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  • Articles  (217,380)
  • Elsevier  (122,051)
  • Cell Press  (32,160)
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  • Biology  (217,380)
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  • 101
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    Electronic Resource
    HOMOLOGOUS RECOMBINATION NEAR AND FAR FROM DNA BREAKS: Alternative Roles and Contrasting Views (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 35 (2001), S. 243-274 
    Details
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Double-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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.genet.35.102401.090509
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  • 102
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    MECHANISMS OF RETROVIRAL RECOMBINATION (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 35 (2001), S. 275-302 
    Details
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Recombination 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.genet.35.102401.090551
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  • 103
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    NEW PERSPECTIVES ON NUCLEAR TRANSPORT (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 35 (2001), S. 341-364 
    Details
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract A 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.genet.35.102401.090720
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  • 104
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    THE GENETIC ARCHITECTURE OF QUANTITATIVE TRAITS (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 35 (2001), S. 303-339 
    Details
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Phenotypic 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.genet.35.102401.090633
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  • 105
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    TRANSLATIONAL REGULATION AND RNA LOCALIZATION IN DROSOPHILA OOCYTES AND EMBRYOS (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 35 (2001), S. 365-406 
    Details
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Translational 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.genet.35.102401.090756
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  • 106
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    MODELS AND DATA ON PLANT-ENEMY COEVOLUTION (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 35 (2001), S. 469-499 
    Details
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Although 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.genet.35.102401.090954
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  • 107
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    GENETIC ANALYSIS OF CALMODULIN AND ITS TARGETS IN SACCHAROMYCES CEREVISIAE (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 35 (2001), S. 647-672 
    Details
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Calmodulin, a small, ubiquitous Ca2+-binding protein, regulates a wide variety of proteins and processes in all eukaryotes. CMD1, the single gene encoding calmodulin in S. cerevisiae, is essential, and this review discusses studies that identified many of calmodulin's physiological targets and their functions in yeast cells. Calmodulin performs essential roles in mitosis, through its regulation of Nuf1p/Spc110p, a component of the spindle pole body, and in bud growth, by binding Myo2p, an unconventional class V myosin required for polarized secretion. Surprisingly, mutant calmodulins that fail to bind Ca2+ can perform these essential functions. Calmodulin is also required for endocytosis in yeast and participates in Ca2+-dependent, stress-activated signaling pathways through its regulation of a protein phosphatase, calcineurin, and the protein kinases, Cmk1p and Cmk2p. Thus, calmodulin performs important physiological functions in yeast cells in both its Ca2+-bound and Ca2+-free form.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.genet.35.102401.091302
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  • 108
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    IDENTIFICATION OF EPILEPSY GENES IN HUMAN AND MOUSE1 (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 35 (2001), S. 567-588 
    Details
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract The 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.genet.35.102401.091142
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  • 109
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    MOLECULAR GENETICS OF HEARING LOSS (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 35 (2001), S. 589-645 
    Details
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Hereditary isolated hearing loss is genetically highly heterogeneous. Over 100 genes are predicted to cause this disorder in humans. Sixty loci have been reported and 24 genes underlying 28 deafness forms have been identified. The present epistemic stage in the realm consists in a preliminary characterization of the encoded proteins and the associated defective biological processes. Since for several of the deafness forms we still only have fuzzy notions of their pathogenesis, we here adopt a presentation of the various deafness forms based on the site of the primary defect: hair cell defects, nonsensory cell defects, and tectorial membrane anomalies. The various deafness forms so far studied appear as monogenic disorders. They are all rare with the exception of one, caused by mutations in the gene encoding the gap junction protein connexin26, which accounts for between one third to one half of the cases of prelingual inherited deafness in Caucasian populations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.genet.35.102401.091224
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  • 110
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    DISSEMINATING THE GENOME: Joining, Resolving, and Separating Sister Chromatids During Mitosis and Meiosis (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 35 (2001), S. 673-745 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract The separation of sister chromatids at the metaphase to anaphase transition is one of the most dramatic of all cellular events and is a crucial aspect of all sexual and asexual reproduction. The molecular basis for this process has until recently remained obscure. New research has identified proteins that hold sisters together while they are aligned on the metaphase plate. It has also shed insight into the mechanisms that dissolve sister chromatid cohesion during both mitosis and meiosis. These findings promise to provide insights into defects in chromosome segregation that occur in cancer cells and into the pathological pathways by which aneuploidy arises during meiosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.genet.35.102401.091334
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  • 111
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    EPITHELIAL CELL POLARITY AND CELL JUNCTIONS IN DROSOPHILA (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 35 (2001), S. 747-784 
    Details
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract The polarized architecture of epithelial cells and tissues is a fundamental determinant of animal anatomy and physiology. Recent progress made in the genetic and molecular analysis of epithelial polarity and cellular junctions in Drosophila has led to the most detailed understanding of these processes in a whole animal model system to date. Asymmetry of the plasma membrane and the differentiation of membrane domains and cellular junctions are controlled by protein complexes that assemble around transmembrane proteins such as DE-cadherin, Crumbs, and Neurexin IV, or other cytoplasmic protein complexes that associate with the plasma membrane. Much remains to be learned of how these complexes assemble, establish their polarized distribution, and contribute to the asymmetric organization of epithelial cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.genet.35.102401.091415
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  • 112
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    INFORMED CONSENT AND OTHER ETHICAL ISSUES IN HUMAN POPULATION GENETICS (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 35 (2001), S. 785-800 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Human population genetics has entered a new era of public interest, of controversy, and of ethical problems. Population genetics raises novel ethical problems because both the individuals and the populations being studied are, in effect, "subjects" of the research. Those populations are collectively subject to possible benefits and harms from the research and have interests, somewhat different from those of the individuals, that must be considered from both ethical and practical standpoints. The chapter first describes the new setting for research in human population genetics. It then examines the most controversial ethical issue in population genetics-whether researchers must obtain the informed consent of both the individual subjects and the group as a collectivity. Other vexing issues, including special problems caused by researchers' commercial interests, confidentiality, control over research uses and materials, and return of information to the population are also considered.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.genet.35.102401.091453
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  • 113
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    G. LEDYARD STEBBINS AND THE EVOLUTIONARY SYNTHESIS (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 35 (2001), S. 803-814 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Figure 1 G. LEDYARD STEBBINS Reproduction from Original Negative by Ansel Adams, Courtesy UCR/California Museum of Photography, Sweeney/Rubin Ansel Adams FIAT LUX Collection, University of California at Riverside. Figure 1 G. LEDYARD STEBBINS Reproduction from Original Negative by Ansel Adams, Courtesy UCR/Californ... More than any other individual, Stebbins synthesized knowledge from a disparate set of areas that included plant genetics, systematics, and evolution. This work culminated in 1950 with the appearance of his magnum opus, Variation and Evolution in Plants. This book gave plant evolution a coherent framework that was compatible with that emerging from the work of Theodosius Dobzhansky, Ernst Mayr, G. G. Simpson, and Julian Huxley, and others associated with establishing the synthetic theory of evolution. For this work he is regarded as the botanical "architect" of the evolutionary synthesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.genet.35.102401.091525
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  • 114
