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  • Articles: DFG German National Licenses  (294)
  • 2000-2004  (294)
  • apoptosis  (117)
  • Analytical Chemistry and Spectroscopy  (101)
  • evolution  (76)
  • Nuclear reactions
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  • Articles: DFG German National Licenses  (294)
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    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.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    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.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    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.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    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.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    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.
    Type of Medium: Electronic Resource
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  • 6
    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.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    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.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    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.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    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.
    Type of Medium: Electronic Resource
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  • 10
    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.
    Type of Medium: Electronic Resource
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    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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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    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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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 202 (2000), S. 281-290 
    ISSN: 1432-0568
    Keywords: Key words Extracellular matrix ; cartilage ; bone ; evolution ; lamprey ; agnathan
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Previous evidence from our laboratories showed that collagen is not the major matrix protein of the cartilaginous endoskeleton of the lamprey (Petromyzon marinus). Here we have characterized the cartilage matrix proteins of the only other extant agnathan, the hagfish (Myxine glutinosa). Using morphological, immunochemical and biochemical methods, we show that the structural proteins of the cartilaginous endoskeleton of the hagfish are also non-collagenous in nature. Although these hagfish cartilage proteins share properties both with each other and with lamprey cartilage proteins, including resistance to solubilization with cyanogen bromide and an usual amino acid composition rich in glycine and non-polar amino acids, it is clear that at least two and probably more hagfish cartilage proteins can be distinguished, with distinct distributions in different cartilage structures. Furthermore, in spite of their similarities, matrix proteins from hagfish cartilage are not identical to the proteins we have previously characterized in lamprey cartilage. These results suggest the existence of a larger family of similar but not identical proteins that form the major structural elements of cartilage tissues of agnathans. These data also support our previous conclusion that type II collagen became the predominant structural protein of cartilage only after the divergence of the agnathans from the ancestral line of the vertebrates.
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  • 14
    ISSN: 1432-2013
    Keywords: Key words vitamin C (L-ascorbic acid) ; apoptosis ; human articular chondrocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chondrocytes present in articular cartilage survive as a resident cell population throughout the lifespan of the individual organism. However, articular chondrocytes as other cells also undergo apoptosis and there is an ever increasing list of diverse stimuli that can induce this phenomenon in vitro. Our main interest was to investigate potential cytotoxic effects of vitamin C (L-ascorbic acid) on human articular chondrocytes. The present study suggests that vitamin C can induce apoptosis in a cell culture of chondrocytes after 18 h of cultivation. Apoptosis-inducing activity of L-ascorbic acid is dose dependent and significantly affected by the presence of serum. The increased number of vitamin C induced apoptotic cells was associated with DNA fragmentation and morphological changes of the cells.
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  • 15
    ISSN: 1569-8041
    Keywords: 5-fluorouracil ; antifolates ; apoptosis ; DNA repair ; p53 ; thymidylate synthase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thymidylate synthase (TS) is an essential enzyme for the de novo synthesis of thymidylate and subsequently DNA synthesis. TS has been usedas a target for cancer chemotherapy in the development of fluoropyrimidinessuch as 5-fluorouracil (5-FU) and 5-fluorodeoxyuridine and of novelfolate-based TS inhibitors such as ZD1694 (Tomudex, Raltitrexed), ZD9331,LY231514 (ALIMTA, Pemetrexed), AG337 (Thymitaq, Nolatrexed) and AG331.Although TS has been considered as a target for chemotherapy, the precisemechanism by which TS inhibition leads to cell death is still not completelyresolved. TS inhibition results in depletion of dTTP, an essential precursorfor DNA, and an increase in dUTP. This results in the so-called thymine-lessdeath due to misincorporation of dUTP into DNA; its excision, catalysed byuracil-DNA glycosylase, results in DNA damage. Both this imbalance indTTP/dUTP and DNA damage can result in induction of downstream events, leadingto apoptosis. On the other hand a specific interaction exists betweenoncogenes and TS, by binding of TS protein to the p53and c-mycRNA, while wt p53can also inhibit TS promotor activity. TSinhibition by either 5-FU or antifolates can also result in a depression ofTS protein mediated inhibition of TS mRNA translation leading to induction ofmore TS protein synthesis, and p53protein may further deregulatethis process. These complex indirect and direct interactions between oncogenesand TS may have as yet unclear clinical implications, since most data arebased on in vitroor in vivo studies and some results arecontradictive. In some preliminary clinical studies evidence was postulatedfor a combined prognostic role for TS and p53.This knowledge shouldbe used to design clinical studies with the aim to deliver effective treatmentto potentially sensitive patients both in the adjuvant setting and in advancedstage disease.
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  • 16
    ISSN: 1573-4919
    Keywords: endosulfan ; cytotoxicity ; mitochondria ; apoptosis ; Jurkat cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Several organochlorinated pesticides including DDT, PCBs and dieldrin have been reported to cause immune suppression and increase susceptibility to infection in animals. Often this manifestation is accompanied by atrophy of major lymphoid organs. It has been suggested that increased apoptotic cell death leading to altered T-B cell ratios, and loss of regulatory cells in critical numbers leads to perturbations in immune function. The major objective of our study was to define the mechanism by which endosulfan, an organochlorinated pesticide, induces human T-cell death using Jurkat, a human T-cell leukemic cell line, as an in vitro model. We exposed Jurkat cells to varying concentrations of endosulfan for 0-48 h and analyzed biochemical and molecular features characteristic of T-cell apoptosis. Endosulfan lowered cell viability and inhibited cell growth in a dose- and time-dependent manner. DAPI staining was used to enumerate apoptotic cells and we observed that endosulfan at 10-200 μM induced a significant percentage of cells to undergo apoptotic cell death. At 48 h, more than 90% cells were apoptotic with 50 μM of endosulfan. We confirmed these observations using both DNA fragmentation and annexin-V binding assays. It is now widely being accepted that mitochondria undergo major changes early during the apoptotic process. We examined mitochondrial transmembrane potential (ΔΨm) in endosulfan treated cells to understand the role of the mitochondria in T-cell apoptosis. Within 30 min of chemical exposure, a significant percentage of cells exhibited a decreased incorporation of DiOC6(3), a cationic lipophilic dye into mitochondria indicating the disruption of ΔΨm. This drop in ΔΨm was both dose- and time-dependent and correlated well with other parameters of apoptosis. We also examined whether this occurred by the down regulation of bcl-2 protein expression that is likely to increase the susceptibility of Jurkat cells to endosulfan toxicity. Paradoxically, the intracellular expression of bcl-2 protein was elevated in a dose dependent manner suggesting endosulfan-induced apoptosis occurred by a non-bcl-2 pathway. Based on these data, as well as those reported elsewhere, we propose the following sequence of events to account for T-cell apoptosis induced by endosulfan: uncoupling of oxidative phosphorylation → excess ROS production → GSH depletion → oxidative stress → disruption of ΔΨm → release of cytochrome C and other apoptosis related proteins to cytosol → apoptosis. This study reports for the first time that endosulfan can induce apoptosis in a human T-cell leukemic cell line which may have direct relevance to loss of T cells and thymocytes in vivo. Furthermore, our data strongly support a role of mitochondrial dysfunction and oxidative stress in endosulfan toxicity.
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Molecular and cellular biochemistry 204 (2000), S. 83-88 
    ISSN: 1573-4919
    Keywords: FHIT ; cell cycle ; ecdysone ; tumor suppressor ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The mechanism of tumor suppressor action of the fragile histidine triad (FHIT) gene is unknown. Disruption of cell cycle regulation leads to the tumor formation and many tumor suppressor genes suppress tumorigenesis through their effect on cell cycle regulation. We examined the expression of FHIT during the cell cycle, and determined whether overexpression of FHIT affects cell cycle kinetics and apoptosis. The FHIT cDNA was cloned into the ecdysone-inducible expression vector in both the sense and antisense orientations. Overexpression of the sense or antisense construct did not affect cell proliferation, cell cycle distribution or apoptosis in human 293T cells. Analysis of the FHIT expression in 293T cells collected at various cell cycle phases showed that the expression of FHIT is not under cell cycle regulation. These results indicate that the tumor suppressor activity of the FHIT gene may be independent of an effect on the cell cycle and apoptosis mechanisms.
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    Molecular and cellular biochemistry 212 (2000), S. 19-28 
    ISSN: 1573-4919
    Keywords: melanoma ; transcription factors ; CREB ; invasion ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The purpose of this study was to determine the role of CREB and its associated proteins in melanoma progression. We used MeWo human melanoma cells transfected with a dominant negative construct of CREB, KCREB. KCREB has a mutation in its DNA-binding domain and can not bind the CRE element. Expression of KCREB yields proper heterodimerization with CREB and its associated proteins, but the proteins associated with KCREB do not confer the same degree of transcriptional activity as they would in the case of wild-type CREB. Here, we demonstrate that expression of KCREB in MeWo melanoma cells leads to a decrease in their tumorigenicity and metastatic potential in nude mice. We identified two mechanisms that explain at least partially this effect of KCREB. The first, is one in which CREB and its associated proteins play an essential role in invasion. We showed that the invasive properties of KCREB-transfected MeWo cells were reduced due to the downregulation of the CRE-dependent expression of the type IV collagenase MMP-2 and the adhesion molecule MCAM/MUC18. In the second mechanism, CREB and its associated proteins act as survival factors for human melanoma cells. Here we demonstrated that expression of KCREB in MeWo cells rendered them susceptible to apoptosis induced by thapsigargin, which in turn increased the intracellular level of Ca2+. Thapsigargin induced CREB and ATF-1 phosphorylation and activated CRE-dependent transcription in MeWo cells. Collectively, our data demonstrate that CREB and its associated proteins play an important role in tumor growth and metastasis of human melanoma.
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  • 19
    ISSN: 1573-4919
    Keywords: T-type Ca2+ channel ; polyglutamine-expanded androgen receptor ; CAG trinucleotide repeats ; spinobulbar muscular atrophy ; apoptosis ; motorneuron ; cell lines ; neuroblastoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract We have analyzed Ca2+ currents in two neuroblastoma-motor neuron hybrid cell lines that expressed normal or glutamine-expanded human androgen receptors (polyGln-expanded AR) either transiently or stably. The cell lines express a unique, low-threshold, transient type of Ca2+ current that is not affected by L-type Ca2+ channel blocker (PN 200-110), N-type Ca2+ channel blocker (ω-conotoxin GVIA) or P-type Ca2+ channel blocker (Agatoxin IVA) but is blocked by either Cd2+ or Ni2+. This pharmacological profile most closely resembles that of T-type Ca2+ channels [1-3]. Exposure to androgen had no effect on control cell lines or cells transfected with normal AR but significantly changed the steady-state activation in cells transfected with expanded AR. The observed negative shift in steady-state activation results in a large increase in the T-type Ca2+ channel window current. We suggest that Ca2+ overload due to abnormal voltage-dependence of transient Ca2+ channel activation may contribute to motor neuron toxicity in spinobulbar muscular atrophy (SBMA). This hypothesis is supported by the additional finding that, at concentrations that selectively block T-type Ca2+ channel currents, Ni2+ significantly reduced cell death in cell lines transfected with polyGln-expanded AR.
