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- Volume 35, 2001
Annual Review of Genetics - Volume 35, 2001
Volume 35, 2001
- Review Articles
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Hypoviruses and Chestnut Blight: Exploiting Viruses to Understand and Modulate Fungal Pathogenesis
Vol. 35 (2001), pp. 1–29More Less▪ AbstractFungal viruses are considered unconventional because they lack an extracellular route of infection and persistently infect their hosts, often in the absence of apparent symptoms. Because mycoviruses are limited to intracellular modes of transmission, they can be considered as intrinsic fungal genetic elements. Such long-term genetic interactions, even involving apparently asymptomatic mycoviruses, are likely to have an impact on fungal ecology and evolution. One of the clearest examples supporting this view is the phenomenon of hypovirulence (virulence attenuation) observed for strains of the chestnut blight fungus, Cryphonectria parasitica, harboring members of the virus family Hypoviridae. The goal of this chapter is to document recent advances in hypovirus molecular genetics and to provide examples of how that progress is leading to the identification of virus-encoded determinants responsible for altering fungal host phenotype, insights into essential and dispensable elements of hypovirus replication, revelations concerning the role of G-protein signaling in fungal pathogenesis, and new avenues for enhancing biological control potential.
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Genetics and the Fitness of Hybrids
Vol. 35 (2001), pp. 31–52More Less▪ AbstractOver the years, the evolutionary importance of natural hybridization has been a contentious issue. At one extreme is the relatively common view of hybridization as an evolutionarily unimportant process. A less common perspective, but one that has gained support over the past decade, is that of hybridization as a relatively widespread and potentially creative evolutionary process. Indeed, studies documenting the production of hybrid genotypes exhibiting a wide range of fitnesses have become increasingly common. In this review, we examine the genetic basis of such variation in hybrid fitness. In particular, we assess the genetic architecture of hybrid inferiority (both sterility and inviability). We then extend our discussion to the genetic basis of increased fitness in certain hybrid genotypes. The available evidence argues that hybrid inferiority is the result of widespread negative epistasis in a hybrid genetic background. In contrast, increased hybrid fitness can be most readily explained through the segregation of additive genetic factors, with epistasis playing a more limited role.
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Recombinational DNA Repair of Damaged Replication Forks in Escherichia coli: Questions
Vol. 35 (2001), pp. 53–82More Less▪ AbstractIt has recently become clear that the recombinational repair of stalled replication forks is the primary function of homologous recombination systems in bacteria. In spite of the rapid progress in many related lines of inquiry that have converged to support this view, much remains to be done. This review focuses on several key gaps in understanding. Insufficient data currently exists on: (a) the levels and types of DNA damage present as a function of growth conditions, (b) which types of damage and other barriers actually halt replication, (c) the structures of the stalled/collapsed replication forks, (d) the number of recombinational repair paths available and their mechanistic details, (e) the enzymology of some of the key reactions required for repair, (f) the role of certain recombination proteins that have not yet been studied, and (g) the molecular origin of certain in vivo observations associated with recombinational DNA repair during the SOS response. The current status of each of these topics is reviewed.
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Sir Francis Galton and the Birth of Eugenics
Vol. 35 (2001), pp. 83–101More Less▪ AbstractThe eugenics movement was initiated by Sir Francis Galton, a Victorian scientist. Galton's career can be divided into two parts. During the first, Galton was engaged in African exploration, travel writing, geography, and meteorology. The second part began after he read the Origin of Species by his cousin Charles Darwin. The book convinced Galton that humanity could be improved through selective breeding. During this part of his career he was interested in the factors that determine what he called human “talent and character” and its hereditary basis. Consequently, he delved into anthropometrics and psychology and played a major role in the development of fingerprinting. He also founded the field of biometrics, inventing such familiar statistical procedures as correlation and regression analysis. He constructed his own theory of inheritance in which nature and not nurture played the leading role. He actively began to promote eugenics and soon gained important converts.