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    THE SOS RESPONSE: Recent Insights into umuDC-Dependent Mutagenesis and DNA Damage Tolerance (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 34 (2000), S. 479-497 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Be they prokaryotic or eukaryotic, organisms are exposed to a multitude of deoxyribonucleic acid (DNA) damaging agents ranging from ultraviolet (UV) light to fungal metabolites, like Aflatoxin B1. Furthermore, DNA damaging agents, such as reactive oxygen species, can be produced by cells themselves as metabolic byproducts and intermediates. Together, these agents pose a constant threat to an organism's genome. As a result, organisms have evolved a number of vitally important mechanisms to repair DNA damage in a high fidelity manner. They have also evolved systems (cell cycle checkpoints) that delay the resumption of the cell cycle after DNA damage to allow more time for these accurate processes to occur. If a cell cannot repair DNA damage accurately, a mutagenic event may occur. Most bacteria, including Escherichia coli, have evolved a coordinated response to these challenges to the integrity of their genomes. In E. coli, this inducible system is termed the SOS response, and it controls both accurate and potentially mutagenic DNA repair functions [reviewed comprehensively in (25) and also in (78, 94)]. Recent advances have focused attention on the umuD+C+-dependent, translesion DNA synthesis (TLS) process that is responsible for SOS mutagenesis (70, 86). Here we discuss the SOS response of E. coli and concentrate in particular on the roles of the umuD+C+ gene products in promoting cell survival after DNA damage via TLS and a primitive DNA damage checkpoint.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.genet.34.1.479
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  • 115
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    Population Genetics and Evolution of Genomic Imprinting (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 34 (2000), S. 457-477 
    Details
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract At a small number of mammalian loci, only one of the two copies of a gene is expressed. Just which copy is expressed depends on the sex of the parent from which that copy was inherited. Such genes are said to be imprinted. The functional haploidy implied by imprinting has a number of population genetic consequences. Moreover, since diploidy is widely believed to be advantageous, the evolution of this non-Mendelian form of expression requires an explanation. Here I examine some of the theoretical and mathematical models investigating these two aspects of imprinting. For instance, the dynamics and equilibrium properties of many models of natural selection at imprinted loci are formally equivalent to models without imprinting. And different approaches to modeling the problem of the evolution of imprinting reveal the weakness of several of the apparent predictions of various verbal hypotheses about why imprinting has evolved.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.genet.34.1.457
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  • 116
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    GENETIC MODELS OF OBESITY AND ENERGY BALANCE IN THE MOUSE (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 34 (2000), S. 687-745 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Obesity is a health problem of epidemic proportions in the industrialized world. The cloning and characterization of the genes for the five naturally occurring monogenic obesity syndromes in the mouse have led to major breakthroughs in understanding the physiology of energy balance and the contribution of genetics to obesity in the human population. However, the regulation of energy balance is an extremely complex process, and it is quickly becoming clear that hundreds of genes are involved. In this article, we review the naturally occurring monogenic and polygenic obese mouse strains, as well as the large number of transgenic and knockout mouse models currently available for the study of obesity and energy balance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.genet.34.1.687
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  • 117
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    FUNCTIONS AND MECHANISMS OF RNA EDITING (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 34 (2000), S. 499-531 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract RNA editing can be broadly defined as any site-specific alteration in an RNA sequence that could have been copied from the template, excluding changes due to processes such as RNA splicing and polyadenylation. Changes in gene expression attributed to editing have been described in organisms from unicellular protozoa to man, and can affect the mRNAs, tRNAs, and rRNAs present in all cellular compartments. These sequence revisions, which include both the insertion and deletion of nucleotides, and the conversion of one base to another, involve a wide range of largely unrelated mechanisms. Recent advances in the development of in vitro editing and transgenic systems for these varied modifications have provided a better understanding of similarities and differences between the biochemical strategies, regulatory sequences, and cellular factors responsible for such RNA processing events.
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    URL: http://dx.doi.org/10.1146/annurev.genet.34.1.499
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  • 118
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    CONSERVATION AND DIVERGENCE IN MOLECULAR MECHANISMS OF AXIS FORMATION (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 35 (2001), S. 407-437 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Genetic 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.genet.35.102401.090832
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  • 119
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    REGULATION OF GENE EXPRESSION BY CELL-TO-CELL COMMUNICATION: Acyl-Homoserine Lactone Quorum Sensing (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 35 (2001), S. 439-468 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Quorum 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.genet.35.102401.090913
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  • 120
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    BIOLOGY OF MAMMALIAN L1 RETROTRANSPOSONS (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 35 (2001), S. 501-538 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract L1 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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    URL: http://dx.doi.org/10.1146/annurev.genet.35.102401.091032
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  • 121
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    DOES NONNEUTRAL EVOLUTION SHAPE OBSERVED PATTERNS OF DNA VARIATION IN ANIMAL MITOCHONDRIAL GENOMES? (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 35 (2001), S. 539-566 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Early 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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    URL: http://dx.doi.org/10.1146/annurev.genet.35.102401.091106
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  • 122
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    GENETICS OF CRYPTOCOCCUS NEOFORMANS (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 36 (2002), S. 557-615 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Cryptococcus neoformans is a pathogenic fungus that primarily afflicts immunocompromised patients, infecting the central nervous system to cause meningoencephalitis that is uniformly fatal if untreated. C. neoformans is a basidiomycetous fungus with a defined sexual cycle that has been linked to differentiation and virulence. Recent advances in classical and molecular genetic approaches have allowed molecular descriptions of the pathways that control cell type and virulence. An ongoing genome sequencing project promises to reveal much about the evolution of this human fungal pathogen into three distinct varieties or species. C. neoformans shares features with both model ascomycetous yeasts (Saccharomyces cerevisiae, Schizosaccharomyces pombe) and basidiomycetous pathogens and mushrooms (Ustilago maydis, Coprinus cinereus, Schizophyllum commune), yet ongoing studies reveal unique features associated with virulence and the arrangement of the mating type locus. These advances have catapulted C. neoformans to center stage as a model of both fungal pathogenesis and the interesting approaches to life that the kingdom of fungi has adopted.
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    URL: http://dx.doi.org/10.1146/annurev.genet.36.052402.152652
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    CLOSING MITOSIS: The Functions of the Cdc14 Phosphatase and Its Regulation (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 38 (2004), S. 203-232 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Completion of the cell cycle requires the temporal and spatial coordination of chromosome segregation with mitotic spindle disassembly and cytokinesis. In budding yeast, the protein phosphatase Cdc14 is a key regulator of these late mitotic events. Here, we review the functions of Cdc14 and how this phosphatase is regulated to accomplish the coupling of mitotic processes. We also discuss the function and regulation of Cdc14 in other eukaryotes, emphasizing conserved features.
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    URL: http://dx.doi.org/10.1146/annurev.genet.38.072902.093051
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    COMPARATIVE GENOMIC STRUCTURE OF PROKARYOTES (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 38 (2004), S. 771-791 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Recent advances in DNA-sequencing technologies have made available an enormous resource of data for the study of bacterial genomes. The broad sample of complete genomes currently available allows us to look at variation in the gross features and characteristics of genomes while the detail of the sequences reveal some of the mechanisms by which these genomes evolve. This review aims to describe bacterial genome structures according to current knowledge and proposed hypotheses. We also describe examples where mechanisms of genome evolution have acted in the adaptation of bacterial species to particular niches.
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    URL: http://dx.doi.org/10.1146/annurev.genet.38.072902.094318
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    rRNA TRANSCRIPTION IN ESCHERICHIA COLI (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 38 (2004), S. 749-770 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Ribosomal RNA transcription is the rate-limiting step in ribosome synthesis in bacteria and has been investigated intensely for over half a century. Multiple mechanisms ensure that rRNA synthesis rates are appropriate for the cell's particular growth condition. Recently, important advances have been made in our understanding of rRNA transcription initiation in Escherichia coli. These include (a) a model at the atomic level of the network of protein-DNA and protein-protein interactions that recruit RNA polymerase to rRNA promoters, accounting for their extraordinary strength; (b) discovery of the nonredundant roles of two small molecule effectors, ppGpp and the initiating NTP, in regulation of rRNA transcription initiation; and (c) identification of a new component of the transcription machinery, DksA, that is absolutely required for regulation of rRNA promoter activity. Together, these advances provide clues important for our molecular understanding not only of rRNA transcription, but also of transcription in general.