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  • 20
    ISSN: 1573-4919
    Keywords: retinoic acid ; RARβ ; protein kinase A ; apoptosis ; caspase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Both cAMP and retinoids play a role in cell differentiation and the control of cell growth. A site-selective cAMP analog, 8-Cl-cAMP and retinoic acid synergistically inhibit growth and induce apoptosis in certain cancer cells. In advanced or recurrent malignant diseases, retinoic acid (RA) is not effective even at doses that are toxic to the host. The objective of our present study was to examine the mechanism(s) of synergistic effects of retinoic acid (9-cis, 13-cis or all-trans RA) and 8-Cl-cAMP on apoptosis in human ovarian cancer NIH: OVCAR-3 and OVCAR-8 cells. RA induced growth inhibition and apoptosis in OVCAR-3 and OVCAR-8 cells. 8-Cl-cAMP acted synergistically with RA in inducing and activating retinoic acid receptor β (RARβ) which correlates with growth inhibition and apoptosis in both cell types. In addition, induction of apoptosis by RA plus 8-Cl-cAMP requires caspase-3 activation followed by cleavage of anti-poly(ADP-ribose) polymerase. Furthermore, mutations in CRE-related motif within the RARβ promoter resulted in loss of both transcriptional activation of RARβ and synergy between RA and 8-Cl-cAMP. RARβ expression appears to be associated with induction of apoptosis. Introduction of the RARβ gene into OVCAR-3 cells resulted in gain of RA sensitivity. Loss of RARβ expression, therefore, may contribute to the tumorigenicity of human ovarian cancer cells. Thus, combined treatment with RA and 8-Cl-cAMP may provide an effective means for inducing RARβ expression leading to apoptosis in ovarian cancer cells.
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  • 21
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    Molecular and cellular biochemistry 203 (2000), S. 59-71 
    ISSN: 1573-4919
    Keywords: PTEN tumor suppressor ; cyclin-dependent kinase inhibitors ; apoptosis ; chemosensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The recently discovered tumor suppressor gene PTEN has been found mutated in many types of advanced tumors. When introduced into tumor cells that lack the wild-type allele of the gene, PTEN was able to suppress the growth of these cells. Here, we have analyzed how PTEN might alter cell cycle-regulatory controls to achieve this growth-inhibitory effect. We found that overexpression of PTEN stimulates the synthesis of three inhibitors of cyclin-dependent kinases, p21WAF1, p27KIP1, and p57,KIP2. This effect is very specific, as the expression of other components of the cell cycle engine, various cyclins and cyclin-dependent kinases, is not affected. For p21WAF1 we show that this induction is due to the p53-independent transcriptional activation of its promoter. In addition, increased expression of PTEN rendered the cells more sensitive to apoptotic cell death. Therefore, our data suggest a two-fold mechanism of growth inhibition by PTEN: one that acts via the increased expression of CKIs such as p21WAF1, and another that augments the cellular propensity for apoptotic cell death.
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  • 22
    ISSN: 1573-4919
    Keywords: tumour necrosis factor ; receptors ; subtypes ; calcium ; apoptosis ; cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Tumour necrosis factor-α (TNF) receptors mediate a variety of effects dependent on cell type. A role for Ca2+ in TNF-induced death remains uncertain. Here we investigated restricting intracellular/extracellular Ca2+ in HeLa epithelial carcinoma cells expressing low and high levels of p75TNFR receptor subtype and KYM-1 rhabdomyosarcoma cells, models of rapid TNF-induced apoptosis. Ca2+-chelators EGTA and BAPTA-AM as well as microsomal Ca2+-ATPase inhibitor thapsigargin, did not alter TNF-induced death. TNF was also unable to alter resting [Ca2+]i levels which remained 〈 200 nM even during times when these cells were undergoing apoptotic cell death. These findings indicate no role for modulated Ca2+ concentrations in TNF-induced apoptotic cell death.
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  • 23
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    Journal of clinical immunology 20 (2000), S. 229-239 
    ISSN: 1573-2592
    Keywords: Aging ; apoptosis ; TNF receptor ; Fas ; Fas ligand ; mitochondria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The cellular and molecular basis of immune senescence is unclear. A number of mechanisms have been proposed. In this issue of the Journal of Clinical Immunology, some of the mechanisms for various immunologic abnormalities in aging are presented. In this article, various molecular steps of both death receptor and mitochondrial pathways of apoptosis in general are reviewed. In particular, the role of apoptosis in T-cell immune senescence is discussed.
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  • 24
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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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  • 25
    ISSN: 1573-4919
    Keywords: etoposide ; Bcl-XL ; Bax ; apoptosis ; K562 cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Etoposide is a potent anticancer agent that is used to treat various tumors. We have investigated the dose-dependent effect of etoposide on apoptosis using chronic myeloid leukemia K562 cells treated with low (5 μM) or high (100 μM) concentrations of the drug. At a low concentration, etoposide induced little apoptosis at 24 h, while about 20% of the cells showed apoptosis morphologically at a high concentration. Processing of caspase-3 was slightly detected from 12 h and became obvious at 24 h with 100 μM etoposide. Caspase-3-like protease activity was detected at 24 h with a high concentration. Moreover, these changes were accompanied by cleavage of poly ADP ribose polymerase (PARP). Changes of the mRNA levels of most apoptosis-regulating genes were not prominent at both concentrations, except for the rapid induction of c-IAP-2/HIAP-1 and the down-regulation of Bcl-XL by 100 μM etoposide. The downregulation of Bcl-XL protein occurred from 6 h, while Bax protein conversely showed a slight increase from 6 h. Taken together, the present findings show that the dose-dependent apoptotic effect of etoposide is based on a change in the balance between Bcl-XL and Bax, which precedes the activation of caspase-3.
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  • 26
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    Molecular and cellular biochemistry 207 (2000), S. 19-27 
    ISSN: 1573-4919
    Keywords: PKC ; apoptosis ; bile acid ; hepatocyte
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of GCDC-induced apoptosis on PKC activity and PKC's role in GCDC-induced hepatocyte apoptosis is unclear. The specific aims of this study were to determine if GCDC-induced apoptosis changed intracellular PKC activity and if modulation of PKC activity affected GCDC-induced hepatocyte apoptosis. Apoptosis was induced in isolated hepatocytes using GCDC. PKC activity was measured and specific PKC and calpain inhibitors were used to study the effects of PKC and calpain modulation on GCDC-induced apoptosis. After 4 h exposure, 50 μM GCDC induced apoptosis in 42% of hepatocytes. Intracellular PKC activity decreased to 44% of controls 2 h after exposure of hepatocytes to GCDC (p 〈 0.001). Pre-incubation of hepatocytes with the calpain protease inhibitor restored PKC activity in GCDC exposed hepatocytes to 91± 5% of control cells. Pre-incubation of hepatocytes with a calpain inhibitor decreased GCDC-induced apoptosis as did pre-incubation with the PKC activating phorbol ester, PMA. The combination of calpain inhibition and PMA further reduced GCDC-induced apoptosis but caused low level hepatic apoptosis. Inhibition of PKC with chelerythrine also substantially reduced GCDC-induced hepatocyte apoptosis. GCDC-induced apoptosis is associated with decreases in total cellular PKC activity, which appear to be dependent on intracellular calpain-like protease activity. The combination of protease inhibition and phorbol ester pretreatment preserved total cellular PKC activity and decreased GCDC-induced apoptosis but induced low level apoptosis in the absence of GCDC exposure. PKC inhibition also decreased GCDC-induced hepatocyte apoptosis highlighting the complex interactions of PKC and proteases during GCDC-induced apoptosis.
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  • 27
    ISSN: 1573-4919
    Keywords: phosphatidylserine ; base exchange ; apoptosis ; thymocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The exposure of phosphatidylserine toward the external surface of the membrane is a well-established event of programmed cell death. The possibility that an apoptotic stimulus influences the metabolism of this phospholipid could be relevant not only in relation to the previously mentioned event but also in relation to the capability of membrane phosphatidylserine to influence PKC activity. The present investigation demonstrates that treatment of mouse thymocytes with the apoptotic stimulus dexamethasone, enhances the incorporation of [3H]serine into phosphatidylserine. Cell treatment with dexamethasone also enhanced the activity of serine base exchange enzyme, assayed in thymocyte lysate. Both the effects were observed at periods of treatment preceding DNA fragmentation. The addition of unlabelled ethanolamine, together with [3H]serine to the medium containing dexamethasone-treated thymocytes lowered the radioactivity into phosphatidylserine. Serine base exchange enzyme activity was influenced by the procedure used to prepare thymocyte lysate and was lowered by the addition of fluoroaluminate, that is widely used as a G-protein activator. The increase of serine base exchange enzyme activity induced by dexamethasone treatment was observed independently by the procedure used to prepare cell lysate and by the presence or absence of fluoroaluminate.
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  • 28
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    Molecular and cellular biochemistry 212 (2000), S. 35-43 
    ISSN: 1573-4919
    Keywords: cAMP ; CRE ; Cox-2 ; NO ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Previous studies revealed that expression and activation of cyclooxygenase-2 (Cox-2) conveyed a protective principle in murine macrophages, thus attenuating pro-apoptotic actions of chemotherapeutic agents or programmed cell death as a result of massive nitric oxide (NO) generation. Expression of Cox-2 was achieved by treatment of cells with lipopolysaccharide/interferon-γ or nontoxic doses of NO releasing agents. We reasoned E-type prostanoid formation, and in turn an intracellular cAMP increase as the underlying protective mechanism. To prove our hypothesis, we analyzed the effects of lipophilic cAMP-analogs on NO, cisplatin, or etoposide induced apoptosis in RAW 264.7 macrophages. Selected apoptotic parameters comprised DNA fragmentation (diphenylamine assay), annexin V staining of phosphatidylserine, caspase activity (quantitated by the cleavage of a fluorogenic caspase-3-like substrate Ac-DEVD-AMC), and mitochondrial membrane depolarisation (ΔΨ). Western blots detected accumulation of the tumor suppressor protein p53, relocation of cytochrome c to the cytosol, and expression of the anti-apoptotic protein Bcl-xL. Prestimulation with lipophilic cAMP-analogs attenuated apoptosis with the notion that cell death parameters were basically absent. To verify gene induction by cAMP in association with protection we established activation of cAMP response element binding protein (CREB) by gel-shift analysis and moreover, treated macrophages with oligonucleotides containing a cAMP-responsive element (CRE) in order to scavenge CREB. Decoy oligonucleotides, but not control oligonucleotides, attenuated cAMP-evoked protection and reestablished pro-apoptotic parameters. We conclude that gene induction by cAMP protects macrophages towards apoptosis that occurs as a result of excessive NO formation or addition of chemotherapeutica. Attenuating programmed cell death by the cAMP-signaling system may be found in association with Cox-2 expression and tumor formation.