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Building a Multicellular Organism
Vol. 35 (2001), pp. 103–123More Less▪ AbstractMulticellular organisms appear to have arisen from unicells numerous times. Multicellular cyanobacteria arose early in the history of life on Earth. Multicellular forms have since arisen independently in each of the kingdoms and several times in some phyla. If the step from unicellular to multicellular life was taken early and frequently, the selective advantage of multicellularity may be large. By comparing the properties of a multicellular organism with those of its putative unicellular ancestor, it may be possible to identify the selective force(s). The independent instances of multicellularity reviewed indicate that advantages in feeding and in dispersion are common. The capacity for signaling between cells accompanies the evolution of multicellularity with cell differentiation.
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The Inheritance of Genes in Mitochondria and Chloroplasts: Laws, Mechanisms, and Models
Vol. 35 (2001), pp. 125–148More Less▪ AbstractThe inheritance of mitochondrial and chloroplast genes differs from that of nuclear genes in showing vegetative segregation, uniparental inheritance, intracellular selection, and reduced recombination. Vegetative segregation and some cases of uniparental inheritance are due to stochastic replication and partitioning of organelle genomes. The rate and pattern of vegetative segregation depend partly on the numbers of genomes and of organelles per cell, but more importantly on the extent to which genomes are shared between organelles, their distribution in the cell, the variance in number of replications per molecule, and the variance in numerical and genotypic partitioning of organelles and genomes. Most of these parameters are unknown for most organisms, but a simple binomial probability model using the effective number of genomes is a useful substitute. Studies using new cytological, molecular, and genetic methods are shedding some light on the processes involved in segregation, and also on the mechanisms of intracellular selection and uniparental inheritance in mammals. But significant issues remain unresolved, notably about the extent of paternal transmission and mitochondrial fusion in mammals.
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The Action of Molecular Chaperones in the Early Secretory Pathway
Vol. 35 (2001), pp. 149–191More Less▪ AbstractThe endoplasmic reticulum (ER) serves as a way-station during the biogenesis of nearly all secreted proteins, and associated with or housed within the ER are factors required to catalyze their import into the ER and facilitate their folding. To ensure that only properly folded proteins are secreted and to temper the effects of cellular stress, the ER can target aberrant proteins for degradation and/or adapt to the accumulation of misfolded proteins. Molecular chaperones play critical roles in each of these phenomena.
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Chromatin Insulators and Boundaries: Effects on Transcription and Nuclear Organization
Vol. 35 (2001), pp. 193–208More Less▪ AbstractChromatin boundaries and insulators are transcriptional regulatory elements that modulate interactions between enhancers and promoters and protect genes from silencing effects by the adjacent chromatin. Originally discovered in Drosophila, insulators have now been found in a variety of organisms, ranging from yeast to humans. They have been found interspersed with regulatory sequences in complex genes and at the boundaries between active and inactive chromatin. Insulators might modulate transcription by organizing the chromatin fiber within the nucleus through the establishment of higher-order domains of chromatin structure.
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Animal Models of Tumor-Suppressor Genes
Vol. 35 (2001), pp. 209–241More Less▪ AbstractThe development of cancer requires multiple genetic alterations perturbing distinct cellular pathways. In human cancers, these alterations often arise owing to mutations in tumor-suppressor genes whose normal function is to either inhibit the proliferation, apoptosis, or differentiation of cells, or maintain their genomic integrity. Mouse models for tumor suppressors frequently provide definitive evidence for the antitumorigenic functions of these genes. In addition, animal models permit the identification of previously unsuspected roles of these genes in development and differentiation. The availability of null and tissue-specific mouse mutants for tumor-suppressor genes has greatly facilitated our understanding of the mechanisms leading to cancer. In this review, we describe mouse models for tumor-suppressor genes.