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    TRANSVECTION EFFECTS IN DROSOPHILA (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 36 (2002), S. 521-556 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract An unusual feature of the Diptera is that homologous chromosomes are intimately synapsed in somatic cells. At a number of loci in Drosophila, this pairing can significantly influence gene expression. Such influences were first detected within the bithorax complex (BX-C) by E.B. Lewis, who coined the term transvection to describe them. Most cases of transvection involve the action of enhancers in trans. At several loci deletion of the promoter greatly increases this action in trans, suggesting that enhancers are normally tethered in cis by the promoter region. Transvection can also occur by the action of silencers in trans or by the spreading of position effect variegation from rearrangements having heterochromatic breakpoints to paired unrearranged chromosomes. Although not demonstrated, other cases of transvection may involve the production of joint RNAs by trans-splicing. Several cases of transvection require Zeste, a DNA-binding protein that is thought to facilitate homolog interactions by self-aggregation. Genes showing transvection can differ greatly in their response to pairing disruption. In several cases, transvection appears to require intimate synapsis of homologs. However, in at least one case (transvection of the iab-5,6,7 region of the BX-C), transvection is independent of synapsis within and surrounding the interacting gene. The latter example suggests that transvection could well occur in organisms that lack somatic pairing. In support of this, transvection-like phenomena have been described in a number of different organisms, including plants, fungi, and mammals.
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    URL: http://dx.doi.org/10.1146/annurev.genet.36.060402.100441
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    TOWARD MAINTAINING THE GENOME: DNA Damage and Replication Checkpoints (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 36 (2002), S. 617-656 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract DNA checkpoints play a significant role in cancer pathology, perhaps most notably in maintaining genome stability. This review summarizes the genetic and molecular mechanisms of checkpoint activation in response to DNA damage. The major checkpoint proteins common to all eukaryotes are identified and discussed, together with how the checkpoint proteins interact to induce arrest within each cell cycle phase. Also discussed are the molecular signals that activate checkpoint responses, including single-strand DNA, double-strand breaks, and aberrant replication forks. We address the connection between checkpoint proteins and damage repair mechanisms, how cells recover from an arrest response, and additional roles that checkpoint proteins play in DNA metabolism. Finally, the connection between checkpoint gene mutation and genomic instability is considered.
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    MECHANISMS OF PATTERN FORMATION IN PLANT EMBRYOGENESIS (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 38 (2004), S. 587-614 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Many of the patterning mechanisms in plants were discovered while studying postembryonic processes and resemble mechanisms operating during animal development. The emergent role of the plant hormone auxin, however, seems to represent a plant-specific solution to multicellular patterning. This review summarizes our knowledge on how diverse mechanisms that were first dissected at the postembryonic level are now beginning to provide an understanding of plant embryogenesis.
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    URL: http://dx.doi.org/10.1146/annurev.genet.38.072902.092231
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    GENETIC APPROACHES TO MOLECULAR AND CELLULAR COGNITION: A Focus on LTP and Learning and Memory (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 36 (2002), S. 687-720 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Long-term potentiation (LTP) is the predominant experimental model for the synaptic plasticity mechanisms thought to underlie learning and memory. This review is focused on the contributions of genetics to the understanding of the role of LTP in learning and memory. These studies have used a combination of genetics, molecular biology, neurophysiology, and psychology to demonstrate that molecular mechanisms of synaptic plasticity are critical for learning and memory. Because of the large scope of this literature, we focus primarily on genetic studies of hippocampal-dependent learning. Altogether, these findings not only demonstrate a role for plasticity in learning, they also lay down the foundations for the new field of molecular and cellular cognition.
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    URL: http://dx.doi.org/10.1146/annurev.genet.36.062802.091007
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    THE FELINE GENOME PROJECT1 (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 36 (2002), S. 657-686 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract The compilation of a dense gene map and eventually a whole genome sequence (WGS) of the domestic cat holds considerable value for human genome annotation, for veterinary medicine, and for insight into the evolution of genome organization among mammals. Human association and veterinary studies of the cat, its domestic breeds, and its charismatic wild relatives of the family Felidae have rendered the species a powerful model for human hereditary diseases, for infectious disease agents, for adaptive evolutionary divergence, for conservation genetics, and for forensic applications. Here we review the advantages, rationale, and present strategy of a feline genome project, and we describe the disease models, comparative genomics, and biological applications posed by the full resolution of the cat's genome.
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    URL: http://dx.doi.org/10.1146/annurev.genet.36.060602.145553
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    ESTIMATING F-STATISTICS (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 36 (2002), S. 721-750 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract A moment estimator of theta, the coancestry coefficient for alleles within a population, was described by Weir & Cockerham in 1984 (100) and is still widely cited. The estimate is used by population geneticists to characterize population structure, by ecologists to estimate migration rates, by animal breeders to describe genetic variation, and by forensic scientists to quantify the strength of matching DNA profiles. This review extends the work of Weir & Cockerham by allowing different levels of coancestry for different populations, and by allowing non-zero coancestries between pairs of populations. All estimates are relative to the average value of theta between pairs of populations. Moment estimates for within- and between-population theta values are likely to have large sampling variances, although these may be reduced by combining information over loci. Variances also decrease with the numbers of alleles at a locus, and with the numbers of populations sampled. This review also extends the work of Weir & Cockerham by employing maximum likelihood methods under the assumption that allele frequencies follow the normal distribution over populations. For the case of equal theta values within populations and zero theta values between populations, the maximum likelihood estimate is the same as that given by Robertson & Hill in 1984 (70). The review concludes by relating functions of theta values to times of population divergence under a pure drift model.
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    GENOMIC IMPRINTING AND KINSHIP: How Good is the Evidence? (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 38 (2004), S. 553-585 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: The kinship theory of genomic imprinting proposes that parent-specific gene expression evolves at a locus because a gene's level of expression in one individual has fitness effects on other individuals who have different probabilities of carrying the maternal and paternal alleles of the individual in which the gene is expressed. Therefore, natural selection favors different levels of expression depending on an allele's sex-of-origin in the previous generation. This review considers the strength of evidence in support of this hypothesis for imprinted genes in four "clusters," associated with the imprinted loci Igf2, Igf2r, callipyge, and Gnas. The clusters associated with Igf2 and Igf2r both contain paternally expressed transcripts that act as enhancers of prenatal growth and maternally expressed transcripts that act as inhibitors of prenatal growth. This is consistent with predictions of the kinship theory. However, the clusters also contain imprinted genes whose phenotypes as yet remain unexplained by the theory. The principal effects of imprinted genes in the callipyge and Gnas clusters appear to involve lipid and energy metabolism. The kinship theory predicts that maternally expressed transcripts will favor higher levels of nonshivering thermogenesis (NST) in brown adipose tissue (BAT) of animals that huddle for warmth as offspring. The phenotypes of reciprocal heterozygotes for Gnas knockouts provide provisional support for this hypothesis, as does some evidence from other imprinted genes (albeit more tentatively). The diverse effects of imprinted genes on the development of white adipose tissue (WAT) have so far defied a unifying hypothesis in terms of the kinship theory.
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    SPECIES SPECIFICITY IN POLLEN-PISTIL INTERACTIONS (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 38 (2004), S. 793-818 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: For pollination to succeed, pollen must carry sperm through a variety of different floral tissues to access the ovules within the pistil. The pistil provides everything the pollen requires for success in this endeavor including distinct guidance cues and essential nutrients that allow the pollen tube to traverse enormous distances along a complex path to the unfertilized ovule. Although the pistil is a great facilitator of pollen function, it can also be viewed as an elaborate barrier that shields ovules from access from inappropriate pollen, such as pollen from other species. Each discrete step taken by pollen tubes en route to the ovules is a potential barrier point to ovule access and waste by inappropriate mates. In this review, we survey the current molecular understanding of how pollination proceeds, and ask to what extent is each step important for mate discrimination. As this field progresses, this synthesis of functional biology and evolutionary studies will provide insight into the molecular basis of the species barriers that maintain the enormous diversity seen in flowering plants.