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  • 29
    ISSN: 1573-4927
    Keywords: ancient endogenous provirus ; evolution ; retrotransposition
    Source: Springer Online Journal Archives 1860-2000
    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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  • 30
    ISSN: 1573-4978
    Keywords: apoptosis ; CD95 ; human hepatoma cell ; hydrogen peroxide ; p53
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Reactive oxygen species (ROS) play an important role in cell death induced by many different stimuli. Direct exposure of human hepatoma cell line SMMC-7221 to hydrogen peroxide (H2O2) can induce apoptosis characterized by morphological evidence and fragmentation of DNA assayed by terminal deoxynucleotidyl transferase assay (TUNEL assay). Analysis of flow cytometry indicated that H2O2 can decrease the level of CD95(APO-1/Fas), and it is confirmed that H2O2 can also activate the differential expression of some specific gene such as p53 by means of RT-PCR technique. The results indicated that CD95 signal transduction system may be involved in the H2O2-induced apoptosis, and can regulate some specific genes associated with apoptosis in transcription and translation levels such as p53.
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  • 31
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    Molecular biology 34 (2000), S. 875-887 
    ISSN: 1608-3245
    Keywords: antisense oligonucleotides ; oncogenesis ; therapy of cancer ; apoptosis ; bcl family
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Members of the bcl-2 family genes are thought to be central regulators of apoptosis. Overexpression of antiapoptotic proteins, such as Bcl-2 and Bcl-xL, contributes not only to the development of cancer but also to its resistance against a wide variety of anticancer agents. Thus, downregulation of Bcl-2 and Bcl-xL can potentially be used to improve therapeutic approaches to advanced cancer. The use of antisense biotechnology to downregulate antiapoptotic bcl family members in diverse cancers in vitro and in vivo is reviewed. The effects and potential limitations of antisense strategies are also discussed in the context of a critical view of recent research in the field.
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  • 32
    ISSN: 1618-2545
    Keywords: biogeography ; calmodulin ; DNA sequence ; elongation factor EF-1α ; evolution
    Source: Springer Online Journal Archives 1860-2000
    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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  • 33
    ISSN: 1618-2545
    Keywords: Ascomycota ; evolution ; pyrenomycetes ; systematics
    Source: Springer Online Journal Archives 1860-2000
    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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  • 34
    ISSN: 1618-2545
    Keywords: apoptosis ; caspase-3 ; E2F factor ; Lentinula edodes ; mycelial culture broth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Extracts fromshiitake (Lentinula edodes) mycelial culture broth, by an organic solvent ethyl acetate, inhibited the proliferation of cultured cells. At lower concentrations (1.25–15 μg/ml), this inhibition, measured by the MTT assay, was dose- and cell line-dependent. Inhibition of tumor cells, such as Caski, SiHa, HeLa, HP-1 and A375, byL. edodes-436 extracts was stronger than inhibition of normal cells (3T3). At 20 μg/ml, the extracts induced changes in cell shape, DNA-fragmentation and the activation of caspase-3. The extracts also inhibited the binding of E2F protein to its promoter. The results suggest that extracts ofL. edodes culture broth contain substances that have the ability to induce apoptosis in the cultured cells.
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  • 35
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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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  • 36
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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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  • 37
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    Biology and philosophy 15 (2000), S. 443-463 
    ISSN: 1572-8404
    Keywords: David Hull ; evolution ; selection
    Source: Springer Online Journal Archives 1860-2000
    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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  • 38
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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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  • 39
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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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  • 40
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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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  • 41
    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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  • 42
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    Cytotechnology 34 (2000), S. 131-139 
    ISSN: 1573-0778
    Keywords: apoptosis ; bcl-xL ; cell growth ; cell viability ; hybridoma ; myeloma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract While the ectopic expression of the anti-apoptoticprotein Bcl-2 has been shown to significantly increaseboth cell viability and antibody production in batchculture, some cell lines are refractory to thesemanipulations. For example, the NS/O and theP3x63Ag8.653 murine myelomas, which express highendogenous levels of the Bcl-2 homologue Bcl-xL, areboth resistant to the anti-apoptotic effect of Bcl-2.This indicates that, in these cells, Bcl-2 and Bcl-xLmay be functionally redundant. In order to define therole which Bcl-xL plays in hybridoma cultures, we usedthe Sp2/0-Ag14 cell line. This murine hybridomaexpresses low levels of Bcl-xL and is highly sensitiveto apoptosis induction by cycloheximide (CHX) and byamino acid depletion. Bcl-xL-transfected Sp2/0-Ag14cells were more resistant than the wild type and theplasmid-containing cells to apoptosis induced by CHXand by glutamine depletion. Moreover, when compared tothe vector-transfected control, Bcl-xL-Sp2/0 cellsexhibited a substantial increase in viability instationary batch culture. Interestingly, Sp2/0-Ag14cells overexpressing Bcl-xL showed a growth behaviourthat was similar to the parent myeloma cell lineP3x63Ag8.653. Our results suggest that Bcl-xLexpression levels are sufficient to account for therelative robustness of some hybridoma cell lines instationary batch cultures.
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  • 43
    ISSN: 1573-0778
    Keywords: antisense ; apoptosis ; cell cycle ; c-jun ; protein production
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Expression of c-jun gene induces apoptosis ofcells cultured in serum-free medium. It also promotescell-cycling in serum-containing medium, leading cellsto die by overgrowth. Previously, we established anapoptosis-suppressible, cell-cycle arrestable cellline, c-jun AS, by transfecting Friend murineerythroleukemia (F-MEL) cells with adexamethasone-inducible antisense c-jun gene.Induction of the antisense c-jun transcriptionwith dexamethasone suppressed c-jun expression.As a result, c-jun AS cells survived inserum-free medium containing dexamethasone for a longtime, while F-MEL cells died quickly in the presenceor absence of dexamethasone. In serum-containingmedium, the growth of c-jun AS cells was viablyblocked by inducing antisense c-juntranscription, and the cells survived at thenon-growth state avoiding overgrowth. In the presentstudy, protein productivity of c-jun AS cellswas examined in comparison with that of wild typeF-MEL cells. C-jun AS and F-MEL cells werefurther transfected with a vector for expressingalkaline phosphatase as a protein to be produced, andnamed c-jun AS-SEAP and F-MEL-SEAP cells,respectively. In the serum-free medium withdexamethasone, c-jun AS-SEAP cells produced theprotein for up to 6 days, while F-MEL-SEAP cellsstopped production on day 3 due to cell death causedby serum deprivation. In the serum-containing mediumwith dexamethasone, c-jun AS-SEAP cells wereviably arrested in the cell cycle, and cell death dueto overgrowth was avoided. As the result, they couldproduce the protein for up to 18 days, whileF-MEL-SEAP cells stopped production within 7 days dueto cell death caused by overgrowth.
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  • 44
    ISSN: 1573-4986
    Keywords: sialidase ; sialyltransferase ; apoptosis ; Jurkat cells ; etoposide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The present study investigated the mechanism underlying alterations of cell surface sugar chains of Jurkat cells by inducing apoptosis with etoposide, an inhibitor of topoisomerase II. Within 3[emsp4 ]h of etoposide treatment, flowcytometric analysis revealed a decrease in Maackia amurensis agglutinin recognized α2,3-linked sialic acid moieties and an increase in Ricinus communis agglutinin recognized galactose. The results suggested that asialo-sugar chains on glycoconjugates were rapidly induced on the etoposide-treated cell surface. To clarify the desialylation mechanism, we studied α2,3-sialyltransferase mRNA expression and the activity of sialidase on the cell surface during etoposide-induced apoptosis. The expression of hST3Gal III and hST3Gal IV mRNAs were down-regulated and sialidase activity on the cell surface increased threefold within 2[emsp4 ]h of etoposide treatment. Moreover, the decrease in α2,3-linked sialic acid levels was significantly suppressed in the presence of 2,3-dehydro-2-deoxy-N-acetylneuraminic acid, an inhibitor of sialidase. These results suggested that activation or exposure of sialidase on the cell surface was induced by etoposide treatment and was the main cause of the decrease in sialic acids.
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  • 45
    ISSN: 1573-7276
    Keywords: apoptosis ; Bcl-2 ; cell cycle ; invasion ; metastasis ; mobility ; melanoma B16-BL6 cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Quercetin has been known to have anti-tumor and anti-oxidation activities. In the present study, we have investigated its in vitro anti-metastatic activity. Quercetin inhibited the invasion and mobility of murine melanoma B16-BL6 cells in a dose-dependent manner but did not affect their adhesion to either laminin, fibronectin, or type VI collagen. Moreover, quercetin significantly inhibited the proliferation of B16-BL6 cells only in the case of time incubation longer than 48 h. Quercetin dose-dependently decreased the cell rates in S and G2–M phases of cell cycle. The effect of quercetin to cause a remarkable apoptosis of B16-BL6 cells was also demonstrated by flow cytometric assay as well as DNA fragmentation with a typical 180-bp ladder band in agarose electrophoresis and a quantitative analysis. Furthermore, quercetin markedly inhibited the expression of anti-apoptotic protein Bcl-2 but hardly influenced Bcl-XL. These results suggest that the inhibition of quercetin on invasiveness and migration of B16-BL6 cells are closely associated with the arrest of cell cycle as well as the induction of apoptosis by decreasing the Bcl-2 expression.
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  • 46
    ISSN: 1573-7276
    Keywords: apoptosis ; butyrate ; cell cycle ; cholesteryl butyrate ; drug delivery ; melanoma ; solid lipid nanospheres
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Literature data show that butyric acid derivatives bear a dose-dependent differentiative anti-proliferative activity on cancer cell lines and that apoptosis induction may play a major role. Although it was recently shown that solid lipid nanospheres (SLNs) are a suitable tool for several in vivo drug administration routes, there is little available information on melanoma cell lines. This study was aimed at evaluating the anti-proliferative and apoptotic in vitro effects of cholesteryl butyrate (chol-but) SLNs on melanoma cells. Increasing concentrations of chol-but SLNs were used to test two melanoma cell lines. Both cell lines were treated with Na-butyrate (Na-but) and chol-but SLNs for viability. Those tested with chol-but SLNs were more effective than Na-butirate (3 to 72 h). The apoptotic effects of chol-but SLNs were evaluated between 3 and 72 h by annexin-V (ANX-V)/propidium iodide (PI) staining and the antiproliferative effect by PI staining. Apoptosis anti-proliferative-regulatory proteins as bcl-2, Fas/APO1 (CD95) and PCNA (PC10) were also investigated. Flow cytometric analyses evidenced a G0/1-S transition block and a `sub-G0/1' apoptotic peak from 0.5 to 1.0 mM butyric acid. In ANX-V/PI flow cytometric staining, a dose- and time-dependent increase in the apoptotic cell percentage (ANX-V+) coupled with a down-regulation of PC10 and bcl-2 and a parallel up-regulation of Fas/APO1 (CD95) were found in both lines started after 3 to 24 h of chol-but SLNs treatment. Results show that chol-but SLNs exerts a dose/time-dependent effect in melanoma cell apoptosis induction between 3 and 24 h and a dose but not time-dependent effect after 24 h of treatment.