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Homologous Recombination Near and Far from DNA Breaks: Alternative Roles and Contrasting Views
Vol. 35 (2001), pp. 243–274More Less▪ AbstractDouble-strand breaks and other lesions in DNA can stimulate homologous genetic recombination in two quite different ways: by promoting recombination near the break (roughly within a kb) or far from the break. Recent emphasis on the repair aspect of recombination has focused attention on DNA interactions and recombination near breaks. Here I review evidence for recombination far from DNA breaks in bacteria and fungi and discuss mechanisms by which this can occur. These mechanisms include entry of a traveling entity (“recombination machine”) at a break, formation of long heteroduplex DNA, priming of DNA replication by a broken end, and induction of recombination potential in trans. Special emphasis is placed on contrasting views of how the RecBCD enzyme of Escherichia coli promotes recombination far (tens of kb) from a double-strand break. The occurrence of recombination far from DNA breaks and of correlated recombination events far apart suggests that “action at a distance” during recombination is a widespread feature among diverse organisms.
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Mechanisms of Retroviral Recombination
Matteo Negroni, and Henri BucVol. 35 (2001), pp. 275–302More Less▪ AbstractRecombination is a major source of genetic variability in retroviruses. Each viral particle contains two single-stranded genomic RNAs. Recombination mostly results from a switch in template between these two RNAs during reverse transcription. Here we emphasize the main mechanisms underlying recombination that are emerging from recent advances in biochemical and cell culture techniques. Increasing evidence supporting the involvement of RNA secondary structures now complements the predominant role classically attributed to enzyme pausing during reverse transcription. Finally, the implications of recombination on the dynamics of emergence of genomic aberrations in retroviruses are discussed.
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The Genetic Architecture of Quantitative Traits
Vol. 35 (2001), pp. 303–339More Less▪ AbstractPhenotypic variation for quantitative traits results from the segregation of alleles at multiple quantitative trait loci (QTL) with effects that are sensitive to the genetic, sexual, and external environments. Major challenges for biology in the post-genome era are to map the molecular polymorphisms responsible for variation in medically, agriculturally, and evolutionarily important complex traits; and to determine their gene frequencies and their homozygous, heterozygous, epistatic, and pleiotropic effects in multiple environments. The ease with which QTL can be mapped to genomic intervals bounded by molecular markers belies the difficulty in matching the QTL to a genetic locus. The latter requires high-resolution recombination or linkage disequilibrium mapping to nominate putative candidate genes, followed by genetic and/or functional complementation and gene expression analyses. Complete genome sequences and improved technologies for polymorphism detection will greatly advance the genetic dissection of quantitative traits in model organisms, which will open avenues for exploration of homologous QTL in related taxa.
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New Perspectives on Nuclear Transport
Vol. 35 (2001), pp. 341–364More Less▪ AbstractA central aspect of cellular function is the proper regulation of nucleocytoplasmic transport. In recent years, significant progress has been made in identifying and characterizing the essential components of the transport machinery. Despite these advances, some facets of this process are still unclear. Furthermore, recent work has uncovered novel molecules and mechanisms of nuclear transport. This review focuses on the unresolved and novel aspects of nuclear transport and explores issues in tRNA, snRNA, and mRNA export that highlight the diversity of nuclear transport mechanisms.
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Translational Regulation and RNA Localization in Drosophila Oocytes and Embryos
Oona Johnstone, and Paul LaskoVol. 35 (2001), pp. 365–406More Less▪ AbstractTranslational control is a prevalent means of gene regulation during Drosophila oogenesis and embryogenesis. Multiple maternal mRNAs are localized within the oocyte, and this localization is often coupled to their translational regulation. Subsequently, translational control allows maternally deposited mRNAs to direct the early stages of embryonic development. In this review we outline some general mechanisms of translational regulation and mRNA localization that have been uncovered in various model systems. Then we focus on the posttranscriptional regulation of four maternal transcripts in Drosophila that are localized during oogenesis and are critical for embryonic patterning: bicoid (bcd), nanos (nos), oskar (osk), and gurken (grk). Cis- and trans-acting factors required for the localization and translational control of these mRNAs are discussed along with potential mechanisms for their regulation.