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    URL: http://dx.doi.org/10.1146/annurev.genet.38.072902.092356
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    INTEGRATION OF ADENO-ASSOCIATED VIRUS (AAV) AND RECOMBINANT AAV VECTORS (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 38 (2004), S. 819-845 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: The driving interest in adeno-associated virus (AAV) has been its potential as a gene delivery vector. The early observation that AAV can establish a latent infection by integrating into the host chromosome has been central to this interest. However, chromosomal integration is a two-edged sword, imparting on one hand the ability to maintain the therapeutic gene in progeny cells, and on the other hand, the risk of mutations that are deleterious to the host. A clearer understanding of the mechanism and efficiency of AAV integration, in terms of contributing viral and host-cell factors and circumstances, will provide a context in which to evaluate these potential benefits and risks. Research to date suggests that AAV integration in any context is inefficient, and that the persistence of AAV gene delivery vectors in tissues is largely attributable to episomal genomes.
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    LIGHT SIGNAL TRANSDUCTION IN HIGHER PLANTS (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 38 (2004), S. 87-117 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Plants utilize several families of photoreceptors to fine-tune growth and development over a large range of environmental conditions. The UV-A/blue light sensing phototropins mediate several light responses enabling optimization of photosynthetic yields. The initial event occurring upon photon capture is a conformational change of the photoreceptor that activates its protein kinase activity. The UV-A/blue light sensing cryptochromes and the red/far-red sensing phytochromes coordinately control seedling establishment, entrainment of the circadian clock, and the transition from vegetative to reproductive growth. In addition, the phytochromes control seed germination and shade-avoidance responses. The molecular mechanisms involved include light-regulated subcellular localization of the photoreceptors, a large reorganization of the transcriptional program, and light-regulated proteolytic degradation of several photoreceptors and signaling components.
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    URL: http://dx.doi.org/10.1146/annurev.genet.38.072902.092259
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    ELECTROKINETICALLY CONTROLLED MICROFLUIDIC ANALYSIS SYSTEMS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 155-181 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Electrokinetic forces are emerging as a powerful means to drive microfluidic systems with flow channel cross-sectional dimensions in the tens of micrometers and flow rates in the nanoliter per second range. These systems provide many advantages such as improved analysis speed, improved reproducibility, greatly reduced reagent consumption, and the ability to perform multiple operations in an integrated fashion. Planar microfabrication methods are used to make these analysis chips in materials such as glass or polymers. Many applications of this technology have been demonstrated, such as DNA separations, enzyme assays, immunoassays, and PCR amplification integrated with microfluidic assays. Further development of this technology is expected to yield higher levels of functionality of sample throughput on a single microfluidic analysis chip.
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    STRUCTURAL SYMMETRY AND PROTEIN FUNCTION (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 105-153 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract The majority of soluble and membrane-bound proteins in modern cells are symmetrical oligomeric complexes with two or more subunits. The evolutionary selection of symmetrical oligomeric complexes is driven by functional, genetic, and physicochemical needs. Large proteins are selected for specific morphological functions, such as formation of rings, containers, and filaments, and for cooperative functions, such as allosteric regulation and multivalent binding. Large proteins are also more stable against denaturation and have a reduced surface area exposed to solvent when compared with many individual, smaller proteins. Large proteins are constructed as oligomers for reasons of error control in synthesis, coding efficiency, and regulation of assembly. Symmetrical oligomers are favored because of stability and finite control of assembly. Several functions limit symmetry, such as interaction with DNA or membranes, and directional motion. Symmetry is broken or modified in many forms: quasisymmetry, in which identical subunits adopt similar but different conformations; pleomorphism, in which identical subunits form different complexes; pseudosymmetry, in which different molecules form approximately symmetrical complexes; and symmetry mismatch, in which oligomers of different symmetries interact along their respective symmetry axes. Asymmetry is also observed at several levels. Nearly all complexes show local asymmetry at the level of side chain conformation. Several complexes have reciprocating mechanisms in which the complex is asymmetric, but, over time, all subunits cycle through the same set of conformations. Global asymmetry is only rarely observed. Evolution of oligomeric complexes may favor the formation of dimers over complexes with higher cyclic symmetry, through a mechanism of prepositioned pairs of interacting residues. However, examples have been found for all of the crystallographic point groups, demonstrating that functional need can drive the evolution of any symmetry.
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    QUANTITATIVE CHEMICAL ANALYSIS OF SINGLE CELLS1 (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 239-263 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract A fundamental perspective can be achieved by targeting single cells for analysis with the goal of deconvoluting complex biological functions. However, single-cell studies have their own difficulties, such as minute volumes and sample amounts. Quantitative chemical analysis of single cells has emerged as a powerful new area in recent years due to several technological advancements. The development of microelectrodes has allowed the measurement of redox-active species as a function of cellular dynamics. This miniaturization trend is also evident in the separation sciences with the application of small column separations to single cells. Desorption ionization methods with mass spectrometric detection have shown single-cell capability owing to numerous technological developments. Finally, fluorescence imaging has also progressed to the point where single-cell dynamics can be probed by native fluorescence utilizing either single or multiple photon excitation. The results of these studies are reviewed with an emphasis on the quantitation of single-cell dynamics.
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    THE STRUCTURAL BIOLOGY OF MOLECULAR RECOGNITION BY VANCOMYCIN (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 265-289 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Vancomycin is the archetype among naturally occurring compounds known as glycopeptide antibiotics. Because it is a vital therapeutic agent used worldwide for the treatment of infections with gram-positive bacteria, emerging bacterial resistance to vancomycin is a major public health threat. Recent investigations into the mechanisms of action of glycopeptide antibiotics are driven by a need to understand their detailed mechanism of action so that new agents can be developed to overcome resistance. These investigations have revealed that glycopeptide antibiotics exhibit a rich array of complex cooperative phenomena when they bind target ligands, making them valuable model systems for the study of molecular recognition.
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    COMPARATIVE PROTEIN STRUCTURE MODELING OF GENES AND GENOMES (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 291-325 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Comparative modeling predicts the three-dimensional structure of a given protein sequence (target) based primarily on its alignment to one or more proteins of known structure (templates). The prediction process consists of fold assignment, target-template alignment, model building, and model evaluation. The number of protein sequences that can be modeled and the accuracy of the predictions are increasing steadily because of the growth in the number of known protein structures and because of the improvements in the modeling software. Further advances are necessary in recognizing weak sequence-structure similarities, aligning sequences with structures, modeling of rigid body shifts, distortions, loops and side chains, as well as detecting errors in a model. Despite these problems, it is currently possible to model with useful accuracy significant parts of approximately one third of all known protein sequences. The use of individual comparative models in biology is already rewarding and increasingly widespread. A major new challenge for comparative modeling is the integration of it with the torrents of data from genome sequencing projects as well as from functional and structural genomics. In particular, there is a need to develop an automated, rapid, robust, sensitive, and accurate comparative modeling pipeline applicable to whole genomes. Such large-scale modeling is likely to encourage new kinds of applications for the many resulting models, based on their large number and completeness at the level of the family, organism, or functional network.
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    URL: http://dx.doi.org/10.1146/annurev.biophys.29.1.291
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    PROTEIN FOLDING INTERMEDIATES AND PATHWAYS STUDIED BY HYDROGEN EXCHANGE (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 213-238 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract In order to solve the immensely difficult protein-folding problem, it will be necessary to characterize the barriers that slow folding and the intermediate structures that promote it. Although protein-folding intermediates are not accessible to the usual structural studies, hydrogen exchange (HX) methods have been able to detect and characterize intermediates in both kinetic and equilibrium modes-as transient kinetic folding intermediates on a subsecond time scale, as labile equilibrium molten globule intermediates under destabilizing conditions, and as infinitesimally populated intermediates in the high free-energy folding landscape under native conditions. Available results consistently indicate that protein-folding landscapes are dominated by a small number of discrete, metastable, native-like partially unfolded forms (PUFs). The PUFs appear to be produced, one from another, by the unfolding and refolding of the protein's intrinsically cooperative secondary structural elements, which can spontaneously create stepwise unfolding and refolding pathways. Kinetic experiments identify three kinds of barrier processes: (a) an initial intrinsic search-nucleation-collapse process that prepares the chain for intermediate formation by pinning it into a condensed coarsely native-like topology; (b) smaller search-dependent barriers that put the secondary structural units into place; and (c) optional error-dependent misfold-reorganization barriers that can cause slow folding, intermediate accumulation, and folding heterogeneity. These conclusions provide a coherent explanation for the grossly disparate folding behavior of different globular proteins in terms of distinct folding pathways.