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  • 47
    ISSN: 1573-7373
    Keywords: apoptosis ; DNA ; glioma ; estramustine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The drug effect of estramustine phosphate (EMP), an anti-microtubule agent on human glioma cells has been studied with the focus being mainly its cytotoxity or its targeting of organelles. However, the pharmacological knowledge of estramustine with respect to its cytotoxity and mechanism is limited. To acquire such knowledge, the present study investigates the ability of EMP to induce apoptosis in a human malignant glioma cell line. Transmission electron microscope (TEM) images were examined to monitor periodic changes. Agarose gel electrophoresis was also examined. Cellular DNA fragmentation ELISA was performed to investigate the DNA fragmentation rates and an MTT assay was studied to evaluate the ID50. A TEM study revealed condensing and fragmentation of the chromatin. Laddering of the bands was observed in all EMP exposure groups in agarose gel electrophoresis. DNA fragmentation in all EMP groups began at 0.5 h following an exposure with EMP and increased in a dose- and time-dependent manner as revealed by DNA ELISA fragmentation. ID50 at 24 h was 5.0 µM according to the MTT assay, a value close to 4.8 µM of ID50 was revealed by the DNA fragmentation assay. None of the above mentioned changes was observed in the control group. These results indicated that EMP caused a drug-induced apoptosis in the human malignant glioma cell line, U87MG.
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  • 48
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    International journal of historical archaeology 4 (2000), S. 71-112 
    ISSN: 1573-7748
    Keywords: evolution ; archaeology ; natural selection ; classification ; style ; function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Archaeology
    Notes: Abstract Over the past decade or so, an increasing number of archaeologists have begun to show interest in employing Darwinian evolutionary theory to explain variations in the material record. Epistemological and methodological issues surrounding the implementation of Darwinian evolutionism in archaeology are numerous, the most basic of which is that Darwinism embodies a materialist perspective, whereas archaeology traditionally has maintained an essentialist outlook. Stemming from this dichotomy are fundamental differences in such things as how units are created and how they are used to measure change. As archaeologists grapple with these issues, specific examples of how Darwinian evolutionism can be used to build historical narratives and create historical explanations are appearing with more frequency, but with few exceptions, proponents have focused specifically on the prehistoric record. This gives the impression that Darwinian evolutionism is not applicable to the more-recent material record, which is decidedly not the case. The kind of evolutionism proposed here transcends the age of the record under investigation.
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  • 49
    ISSN: 1573-7373
    Keywords: selenium ; human glioma cells ; mitochondria ; apoptosis ; fibroblasts ; ultrastructure ; MTT
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined the effect of the trace element selenium on human glioma cell lines: T98G, U373MG, and U87MG, in addition to dermal fibroblast cells. Cultures were incubated with sodium selenite, and the following parameters were studied: cell growth, mitochondrial function, and ultrastructure. Cell growth was assayed by counting the number of viable cells after treatment with selenium. Mitochondrial function was analyzed using the MTT (tetrazolium salt reduction) assay. Apoptosis was determined by evaluating nuclear chromatin condensation by electron microscopy. The results indicated that selenium had a significant inhibitory effect on the growth of the tumor cells but had little effect upon dermal fibroblasts which had been passaged numerous times. Selenium also induced mitochondrial damage as shown by MTT assay in two brain tumor cell lines and in minimally passaged fibroblasts, but it had little effect upon the high-passage fibroblasts. Ultrastructurally, mitochondria had electron-dense inclusions resulting from selenium treatment. High rates of apoptosis were induced by selenium in the tumor cell lines and in the minimally passaged fibroblasts, whereas the fibroblasts with a high number of passages had some resistance to selenium treatment. This study correlates the adverse effects of selenium on mitochondrial function, inhibition of cell growth, and apoptosis and shows that selenium similarly affects three different brain tumor cell lines and minimally passaged fibroblasts. Further, the results with fibroblasts show that some types of cells after repeated passages can develop resistance to selenium damage.
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  • 50
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    Journal of neuro-oncology 47 (2000), S. 31-38 
    ISSN: 1573-7373
    Keywords: glioma ; apoptosis ; vitamin K ; reactive oxygen intermediates ; Fas/APO-1 ; flow cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Congeners of vitamin K have been found to inhibit growth in various rodent and human tumor cells, but the mechanisms of the inhibitory action are still not well understood. To investigate the modes of actions of vitamin K, we used several vitamin K analogs and examined their cytotoxic effect for human glioma cell lines RBR17T and U251. The analogs included vitamin K1 (VK1), vitamin K2 (VK2), vitamin K3 (VK3), and geranylgeraniol (GGO) which form an unsaturated side chain of VK2. Cell viability was estimated by MTT assay. DNA fragmentation was demonstrated by gel electrophoresis and flow cytometry. In order to study the mechanism of apoptosis, we measured the changes of intracellular reactive oxygen intermediates (ROI) and Fas/APO-1 expression by flow cytometry. The results showed: (1) VK2, VK3, and GGO inhibited cell growth; (2) VK3 had a more potent cytotoxic effect than VK2, and VK3 enhanced the cytotoxic effect of antitumor agents (ACNU and IFN-beta) in RBR17T cells; (3) VK2, VK3, and GGO induce apoptosis; (4) VK3 increased the expression of Fas/APO-1 although VK2 and GGO did not increase its expression in glioma cells; (5) VK3 increased the production of intracellular ROI. Catalase and reduced glutathione (GSH) inhibited production of intracellular ROI and antagonized inhibition of cell-growth induced by VK2, but failed to antagonize that of VK2 and GGO. We hypothesize that VK3 induces apoptosis by promoting the generation of intracellular ROI and Fas/APO-1 expression. On the other hand, VK2 and GGO induce apoptosis but most likely by some other unknown pathway.
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  • 51
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    Journal of neuro-oncology 47 (2000), S. 153-160 
    ISSN: 1573-7373
    Keywords: tumour ; apoptosis ; incidence ; p53 ; bax ; immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We sought to determine the relative incidence of meningiomas compared to other central nervous system tumours in an Asian surgical series, as well as the demographic and biological characteristics of these meningiomas. A review of 655 consecutive cases of central nervous system tumours from 583 patients representing the last five years admissions to one hospital in Singapore was undertaken. A total of 33 malignant/atypical tumours from 19 patients and 196 benign meningiomas from 187 patients were identified. Twenty malignant/atypical and 20 benign tumours were selected at random and subjected to histochemical and immunohistochemical analysis using antibodies directed against p53, bax and 3′-DNA hydroxy groups (TUNEL). Meningiomas comprised some 35.2% of all central nervous system tumours with malignant/atypical meningiomas representing 9.2% of meningiomas. Histochemically, necrosis was the predominant finding. However, peri-necrotic areas displayed p53 positivity in 10% of cases and bax positivity in 25% of cases. Apoptotic cells were detected in the peri-necrotic areas in 90% of benign and 75% of malignant/atypical meningiomas. Meningiomas represent the predominant form of central nervous system tumour in the Singaporean population, and aberration of p53 expression is not associated with tumour formation or progression. There was a slight but non-significant reduction in apoptosis in the progression from benign to malignant meningioma, suggesting that in contrast to many other tumour types disruption of cellular apoptosis is not a predominant driving force in Asian meningioma tumourigenesis.
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  • 52
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    Journal of happiness studies 1 (2000), S. 323-349 
    ISSN: 1573-7780
    Keywords: progress ; quality of life ; happiness ; optimism ; pessimism ; social indicators ; forecasting ; world view ; evolution ; development.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Psychology
    Notes: Abstract This paper argues that both the relativist and the pessimist critiques of the idea of progress are inadequate. Progress is defined as increase in global quality of life (QOL). Such QOL is intrinsically subjective, but not relative. It can be reliably measured through “life satisfaction”-type questions. The “World Database of Happiness” provides extensive data on social, economic and psychological factors that correlate with overall QOL. They include wealth, health, security, knowledge, freedom and equality. Various statistical data suggest that all these QOL indicators have undergone significant improvements during the last half century, in most of the world. This gives strong support to the thesis that progress objectively occurs.
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  • 53
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    Journal of happiness studies 1 (2000), S. 351-374 
    ISSN: 1573-7780
    Keywords: progress ; quality of life ; optimism ; pessimism ; social indicators ; world view ; evolution ; development ; global change ; information overload.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Psychology
    Notes: Abstract This paper attempts to update the 18th century concept of progress by an evolutionary theoretical framework, while replying to some of the contemporary critiques. Progress, understood as increase in fitness (or its proxy, quality of life) necessarily accompanies evolution by natural selection. In socio-cultural evolution, this mechanism is reinforced by growth of knowledge and virtuous cycles, but can be accompanied by negative side-effects such as overshooting and parasitism. The most pressing of the contemporary side-effects, such as pollution and the increased pace of life, are discussed, but it is concluded that they can be tackled without really endangering global progress. The anxiety that they engender is unfortunately amplified by a “bad news” bias in the media, leading to an inappropriately pessimistic view of the situation by the public.
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  • 54
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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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  • 55
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    Journal of neuro-oncology 46 (2000), S. 135-144 
    ISSN: 1573-7373
    Keywords: apoptosis ; cRGDfV ; human gliomas ; integrin αVβ3 ; mouse glioma model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor in adults and is invariably fatal. We have investigated the effect of cyclo-(Arg-Gly-Asp-D-Phe-Val) (cRGDfV) peptide on survival of human malignant glioma cells in vitro and in vivo. Immunofluorescent analyses revealed the presence of αVβ3 integrin on U-87MG and U-373MG cells, but minimal expression on U-251MG cells. Treatment of U-87MG and U-373MG cells in vitro with cRGDfV (20 µg/ml), but not the linear peptide, resulted in the appearance of rounded and loosely attached cells with subsequent cell death. By comparison, neither this cyclic peptide nor its linear homolog had any significant effect on growth and morphology of U-251MG cells. The death of cRGDfV-treated (20 µg/ml) glioma cells was blocked by pretreatment (10 µM) of cells with DEVD-FMK and LEHD-FMK, inhibitors of caspase-3 and caspase-9, respectively. Moreover, when glioma cells grown as spheroids were treated with cRGDfV (50 µg/ml), spheroid formation was markedly reduced. Further, treatment of intracranial U-87MG tumors in scid mice with cyclic peptide significantly (p〈0.001) prolonged their survival. These results indicated (i) that cRGDfV induced apoptosis of human glioma cells by binding αVβ3 integrin expressed on their cell surfaces and (ii) that cRGDfV may be an effective and non-toxic direct anti-tumor therapy for αVβ3-expressing GBMs.
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  • 56
    ISSN: 1573-7373
    Keywords: apoptosis ; proliferation ; p53 ; Bcl-2 ; transglutaminase ; immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Several protocols for the adjuvant treatment of glioblastoma multiforme (GBM) are currently being evaluated. In this context, little is known about the influence of radiochemotherapy on apoptosis and the expression of apoptosis-related proteins in vivo. We have analyzed the incidence of apoptosis using in situ nick translation (ISNT) and expression of Ki-67 (MIB-1), p53 (DO-1 and DO-7), Bcl-2 and transglutaminase II (TGase II) by immunohistochemistry in 41 patients with GBM and their matched relapses. Sixteen patients received radiochemotherapy, 18 irradiation and 7 no treatment. Radiochemotherapy resulted in an increase in Bcl-2+ cells (p=0.013). Irradiation caused the reduction of MIB-1+ (p=0.0015), DO-7+ (p=0.0043) and the increase of Bcl-2+ cells (p=0.016). We calculated a positive correlation between high TGase II scores in patients preceding radiochemotherapy (p=0.0186) and no treatment (p=0.0158), low ISNT scores (p=0.0018) and high DO-1 scores (p=0.0233) in patients preceding irradiation and short time to progression. These data show that distinct postsurgical radiochemotherapy protocols differentially alter cellular proliferation and expression of p53 and Bcl-2 in GBM relapses. Furthermore, we show that ISNT, DO-1 and TGase II labeling scores are therapy-specific predictors of time to progression in GBM patients.
