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- Volume 48, 2014
Annual Review of Genetics - Volume 48, 2014
Volume 48, 2014
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L1 Retrotransposons and Somatic Mosaicism in the Brain
Vol. 48 (2014), pp. 1–27More LessLong interspersed element 1 (LINE-1 or L1) retrotransposons have generated one-third of the human genome, and their ongoing mobility is a source of inter- and intraindividual genetic diversity. Although retrotransposition in metazoans has long been considered a germline phenomenon, recent experiments using cultured cells, animal models, and human tissues have revealed extensive L1 mobilization in rodent and human neurons, as well as mobile element activity in the Drosophila brain. In this review, we evaluate the available evidence for L1 retrotransposition in the brain and discuss mechanisms that may regulate neuronal retrotransposition in vivo. We compare experimental strategies used to map de novo somatic retrotransposition events and present the optimal criteria to identify a somatic L1 insertion. Finally, we discuss the unresolved impact of L1-mediated somatic mosaicism upon normal neurobiology, as well as its potential to drive neurological disease.
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Factors Underlying Restricted Crossover Localization in Barley Meiosis
Vol. 48 (2014), pp. 29–47More LessMeiotic recombination results in the formation of cytological structures known as chiasmata at the sites of genetic crossovers (COs). The formation of at least one chiasma/CO between homologous chromosome pairs is essential for accurate chromosome segregation at the first meiotic division as well as for generating genetic variation. Although DNA double-strand breaks, which initiate recombination, are widely distributed along the chromosomes, this is not necessarily reflected in the chiasma distribution. In many species there is a tendency for chiasmata to be distributed in favored regions along the chromosomes, whereas in others, such as barley and some other grasses, chiasma localization is extremely pronounced. Localization of chiasma to the distal regions of barley chromosomes restricts the genetic variation available to breeders. Studies reviewed herein are beginning to provide an explanation for chiasma localization in barley. Moreover, they suggest a potential route to manipulating chiasma distribution that could be of value to plant breeders.
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pENCODE: A Plant Encyclopedia of DNA Elements
Vol. 48 (2014), pp. 49–70More LessENCODE projects exist for many eukaryotes, including humans, but as of yet no defined project exists for plants. A plant ENCODE would be invaluable to the research community and could be more readily produced than its metazoan equivalents by capitalizing on the preexisting infrastructure provided from similar projects. Collecting and normalizing plant epigenomic data for a range of species will facilitate hypothesis generation, cross-species comparisons, annotation of genomes, and an understanding of epigenomic functions throughout plant evolution. Here, we discuss the need for such a project, outline the challenges it faces, and suggest ways forward to build a plant ENCODE.
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Archaeal DNA Replication
Lori M. Kelman, and Zvi KelmanVol. 48 (2014), pp. 71–97More LessDNA replication is essential for all life forms. Although the process is fundamentally conserved in the three domains of life, bioinformatic, biochemical, structural, and genetic studies have demonstrated that the process and the proteins involved in archaeal DNA replication are more similar to those in eukaryal DNA replication than in bacterial DNA replication, but have some archaeal-specific features. The archaeal replication system, however, is not monolithic, and there are some differences in the replication process between different species. In this review, the current knowledge of the mechanisms governing DNA replication in Archaea is summarized. The general features of the replication process as well as some of the differences are discussed.
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Molecular Genetic Dissection of Quantitative Trait Loci Regulating Rice Grain Size
Jianru Zuo, and Jiayang LiVol. 48 (2014), pp. 99–118More LessGrain size is one of the most important factors determining rice yield. As a quantitative trait, grain size is predominantly and tightly controlled by genetic factors. Several quantitative trait loci (QTLs) for grain size have been molecularly identified and characterized. These QTLs may act in independent genetic pathways and, along with other identified genes for grain size, are mainly involved in the signaling pathways mediated by proteasomal degradation, phytohormones, and G proteins to regulate cell proliferation and cell elongation. Many of these QTLs and genes have been strongly selected for enhanced rice productivity during domestication and breeding. These findings have paved new ways for understanding the molecular basis of grain size and have substantial implications for genetic improvement of crops.
