccharomyces cerevisiae CSIR Y217 K − R − was subjected to the K2 killer effect of Saccharomyces cerevisiae T206 K + R + in a liquid grape medium. The lethal effect of the K2 mycoviral toxin was confirmed by methylene blue staining. Scanning electron microscopy of cells from challenge experiments revealed rippled cell surfaces, accompanied by cracks and pores, while those unaffected by the toxin, as in the control experiments, showed a smooth surface. Transmission electron microscopy revealed that the toxin damaged the cell wall structure and perturbed cytoplasmic membranes to a limited extent.
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  • 91
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    Antonie van Leeuwenhoek 77 (2000), S. 235-239 
    ISSN: 1572-9699
    Keywords: Aspergillus section Fumigati ; β-tubulin gene ; evolution ; phylogenetic analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Isolates representing newly described Neosartorya species, and isolates with abnormal morphologies from Aspergillus section Fumigati were examined by phylogenetic analysis of sequences of part of their β-tubulin gene. Phylogenetic analyses supported the earlier suggestions that heterothallism is a derived character, and that sexuality was lost several times during the evolution of Aspergillus section Fumigati. The heterothallic N. fennelliae and N. udagawae strains were found to be closely related to the homothallic Neosartorya sp. NRRL 4179 and N. aureola, respectively. Aspergillus sp. FRR 1266, which was earlier described as a variant of A. fumigatus, was found to be closely related to A. viridinutans. Another abnormal asexual isolate was found to be closely related to A. fumigatus and N. fischeri. Phylogenetic relationships among newly described Neosartorya species and other taxa were successfully established based on phylogenetic analysis of β-tubulin sequences.
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  • 92
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    Antonie van Leeuwenhoek 78 (2000), S. 187-194 
    ISSN: 1572-9699
    Keywords: cAMP ; pseudohyphae ; Saccharomyces cerevisiae ; stress
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In Saccharomyces cerevisiae pseudohyphae formation may be triggered by nitrogen deprivation and is stimulated by cAMP. It was observed that even in a medium with an adequate nitrogen supply, cAMP can induce pseudohyphal growth when S. cerevisiae uses ethanol as carbon source. This led us to investigate the effects of the carbon source and of a variety of stresses on yeast morphology. Pseudohyphae formation and invasive growth were observed in a rich medium (YP) with poor carbon sources such as lactate or ethanol. External cAMP was required for the morphogenetic transition in one genetic background, but was dispensable in strain Σ1278b which has been shown to have an overactive Ras2/cAMP pathway. Pseudohyphal growth and invasiveness also took place in YPD plates when the yeast was subjected to different stresses: a mild heat-stress (37 °C), an osmotic stress (1 m NACl), or addition of compounds which affect the lipid bilayer organization of the cell membrane (aliphatic alcohols at 2%) or alter the glucan structure of the cell wall (Congo red). We conclude that pseudohyphal growth is a physiological response not only to starvation but also to a stressful environment; it appears to require the coordinate action of a MAP kinase cascade and a cAMP-dependent pathway.
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  • 93
    ISSN: 1573-5079
    Keywords: chlorophyll a ; Chl a-binding protein ; evolution ; light-harvesting complex ; LHC I ; Porphyridium cruentum ; reconstitution ; red alga ; zeaxanthin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The Porphyridium cruentum light harvesting complex (LHC) binds Chl a, zeaxanthin and β-carotene and comprises at least 6 polypeptides of a multigene family. We describe the first in vitro reconstitution of a red algal light-harvesting protein (LHCaR1) with Chl a/carotenoid extracts from P. cruentum. The reconstituted pigment complex (rLHCaR1) is spectrally similar to the native LHC I, with an absorption maximum at 670 nm, a 77 K fluorescence emission peak at 677 nm (ex. 440 nm), and similar circular dichroism spectra. Molar ratios of 4.0 zeaxanthin, 0.3 β-carotene and 8.2 Chl a per polypeptide for rLHCaR1 are similar to those of the native LHC I complex (3.1 zeaxanthin, 0.5 β-carotene, 8.5 Chl a). The binding of 8 Chl a molecules per apoprotein is consistent with 8 putative Chl-binding sites in the predicted transmembrane helices of LHCaR1. Two of the putative Chl a binding sites (helix 2) in LHCaR1 were assigned to Chl b in Chl a/b-binding (CAB) LHC II [Kühlbrandt et al. (1994) Nature 367: 614–21]. This suggests either that discrimination for binding of Chl a or Chl b is not very specific at these sites or that specificity of binding sites evolved separately in CAB proteins. LHCaR1 can be reconstituted with varying ratios of carotenoids, consistent with our previous observation that the carotenoid to Chl ratio is substantially higher in P. cruentum grown under high irradiance. Also notable is that zeaxanthin does not act as an accessory light-harvesting pigment, even though it is highly likely that it occupies the position assigned to lutein in the CAB LHCs.