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  • 57
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    Journal of neuro-oncology 49 (2000), S. 117-129 
    ISSN: 1573-7373
    Keywords: apoptosis ; chemotherapy resistance ; bcl-2 ; bax ; glioma ; nucleolus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate the role of apoptosis suppression in glioma chemotherapy resistance, protein levels and subcellular localization of bcl-2 family members were investigated in 2 pairs of sensitive cell lines and their in vitro generated resistant derivatives. The alkylating agent, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), induced apoptosis in both sensitive cell strains and apoptosis was suppressed in both resistant derivatives. Both resistant cell lines contained altered regulation of a bcl-2 related protein consistent with the suppression of apoptosis. Independent of which bcl-2 family member was dysregulated, resistance was associated with altered regulation in the subcellular localization of bax protein. Following BCNU treatment, bax accumulated in nucleoli and a nuclei containing fraction of sensitive cells but not their resistant derivatives. Nuclear accumulation was an early event in apotosis induction. These data indicates altered subcellular localization of bax may play a role in resistance. In addition, the association between an early, nucleolar localization of bax and the induction of apoptosis suggests that localization of bax to nucleoli may play a role in apoptosis-induction of glioma cells.
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  • 58
    ISSN: 1573-8469
    Keywords: apoptosis ; bacteria ; chromatin condensation ; DNA degradation analysis ; plant ; programmed cell death
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Ultrastructural details of the hypersensitive reaction induced by infiltration with avirulent race 2 Xanthomonas campestris pv. vesicatoria in pepper ‘Early Calwonder-10R’ leaves (incompatible interaction) are reported. Affected cells displayed plasmalemma undulations and disruption, lysis of the chloroplast membrane, degeneration of other organelles, general cytoplasm disorganisation and, often, protoplast shrinkage. The nuclei contained large masses of electron-dense material, apparently formed by chromatin aggregation. In many cases a single chromatin-like layer was deposited on the inner side of the nuclear envelope leaving a finely granular matrix in the centre of the nucleus; the nucleolus usually disappeared. The nuclear envelope was sometimes ruptured and the internal matrix leaked into the cytoplasm. The content of many affected cells eventually coagulated and became very electron-dense. The walls often collapsed. All these alterations were especially visible in spongy mesophyll cells at sites where bacteria occurred in the intercellular spaces. Although some of the nuclear and cytoplasmic alterations recall certain aspects of apoptotic cell death, molecular determinations did not reveal any DNA degradation in hypersensitively reacting tissues. The first cell alterations in leaves infected with the virulent bacterial race 1 (compatible interaction) were observed only 27 h after inoculation, when the cytoplasm of some cells showed limited internal disorganisation and plasmolysis at sites where bacterial colonies developed.
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  • 59
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    Cancer and metastasis reviews 19 (2000), S. 97-107 
    ISSN: 1573-7233
    Keywords: angiogenesis ; angiostatin ; cancer biology ; cancer therapy ; proteolysis ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The study of angiogenesis, and the promise of angiogenesis inhibition as a means of cancer therapy, has dramatically accelerated in the last several years. The discovery and publication of angiostatin by O'Reilly and colleagues in Judah Folkman's lab in 1994 has greatly contributed to this progress. Angiostatin is a kringle-containing fragment of plasminogen, which is a potent inhibitor of angiogenesis in-vivo, and selectively inhibits endothelial cell proliferation and migration in-vitro. There have been a number of proposed proteolytic mechanisms by which plasminogen is cleaved to form angiostatin, and the resulting cleavage products contain different NH2 and COOH termini of the angiostatin. Therefore, it is possible that there are more than one angiostatin isoforms (or angiostatin-related proteins) which occur in one or more normal or pathophysiological situations. It is also possible that some of the proteolytic processes which can convert plasminogen to angiostatin-like proteins are simply laboratory artifacts. Angiostatin-related proteins exert potent endothelial cell inhibitory activity, including the induction of apoptosis, and inhibition of migration, and the intact kringle structures are believed to be necessary for the antiangiogenic activity. Efforts are now underway to translate the understanding of the biology of angiostatin to clinical practice, which includes phase 1 clinical trials with recombinant angiostatin K1–3 (kringles 1–3) as well as phase 1 trials of an Angiostatin Cocktail, which induces the direct in vivo conversion of plasminogen to angiostatin 4.5 (kringles 1–4, plus most of kringle 5). The translation of the basic science of angiostatin and angiostatin-related proteins to clinical trial promises to provide an important new tool in the treatment of cancer by inhibition of angiogenesis.
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  • 60
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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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  • 61
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    Apoptosis 5 (2000), S. 203-209 
    ISSN: 1573-675X
    Keywords: apoptosis ; lens development ; organelle loss ; denucleation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The lens represents an ideal model system for studying many of the cellular and molecular events of differentiation. It is composed of two ectodermally-derived cell types: the lens epithelial cells and the lens fibre cells, which are derived from the lens epithelial cells by differentiation. Programmed removal of nuclei and other organelles from the lens fibre cells ensures that an optically clear structure is created, while the morphology of the degenerating nuclei is similar to that observed during apoptosis and is accompanied by DNA fragmentation. These observations suggest the existence of biochemical parallels between the process of lens fibre cell organelle loss and classical apoptosis. For example, proteins encoded by the bcl-2 and caspase gene families are expressed in developing lenses and nuclear degeneration in lens fibre cells can be inhibited in vivo by overexpression of bcl-2 and in vitro by incubation of differentiating lens epithelial cell cultures with caspase inhibitors. Thus, the developing lens may represent a particularly useful model system for researchers interested in apoptosis. In this review, the recent literature pertaining to lens fibre cell organelle loss and its relationship to apoptosis is reviewed and possible future research directions are suggested.
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  • 62
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    Apoptosis 5 (2000), S. 217-220 
    ISSN: 1573-675X
    Keywords: Daxx ; apoptosis ; Fas ; PML ; ND10
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Several reports describing Daxx and its putative role have emerged without a unifying theme. While Daxx has been implicated in apoptosis, it remains unclear whether Daxx is pro- or anti-apoptotic, and whether its role in apoptosis is direct or indirect. Moreover, whether Daxx plays alternative or additional roles in regulating transcription, centromere binding or any number of other activities within the cell, is uncertain. The ability of Daxx to interact with a wide variety of molecules in yeast-interaction trap systems (Table 1) has allowed for this range of speculation. The fact that Daxx contains no significant homology to other known proteins has rendered its study all the more challenging.
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  • 63
    ISSN: 1573-675X
    Keywords: apoptosis ; cyclin B1/CDC 2 ; G2/M arrest ; MAD 2 ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Paclitaxel (Taxol™) is a microtubule-interfering agent that induced persistent and transient G2/M arrest before apoptosis in human nasopharyngeal carcinoma (NPC) cells at high and low concentrations, respectively. In this study, we intended to explore the underlying molecular events and found that cellular cyclin B1/CDC 2 kinase activity was increased and persisted for 〉6 h upon paclitaxel treatment both at high and low concentrations. Furthermore, activation of MAD 2 checkprotein could account for the loss of cyclin B1 ubiquitination and the persistence of cyclin B1/CDC 2 activation in the cases. To investigate the involvement of cyclin B1 and MAD 2 activation in paclitaxel-induced apoptosis, we introduced affinity-purified anti-cyclin B1 and MAD 2 antibodies into NPC cells by electroporation before the further paclitaxel treatment. The antibodies against cyclin B1 and MAD 2 indeed attenuated paclitaxel-induced cytotoxicity and DNA fragmentation. Our study suggests that activation of cyclin B1/CDC 2 and MAD 2 were the M-phase events required for paclitaxel-induced apoptosis in NPC cells. The dys-regulated cyclin B1/CDC 2 activation could enhance the prometaphase progression, but activation of MAD 2 rendered cells inable to exit from the metaphase. Under this circumstance, cells were probably going to “mitotic catastrophe” and ultimately, destined to apoptosis.
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  • 64
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    Biogerontology 1 (2000), S. 289-307 
    ISSN: 1573-6768
    Keywords: comparative nematode ageing ; evolution ; Caenorhabditis elegans ; Onchocerca volvulus ; Strongyloides ratti
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the developing field of biological gerontology, rapid advances have recently been made in the genetics of ageing in the nematode Caenorhabditis elegans. The aim of this work is to develop an understanding of the general mechanisms determining the ageing process. Within the last decade the prospect of actually achieving this somewhat hubristic aim has begun to look startlingly real. In this context, knowledge of every aspect of the biology of ageing in nematodes is of added interest. Here the patterns of ageing observed among parasitic and free-living nematodes are surveyed and compared. Like insects, nematode species exhibit enormous differences in the rate of ageing, with maximum life spans varying over more than a 1000-fold range, from three days in free-living Rhabdias bufonis adults, to at least 15 years in the filarial parasite Loa loa. The possible evolutionary and mechanistic causes of such differences in ageing are discussed.
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  • 65
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    Apoptosis 5 (2000), S. 211-215 
    ISSN: 1573-675X
    Keywords: adenovirus ; E4orf4 ; apoptosis ; protein phosphatase 2A (PP2A) ; caspases ; cancer ; gene therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Adenovirus E4orf4 protein is a multifunctional viral regulator that induces p53-independent apoptosis in transformed cells, but not in normal cells. E4orf4-induced apoptosis can occur without activation of known caspases, although E4orf4 induces caspase activity in some cell lines. The interaction of E4orf4 with a specific subpopulation of protein phosphatase 2A (PP2A) molecules that contain B subunits, but not with those that contain B′ subunits, is required for induction of apoptosis. This review suggests the potential use of E4orf4 in cancer therapy, and discusses whether E4orf4-induced apoptosis plays a role in the viral life cycle. Future research directions are also highlighted.
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  • 66
    ISSN: 1573-675X
    Keywords: Amphibia ; apoptosis ; cancer ; cell cycle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Spontaneous and induced cancers are rare in non-isogeneic or inbred amphibians. Neoplastic cells become immortalized through loss of a normal capacity to die by apoptosis. Mature lymphocytes of mammals require activation and entry into the cell cycle in order to become susceptible to apoptosis. Whether Xenopus lymphocytes differ from mammalian lymphocytes in this regard is examined. In vitro exposure of PMA, or its analogue, MPMA, to adult splenocytes of Xenopus laevis was used to affect apoptosis. Flow cytometric analysis of FITC-Annexin V/propidium iodide (PI) fluorescence (apoptosis) and BrdU uptake (DNA synthesis) were assayed concurrently in the same lymphocyte population over time. Significant increases in apoptotic levels were induced throughout a 72 hour period in PMA-treated cells only. Lymphocytes were also separated by size for analysis. Several sub-populations of lymphocytes were identified, the most interesting of which was small and apoptotic within 4 hours, after PMA exposure. PMA-induced DNA synthesis did not become elevated until after 24 hours. “Direct” apoptosis, i.e. without cell cycle entry, was found only in these small, mature lymphocytes. Since small lymphocytes make up the vast majority of those being analyzed, “direct” apoptosis may be a determining mechanism in the resistance to neoplasia observed in Amphibia. Cells that die more readily are less likely to transform into neoplastic cells.