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    A STRUCTURAL VIEW OF Cre-loxP SITE-SPECIFIC RECOMBINATION (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 87-104 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Structural models of site-specific recombinases from the lambda integrase family of enzymes have in the last four years provided an important new perspective on the three-dimensional nature of the recombination pathway. Members of this family, which include the bacteriophage P1 Cre recombinase, bacteriophage lambda integrase, the yeast Flp recombinase, and the bacterial XerCD recombinases, exchange strands between DNA substrates in a stepwise process. One pair of strands is exchanged to form a Holliday junction intermediate, and the second pair of strands is exchanged during resolution of the junction to products. Crystal structures of reaction intermediates in the Cre-loxP site-specific recombination system, together with recent biochemical studies in the field, support a "strand swapping" model for recombination that does not require branch migration of the Holliday junction intermediate in order to test homology between recombining sites.
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    PROBING THE RELATION BETWEEN FORCE-LIFETIME-AND CHEMISTRY IN SINGLE MOLECULAR BONDS (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 105-128 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract On laboratory time scales, the energy landscape of a weak bond along a dissociation pathway is fully explored through Brownian-thermal excitations, and energy barriers become encoded in a dissociation time that varies with applied force. Probed with ramps of force over an enormous range of rates (force/time), this kinetic profile is transformed into a dynamic spectrum of bond rupture force as a function of loading rate. On a logarithmic scale in loading rate, the force spectrum provides an easy-to-read map of the prominent energy barriers traversed along the force-driven pathway and exposes the differences in energy between barriers. In this way, the method of dynamic force spectroscopy (DFS) is being used to probe the complex relation between force-lifetime-and chemistry in single molecular bonds. Most important, DFS probes the inner world of molecular interactions to reveal barriers that are difficult or impossible to detect in assays of near equilibrium dissociation but that determine bond lifetime and strength under rapid detachment. To use an ultrasensitive force probe as a spectroscopic tool, we need to understand the physics of bond dissociation under force, the impact of experimental technique on the measurement of detachment force (bond strength), the consequences of complex interactions in macromolecular bonds, and effects of multiply-bonded attachments.
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    PULSED AND PARALLEL-POLARIZATION EPR CHARACTERIZATION OF THE PHOTOSYSTEM II OXYGEN-EVOLVING COMPLEX (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 463-495 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Photosystem II uses visible light to drive the oxidation of water, resulting in bioactivated electrons and protons, with the production of molecular oxygen as a byproduct. This water-splitting reaction is carried out by a manganese cluster/tyrosine radical ensemble, the oxygen-evolving complex. Although conventional continuous-wave, perpendicular-polarization electron paramagnetic resonance (EPR) spectroscopy has significantly advanced our knowledge of the structure and function of the oxygen-evolving complex, significant additional information can be obtained with the application of additional EPR methodologies. Specifically, parallel-polarization EPR spectroscopy can be used to obtain highly resolved EPR spectra of integer spin Mn species, and pulsed EPR spectroscopy with electron spin echo-based sequences, such as electron spin echo envelope modulation and electron spin echo-electron nuclear double resonance, can be used to measure weak interactions obscured in continuous-wave spectroscopy by inhomogeneous broadening.
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    STRESS-INDUCED STRUCTURAL TRANSITIONS IN DNA AND PROTEINS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 523-543 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract The ability to manipulate, stretch and twist biomolecules opens the way to an understanding of their structural transitions. We review some of the recently discovered stress-induced structural transitions in DNA as well as the application of single molecule manipulation techniques to DNA unzipping and to the study of protein folding/unfolding transitions.
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    URL: http://dx.doi.org/10.1146/annurev.biophys.29.1.523
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    ELECTROSTATIC MECHANISMS OF DNA DEFORMATION (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 497-521 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract The genomes of higher cells consist of double-helical DNA, a densely charged polyelectrolyte of immense length. The intrinsic physical properties of DNA, as well as the properties of its complexes with proteins and ions, are therefore of fundamental interest in understanding the functions of DNA as an informational macromolecule. Because individual DNA molecules often exceed 1 cm in length, it is clear that DNA bending, folding, and interaction with nuclear proteins are necessary for packaging genomes in small volumes and for integrating the nucleotide sequence information that guides genetic readout. This review first focuses on recent experiments exploring how the shape of the densely charged DNA polymer and asymmetries in its surrounding counterion distribution mutually influence one another. Attention is then turned to experiments seeking to discover the degree to which asymmetric phosphate neutralization can lead to DNA bending in protein-DNA complexes. It is argued that electrostatic effects play crucial roles in the intrinsic, sequence-dependent shape of DNA and in DNA shapes induced by protein binding.
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    ATOMIC FORCE MICROSCOPY IN THE STUDY OF MACROMOLECULAR CRYSTAL GROWTH (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 361-410 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Atomic force microscopy (AFM) has been used to study protein, nucleic acid, and virus crystals in situ, in their mother liquors, as they grow. From sequential AFM images taken at brief intervals over many hours, or even days, the mechanisms and kinetics of the growth process can be defined. The appearance of both two- and three-dimensional nuclei on crystal surfaces have been visualized, defect structures of crystals were clearly evident, and defect densities of crystals were also determined. The incorporation of a wide range of impurities, ranging in size from molecules to microns or larger microcrystals, and even foreign particles were visually recorded. From these observations and measurements, a more complex understanding of the detailed character of macromolecular crystals is emerging, one that reveals levels of complexity previously unsuspected. The unique features of these crystals, apparently in AFM images, undoubtedly influence the diffraction properties of the crystals and the quality of the molecular images obtained by X-ray crystallography.
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    MOLECULAR MECHANISMS CONTROLLING ACTIN FILAMENT DYNAMICS IN NONMUSCLE CELLS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 545-576 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract We review how motile cells regulate actin filament assembly at their leading edge. Activation of cell surface receptors generates signals (including activated Rho family GTPases) that converge on integrating proteins of the WASp family (WASp, N-WASP, and Scar/WAVE). WASP family proteins stimulate Arp2/3 complex to nucleate actin filaments, which grow at a fixed 70o angle from the side of pre-existing actin filaments. These filaments push the membrane forward as they grow at their barbed ends. Arp2/3 complex is incorporated into the network, and new filaments are capped rapidly, so that activated Arp2/3 complex must be supplied continuously to keep the network growing. Hydrolysis of ATP bound to polymerized actin followed by phosphate dissociation marks older filaments for depolymerization by ADF/cofilins. Profilin catalyzes exchange of ADP for ATP, recycling actin back to a pool of unpolymerized monomers bound to profilin and thymosin-beta4 that is poised for rapid elongation of new barbed ends.
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    HYDROGEN BONDING, BASE STACKING, AND STERIC EFFECTS IN DNA REPLICATION (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 1-22 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Understanding the mechanisms by which genetic information is replicated is important both to basic knowledge of biological organisms and to many useful applications in biomedical research and biotechnology. One of the main functions of a DNA polymerase enzyme is to help DNA recognize itself with high specificity when a strand is being copied. Recent studies have shed new light on the question of what physical forces cause a polymerase enzyme to insert a nucleotide into a strand of DNA and to choose the correct nucleotide over the incorrect ones. This is discussed in the light of three main forces that govern DNA recognition: base stacking, Watson-Crick hydrogen bonding, and steric interactions. These factors are studied with natural and structurally altered DNA nucleosides.
