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- Volume 51, 1997
Annual Review of Microbiology - Volume 51, 1997
Volume 51, 1997
- Preface
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- Review Articles
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XENORHABDUS AND PHOTORHABDUS SPP.: Bugs That Kill Bugs
Vol. 51 (1997), pp. 47–72More Less▪ AbstractXenorhabdus and Photorhabdus spp. are gram negative gamma proteobacteria that form entomopathogenic symbioses with soil nematodes. They undergo a complex life cycle that involves a symbiotic stage, in which the bacteria are carried in the gut of the nematodes, and a pathogenic stage, in which susceptible insect prey are killed by the combined action of the nematode and the bacteria. Both bacteria produce antibiotics, intracellular protein crystals, and numerous other products. These traits change in phase variants, which arise when the bacteria are maintained under stationary phase conditions in the laboratory. Molecular biological studies suggest that Xenorhabdus and Photorhabdus spp. may serve as valuable model systems for studying signal transduction and transcriptional and posttranscriptional regulation of gene expression. Such studies also indicate that these bacterial groups, which had been previously considered to be very similar, may actually be quite different at the molecular level.
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MOLECULAR GENETICS OF SULFUR ASSIMILATION IN FILAMENTOUS FUNGI AND YEAST
Vol. 51 (1997), pp. 73–96More Less▪ AbstractThe filamentous fungi Aspergillus nidulans and Neurospora crassa and the yeast Saccharomyces cerevisiae each possess a global regulatory circuit that controls the expression of permeases and enzymes that function both in the acquisition of sulfur from the environment and in its assimilation. Control of the structural genes that specify an array of enzymes that catalyze reactions of sulfur metabolismoccurs at the transcriptional level and involves both positive-acting and negative-acting regulatory factors. Positive trans-acting regulatory proteins that contain a basic region, leucine zipper–DNA binding domain, are found in Neurospora and yeast. Each of these fungi contain a sulfur regulatory protein of the ß-transducin family that acts in a negative fashion to control gene expression. Sulfur regulation in yeast also involves the general DNA binding protein, centromere binding factor I. Sulfate uptake is a highly regulated step and appears to occur in fungi, plants, and mammals via a family of related transporter proteins. Recent developments have provided new insight into the nature and control of the enzymes ATP sulfurylase and APS kinase, which catalyze the early steps of sulfate assimilation, and of the Aspergillus enzyme, cysteine synthase, which produces cysteine from O-acetylserine.
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HEMOGLOBIN METABOLISM IN THE MALARIA PARASITE PLASMODIUM FALCIPARUM
Vol. 51 (1997), pp. 97–123More Less▪ AbstractHemoglobin degradation in intraerythrocytic malaria parasites is a vast process that occurs in an acidic digestive vacuole. Proteases that participate in this catabolic pathway have been defined. Studies of protease biosynthesis have revealed unusual targeting and activation mechanisms. Oxygen radicals and heme are released during proteolysis and must be detoxified by dismutation and polymerization, respectively. The quinoline antimalarials appear to act by preventing sequestration of this toxic heme. Understanding the disposition of hemoglobin has allowed identification of essential processes and metabolic weakpoints that can be exploited to combat this scourge of mankind.
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GETTING STARTED: Regulating the Initiation of DNA Replication in Yeast
Vol. 51 (1997), pp. 125–149More Less▪ AbstractInitiation of DNA replication in yeast appears to operate through a two-step process. The first step occurs at the end of mitosis in the previous cell cycle, where, following the decrease in B cyclin-dependent kinase activity, an extended protein complex called the prereplicative complex (pre-RC) forms over the origin of replication. This complex is dependent on the association of the Cdc6 protein with the Origin Recognition Complex (ORC) and appears concomitantly with the nuclear entry of members of the Mcm family of proteins. The second step is dependent upon the cell passing through a G1 decision point called Start. If the environmental conditions are favorable, and the cells reach a critical size, then there is a rise in G1 cyclin-dependent kinase activity, which leads to the activation of downstream protein kinases; the protein kinases are, in turn, required for triggering initiation from the preformed initiation complexes. These protein kinases, Dbf4-Cdc7 and Clb5/6(B-cyclin)-Cdc28, are thought to phosphorylate targets within the pre-RC. The subsequent rise in B cyclin protein kinase activity following Start not only triggers origin firing, but also inhibits the formation of new pre-RCs, which ensures that there is only one S phase in each cell cycle. The destruction of B-cyclin protein kinase activity at the end of the cell cycle potentiates the formation of new pre-RCs—resetting origins for the next S phase.