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  • 67
    ISSN: 1573-675X
    Keywords: apoptosis ; caspase-3 ; nuclease ; endo-exonuclease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Single-strand DNase and poly rAase, activities characteristic of endo-exonuclease, were co-activated in nuclear fractions of HL-60 cells by caspase-3. Activation was accompanied by cleavages of large soluble polypeptides (130–185 kDa) and a 65 kDa inactive chromatin-associated polypeptide related to the endo-exonuclease of Neurospora crassa as detected on immunoblots. The major products seen in vitro were a 77 kDa soluble polypeptide and an active chromatin-associated 34 kDa polypeptide. When HL-60 cells were induced to undergo apoptosis by treating with 50 μM etoposide (VP-16) for 4 hours, 77 kDa and 40 kDa polypeptides accumulated in nuclear fractions. Chromatin DNA fragmentation activity was also activated in cytosol and nuclear extract either by pre-treating the cells in vivo with VP-16 or by treating the cytosol in vitro with caspase-3 or dATP and cytochrome c. Endo-exonuclease activated by caspase-3 in cytosol-derived fractions augmented chromatin DNA fragmentation activity in vitro. Endo-exonuclease is proposed to act in vivo in conjunction with the caspase-activated DNase (CAD) to degrade chromatin DNA during apoptosis of HL-60 cells.
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  • 68
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    Apoptosis 5 (2000), S. 307-314 
    ISSN: 1573-675X
    Keywords: apoptosis ; cancer ; cross-priming ; cross-tolerance ; dendritic cells ; T lymphocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Induction of cell death by apoptosis, also called programmed cell death, and clearance of apoptotic bodies by scavenger cells has long thought to be an efficient means to dispose of unwanted cells without causing inflammatory responses able to mediate specific reactions. However, a number of evidences have been accumulated suggesting that apoptotic cell death is implicated in the pathogenesis of systemic and organ specific autoimmune diseases. In addition, recognition and engulfement of apoptotic cells by professional antigen presenting cells, such as dendritic cells, and their interaction with effector immune cells have been recently described to result in apoptotic cell-derived antigen specific tolerance. This review will summarise the most recent findings on the immunogenic potential of cells undergoing programmed death.
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  • 69
    ISSN: 1573-675X
    Keywords: Angiogenesis ; angiopoietins ; apoptosis ; integrins ; vascular endothelial growth factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Angiogenesis is essential for the growth and metastasis of solid tumors. The balance of endothelial cell (EC) proliferation and apoptosis is a major determinant in tumor angiogenesis. Recently, several studies demonstrated that numerous angiogenic factors not only induce angiogenesis but also function as EC survival factors. Vascular endothelial growth factor (VEGF), a potent angiogenic factor, is also an EC survival factor in embryonic vasculogenesis and tumor angiogenesis. VEGF activates specific intracellular survival pathways in ECs including Bcl-2, A1, IAP, Akt, and Erk. Integrins may function as EC survival factors by preventing anoikis by enhancing binding to the extracellular matrix. In addition, integrins may function in concert with VEGF to promote EC survival. Angiopoietin-1 (Ang-1) has recently been shown to stabilize EC networks by binding to the EC-specific tyrosine kinase receptor Tie-2. Pericytes also function as EC survival factors, by cell-cell contact, secretion of survival factors, or both. Targeting any of the above mechanisms for EC survival may provide novel antineoplastic strategies.
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  • 70
    ISSN: 1573-675X
    Keywords: apoptosis ; antimicrotubule agent ; cell cycle ; dolastatin 10 ; TZT-1027
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract TZT-1027, a newly synthesized dolastatin 10 derivative, is a potent antitumor agent which inhibits microtubule polymerization and perturbs microtubule dynamics. In this report, we investigated whether TZT-1027 inhibited the growth of various human cancer cells, and the cell death caused by TZT-1027 was due to apoptosis. In addition, we elucidated the apoptosis machinery induced by treatment with TZT-1027. The 50% growth-inhibitory concentrations (IC50 values) of TZT-1027 on cancer cells derived from various sources were not more than 5.9 ng/ml. TZT-1027 showed superior cytotoxicity than any other antitumor agents. Next, we evaluated morphological nuclear change, namely, chromatin condensation and DNA fragmentation. We used three cancer cell lines derived from different types in view of having apoptosis related protein, human leukemia HL-60 (in the presence of both Caspase-3 and Bcl-2), human breast cancer MCF-7 (in the absence of Caspase-3), and human prostate cancer DU145 (in the absence of Bcl-2). TZT-1027 induced DNA fragmentation in the presence but not absence of Caspase-3. Nevertheless, apoptic chromatin condensation was observed in all cancer cells even if there was no Caspase-3. Furthermore, we examined whether TZT-1027, microtubule-disrupting agent, influenced cell cycle progression. Flow cytometric analysis revealed the cells treated with TZT-1027, and with the other antimicrotubule agents, to be arrested at the G2/M phase and subsequently to show fragmented DNA smaller than that of G1 phase cells. Moreover, we tested TZT-1027 for its ability to induce Bcl-2 phosphorylation in human cancer cell lines. TZT-1027 and other agents which interacted with microtubules induced Bcl-2 phosphorylation, whereas DNA-damaging agents did not. The present results suggested an association of the growth-inhibitory effect of TZT-1027 with the induction of apoptosis and indicated that the apoptosis induced by TZT-1027 was followed by G2/M arrest even if there was no Caspase-3 or Bcl-2.
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  • 71
    ISSN: 1573-675X
    Keywords: apoptosis ; chemotherapy resistance ; clonogenicity ; ras
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Mutationally activated Ras is involved in tumor progression and likely also in drug resistance. Using survival, viability and apoptosis assays, we have here compared the cisplatin sensitivities of FR3T3 rat fibroblasts and a 12V-H-ras transformed subline (Ras2:3). Around 24 h after cisplatin treatment Ras2:3 cells showed higher apoptosis levels and lower viability than FR3T3. This increased sensitivity correlated with weaker cisplatin-induced activation of Jun N-terminal kinase (JNK). In contrast to apoptosis assays, colony formation assays showed that Ras2:3 were more resistant to cisplatin than were FR3T3. This was partly due to the increased cisplatin sensitivity of FR3T3 seeded at low densities, as required in colony formation assays. In addition, Ras2:3 cisplatin survivors had a higher relative proliferative capacity. Cell cycle analyses showed that FR3T3 cells initially responded with a dose-dependent G2 arrest, while Ras2:3 accumulated in S-phase. Experiments with an anti-apoptotic mutant of MEKK1 suggested that the apoptotic response of Ras2:3 cells is not specific to the S-phase fraction. In summary, the cisplatin response of ras-transformed fibroblasts is distinct from that of parental cells, in that they show increased apoptosis, a different cell cycle response and increased post-treatment proliferative capacity. The results illustrate the need to carefully consider methods and protocols for in vitro studies on chemotherapy sensitivity.
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  • 72
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    Apoptosis 5 (2000), S. 415-418 
    ISSN: 1573-675X
    Keywords: apoptosis ; death receptors ; inflammation ; reactive oxygen species (ROS)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Reactive oxygen species (ROS) and mitochondria play an important role in apoptosis induction under both physiologic and pathologic conditions. Interestingly, mitochondria are both source and target of ROS. Cytochrome c release from mitochondria, that triggers caspase activation, appears to be largely mediated by direct or indirect ROS action. On the other hand, ROS have also anti-apoptotic effects. This review focuses on the role of ROS in the regulation of apoptosis, especially in inflammatory cells.
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  • 73
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    Apoptosis 5 (2000), S. 419-424 
    ISSN: 1573-675X
    Keywords: apoptosis ; diabetes ; Fas ; organ-specific auto-immunity ; thyroiditis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract CD95 (Fas/Apo-1) is a broadly expressed death receptor involved in a variety of physiological and pathological apoptotic processes. Since its discovery, defects in CD95/CD95L system have been proposed as major pathogenic factors responsible for impaired immunological tolerance to self antigens and autoimmunity. Later, analysis of altered sensitivity to CD95-induced apoptosis in cells targeted by the immune response has revealed an unexpected role for CD95 and CD95L in organ-specific autoimmunity. CD95 has been shown to be expressed and functional in virtually all cell types that are target of the organ-specific autoimmune response. Here we review some of the major findings concerning the role of CD95 in autoimmunity, in dysfunctions due to increased or decreased CD95-induced apoptosis.
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  • 74
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    Apoptosis 5 (2000), S. 443-449 
    ISSN: 1573-675X
    Keywords: apoptosis ; autoimmunity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Apoptosis is a physiological form of cell death required to ensure that the rate of cell division is balanced by the rate of cell death in multicellular organisms. Dysregulation of apoptosis is associated with the pathogenesis of a wide array of diseases: cancer, neurodegeneration, autoimmunity, heart disease and others. In this review we collect arguments supporting a hypothesis of a dysregulated apoptosis leading to development of autoimmunity like systemic lupus erythematosus (SLE). This notion is supported by occurence of known autoantigens in apoptotic blebs, in vitro findings of an increased rate of apoptotic lymphoblasts despite optimal cytokine stimulation combined with a defective in vitro clearance of apoptotic bodies by SLE phagocytes. Moreover, we and others could generate histone-specific lymphocytic cell lines from cells after activation with autologous apoptotic material. These lymphocytes could stimulate autologous B-lymphocytes to produce of anti-dsDNA antibodies, a diagnostic hallmark for SLE. Finally, antibodies against phospholipids like phosphatidylserine are often associated with systemic autoimmunopathies like SLE and others. Phosphatidylserine is exposed on apoptotic cells as early sign of programmed cell death and serves as phagocyte recognition molecule for apoptotic cells. Formation of immune complexes and deposition in tissues might lead to organ damage and disease. This scenario will be discussed in this review in detail.
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  • 75
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    Apoptosis 5 (2000), S. 9-16 
    ISSN: 1573-675X
    Keywords: Aging ; Alzheimer's disease ; amyloid precursor protein ; apoptosis ; Bcl-2 ; caspase ; presenilin ; transcription factor ; β amyloid.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Alzheimer's disease (AD) is the most common human neurodegenerative disorder characterized by the progressive deterioration of cognition and memory in association with the presence of senile plaques, neurofibrillary tangles, and massive loss of neurons. Most cases of AD are late-onset and sporadic, but in some cases the disease is inherited as an autosomal dominant trait. Four different genes, the amyloid precursor protein, apolipoprotein E, and presenilins 1 and 2 have been implicated in the etiology of familial AD. It is now generally accepted that massive neuronal death due to apoptosis is a commmon characteristic in the brains of patients suffering from neurodegenerative diseases, and apoptotic cell death has been found in neurons and glial cells in AD. This review summarizes the current findings regarding the evidence for apoptosis in AD and discusses the possible involvement of apoptosis-regulating factors in the pathology of AD. Modification of the apoptotic cascade could be considered as a primary therapeutic strategy for the disease.