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    UNNATURAL LIGANDS FOR ENGINEERED PROTEINS: New Tools for Chemical Genetics (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 577-606 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Small molecules that modulate the activity of biological signaling molecules can be powerful probes of signal transduction pathways. Highly specific molecules with high affinity are difficult to identify because of the conserved nature of many protein active sites. A newly developed approach to discovery of such small molecules that relies on protein engineering and chemical synthesis has yielded powerful tools for the study of a wide variety of proteins involved in signal transduction (G-proteins, protein kinases, 7-transmembrane receptors, nuclear hormone receptors, and others). Such chemical genetic tools combine the advantages of traditional genetics and the unparalleled temporal control over protein function afforded by small molecule inhibitors/activators that act at diffusion controlled rates with targets.
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    STRUCTURES AND PROTON-PUMPING STRATEGIES OF MITOCHONDRIAL RESPIRATORY ENZYMES (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 23-65 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Enzymes of the mitochondrial respiratory chain serve as proton pumps, using the energy made available from electron transfer reactions to transport protons across the inner mitochondrial membrane and create an electrochemical gradient used for the production of ATP. The ATP synthase enzyme is reversible and can also serve as a proton pump by coupling ATP hydrolysis to proton translocation. Each of the respiratory enzymes uses a different strategy for performing proton pumping. In this work, the strategies are described and the structural bases for the action of these proteins are discussed in light of recent crystal structures of several respiratory enzymes. The mechanisms and efficiency of proton translocation are also analyzed in terms of the thermodynamics of the substrate transformations catalyzed by these enzymes.
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    MASS SPECTROMETRY AS A TOOL FOR PROTEIN CRYSTALLOGRAPHY (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 67-85 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Atomic resolution structure determinations of proteins by X-ray crystallography are formidable multidisciplinary undertakings, requiring protein construct design, expression and purification, crystallization trials, phase determination, and model building. Modern mass spectrometric methods can greatly facilitate these obligate tasks. Thus, mass spectrometry can be used to verify that the desired protein construct has been correctly expressed, to define compact domains in the target protein, to assess the components contained within the protein crystals, and to screen for successful incorporation of seleno-methionine and other heavy metal reagents used for phasing. In addition, mass spectrometry can be used to address issues of modeling, topology, and side-chain proximity. Here, we demonstrate how rational use of mass spectrometry assists and expedites high resolution X-ray structure determination through each stage of the process of protein crystallography.
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    PHOTOSYSTEM II: The Solid Structural Era (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 307-328 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Understanding the precise role of photosystem II as an element of oxygenic photosynthesis requires knowledge of the molecular structure of this membrane protein complex. The past few years have been particularly exciting because the structural era of the plant photosystem II has begun. Although the atomic structure has yet to be determined, the map obtained at 6 A resolution by electron crystallography allows assignment of the key reaction center subunits with their associated pigment molecules. In the following, we first review the structural details that have recently emerged and then discuss the primary and secondary photochemical reaction pathways. Finally, in an attempt to establish the evolutionary link between the oxygenic and the anoxygenic photosynthesis, a framework structure common to all photosynthetic reaction centers has been defined, and the implications have been described.
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    PROTEIN FOLDING THEORY: From Lattice to All-Atom Models (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 361-396 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract This review focuses on recent advances in understanding protein folding kinetics in the context of nucleation theory. We present basic concepts such as nucleation, folding nucleus, and transition state ensemble and then discuss recent advances and challenges in theoretical understanding of several key aspects of protein folding kinetics. We cover recent topology-based approaches as well as evolutionary studies and molecular dynamics approaches to determine protein folding nucleus and analyze other aspects of folding kinetics. Finally, we briefly discuss successful all-atom Monte-Carlo simulations of protein folding and conclude with a brief outlook for the future.
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    THE SEARCH AND ITS OUTCOME: High-Resolution Structures of Ribosomal Particles from Mesophilic, Thermophilic, and Halophilic Bacteria at Various Functional States (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 257-273 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract We determined the high-resolution structures of large and small ribosomal subunits from mesophilic and thermophilic bacteria and compared them with those of the thermophilic ribosome and the halophilic large subunit. We confirmed that the elements involved in intersubunit contacts and in substrate binding are inherently flexible and that a common ribosomal strategy is to utilize this conformational variability for optimizing its functional efficiency and minimizing nonproductive interactions. Under close-to-physiological conditions, these elements maintain well-ordered characteristic conformations. In unbound subunits, the features creating intersubunit bridges within associated ribosomes lie on the interface surface, and the features that bind factors and substrates reach toward the binding site only when conditions are ripe.
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    CONFORMATIONAL DYNAMICS OF THE CHROMATIN FIBER IN SOLUTION: Determinants, Mechanisms, and Functions (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 361-392 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Chromatin fibers are dynamic macromolecular assemblages that are intimately involved in nuclear function. This review focuses on recent advances centered on the molecular mechanisms and determinants of chromatin fiber dynamics in solution. Major points of emphasis are the functions of the core histone tail domains, linker histones, and a new class of proteins that assemble supramolecular chromatin structures. The discussion of important structural issues is set against a background of possible functional significance.
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    PARAMAGNETIC RESONANCE OF BIOLOGICAL METAL CENTERS (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 393-422 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract The review deals with recent advances in magnetic resonance spectroscopy (hf EPR and NMR) of paramagnetic metal centers in biological macromolecules. In the first half of our chapter, we present an overview of recent technical developments in the NMR of paramagnetic bio-macromolecules. These are illustrated by a variety of examples deriving mainly from the spectroscopy of metalloproteins and their complexes. The second half focuses on recent developments in high-frequency EPR spectroscopy and the application of the technique to copper, iron, and manganese proteins. Special attention is given to the work on single crystals of copper proteins.
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    FORCE EXERTION IN FUNGAL INFECTION (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 321-341 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Fungal pathogens of plants or animals invade their hosts either by secretion of lytic enzymes, exerting force, or by a combination of both. Although many fungi are thought to rely mostly on lysis of the host tissue, some plant pathogenic fungi differentiate complex infection cells that develop enormous turgor pressure, which in turn is translated into force used for invasion. In order to understand mechanisms of fungal infection in detail, methods have been developed that indirectly or directly measure turgor pressure and force. In this article, these methods are described and critically discussed, and their importance in analysis of fungal infection are outlined.
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    COMPUTATIONAL CELL BIOLOGY: Spatiotemporal Simulation of Cellular Events (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 423-441 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract The field of computational cell biology has emerged within the past 5 years because of the need to apply disciplined computational approaches to build and test complex hypotheses on the interacting structural, physical, and chemical features that underlie intracellular processes. To meet this need, newly developed software tools allow cell biologists and biophysicists to build models and generate simulations from them. The construction of general-purpose computational approaches is especially challenging if the spatial complexity of cellular systems is to be explicitly treated. This review surveys some of the existing efforts in this field with special emphasis on a system being developed in the authors' laboratory, Virtual Cell. The theories behind both stochastic and deterministic simulations are discussed. Examples of respective applications to cell biological problems in RNA trafficking and neuronal calcium dynamics are provided to illustrate these ideas.