“… Or say that the end precedes the beginning.” TS Eliot
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RNA VIRUS MUTATIONS AND FITNESS FOR SURVIVAL
E. Domingo, and J. J. HollandVol. 51 (1997), pp. 151–178More Less▪ AbstractRNA viruses exploit all known mechanisms of genetic variation to ensure their survival. Distinctive features of RNA virus replication include high mutation rates, high yields, and short replication times. As a consequence, RNA viruses replicate as complex and dynamic mutant swarms, called viral quasispecies. Mutation rates at defined genomic sites are affected by the nucleotide sequence context on the template molecule as well as by environmental factors. In vitro hypermutation reactions offer a means to explore the functional sequence space of nucleic acids and proteins. The evolution of a viral quasispecies is extremely dependent on the population size of the virus that is involved in the infections. Repeated bottleneck events lead to average fitness losses, with viruses that harbor unusual, deleterious mutations. In contrast, large population passages result in rapid fitness gains, much larger than those so far scored for cellular organisms. Fitness gains in one environment often lead to fitness losses in an alternative environment. An important challenge in RNA virus evolution research is the assignment of phenotypic traits to specific mutations. Different constellations of mutations may be associated with a similar biological behavior. In addition, recent evidence suggests the existence of critical thresholds for the expression of phenotypic traits. Epidemiological as well as functional and structural studies suggest that RNA viruses can tolerate restricted types and numbers of mutations during any specific time point during their evolution. Viruses occupy only a tiny portion of their potential sequence space. Such limited tolerance to mutations may open new avenues for combating viral infections.
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MAKING AND BREAKING DISULFIDE BONDS
S. Raina, and D. MissiakasVol. 51 (1997), pp. 179–202More Less▪ AbstractIt is now well established that protein folding requires the assistance of folding helpers in vivo. The formation or isomerization of disulfide bonds in proteins is a slow process requiring catalysis. In nascent polypeptide chains the cysteine residues are in the thiol form. The formation of the disulfide bonds usually occurs simultaneously with the folding of the polypeptide, which means in the endoplasmic reticulum of eukaryotes or in the periplasm of Gram-negative bacteria. In prokaryotes, the existence of redox proteins involved in the formation of disulfide bonds containing proteins has recently been revealed in the periplasm. The discovery of these redox proteins through various genetic approaches will be summarized, as well as the most recent insights regarding their biochemical and biological activities.
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AGAINST ALL ODDS: The Survival Strategies of Deinococcus radiodurans
Vol. 51 (1997), pp. 203–224More Less▪ AbstractBacteria of the genus Deinococcus exhibit an extraordinary ability to withstand the lethal and mutagenic effects of DNA damaging agents—particularly the effects of ionizing radiation. These bacteria are the most DNA damage–tolerant organisms ever identified. Relatively little is known about the biochemical basis for this phenomenon; however, available evidence indicates that efficient repair of DNA damage is, in large part, responsible for the deinococci's radioresistance. Obviously, an explanation of the deinococci's DNA damage tolerance cannot be developed solely on the basis of the DNA repair strategies of more radiosensitive organisms. The deinococci's capacity to survive DNA damage suggests that (a) they employ repair mechanisms that are fundamentally different from other prokaryotes, or that (b) they have the ability to potentiate the effectiveness of the conventional complement of DNA repair proteins. An argument is made for the latter alternative.