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  • 94
    ISSN: 1573-5109
    Keywords: evolution ; genetic resources ; RAPDs ; seed protein electrophoresis ; taxonomy ; Vicia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The genetic diversity of 58 wild and weedy populations representing taxa within the V. sativa aggregate from the former USSR, 4 cultivars of V. sativa, 2 accessions of V. cordata and 3 accessions of V. macrocarpa from Mediterranean countries were analysed using randomly amplified DNA fragments (RAPDs) and seed protein electrophoresis (SDS-PAGE). Interspecific variation between taxa in the V. sativa aggregate could readily be detected using both techniques. RAPDs and seed protein patterns were found to be an effective means of identifying accessions that cannot be identified clearly by morphological criteria alone. RAPD and seed protein analysis revealed a clear relationship between observed genetic variation of populations and their geographical distribution. Populations from each region had their own gene pools. Geographical variation was detected in V. segetalis. The degree of genetic divergence between local populations was usually related to proximity. In several locations where wild and weedy populations of different V. sativa agg. taxa grow sympatrically, intermediate forms could be detected at the DNA and protein levels. Both RAPD and seed protein analysis support the view that the V. sativa aggregate consists of 8 taxa warranting recognition at the species level. Several species in this aggregate are evolving intra-specific groups which can readily be detected at the molecular level.
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  • 95
    ISSN: 1573-5028
    Keywords: gene expression ; heterologous expression ; H+/hexose symporter ; Lycopersicon esculentum ; quantitative PCR ; Saccharomyces cerevisiae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A full-length (LeHT2) and two partial (LeHT1 and LeHT3) cDNA clones, encoding hexose transporters, were isolated from tomato (Lycopersicon esculentum) fruit and flower cDNA libraries. Southern blot analysis confirmed the presence of a gene family of hexose transporters in tomato consisting of at least three members. The full-length cDNA (LeHT2) encodes a protein of 523 amino acids, with a calculated molecular mass of 57.6 kDa. The predicted protein has 12 putative membrane-spanning domains and belongs to the Major Facilitator Superfamily of membrane carriers. The three clones encode polypeptides that are homologous to other plant monosaccharide transporters and contain conserved amino acid motifs characteristic of this superfamily. Expression of the three genes in different organs of tomato was investigated by quantitative PCR. LeHT1 and LeHT3 are expressed predominantly in sink tissues, with both genes showing highest expression in young fruit and root tips. LeHT2 is expressed at relatively high levels in source leaves and certain sink tissues such as flowers. LeHT2 was functionally expressed in a hexose transport-deficient mutant (RE700A) of Saccharomyces cerevisiae. LeHT2-dependent transport of glucose in RE700A exhibited properties consistent with the operation of an energy-coupled transporter and probably a H+/hexose symporter. The K m of the symporter for glucose is 45 μM.
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  • 96
    ISSN: 1573-5117
    Keywords: cladocerans ; life history ; demography ; size structure ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Daphnia models for individual growth and population dynamics have been developed in the manner of models developed by Gurney, McCauley, Andersen and others. All or most of the earlier models were parameterized for Daphnia pulex; we have used the D. pulex model as a baseline model for other species of Daphnia such as magna, galeata and also Bosmina longirostris. Because of the lack of ample data for D. magna, D. galeata and B. longirostris, some of the physiological data had to be relied on the other species whose data were available and in some case calibrated. We were able to produce reasonable results for individual growth as well as population dynamics under the controlled laboratory conditions. Most of the results were compared with the available laboratory data for population as well as growth. All the simulations have been done under high and low food concentrations. The animals are assumed to be feeding on green algae (Chlamydomonas reinhardtti) under the laboratory conditions of 18–20°C. The continuous growth until the end of the life was observed in smaller B. longirostris, whereas rapid growth in the beginning and slower after the start of the reproduction was observed in Daphnia species. The smaller species matured earlier than larger species. B. longirostris population sustained better than Daphnia species in medium food concentrations.
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  • 97
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    Genetica 108 (2000), S. 57-72 
    ISSN: 1573-6857
    Keywords: Alu ; evolution ; human specific ; polymorphism ; retroposition ; SINES ; 7SL RNA ; YAP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Aluinsertional elements, the most abundant class of SINEs in humans are dimeric sequences approximately 300 bp in length derived from the 7SL RNA gene. These sequences contain a bipartite RNA pol III promoter, a central poly A tract, a 3′ poly A tail, numerous CpG islands and are bracketed by short direct repeats. An estimated 500,000 to 1 × 106units are dispersed throughout the human haploid genome primarily in AT rich neighborhoods located within larger GC dense chromosomal regions via a mechanism known as retroposition. Retroposition activity of Aluelements is determined by both internal and flanking regulatory elements as well as distant genes affecting transcription or transcript stability. Aluelements impact the organization and expression of the human genome at many levels including the processes of recombination, transcription and translation. Twelve subfamilies of Aluare defined by distinct patterns of diagnostic base substitutions. Subfamilies may be classified as young, intermediate or old reflecting the time since the start of retroposition by their members. Some insertions of the youngest subfamilies are not yet fixed in the human species and represent polymorphic loci. Alus are excellent molecular markers for a variety of reasons. They aid in tracing the complex pattern of duplication and rearrangements that occurred during the evolution of primate genome. Unlike other mutations, Alusequences are rarely lost completely once retroposed, have a defined ancestral state and are free from homoplasy since independent and identical insertions are highly unlikely. Because of these characteristics, Alus are literally molecular fossils. Polymorphic Aluloci are especially useful in studies of human genetic diversity and in pedigree and forensicanalysis.