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    THE STRUCTURE OF MAMMALIAN CYCLOOXYGENASES (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 32 (2003), S. 183-206 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Cyclooxygenases-1 and -2 (COX-1 and COX-2, also known as prostaglandin H2 synthases-1 and -2) catalyze the committed step in prostaglandin synthesis. COX-1 and -2 are of particular interest because they are the major targets of nonsteroidal antiinflammatory drugs (NSAIDs) including aspirin, ibuprofen, and the new COX-2-selective inhibitors. Inhibition of the COXs with NSAIDs acutely reduces inflammation, pain, and fever, and long-term use of these drugs reduces the incidence of fatal thrombotic events, as well as the development of colon cancer and Alzheimer's disease. In this review, we examine how the structures of COXs relate mechanistically to cyclooxygenase and peroxidase catalysis and how alternative fatty acid substrates bind within the COX active site. We further examine how NSAIDs interact with COXs and how differences in the structure of COX-2 result in enhanced selectivity toward COX-2 inhibitors.
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    COMPUTER SIMULATIONS OF ENZYME CATALYSIS: Methods, Progress, and Insights (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 32 (2003), S. 425-443 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Understanding the action of enzymes on an atomistic level is one of the important aims of modern biophysics. This review describes the state of the art in addressing this challenge by simulating enzymatic reactions. It considers different modeling methods including the empirical valence bond (EVB) and more standard molecular orbital quantum mechanics/molecular mechanics (QM/MM) methods. The importance of proper configurational averaging of QM/MM energies is emphasized, pointing out that at present such averages are performed most effectively by the EVB method. It is clarified that all properly conducted simulation studies have identified electrostatic preorganization effects as the source of enzyme catalysis. It is argued that the ability to simulate enzymatic reactions also provides the chance to examine the importance of nonelectrostatic contributions and the validity of the corresponding proposals. In fact, simulation studies have indicated that prominent proposals such as desolvation, steric strain, near attack conformation, entropy traps, and coherent dynamics do not account for a major part of the catalytic power of enzymes. Finally, it is pointed out that although some of the issues are likely to remain controversial for some time, computer modeling approaches can provide a powerful tool for understanding enzyme catalysis.
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    FORCE AS A USEFUL VARIABLE IN REACTIONS: Unfolding RNA (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 33 (2004), S. 363-385 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: The effect of force on the thermodynamics and kinetics of reactions is described. The key parameters are the difference in end-to-end distance between reactant and product for thermodynamics, and the distance to the transition state for kinetics. I focus the review on experimental results on force unfolding of RNA. Methods to measure Gibbs free energies and kinetics for reversible and irreversible reactions are described. The use of the worm-like-chain model to calculate the effects of force on thermodynamics and kinetics is illustrated with simple models. The main purpose of the review is to describe the simple experiments that have been done so far, and to encourage more people to enter a field that is new and full of opportunities.
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    MOLECULES OF THE BACTERIAL CYTOSKELETON (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 33 (2004), S. 177-198 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: The structural elucidation of clear but distant homologs of actin and tubulin in bacteria and GFP labeling of these proteins promises to reinvigorate the field of prokaryotic cell biology. FtsZ (the tubulin homolog) and MreB/ParM (the actin homologs) are indispensable for cellular tasks that require the cell to accurately position molecules, similar to the function of the eukaryotic cytoskeleton. FtsZ is the organizing molecule of bacterial cell division and forms a filamentous ring around the middle of the cell. Many molecules, including MinCDE, SulA, ZipA, and FtsA, assist with this process directly. Recently, genes much more similar to tubulin than to FtsZ have been identified in Verrucomicrobia. MreB forms helices underneath the inner membrane and probably defines the shape of the cell by positioning transmembrane and periplasmic cell wall-synthesizing enzymes. Currently, no interacting proteins are known for MreB and its relatives that help these proteins polymerize or depolymerize at certain times and places inside the cell. It is anticipated that MreB-interacting proteins exist in analogy to the large number of actin binding proteins in eukaryotes. ParM (a plasmid-borne actin homolog) is directly involved in pushing certain single-copy plasmids to the opposite poles by ParR/parC-assisted polymerization into double-helical filaments, much like the filaments formed by actin, F-actin. Mollicutes seem to have developed special systems for cell shape determination and motility, such as the fibril protein in Spiroplasma.
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    STRUCTURE, DYNAMICS, AND CATALYTIC FUNCTION OF DIHYDROFOLATE REDUCTASE (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 33 (2004), S. 119-140 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Molecular motions are widely regarded as contributing factors in many aspects of protein function. The enzyme dihydrofolate reductase (DHFR), and particularly that from Escherichia coli, has become an important system for investigating the linkage between protein dynamics and catalytic function, both because of the location and timescales of the motions observed and because of the availability of a large amount of structural and mechanistic data that provides a detailed context within which the motions can be interpreted. Changes in protein dynamics in response to ligand binding, conformational change, and mutagenesis have been probed using numerous experimental and theoretical approaches, including X-ray crystallography, fluorescence, nuclear magnetic resonance (NMR), molecular dynamics simulations, and hybrid quantum/classical dynamics methods. These studies provide a detailed map of changes in conformation and dynamics throughout the catalytic cycle of DHFR and give new insights into the role of protein motions in the catalytic activity of this enzyme.
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    TETHERING: Fragment-Based Drug Discovery (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 33 (2004), S. 199-223 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: The genomics revolution has provided a deluge of new targets for drug discovery. To facilitate the drug discovery process, many researchers are turning to fragment-based approaches to find lead molecules more efficiently. One such method, Tethering1, allows for the identification of small-molecule fragments that bind to specific regions of a protein target. These fragments can then be elaborated, combined with other molecules, or combined with one another to provide high-affinity drug leads. In this review we describe the background and theory behind Tethering and discuss its use in identifying novel inhibitors for protein targets including interleukin-2 (IL-2), thymidylate synthase (TS), protein tyrosine phosphatase 1B (PTP-1B), and caspases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.33.110502.140409
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    TAKING X-RAY DIFFRACTION TO THE LIMIT: Macromolecular Structures from Femtosecond X-Ray Pulses and Diffraction Microscopy of Cells with Synchrotron Radiation* (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 33 (2004), S. 157-176 
    Details
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Recent work is extending the methodology of X-ray crystallography to the structure determination of noncrystalline specimens. The phase problem is solved using the oversampling method, which takes advantage of "continuous" diffraction patterns from noncrystalline specimens. Here we review the principle of this newly developed technique and discuss the ongoing experiments of imaging nonperiodic objects, such as cells and cellular structures, using coherent and bright X rays produced by third-generation synchrotron sources. In the longer run, the technique may be applicable to image single biomolecules using anticipated X-ray free electron lasers. Here, computer simulations have so far demonstrated two important steps: (a) by using an extremely intense femtosecond X-ray pulse, a diffraction pattern can be recorded from a macromolecule before radiation damage manifests itself; and (b) the phase information can be retrieved in an ab initio fashion from a set of calculated noisy diffraction patterns of single protein molecules.
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    URL: http://dx.doi.org/10.1146/annurev.biophys.33.110502.140405
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    STRUCTURE, MOLECULAR MECHANISMS, AND EVOLUTIONARY RELATIONSHIPS IN DNA TOPOISOMERASES (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 33 (2004), S. 95-118 
    Details
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Topoisomerases are enzymes that use DNA strand scission, manipulation, and rejoining activities to directly modulate DNA topology. These actions provide a powerful means to effect changes in DNA supercoiling levels, and allow some topoisomerases to both unknot and decatenate chromosomes. Since their initial discovery over three decades ago, researchers have amassed a rich store of information on the cellular roles and regulation of topoisomerases, and have delineated general models for their chemical and physical mechanisms. Topoisomerases are now known to be necessary for the survival of cellular organisms and many viruses and are rich clinical targets for anticancer and antimicrobial treatments. In recent years, crystal structures have been obtained for each of the four types of topoisomerases in a number of distinct conformational and substrate-bound states. In addition, sophisticated biophysical methods have been utilized to study details of topoisomerase reaction dynamics and enzymology. A synthesis of these approaches has provided researchers with new physical insights into how topoisomerases employ chemistry and allostery to direct the large-scale molecular motions needed to pass DNA strands through each other.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.33.110502.140357
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    THREE-DIMENSIONAL ELECTRON MICROSCOPY AT MOLECULAR RESOLUTION* (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 33 (2004), S. 141-155 
    Details
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Emerging methods in cryo-electron microscopy allow determination of the three-dimensional architectures of objects ranging in size from small proteins to large eukaryotic cells, spanning a size range of more than 12 orders of magnitude. Advances in determining structures by "single particle" microscopy and by "electron tomography" provide exciting opportunities to describe the structures of subcellular assemblies that are either too large or too heterogeneous to be investigated by conventional crystallographic methods. Here, we review selected aspects of progress in structure determination by cryo-electron microscopy at molecular resolution, with a particular emphasis on topics at the interface of single particle and tomographic approaches. The rapid pace of development in this field suggests that comprehensive descriptions of the structures of whole cells and organelles in terms of the spatial arrangements of their molecular components may soon become routine.