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GENETICS OF THE ROTAVIRUSES
Vol. 51 (1997), pp. 225–255More Less▪ AbstractGenetic analyses have contributed significantly to our understanding of the biology of the rotaviruses. The distinguishing feature of the virus is a genome consisting of 11 segments of double-stranded RNA. The segmented nature of the genome allows reassortment of genome segments during mixed infections, which is the major distinguishing feature of rotavirus genetics. Reassortment has been a powerful tool for mapping viral mutations and other determinants of biological phenotypes to specific genome segments. However, more detailed genetic analysis of rotaviruses is currently limited by the inability to perform reverse genetics. Development of a reverse genetic system will facilitate analysis of the molecular mechanisms involved in various genetic, biochemical, and biological phenomena of the virus.
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INTRACELLULAR ANTIBODIES (INTRABODIES) FOR GENE THERAPY OF INFECTIOUS DISEASES
Vol. 51 (1997), pp. 257–283More Less▪ AbstractIntracellular antibodies (intrabodies) represent a new class of neutralizing molecules with a potential use in gene therapy. Intrabodies are engineered single-chain antibodies in which the variable domain of the heavy chain is joined to the variable domain of the light chain through a peptide linker, preserving the affinity of the parent antibody. Intrabodies are expressed inside cells and directed to different subcellular compartments where they can exert their function more effectively. The effects of intrabodies have been investigated using structural, regulatory, and enzymatic proteins of the human immunodeficiency virus (HIV-1) as targets. These intrabodies have demonstrated their versatility by controlling early as well as late events of the viral life cycle. In this article, we review studies of the use of intrabodies as research tools and therapeutic agents against HIV-1.
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MICROBIAL ALDOLASES AND TRANSKETOLASES: New Biocatalytic Approaches to Simple and Complex Sugars
Vol. 51 (1997), pp. 285–310More Less▪ AbstractEnzymes have become exceedingly valuable tools in organic synthesis as the reactions they catalyze generally proceed under mild conditions and in high stereo- and regioselectivity. Advances in microbiology and genetic engineering have greatly increased the availability of various enzymes. One of the most useful applications of enzyme-catalyzed chemical transformations is in the synthesis of water-soluble, polyfunctional organic molecules such as carbohydrates. As the pivotal roles that carbohydrates play in biological processes become more evident, access to these compounds becomes increasingly important. This review gives a brief overview of the use of aldolases and transketolases in the synthesis of sugars, sugar analogs, and related compounds.
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INTERACTION OF ANTIGENS AND ANTIBODIES AT MUCOSAL SURFACES
Vol. 51 (1997), pp. 311–340More Less▪ AbstractInfections often involve the mucosal surfaces of the body, which form a boundary with the outside world. This review focuses on immunoglobulin A (IgA) antibodies because IgA is the principal mucosal antibody class. IgA is synthesized by local plasma cells and has a specific polymeric immunoglobulin receptor-mediated transport mechanism for entry into the secretions. By serving as an external barrier capable of inhibiting attachment of microbes to the luminal surface of the mucosal epithelial lining, IgA antibodies form the first line of immune defense. In addition to this traditional mode of extracellular antibody function, recent evidence suggests that IgA antibodies can also function in a nontraditional fashion by neutralizing viruses intracellularly, if a virus is infecting an epithelial cell through which specific IgA antibody is passing on its way to the secretions. IgA antibodies are also envisaged as providing an internal mucosal barrier beneath the mucosal lining. Antigens intercepted by IgA antibodies here can potentially be ferried through the epithelium and thereby excreted. In addition to the polymeric immunoglobulin receptor on mucosal epithelial cells, IgA antibodies can bind to receptors on a variety of leukocytes and have been shown, in some experimental systems, to be capable of activating the alternative complement pathway, making IgA antibodies potential participants in inflammatory reactions. Although the relationship of IgA antibodies to inflammation is not entirely clear, the bias presented is that IgA is basically noninflammatory, perhaps even anti-inflammatory. According to this view, the major role of the Fc portion of IgA antibodies is to transport IgA across mucosal epithelial cells and not, as in the case of the other classes of antibody, to activate secondary phenomena of the kind that contribute to inflammation. Because of IgA's key role as an initial barrier to infection, much current research in mucosal immunology is directed toward developing new vectors and adjuvants that can provide improved approaches to mucosal vaccines. Finally, because of advances in monoclonal antibody technology, topical application of antibodies to mucosal surfaces has significant potential for preventing and treating infections.