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  • 98
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    Journal of logic, language and information 9 (2000), S. 419-424 
    ISSN: 1572-9583
    Keywords: Artificial Intelligence ; computability ; constructibility ; culture ; evolution ; society ; symbol grounding ; Turing ; Turing Machine ; Turing Test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Linguistics and Literary Studies , Computer Science
    Notes: Abstract The Turing Test (TT), as originally specified, centres on theability to perform a social role. The TT can be seen as a test of anability to enter into normal human social dynamics. In this light itseems unlikely that such an entity can be wholly designed in an“off-line” mode; rather a considerable period of training insitu would be required. The argument that since we can pass the TT,and our cognitive processes might be implemented as a Turing Machine(TM), that consequently a TM that could pass the TT could be built, isattacked on the grounds that not all TMs are constructible in a plannedway. This observation points towards the importance of developmentalprocesses that use random elements (e.g., evolution), but in these casesit becomes problematic to call the result artificial. This hasimplications for the means by which intelligent agents could bedeveloped.
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  • 99
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    Pharmaceutical research 17 (2000), S. 1426-1431 
    ISSN: 1573-904X
    Keywords: eplerenone ; selective aldosterone receptor antagonist ; dog ; pharmacokinetics ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The present study was conducted to characterize the pharmacokinetics of eplerenone (EP), a selective aldosterone receptor antagonist, and its open lactone ring form in the dog. Methods. Pharmacokinetic studies of EP were conducted in dogs following i.v., oral, and rectal dosing (15 mg/kg) and following intragastric, intraduodenal, intrajejunal, and intracolonic dosing (7.5 mg/kg). Results. After oral administration, the systemic availability of EP was 79.2%. Systemic availabilities following administration via other routes were similar to that following oral administration. The half-life and plasma clearance of EP were 2.21 hr and 0.329 l/kg/hr, respectively. Plasma concentrations of the open lactone ring form were lower than EP concentrations regardless of the route of administration. The C-14 AUC in red blood cells was approximately 64% and 68% of the plasma AUC for i.v. and oral doses. Percentages of the dose excreted as total radioactivity in urine and feces were 54.2% and 40.6%, respectively, after i.v. administration, and 40.7% and 52.3%, respectively, after oral administration. The percentages of the dose excreted in urine and feces as EP were 13.7% and 2.5%, respectively, after i.v. administration, and 2.1% and 4.6% after oral administration, respectively. Approximately 11% and 15% of the doses were excreted as the open form following i.v. and oral doses. Conclusions. EP was rapidly and efficiently absorbed throughout the gastrointestinal tract, resulting in a good systemic availability. The drug did not preferentially accumulate in red blood cells. EP was extensively metabolized; however, first-pass metabolism after oral and rectal administration was minimal. EP and its metabolites appear to be highly excreted in the bile.
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  • 100
    ISSN: 1573-904X
    Keywords: amphotericin B ; liposomes ; pharmacokinetics ; toxicokinetics ; tissue distribution ; toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Amphotericin B in small, unilamellar liposomes (AmBisome) is safer and produces higher plasma concentrations than other formulations. Because liposomes may increase and prolong tissue exposures, the potential for drug accumulation or delayed toxicity after chronic AmBisome was investigated. Methods. Rats (174/sex) received intravenous AmBisome (1, 4, or 12 mg/kg), dextrose, or empty liposomes for 91 days with a 30-day recovery. Safety (including clinical and microscopic pathology) and toxicokinetics in plasma and tissues were evaluated. Results. Chemical and histopathologic changes demonstrated that the kidneys and liver were the target organs for chronic AmBisome toxicity. Nephrotoxicity was moderate (urean nitrogen [BUN] ≤51 mg/dl; creatinine unchanged). Liposome-related changes (vacuolated macrophages and hypercholesterolemia) were also observed. Although plasma and tissue accumulation was nonlinear and progressive (clearance and volume decreased, half-life increased with dose and time), most toxic changes occurred early, stabilized by the end of dosing, and reversed during recovery. There were no delayed toxicities. Concentrations in liver and spleen greatly exceeded those in plasma; kidney and lung concentrations were similar to those in plasma. Elimination half-lives were 1-4 weeks in all tissues. Conclusions. Despite nonlinear accumulation, AmBisome revealed predictable hepatic and renal toxicities after 91 days, with no new or delayed effects after prolonged treatment at high doses that resulted in plasma levels 〉200 μg/ml and tissue levels 〉3000 μg/g.
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