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Conservation and Divergence in Molecular Mechanisms of Axis Formation
Sabbi Lall, and Nipam H. PatelVol. 35 (2001), pp. 407–437More Less▪ AbstractGenetic screens in Drosophila melanogaster have helped elucidate the process of axis formation during early embryogenesis. Axis formation in the D. melanogaster embryo involves the use of two fundamentally different mechanisms for generating morphogenetic activity: patterning the anteroposterior axis by diffusion of a transcription factor within the syncytial embryo and specification of the dorsoventral axis through a signal transduction cascade. Identification of Drosophila genes involved in axis formation provides a launch-pad for comparative studies that examine the evolution of axis specification in different insects. Additionally, there is similarity between axial patterning mechanisms elucidated genetically in Drosophila and those demonstrated for chordates such as Xenopus. In this review we examine the postfertilization mechanisms underlying axis specification in Drosophila. Comparative data are then used to ask whether aspects of axis formation might be derived or ancestral.
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Regulation of Gene Expression by Cell-to-Cell Communication: Acyl-Homoserine Lactone Quorum Sensing
Vol. 35 (2001), pp. 439–468More Less▪ AbstractQuorum sensing is an example of community behavior prevalent among diverse bacterial species. The term “quorum sensing” describes the ability of a microorganism to perceive and respond to microbial population density, usually relying on the production and subsequent response to diffusible signal molecules. A significant number of gram-negative bacteria produce acylated homoserine lactones (acyl-HSLs) as signal molecules that function in quorum sensing. Bacteria that produce acyl-HSLs can respond to the local concentration of the signaling molecules, and high population densities foster the accumulation of inducing levels of acyl-HSLs. Depending upon the bacterial species, the physiological processes regulated by quorum sensing are extremely diverse, ranging from bioluminescence to swarming motility. Acyl-HSL quorum sensing has become a paradigm for intercellular signaling mechanisms. A flurry of research over the past decade has led to significant understanding of many aspects of quorum sensing including the synthesis of acyl-HSLs, the receptors that recognize the acyl-HSL signal and transduce this information to the level of gene expression, and the interaction of these receptors with the transcriptional machinery. Recent studies have begun to integrate acyl-HSL quorum sensing into global regulatory networks and establish its role in developing and maintaining the structure of bacterial communities.
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Models and Data on Plant-Enemy Coevolution
Vol. 35 (2001), pp. 469–499More Less▪ AbstractAlthough coevolution is complicated, in that the interacting species evolve in response to each other, such evolutionary dynamics are amenable to mathematical modeling. In this article, we briefly review models and data on coevolution between plants and the pathogens and herbivores that attack them. We focus on “arms races,” in which trait values in the plant and its enemies escalate to more and more extreme values. Untested key assumptions in many of the models are the relationships between costs and benefits of resistance in the plant and the level of resistance, as well as how costs of virulence or detoxification ability in the enemy change with levels of these traits. A preliminary assessment of these assumptions finds only mixed support for the models. What is needed are models that are more closely tailored to particular plant-enemy interactions, as well as experiments that are expressly designed to test existing models.
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Biology of Mammalian L1 Retrotransposons
Vol. 35 (2001), pp. 501–538More Less▪ AbstractL1 retrotransposons comprise 17% of the human genome. Although most L1s are inactive, some elements remain capable of retrotransposition. L1 elements have a long evolutionary history dating to the beginnings of eukaryotic existence. Although many aspects of their retrotransposition mechanism remain poorly understood, they likely integrate into genomic DNA by a process called target primed reverse transcription. L1s have shaped mammalian genomes through a number of mechanisms. First, they have greatly expanded the genome both by their own retrotransposition and by providing the machinery necessary for the retrotransposition of other mobile elements, such as Alus. Second, they have shuffled non-L1 sequence throughout the genome by a process termed transduction. Third, they have affected gene expression by a number of mechanisms. For instance, they occasionally insert into genes and cause disease both in humans and in mice. L1 elements have proven useful as phylogenetic markers and may find other practical applications in gene discovery following insertional mutagenesis in mice and in the delivery of therapeutic genes.
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Does Nonneutral Evolution Shape Observed Patterns of DNA Variation in Animal Mitochondrial Genomes?