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TRANSCRIPTIONAL CONTROL OF THE PSEUDOMONAS TOL PLASMID CATABOLIC OPERONS IS ACHIEVED THROUGH AN INTERPLAY OF HOST FACTORS AND PLASMID-ENCODED REGULATORS
Vol. 51 (1997), pp. 341–373More Less▪ AbstractThe xyl genes of Pseudomonas putida TOL plasmid that specify catabolism of toluene and xylenes are organized in four transcriptional units: the upper-operon xylUWCAMBN for conversion of toluene/xylenes into benzoate/alkylbenzoates; the meta-operon xylXYZLTEGFJQKIH, which encodes the enzymes for further conversion of these compounds into Krebs cycle intermediates; and xylS and xylR, which are involved in transcriptional control. The XylS and XylR proteins are members of the XylS/AraC and NtrC families, respectively, of transcriptional regulators. The xylS gene is constitutively expressed at a low level from the Ps2 promoter. The XylS protein is activated by interaction with alkylbenzoates, and this active form stimulates transcription from Pm by σ70- or σS-containing RNA polymerase (the meta loop). The xylR gene is also expressed constitutively. The XylR protein, which in the absence of effectors binds in a nonactive form to target DNA sequences, is activated by aromatic hydrocarbons and ATP; it subsequently undergoes multimerization and structural changes that result in stimulation of transcription from Pu of the upper operon. This latter process is assisted by the IHF protein and mediated by σ54-containing RNA polymerase. Once activated, the XylR protein also stimulates transcription from the Ps1 promoter of xylS without interfering with expression from Ps2. This process is assisted by the HU protein and is mediated by σ54-containing RNA polymerase. As a consequence of hyperexpression of the xylS gene, the XylS protein is hyperproduced and stimulates transcription from Pm even in the absence of effectors (the cascade loop). The two σ54-dependent promoters are additionally subject to global (catabolite repression) control.
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SULFUR TUFT AND TURKEY TAIL: Biosynthesis and Biodegradation of Organohalogens by Basidiomycetes
Ed de Jong, and Jim A. FieldVol. 51 (1997), pp. 375–414More Less▪ AbstractChlorinated aliphatic and aromatic compounds are generally considered to be undesirable xenobiotic pollutants. However, the higher fungi, Basidiomycetes, have a widespread capacity for organohalogen biosynthesis. Adsorbable organic halogens (AOX) and/or low-molecular-weight halogenated compounds are produced by Basidiomycetes of 68 genera from 20 different families. Most of the 81 halogenated metabolites identified from Basidiomycetes to date are chlorinated, although brominated and iodated metabolites have also been described. Two broad categories of Basidiomycete organohalogen metabolites are the halogenated aromatic compounds and the haloaliphatic compounds. Some of these organohalogen metabolites have demonstrable physiological roles as antibiotics and as metabolites involved in lignin degradation. Basidiomycetes produce large amounts of low-molecular-weight organohalogens or adsorbable organic halogens (AOX) when grown on lignocellulosic substrates. In our view, Basidiomycetes, as decomposers of forest litter, are a major source of natural organohalogens in terrestrial environments.
Basidiomycetes are also potent degraders of a wide range of chlorinated pollutants, such as bleachery effluent from kraft mills and pentachlorophenol, polychlorinated dioxins, and polychlorinated biphenyls. The extracellular, lignin-degrading enzymes of the Basidiomycetes are involved in the oxidative degradation of chlorophenols and dioxin and can cause reductive dechlorination of halomethanes.
There is no clear-cut separation between “polluters” and “clean-uppers” within the Basidiomycetes. Several genera, e.g. Bjerkandera, Hericium, Phlebia, and Trametes, produce significant amounts of chlorinated compounds but are also highly effective in metabolizing or biotransforming chlorinated pollutants.