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  • 76
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    Keywords: Anti-tumor drugs ; apoptosis ; cancer ; caspases ; necrosis.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The majority of current anticancer therapies induce tumor cell death through the induction of apoptosis. Alterations in the apoptotic pathways may determine tumor resistance to these therapies. Activation of the proteolytic cascade involving caspase family members is a critical component of the execution of cell death in apoptotic cells. However, recent studies suggest that cell death can proceed in the absence of caspases. In this review we describe the role of caspase-dependent and -independent pathways as targets for anticancer treatment; better understanding of diverse modes of tumor cell death will help to avoid ineffective treatment and provide a molecular basis for the new strategies targeting caspase-independent death pathways in apoptosis-resistant forms of cancer.
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  • 77
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    Keywords: Anti-Fas antibody ; antisense homology box-derived peptide ; apoptosis ; Fas ligand ; ovarian cancer.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We found that a short synthetic peptide corresponding to the “antisense homology box” of Fas ligand induced apoptotic cell death of Fas-expressing human ovarian cancer cell lines. The peptide was deduced from residues 256–265 of human Fas ligand, based on the hypothesis that it should contain a specific binding site to the corresponding Fas. Interestingly, the ovarian cancer cell line NOS4, which was sensitive to anti-Fas antibody induced apoptosis, was not affected by the peptide, whereas another cell line, SKOV-3, which was insensitive to anti-Fas antibody, was killed by the peptide. Thus, this short peptide was shown to have a unique activity to induce apoptosis in human ovarian cancer cells in a manner different from anti-Fas antibody.
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  • 78
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    Keywords: apoptosis ; Bax ; ceramide ; mitochondria ; pH
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Ceramide can induce apoptosis through a caspase independent pathway. Bax has been described as able to kill cells in the absence of caspase activity, therefore we measured Bax in situ during ceramide-induced apoptosis using anti-Bax antibodies and flow cytometry analysis. An early (〈30 min) increase in Bax labeling was observed after the addition of several ceramide species to several hemopoietic-related cell types. On U937, this increase was not due to antigens synthesis or processing, but rather an increased accessibility or reactivity of Bax antigens for antibodies. This increased immuno-reactivity of Bax was not inhibited by Z-VAD-fmk nor leupeptin, and preceded nuclear fragmentation by several hours. Such an increase in immuno-reactivity was also observed after Fas ligation, but it occurred later (〉2 h) accompanying nuclear apoptosis, and was inhibited by Z-VAD-fmk. Bax immuno-reactivity was found to be related to intracellular pH (pHi), and C2-Ceramide (C2-Cer) induced a very early (〈10 min) transitory increase in pHi. Both Bax immuno-reactivity and pHi increases were dependent on the mitochondrial permeability transition pore (PTP) status. It was concluded from these results that C2-Cer induced a transitory increase in pHi in relation to the PTP. This rise in pHi led to conformational changes in Bax which could be responsible for further apoptosis in the C2-Cer pathway while it was a consequence of caspase activation in the Fas pathway.
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  • 79
    ISSN: 1573-675X
    Keywords: apoptosis ; macrophages ; Chagas disease ; Trypanosoma cruzi ; T lymphocytes ; vitronectin receptor ; transforming growth factor-beta ; prostaglandins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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  • 80
    ISSN: 1573-675X
    Keywords: anesthetics ; apoptosis ; barbiturates ; benzodiazepines ; ethanol ; GABAA receptors ; ketamine ; NMDA receptors ; phencyclidine ; synaptogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract It has been known for three decades that ethanol, the most widely abused drug in the world, has deleterious effects on the developing human brain, but progress has been slow in developing animal models for studying this problem, and the underlying mechanisms have remained elusive. Recently, we have shown that during the synaptogenesis period, also known as the brain growth spurt period, ethanol has the potential to trigger massive neuronal suicide in the in vivo mammalian brain. The brain growth spurt period in humans spans the last trimester of pregnancy and first several years after birth. The NMDA antagonist and GABAmimetic properties of ethanol may be responsible for its apoptogenic action, in that other drugs with either NMDA antagonist or GABAmimetic actions also trigger apoptotic neurodegeneration in the developing brain. Our findings provide a likely explanation for the reduced brain mass and neurobehavioral disturbances associated with the human fetal alcohol syndrome. Furthermore, since NMDA antagonist and GABAmimetic drugs are sometimes abused by pregnant women and also are used as anticonvulsants, sedatives or anesthetics in pediatric medicine, our findings raise several complex drug safety issues. In addition, the observation that ethanol and several other drugs trigger massive neuronal apoptosis in the developing brain provides an unprecedented opportunity to study both neuropathological aspects and molecular mechanisms of apoptotic neurodegeneration in the in vivo mammalian brain.
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  • 81
    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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  • 82
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    Apoptosis 5 (2000), S. 379-388 
    ISSN: 1573-675X
    Keywords: apoptosis ; ATP depletion ; cell acidification and shrinkage ; CpG-specific megabase fragmentations ; DCNP (2,6-dichloro-4-nitrophenol) ; housekeeping genes ; microarray (genechip) ; zVAD-fmk
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Previous suggestions of CpG-specific apoptotic commitment implied critical epigenetic modulation of house-keeping genes which have canonical CpG islands at 5′ promoter regions. Differential housekeeping gene activity however has not been shown. Using a focussed microarray (genechip) of 22 housekeeping genes we show this in apoptosis induced in human Chang liver cells by DCNP (2,6-dichloro-4-nitrophenol), a non-genotoxic inhibitor of sulfate detoxification. 3–7 folds downregulation of 9 genes in glycolysis, tricarboxylic acid cycle and the respiratory electron transport chain suggested gene-directed energy depletion which was correlated with observed ATP depletion. 4 folds downregulation of the pyruvate dehydrogenease gene suggested gene-directed metabolic acidosis which was correlated with observed cell acidification. Other differential housekeeping gene activity, including 4 folds upregulation of microtubular alpha-tubulin gene, and 2 folds upregulation of ubiquitin, also had a bearing on apoptosis. Broadspectrum zVAD-fmk caspase inhibition abolished 200 bp DNA ladder fragmentations but not the CpG-specific megabase fragmentations and other hallmarks of cell destruction, suggesting a caspase-independent cell death. Death appeared committed at gene-level.
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  • 83
    ISSN: 1573-675X
    Keywords: apoptosis ; concanavalin A ; cytochrome c release ; mitochondria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Concanavalin A (ConA), normally a mitogen of T-lymphocytes, was found to be a cell cycle-independent apoptosis-inducing agent in cultured murine macrophage PU5-1.8 cells. This assertion is based on the following observations: (1) ConA increased the number of cells with hypo-diploid DNA in a dose dependent manner as revealed by flow cytometry; (2) ConA elicited DNA fragmentation and the cytotoxicity of ConA was suppressed by α-D-methylmannoside which blocks the lectin site of ConA; (3) ConA was able to release cytochrome c (cyto c) into the cytosol of PU5-1.8 cells. When isolated mitochondria were incubated with ConA, release of cyto c was observed too. Interestingly, clustering of mitochondria was found in the cytosol under a confocal microscope after ConA treatment. When cells were incubated with ConA-FITC and subsequently with mitotracker red (a probe for mitochondria), co-localization of fluorescence signals was observed. These results suggest that ConA was delivered to the mitochondria, induced mitochondrial clustering and released cyto c. Our results also show that introduction of exogenous cyto c electroporationally into ConA-untreated cells elicited DNA fragmentation. On the other hand, introduction of specific antibody against cyto c into PU5-1.8 cells suppressed the ConA-mediated cell death. Taken together, our results indicate that ConA induced apoptosis in PU5-1.8 cells through mitochondrial clustering and release of cyto c and the release of cyto c was sufficient to elicit apoptosis in PU5-1.8 cells.
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    Apoptosis 5 (2000), S. 435-441 
    ISSN: 1573-675X
    Keywords: activation ; apoptosis ; death receptors ; glucocorticosteroids ; mast cells ; survival factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Apoptosis is a physiological process of cell death that occurs in all multicellular organisms. Its dysregulation has been postulated as one of the main causes in the development of diseases such as cancer, AIDS, autoimmune diseases and allergy. Apoptosis has been mainly studied in the inflammatory cells that participate in the late and chronic stages of allergy (eosinophils, neutrophils, lymphocytes and macrophages) as a new way to elucidate the pathogenesis of this disease. Nevertheless, much less it is known about the regulation of apoptosis in the “initiators” of the allergic process: The Mast Cells. In normal conditions, mast cells are described as long-living cells that keep a constant number of cells in tissues. However, increased numbers of mast cells are observed in the late phase of asthma and in both the inflammatory and in the repair/remodeling stage of various inflammatory/fibrotic disorders. In this report, we discuss the possible mechanisms that regulate the apoptotic process in normal conditions and disease, such as survival factors and death receptors. A link between mast cell activation, during the early stages of the allergic process, and triggering of anti-apoptotic signaling pathways is also suggested as an important contributor to the extended life of mast cells.
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  • 85
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    Keywords: apoptosis ; asthma ; inflammation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Asthma is a disease characterized by a chronic inflammation of the airways and by structural alterations of bron-chial tissues, often referred to as airway remodelling. The development of chronic airway inflammation in asthma depends upon the continuous recruitment of inflammatory cells from the bloodstream towards the bronchial mucosa and by their subsequent activation. It is however increasingly accepted that mechanisms involved in the regulation of the survival and apoptosis of inflammatory cells may play a central role in the persistent inflammatory process characterizing this disease. Increased cellular recruitment and activation, enhanced cell survival and cell:cell interactions are therefore the key steps in the development of chronic airway inflammation in asthma, and represent the major causes for tissue damge, repair and remodelling.
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  • 86
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    Apoptosis 5 (2000), S. 491-507 
    ISSN: 1573-675X
    Keywords: apoptosis ; Bcl-2 ; caspases ; death receptors ; DNA damage ; p53
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Because of the singular importance of DNA for genetic inheritance, all organisms have evolved mechanisms to recognize and respond to DNA damage. In metazoans, cells can respond to DNA damage either by undergoing cell cycle arrest, to facilitate DNA repair, or by undergoing cell suicide. Cell death can either occur by activation of the apoptotic machinery or simply be a consequence of irreparable damage that prevents further cell division. In germ cells, mechanisms for limiting alterations to the genome are required for faithful propagation of the species whereas in somatic cells, responses to DNA damage prevent the accumulation of mutations that might lead to aberrant cell proliferation or behavior. Several of the genes that regulate cellular responses to DNA damage function as tumor suppressors. The clinical use of DNA damaging agents in the treatment of cancer can activate these tumor suppressors and exploits the cellular suicide and growth arrest mechanisms that they regulate. It appears that in some but not all types of tumors the propensity to undergo apoptosis is a critical determinant of their sensitivity to anti-cancer therapy. This review describes current understanding of the molecular control of DNA damage-induced apoptosis with particular attention to its role in tumor suppression and cancer therapy.