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Exploring Developmental and Physiological Functions of Fatty Acid and Lipid Variants Through Worm and Fly Genetics
Huanhu Zhu, and Min HanVol. 48 (2014), pp. 119–148More LessLipids are more than biomolecules for energy storage and membrane structure. With ample structural variation, lipids critically participate in nearly all aspects of cellular function. Lipid homeostasis and metabolism are closely related to major human diseases and health problems. However, lipid functional studies have been significantly underdeveloped, partly because of the difficulty in applying genetics and common molecular approaches to tackle the complexity associated with lipid biosynthesis, metabolism, and function. In the past decade, a number of laboratories began to analyze the roles of lipid metabolism in development and other physiological functions using animal models and combining genetics, genomics, and biochemical approaches. These pioneering efforts have not only provided valuable insights regarding lipid functions in vivo but have also established feasible methodology for future studies. Here, we review a subset of these studies using Caenorhabditis elegans and Drosophila melanogaster.
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Quality Control and Infiltration of Translation by Amino Acids Outside of the Genetic Code
Vol. 48 (2014), pp. 149–166More LessTranslation of the genome into functional proteins is critical for cellular life. Accurate protein synthesis relies on proper decoding of mRNAs by the ribosome using aminoacyl-tRNAs. During aminoacyl-tRNA synthesis, stringent substrate discrimination and rigorous product proofreading ensure tRNAs are paired with the correct amino acid, as defined by the rules of the genetic code. What has remained far less clear is the extent to which amino acids that are not part of the genetic code might also threaten translational accuracy. Here, we review the broad range of nonproteinogenic, or nonprotein, amino acids that can naturally accumulate under different conditions, the ability of the translation quality control machinery to deal with such substrates, and their potential impact on the integrity of the genetic code and cellular viability.
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Vulnerabilities on the Lagging-Strand Template: Opportunities for Mobile Elements
Vol. 48 (2014), pp. 167–186More LessMobile genetic elements have the ability to move between positions in a genome. Some of these elements are capable of targeting one of the template strands during DNA replication. Examples found in bacteria include (a) Red recombination mediated by bacteriophage λ, (b) integration of group II mobile introns that reverse splice and reverse transcribe into DNA, (c) HUH endonuclease elements that move as single-stranded DNA, and (d) Tn7, a DNA cut-and-paste transposon that uses a target-site-selecting protein to target transposition into certain forms of DNA replication. In all of these examples, the lagging-strand template appears to be targeted using a variety of features specific to this strand. These features appear especially available in certain situations, such as when replication forks stall or collapse. In this review, we address the idea that features specific to the lagging-strand template represent vulnerabilities that are capitalized on by mobile genetic elements.
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Self-Organization of Meiotic Recombination Initiation: General Principles and Molecular Pathways
Vol. 48 (2014), pp. 187–214More LessRecombination in meiosis is a fascinating case study for the coordination of chromosomal duplication, repair, and segregation with each other and with progression through a cell-division cycle. Meiotic recombination initiates with formation of developmentally programmed DNA double-strand breaks (DSBs) at many places across the genome. DSBs are important for successful meiosis but are also dangerous lesions that can mutate or kill, so cells ensure that DSBs are made only at the right times, places, and amounts. This review examines the complex web of pathways that accomplish this control. We explore how chromosome breakage is integrated with meiotic progression and how feedback mechanisms spatially pattern DSB formation and make it homeostatic, robust, and error correcting. Common regulatory themes recur in different organisms or in different contexts in the same organism. We review this evolutionary and mechanistic conservation but also highlight where control modules have diverged. The framework that emerges helps explain how meiotic chromosomes behave as a self-organizing system.
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Cancer: Evolution Within a Lifetime
Vol. 48 (2014), pp. 215–236More LessSubclonal cancer populations change spatially and temporally during the disease course. Studies are revealing branched evolutionary cancer growth with low-frequency driver events present in subpopulations of cells, providing escape mechanisms for targeted therapeutic approaches. Despite such complexity, evidence is emerging for parallel evolution of subclones, mediated through distinct somatic events converging on the same gene, signal transduction pathway, or protein complex in different subclones within the same tumor. Tumors may follow gradualist paths (microevolution) as well as major shifts in evolutionary trajectories (macroevolution). Although macroevolution has been subject to considerable controversy in post-Darwinian evolutionary theory, we review evidence that such nongradual, saltatory leaps, driven through chromosomal rearrangements or genome doubling, may be particularly relevant to tumor evolution. Adapting cancer care to the challenges imposed by tumor micro- and macroevolution and developing deeper insight into parallel evolutionary events may prove central to improving outcome and reducing drug development costs.