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SAFE HAVEN: The Cell Biology of Nonfusogenic Pathogen Vacuoles
Vol. 51 (1997), pp. 415–462More Less▪ AbstractOur understanding of both membrane traffic in mammalian cells and the cell biology of infection with intracellular pathogens has increased dramatically in recent years. In this review, we discuss the cell biology of the host-microbe interaction for four intracellular pathogens: Chlamydia spp., Legionella pneumophila, Mycobacterium spp., and the protozoan parasite Toxoplasma gondii. All of these organisms reside in vacuoles inside cells that have restricted fusion with host organelles of the endocytic cascade. Despite this restricted fusion, the vacuoles surrounding each pathogen display novel interactions with other host cell organelles. In addition to the effect of infection on host membrane traffic, we focus on these novel interactions and relate them where possible to nutrient acquisition by the intracellular organisms.
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TRANSCRIPTION OF PROTEIN- CODING GENES IN TRYPANOSOMES BY RNA POLYMERASE I
Vol. 51 (1997), pp. 463–489More Less▪ AbstractIn eukaryotes, RNA polymerase (pol) II transcribes the protein-coding genes, whereas RNA pol I transcribes the genes that encode the three RNA species of the ribosome [the ribosomal RNAs (rRNAs)] at the nucleolus. Protozoan parasites of the order Kinetoplastida may represent an exception, because pol I can mediate the expression of exogenously introduced protein-coding genes in these single-cell organisms. A unique molecular mechanism, which leads to pre-mRNA maturation by trans-splicing, facilitates pol I–mediated protein-coding gene expression in trypanosomes. Trans-splicing adds a capped 39-nucleotide mini-exon, or spliced leader transcript, to the 5′ end of the main coding exon posttranscriptionally. In other eukaryotes, the addition of a 5′ cap, which is essential for mRNA function, occurs exclusively as a result of RNA pol II–mediated transcription. Given the assumption that cap addition represents the limiting factor, trans-splicing may have uncoupled the requirement for RNA pol II–mediated mRNA production. A comparison of the α-amanitin sensitivity of transcription in naturally occurring trypanosome protein-coding genes reveals that a unique subset of protein-coding genes—the variant surface glycoprotein (VSG) expression sites and the procyclin or the procyclic acidic repetitive protein (PARP) genes—are transcribed by an RNA polymerase that is resistant to the mushroom toxin α-amanitin, a characteristic of transcription by RNA pol I. Promoter analysis and a pharmacological characterization of the RNA polymerase that transcribes these genes have strengthened the proposal that the VSG expression sites and the PARP genes represent naturally occurring protein-coding genes that are transcribed by RNA pol I.
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SYNTHESIS OF ENANTIOPURE EPOXIDES THROUGH BIOCATALYTIC APPROACHES
A. Archelas, and R. FurstossVol. 51 (1997), pp. 491–525More Less▪ AbstractEnantiopure epoxides, as well as their corresponding vicinal diols, are valuable intermediates in fine organic synthesis, in particular for the preparation of biologically active compounds. The necessity of preparing such target molecules in an optically pure form has triggered much research, leading to the emergence of various new methods based on either conventional chemistry or enzymatically catalyzed reactions. In this review, we focus on the biocatalytic approaches, which include direct epoxidation of olefinic double bonds as well as indirect biocatalytic methods, and which allow for the synthesis of these important chiral building blocks in enantiomerically enriched or even enantiopure form.
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CELL-CELL COMMUNICATION IN GRAM-POSITIVE BACTERIA
Vol. 51 (1997), pp. 527–564More Less▪ AbstractIn gram-positive bacteria, many important processes are controlled by cell-to-cell communication, which is mediated by extracellular signal molecules produced by the bacteria. Most of these signaling molecules are peptides or modified peptides. Signal processing, in most cases, involves either transduction across the cytoplasmic membrane or import of the signal and subsequent interaction with intracellular effectors. Concentrations of signal in the nanomolar range or below are frequently sufficient for biological activity. The microbial processes controlled by extracellular signaling include the expression of virulence factors, the expression of gene transfer functions, and the production of antibiotics.