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  • 87
    ISSN: 1573-675X
    Keywords: apoptosis ; protection ; protein A ; pro- and anti-apoptotic factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The word “Apoptosis” or pragrammed cell death is described as the ultimate end of multiple cellular events converging from numerous initiating events to the ultimate death of a cell or organism. Several processes, such as initiation of death signals at the plasma membrane, expression of pro-apoptotic oncoproteins, activation of death proteases, endonucleases etc., that ultimately coalesce to a common irreversible execution phase, lead to cell demise. Counteracting the death signals are cell survival factors. A balance between the cell death and cell survival factors plays a major role in the decision making process as to whether a cell should die or must live. It is, therefore, hypothesized that if the balance can be shifted in favor of cell survival, one might be able to arrest the aging process, save the injured cells or else if the balance is shifted toward cell-kill it might help destroy tumors and other undesirable cells. Protein A (PA) of Staphylococcus aureus has been found to have multifarious biological response modifying properties. It has been shown to possess anti-tumor, anti-toxic, anti-parasitic and antifungal activities. It also acts as a potent immunostimulator. PA can protect bone marrow progenitor cells from zidovudin(AZT)-induced apoptosis and can stimulate immunocyte proliferation, thereby helping to replenish/restore the depleted hematopoietic cell pool. Such ability to replenish hematopoietic cells is a common property of PA observed against a number of toxic drugs/chemicals, such as cyclophosphamide, benzene, aflatoxin, salmonella endotoxin, etc. Interestingly, it was further demonstrated in our laboratory that PA can selectively kill tumor cells without affecting normal cells of the host. A search for the mechanisms of PA action revealed that this bacterial protein could shift the balance between pro- and anti-apoptotic proteins in favor of survival in normal cells, but in favor of cell death in tumor cells at a particular dose level. This unique property of PA suggests that controlled use of such type of Biological Response Modifier might help in controlling both cell growth and death phenomena.
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  • 88
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    Apoptosis 5 (2000), S. 523-529 
    ISSN: 1573-675X
    Keywords: apoptosis ; ATM ; DNA damage ; ionizing radiation ; p53
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Ataxia-telangiectasia is a human syndrome resulting from mutations of the ATM protein kinase that is characterized by radiation sensitivity and neurodegeneration. Although neuroprotective, the molecular details of ATM function in the nervous system are uncertain. However, in the mouse, Atm is essential for ionizing radiation-induced apoptosis in select postmitotic populations of the developing nervous system. Atm-dependent apoptosis in the nervous system also requires p53, consistent with the well-established link of p53 as a major substrate of ATM. Furthermore, the proapoptotic effector Bax is also required for most, but not all, Atm-dependent apoptosis. Therefore, after DNA damage in the developing nervous system, Atm initiates a p53-dependent apoptotic cascade in differentiating neural cells. Together, these data suggest ATM-dependent apoptosis may be important for elimination of neural cells that have accumulated genomic damage during development, thus preventing dysfunction of these cells later in life.
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  • 89
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    Apoptosis 5 (2000), S. 265-275 
    ISSN: 1573-675X
    Keywords: apoptosis ; DNA fragmentation ; necrosis ; phosphorylation ; protease inhibitors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The objective of this study was to establish whether apoptosis in 5123tc rat hepatoma cells required the caspase-3 dependent pathway. Apoptosis was induced by either growth factor deprivation or treatment with a topoisomerase II inhibitor, VM26, in the absence or presence of caspase inhibitors (DEVD-fmk, z-VAD-fmk and BAF). The results indicated that, although these inhibitors at 10 μM concentration completely blocked caspase-3 activity, they had no effect on either the rate of cell death or on any other apoptotic features, e.g., chromatin condensation, DNA fragmentation, protein cleavage, suggesting that caspase-3 was not required to mediate nuclear destruction in these hepatoma cells. At higher concentrations, up to 100 μM, z-VAD-fmk and BAF, but not DEVD-fmk, did block apoptosis, however, they also caused cell swelling and membrane permeabilization, which are the hallmarks of necrotic cell death. Clearly, high concentrations of these inhibitors must have interfered non-specifically with other metabolic pathways, e.g., z-VAD-fmk at a high concentration blocked protein phosphorylation, and caused cell death by a different mechanism.
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  • 90
    ISSN: 1573-675X
    Keywords: apoptosis ; atherosclerosis ; cell culture ; endothelial function ; mitochondria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Objective. Cell death is generally classified into two large categories: apoptosis, which represents active, physiological programmed cell death, and necrosis, which represents passive cell death without underlying regulatory mechanisms. Apoptosis plays an important role in tissue homeostasis and its role in endothelium integrity can be influenced by the functional status of endothelial cells. Homocysteine, a sulfated amino-acid product of methionine demethylation, is an independent risk factor for vascular disease (arterial and venous thombosis). Our goal was to investigate the thiol-derivatives effect on the endothelial cell apoptosis. Methods. Three parameters were measured: mitochondrial membrane potential using DiOC6(3) as the probe, DEVDase activation, and phosphatidylserine exposure on the cell surface with fluorosceinated annexin V labeling which allows apoptosis to be distinguished from necrosis. Results. Homocysteine-thiolactone induced endothelial cell apoptosis in a concentration-dependent manner (range: 50–200 μ M), independently of the caspase pathway. Only homocysteine-thiolactone, among the thiol derivatives tested, induced apoptosis. Apoptosis was not influenced by the serum concentration in culture medium, suggesting that the observed apoptotic process could occur in vivo. None of the inhibitors used (e.g., leupeptin, fumosinin Bl, catalase, or z-VAD-fmk) was able to prevent homocysteine-induced apoptosis of vascular endothelial cells. Conclusion. The apoptosis of vascular endothelial cells induced by high concentration of homocysteine-thiolactone might be one step atherosclerotic cardiovascular disease, and contribute to its complication.
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  • 91
    ISSN: 1573-675X
    Keywords: apoptosis ; inflammation ; neutrophil ; PI-3-kinase ; PKC ; T-cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Neutrophils play a central role in host defense and are recruited in vast numbers to sites of infection where they phagocytose and kill invading bacterial pathogens. Neutrophils have a short half-life that is extended at the inflamed site by pro-inflammatory cytokines and contact with bacterial cell walls. Normal resolution of inflammation involves the removal of neutrophils and other inflammatory cells by the induction of apoptosis. Spontaneous neutrophil apoptosis does not require Fas ligation, but is mediated by caspases 3, 8 and possibly caspase 9 and also involves activation of protein kinase C-δ. With chronic inflammatory disease, neutrophil apoptosis is delayed by pro-inflammatory cytokines, leading to persistence of neutrophils at the inflamed site and non-specific tissue damage. Here we discuss the evidence for inhibition of neutrophil apoptosis via signaling though PI-3-kinase and downstream pathways, including PDK-1 and PKB. Therapeutic strategies to resolve chronic inflammation could therefore usefully target neutrophil apoptosis and the PI-3-kinase or PKC-δ signaling pathways.
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  • 92
    ISSN: 1573-675X
    Keywords: adenocarcinoma cells ; apoptosis ; Bcl-2 family proteins ; chimeric proteins ; GnRH-binding site ; targeting
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract In recent years chimeric proteins carrying bacterial toxins as their killing moiety, have been developed to selectively recognize and kill cell populations expressing speciific receptors. The involvement of Gonadotropin releasing hormone (GnRH) has been demonstrated in several adenocarcinomas and a GnRH-bacterial toxin chimeric protein (GnRH-PE66) was thus developed and found to specifically target and kill adenocarcinoma cells both in vitro and in vivo. Because of the immunogenicity and the non-specific toxicity of the bacterial toxins, we have developed new chimeric proteins, introducing apoptosis inducing proteins of the Bcl-2 family as novel killing components. Sequences encoding the human Bik, Bak or Bax proteins were fused to the GnRH coding sequence at the DNA level and were expressed in E. coli. GnRH-Bik, GnRH-Bak and GnRH-Bax new chimeric proteins efficiently and specifically inhibited the cell growth of adenocarcinoma cell lines and eventually led to cell death. All three Bcl2-proteins-based chimeric proteins seem to induce apoptosis within the target cells, without any additional cell death stimulus. Apoptosis-inducing-proteins of the Bcl-2 family targeted by the GnRH are novel potential therapeutic reagents for adenocarcinoma treatment in humans. This novel approach could be widely applied, using any molecule that binds a specific cell type, fused to an apoptosis-inducing protein.
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  • 93
    ISSN: 1573-675X
    Keywords: apoptosis ; CDK ; cell cycle ; cell death gene ; drosophila ; reaper
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The present study was aimed to investigate whether or not cyclin-dependent kinases (CDKs) participate in different cascades leading to apoptosis. We examined the effects of two CDK inhibitors, olomoucine (OLM) and buty-rolactone-I (BL-I), on apoptosis induced in two kinds of Drosophila cell lines. Increases of caspase activity induced by actinomycin D, cycloheximide, H-7 or A23187 in a Drosophila neuronal cell line, ML-DmBG2-c2, and induced by excessive expression of a Drosophila cell death gene, reaper, in Drosophila S2 cells were suppressed by 24-h pretreatment of each CDK inhibitor. Concomitant with the suppression of the caspase activity, fragmentations of cells and DNA, representatives of apoptosis, were also inhibited. These results suggest that CDK(s) participates in progression of apoptosis. However, these effects of the CDK inhibitors were also observed even at lower doses which did not affect cell proliferation. Therefore, it was shown that apoptosis is not always related to cell cycle in Drosophila cells. It was also suggested that the target(s) of the CDK inhibitors locates upstream of caspase in the cascade(s) of apoptosis.
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  • 94
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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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  • 95
    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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  • 96
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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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  • 97
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    Pharmaceutical research 17 (2000), S. 515-520 
    ISSN: 1573-904X
    Keywords: apoptosis ; cationic liposome ; B cell ; WEHI 231 ; reactive oxygen species
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Liposomes are of considerable interest as drug carriers andimmunoadjuvants. However, few investigators have studied thechanges exerted by liposomes in the cells with which they interact.The purpose of this study was to investigate whether liposomes induceapoptosis in B cells. Methods. The mouse immature B cell line WEHI 231 cells and mousesplenic B cells were treated with liposomes, and the induction ofapoptosis was evaluated by monitoring changes in DNA content, DNAfragmentation and chromatin condensation by flow cytometry, agarosegel electrophoresis and by morphological investigation. Results. Cationic liposomes induced apoptosis in WEHI 231 cells, butneutral and anionic liposomes did not. A contact time of 30 minbetween WEHI 231 cells and cationic liposomes was sufficient toinduce apoptosis, and 80% of the cells showed hypodiploid DNAcontent. Apoptosis induced by cationic liposomes composed ofstearylamine was inhibited by addition of the oxidant scavenger,N-acetyl-cysteine. Conclusions. Cationic liposomes induced apoptosis in WEHI 231 cells,and the production of reactive oxygen species is important in theregulation of apoptosis induced by cationic liposomes. It is well knownthat cationic liposomes show cytotoxicity, and apoptosis may be oneof the causes of this toxicity.
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  • 98
    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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  • 99
    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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  • 100
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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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