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Diverse Epigenetic Mechanisms of Human Disease
Emily Brookes, and Yang ShiVol. 48 (2014), pp. 237–268More LessEpigenetic control of gene expression programs is essential for normal organismal development and cellular function. Abrogation of epigenetic regulation is seen in many human diseases, including cancer and neuropsychiatric disorders, where it can affect disease etiology and progression. Abnormal epigenetic profiles can serve as biomarkers of disease states and predictors of disease outcomes. Therefore, epigenetics is a key area of clinical investigation in diagnosis, prognosis, and treatment. In this review, we give an overarching view of epigenetic mechanisms of human disease. Genetic mutations in genes that encode chromatin regulators can cause monogenic disease or are incriminated in polygenic, multifactorial diseases. Environmental stresses can also impact directly on chromatin regulation, and these changes can increase the risk of, or directly cause, disease. Finally, emerging evidence suggests that exposure to environmental stresses in older generations may predispose subsequent generations to disease in a manner that involves the transgenerational inheritance of epigenetic information.
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From Egg to Gastrula: How the Cell Cycle Is Remodeled During the Drosophila Mid-Blastula Transition
Vol. 48 (2014), pp. 269–294More LessMany, if not most, embryos begin development with extremely short cell cycles that exhibit unusually rapid DNA replication and no gap phases. The commitment to the cell cycle in the early embryo appears to preclude many other cellular processes that only emerge as the cell cycle slows just prior to gastrulation at a major embryonic transition known as the mid-blastula transition (MBT). As reviewed here, genetic and molecular studies in Drosophila have identified changes that extend S phase and introduce a postreplicative gap phase, G2, to slow the cell cycle. Although many mysteries remain about the upstream regulators of these changes, we review the core mechanisms of the change in cell cycle regulation and discuss advances in our understanding of how these might be timed and triggered. Finally, we consider how the elements of this program may be conserved or changed in other organisms.
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Cellular and Molecular Mechanisms of Single and Collective Cell Migrations in Drosophila: Themes and Variations
Vol. 48 (2014), pp. 295–318More LessThe process of cell migration is essential throughout life, driving embryonic morphogenesis and ensuring homeostasis in adults. Defects in cell migration are a major cause of human disease, with excessive migration causing autoimmune diseases and cancer metastasis, whereas reduced capacity for migration leads to birth defects and immunodeficiencies. Myriad studies in vitro have established a consensus view that cell migrations require cell polarization, Rho GTPase–mediated cytoskeletal rearrangements, and myosin-mediated contractility. However, in vivo studies later revealed a more complex picture, including the discovery that cells migrate not only as single units but also as clusters, strands, and sheets. In particular, the role of E-Cadherin in cell motility appears to be more complex than previously appreciated. Here, we discuss recent advances achieved by combining the plethora of genetic tools available to the Drosophila geneticist with live imaging and biophysical techniques. Finally, we discuss the emerging themes such studies have revealed and ponder the puzzles that remain to be solved.
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The Structure and Regulation of Flagella in Bacillus subtilis
Vol. 48 (2014), pp. 319–340More LessBacterial flagellar motility is among the most extensively studied physiological systems in biology, but most research has been restricted to using the highly similar Gram-negative species Escherichia coli and Salmonella enterica. Here, we review the recent advances in the study of flagellar structure and regulation of the distantly related and genetically tractable Gram-positive bacterium Bacillus subtilis. B. subtilis has a thicker layer of peptidoglycan and lacks the outer membrane of the Gram-negative bacteria; thus, not only phylogenetic separation but also differences in fundamental cell architecture contribute to deviations in flagellar structure and regulation. We speculate that a large number of flagella and the absence of a periplasm make B. subtilis a premier organism for the study of the earliest events in flagellar morphogenesis and the type III secretion system. Furthermore, B. subtilis has been instrumental in the study of heterogeneous gene transcription in subpopulations and of flagellar regulation at the translational and functional level.
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Transcription-Associated Mutagenesis
Vol. 48 (2014), pp. 341–359More LessTranscription requires unwinding complementary DNA strands, generating torsional stress, and sensitizing the exposed single strands to chemical reactions and endogenous damaging agents. In addition, transcription can occur concomitantly with the other major DNA metabolic processes (replication, repair, and recombination), creating opportunities for either cooperation or conflict. Genetic modifications associated with transcription are a global issue in the small genomes of microorganisms in which noncoding sequences are rare. Transcription likewise becomes significant when one considers that most of the human genome is transcriptionally active. In this review, we focus specifically on the mutagenic consequences of transcription. Mechanisms of transcription-associated mutagenesis in microorganisms are discussed, as is the role of transcription in somatic instability of the vertebrate immune system.