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REGULATORS OF APOPTOSIS ON THE ROAD TO PERSISTENT ALPHAVIRUS INFECTION
Vol. 51 (1997), pp. 565–592More Less▪ AbstractAlphavirus infection can trigger the host cell to activate its genetically programmed cell death pathway, leading to the morphological features of apoptosis. The ability to activate this death pathway is dependent on both viral and cellular determinants. The more virulent strains of alphavirus induce apoptosis with increased efficiency both in animal models and in some cultured cells. Although the immune system clearly plays a central role in clearing virus, the importance of other cellular factors in determining the outcome of virus infections are evident from the observation that mature neurons are better able to resist alphavirus-induced apoptosis than immature neurons are, both in culture and in mouse brains. These findings are consistent with the age-dependent susceptibility to disease seen in animals. Cellular genes that are known to regulate the cell death pathway can modulate the outcome of alphavirus infection in cultured cells and perhaps in animals. The cellular bax and bak genes, which are known to accelerate cell death, also accelerate virus-induced apoptosis. In contrast, inhibitors of apoptotic cell death such as bcl-2 suppress virus-induced apoptosis, which can facilitate a persistent virus infection. Thus, the balance of cellular factors that regulate cell death may be critical in virus infections. Additional viral factors also contribute to this balance. The more virulent strains of alphavirus have acquired the ability to induce apoptosis in mature neurons, while mature neurons are resistant to cell death upon infection with less virulent strains. Here we discuss a variety of cellular and viral factors that modulate the outcome of virus infection.
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Previous Volumes
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Volume 77 (2023)
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Volume 76 (2022)
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Volume 75 (2021)
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Volume 74 (2020)
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Volume 73 (2019)
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Volume 72 (2018)
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Volume 71 (2017)
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Volume 70 (2016)
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Volume 69 (2015)
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Volume 68 (2014)
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Volume 67 (2013)
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Volume 66 (2012)
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Volume 65 (2011)
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Volume 64 (2010)
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Volume 63 (2009)
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Volume 62 (2008)
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Volume 61 (2007)
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Volume 60 (2006)
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Volume 59 (2005)
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Volume 58 (2004)
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Volume 57 (2003)
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Volume 56 (2002)
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Volume 55 (2001)
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Volume 54 (2000)
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Volume 53 (1999)
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Volume 52 (1998)
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Volume 51 (1997)
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Volume 50 (1996)
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Volume 49 (1995)
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Volume 48 (1994)
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Volume 47 (1993)
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Volume 46 (1992)
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Volume 45 (1991)
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Volume 44 (1990)
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Volume 43 (1989)
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Volume 42 (1988)
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Volume 41 (1987)
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Volume 40 (1986)
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Volume 39 (1985)
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Volume 38 (1984)
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Volume 37 (1983)
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Volume 36 (1982)
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Volume 35 (1981)
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Volume 34 (1980)
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Volume 33 (1979)
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Volume 32 (1978)
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Volume 31 (1977)
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Volume 30 (1976)
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Volume 29 (1975)
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Volume 28 (1974)
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Volume 27 (1973)
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Volume 26 (1972)
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Volume 25 (1971)
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Volume 24 (1970)
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Volume 23 (1969)
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Volume 22 (1968)
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Volume 21 (1967)
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Volume 20 (1966)
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Volume 19 (1965)
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Volume 18 (1964)
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Volume 17 (1963)
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Volume 16 (1962)
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Volume 15 (1961)
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Volume 14 (1960)
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Volume 13 (1959)
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Volume 12 (1958)
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Volume 11 (1957)
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Volume 10 (1956)
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Volume 9 (1955)
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Volume 8 (1954)
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Volume 7 (1953)
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Volume 6 (1952)
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Volume 5 (1951)
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Volume 4 (1950)
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Volume 3 (1949)
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Volume 2 (1948)
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Volume 1 (1947)
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Volume 0 (1932)