Vol. 35 (2001), pp. 539–566More Less▪ AbstractEarly studies of animal mitochondrial DNA (mtDNA) assumed that nucleotide sequence variation was neutral. Recent analyses of sequences from a variety of taxa have brought the validity of this assumption into question. Here we review analytical methods used to test for neutrality and evidence for nonneutral evolution of animal mtDNA. Evaluations of mitochondrial haplotypes in different nuclear backgrounds identified differences in performance, typically favoring coevolved mitochondrial and nuclear genomes. Experimental manipulations also indicated that certain haplotypes have an advantage over others; however, biotic and historical effects and cyto-nuclear interactions make it difficult to assess the relative importance of nonneutral factors. Statistical analyses of sequences have been used to argue for nonneutrality of mtDNA; however, rejection of neutral patterns in the published literature is common but not predominant. Patterns of replacement and synonymous substitutions within and between species identified a trend toward an excess of replacement mutations within species. This pattern has been viewed as support for the existence of mildly deleterious mutations within species; however, other alternative explanations that can produce similar patterns cannot be eliminated.
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Identification of Epilepsy Genes in Human and Mouse1
Vol. 35 (2001), pp. 567–588More Less▪ AbstractThe development of molecular markers and genomic resources has facilitated the isolation of genes responsible for rare monogenic epilepsies in human and mouse. Many of the identified genes encode ion channels or other components of neuronal signaling. The electrophysiological properties of mutant alleles indicate that neuronal hyperexcitability is one cellular mechanism underlying seizures. Genetic heterogeneity and allelic variability are hallmarks of human epilepsy. For example, mutations in three different sodium channel genes can produce the same syndrome, GEFS+, while individuals with the same allele can experience different types of seizures. Haploinsufficiency for the sodium channel SCN1A has been demonstrated by the severe infantile epilepsy and cognitive deficits in heterozygotes for de novo null mutations. Large-scale patient screening is in progress to determine whether less severe alleles of the genes responsible for monogenic epilepsy may contribute to the common types of epilepsy in the human population. The development of pharmaceuticals directed towards specific epilepsy genotypes can be anticipated, and the introduction of patient mutations into the mouse genome will provide models for testing these targeted therapies.
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Previous Volumes
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Volume 58 (2024)
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Volume 57 (2023)
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Volume 56 (2022)
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Volume 55 (2021)
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Volume 54 (2020)
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Volume 53 (2019)
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Volume 52 (2018)
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Volume 51 (2017)
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Volume 50 (2016)
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Volume 49 (2015)
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Volume 48 (2014)
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Volume 47 (2013)
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Volume 46 (2012)
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Volume 45 (2011)
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Volume 44 (2010)
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Volume 43 (2009)
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Volume 42 (2008)
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Volume 41 (2007)
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Volume 40 (2006)
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Volume 39 (2005)
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Volume 38 (2004)
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Volume 37 (2003)
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Volume 36 (2002)
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Volume 35 (2001)
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Volume 34 (2000)
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Volume 33 (1999)
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Volume 32 (1998)
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Volume 31 (1997)
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Volume 30 (1996)
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Volume 29 (1995)
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Volume 28 (1994)
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Volume 27 (1993)
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Volume 26 (1992)
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Volume 25 (1991)
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Volume 24 (1990)
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Volume 23 (1989)
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Volume 22 (1988)
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Volume 21 (1987)
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Volume 20 (1986)
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Volume 19 (1985)
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Volume 18 (1984)
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Volume 17 (1983)
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Volume 16 (1982)
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Volume 15 (1981)
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Volume 14 (1980)
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Volume 13 (1979)
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Volume 12 (1978)
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Volume 11 (1977)
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Volume 10 (1976)
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Volume 9 (1975)
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Volume 8 (1974)
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Volume 7 (1973)
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Volume 6 (1972)
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Volume 5 (1971)
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Volume 4 (1970)
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Volume 3 (1969)
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Volume 2 (1968)
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Volume 1 (1967)
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Volume 0 (1932)