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Gastrointestinal Microbiota–Mediated Control of Enteric Pathogens
Vol. 48 (2014), pp. 361–382More LessThe gastrointestinal (GI) microbiota is a complex community of microorganisms residing within the mammalian gastrointestinal tract. The GI microbiota is vital to the development of the host immune system and plays a crucial role in human health and disease. The composition of the GI microbiota differs immensely among individuals yet specific shifts in composition and diversity have been linked to inflammatory bowel disease, obesity, atopy, and susceptibility to infection. In this review, we describe the GI microbiota and its role in enteric diseases caused by pathogenic Escherichia coli, Salmonella enterica, and Clostridium difficile. We discuss the central role of the GI microbiota in protective immunity, resistance to enteric pathogens, and resolution of enteric colitis.
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The Relations Between Recombination Rate and Patterns of Molecular Variation and Evolution in Drosophila
Vol. 48 (2014), pp. 383–403More LessGenetic recombination affects levels of variability and the efficacy of selection because natural selection acting at one site affects evolutionary processes at linked sites. The variation in local recombination rates across the Drosophila genome provides excellent material for testing hypotheses concerning the evolutionary consequences of recombination. The current state of knowledge from studies of Drosophila genomics and population genetics is reviewed here. Selection at linked sites has influenced the relations between recombination rates and patterns of molecular variation and evolution, such that higher rates of recombination are associated with both higher levels of variability and a greater efficacy of selection. It seems likely that background selection against deleterious mutations is a major factor contributing to these patterns in genome regions in which crossing over is rare or absent, whereas selective sweeps of positively selected mutations probably play an important role in regions with crossing over.
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The Genetics of Neisseria Species
Vol. 48 (2014), pp. 405–431More LessNeisseria gonorrhoeae and Neisseria meningitidis are closely related organisms that cause the sexually transmitted infection gonorrhea and serious bacterial meningitis and septicemia, respectively. Both species possess multiple mechanisms to alter the expression of surface-exposed proteins through the processes of phase and antigenic variation. This potential for wide variability in surface-exposed structures allows the organisms to always have subpopulations of divergent antigenic types to avoid immune surveillance and to contribute to functional variation. Additionally, the Neisseria are naturally competent for DNA transformation, which is their main means of genetic exchange. Although bacteriophages and plasmids are present in this genus, they are not as effective as DNA transformation for horizontal genetic exchange. There are barriers to genetic transfer, such as restriction-modification systems and CRISPR loci, that limit particular types of exchange. These host-restricted pathogens illustrate the rich complexity of genetics that can help define the similarities and differences of closely related organisms.
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Regulation of Transcription by Long Noncoding RNAs
Vol. 48 (2014), pp. 433–455More LessOver the past decade there has been a greater understanding of genomic complexity in eukaryotes ushered in by the immense technological advances in high-throughput sequencing of DNA and its corresponding RNA transcripts. This has resulted in the realization that beyond protein-coding genes, there are a large number of transcripts that do not encode for proteins and, therefore, may perform their function through RNA sequences and/or through secondary and tertiary structural determinants. This review is focused on the latest findings on a class of noncoding RNAs that are relatively large (>200 nucleotides), display nuclear localization, and use different strategies to regulate transcription. These are exciting times for discovering the biological scope and the mechanism of action for these RNA molecules, which have roles in dosage compensation, imprinting, enhancer function, and transcriptional regulation, with a great impact on development and disease.
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Centromeric Heterochromatin: The Primordial Segregation Machine
Vol. 48 (2014), pp. 457–484More LessCentromeres are specialized domains of heterochromatin that provide the foundation for the kinetochore. Centromeric heterochromatin is characterized by specific histone modifications, a centromere-specific histone H3 variant (CENP-A), and the enrichment of cohesin, condensin, and topoisomerase II. Centromere DNA varies orders of magnitude in size from 125 bp (budding yeast) to several megabases (human). In metaphase, sister kinetochores on the surface of replicated chromosomes face away from each other, where they establish microtubule attachment and bi-orientation. Despite the disparity in centromere size, the distance between separated sister kinetochores is remarkably conserved (approximately 1 μm) throughout phylogeny. The centromere functions as a molecular spring that resists microtubule-based extensional forces in mitosis. This review explores the physical properties of DNA in order to understand how the molecular spring is built and how it contributes to the fidelity of chromosome segregation.
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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)