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    URL: http://dx.doi.org/10.1146/annurev.biophys.33.110502.140339
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    ROTATION OF F1-ATPASE: How an ATP-Driven Molecular Machine May Work (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 33 (2004), S. 245-268 
    Details
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: F1-ATPase is a rotary motor made of a single protein molecule. Its rotation is driven by free energy obtained by ATP hydrolysis. In vivo, another motor, Fo, presumably rotates the F1 motor in the reverse direction, reversing also the chemical reaction in F1 to let it synthesize ATP. Here we attempt to answer two related questions, How is free energy obtained by ATP hydrolysis converted to the mechanical work of rotation, and how is mechanical work done on F1 converted to free energy to produce ATP? After summarizing single-molecule observations of F1 rotation, we introduce a toy model and discuss its free-energy diagrams to possibly answer the above questions. We also discuss the efficiency of molecular motors in general.
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    URL: http://dx.doi.org/10.1146/annurev.biophys.33.110502.132716
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    MASS SPECTRAL ANALYSIS IN PROTEOMICS (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 33 (2004), S. 297-316 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Mass spectrometry provides key tools for the analysis of proteins. New types of mass spectrometers that provide enhanced capability to discover protein identities and perform improved proteomic experiments are discussed. Handling the complex mixtures of peptides and proteins generated from protein complexes and whole cells requires multidimensional separations; several forms of separation are discussed. Applications of mass spectrometry-based approaches for contemporary proteomic analyses are described.
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    URL: http://dx.doi.org/10.1146/annurev.biophys.33.111502.082538
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    INFORMATION CONTENT AND COMPLEXITY IN THE HIGH-ORDER ORGANIZATION OF DNA (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 33 (2004), S. 317-342 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Nucleic acids are characterized by a vast structural variability. Secondary structural conformations include the main polymorphs A, B, and Z, cruciforms, intrinsic curvature, and multistranded motifs. DNA secondary motifs are stabilized and regulated by the primary base sequence, contextual effects, environmental factors, as well as by high-order DNA packaging modes. The high-order modes are, in turn, affected by secondary structures and by the environment. This review is concerned with the flow of structural information among the hierarchical structural levels of DNA molecules, the intricate interplay between the various factors that affect these levels, and the regulation and physiological significance of DNA high-order structures.
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    URL: http://dx.doi.org/10.1146/annurev.biophys.33.110502.133328
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    ETHYLENE: A Gaseous Signal Molecule in Plants (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 1-18 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Ethylene regulates a multitude of plant processes, ranging from seed germination to organ senescence. Of particular economic importance is the role of ethylene as an inducer of fruit ripening. Ethylene is synthesized from S-adenosyl-L-methionine via 1-aminocyclopropane-1-carboxylic acid (ACC). The enzymes catalyzing the two reactions in this pathway are ACC synthase and ACC oxidase. Environmental and endogenous signals regulate ethylene biosynthesis primarily through differential expression of ACC synthase genes. Components of the ethylene signal transduction pathway have been identified by characterization of ethylene-response mutants in Arabidopsis thaliana. One class of mutations, exemplified by etr1, led to the identification of the ethylene receptors, which turned out to be related to bacterial two-component signaling systems. Mutations that eliminate ethylene binding to the receptor yield a dominant, ethylene-insensitive phenotype. CTR1 encodes a Raf-like Ser/Thr protein kinase that acts downstream from the ethylene receptor and may be part of a MAP kinase cascade. Mutants in CTR1 exhibit a constitutive ethylene-response phenotype. Both the ethylene receptors and CTR1 are negative regulators of ethylene responses. EIN2 and EIN3 are epistatic to CTR1, and mutations in either gene lead to ethylene insensitivity. Whereas the function of EIN2 in ethylene transduction is not known, EIN3 is a putative transcription factor involved in regulating expression of ethylene-responsive genes. Biotechnological modifications of ethylene synthesis and of sensitivity to ethylene are promising methods to prevent spoilage of agricultural products such as fruits, whose ripening is induced by ethylene.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.16.1.1
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    MECHANISMS OF SYNAPTIC VESICLE EXOCYTOSIS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 19-49 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Chemical synaptic transmission serves as the main form of cell to cell communication in the nervous system. Neurotransmitter release occurs through the process of regulated exocytosis, in which a synaptic vesicle releases its contents in response to an increase in calcium. The use of genetic, biochemical, structural, and functional studies has led to the identification of factors important in the synaptic vesicle life cycle. Here we focus on the prominent role of SNARE (soluble NSF attachment protein receptor) proteins during membrane fusion and the regulation of SNARE function by Rab3a, nSec1, and NSF. Many of the proteins important for transmitter release have homologs involved in intracellular vesicle transport, and all forms of vesicle trafficking share common basic principles. Finally, modifications to the synaptic exocytosis pathway are very likely to underlie certain forms of synaptic plasticity and therefore contribute to learning and memory.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.16.1.19
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    ERM-MERLIN AND EBP50 PROTEIN FAMILIES IN PLASMA MEMBRANE ORGANIZATION AND FUNCTION (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 113-143 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The ezrin-radixin-moesin (ERM) family of proteins have emerged as key regulatory molecules in linking F-actin to specific membrane proteins, especially in cell surface structures. Merlin, the product of the NF2 tumor suppressor gene, has sequence similarity to ERM proteins and binds to some of the same membrane proteins, but lacks a C-terminal F-actin binding site. In this review we discuss how ERM proteins and merlin are negatively regulated by an intramolecular association between their N- and C-terminal domains. Activation of at least ERM proteins can be accomplished by C-terminal phosphorylation in the presence of PIP2. We also discuss membrane proteins to which ERM and merlin bind, including those making an indirect linkage through the PDZ-containing adaptor molecules EBP50 and E3KARP. Finally, the function of these proteins in cortical structure, endocytic traffic, signal transduction, and growth control is discussed.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.16.1.113
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    MOLECULAR REGULATION OF ADIPOGENESIS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 145-171 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Adipogenesis, or the development of fat cells from preadipocytes, has been one of the most intensely studied models of cellular differentiation. In part this has been because of the availability of in vitro models that faithfully recapitulate most of the critical aspects of fat cell formation in vivo. More recently, studies of adipogenesis have proceeded with the hope that manipulation of this process in humans might one day lead to a reduction in the burden of obesity and diabetes. This review explores some of the highlights of a large and burgeoning literature devoted to understanding adipogenesis at the molecular level. The hormonal and transcriptional control of adipogenesis is reviewed, as well as studies on a less well known type of fat cell, the brown adipocyte. Emphasis is placed, where possible, on in vivo studies with the hope that the results discussed may one day shed light on basic questions of cellular growth and differentiation in addition to possible benefits in human health.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.16.1.145
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    GUT FEELINGS: Enteropathogenic E. coli (EPEC) Interactions with the Host (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 173-189 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Enteropathogenic Escherichia coli (EPEC) is a gram-negative bacterial pathogen that adheres to human intestinal epithelial cells, resulting in watery, persistent diarrhea. It subverts the host cell cytoskeleton, causing a rearrangement of cytoskeletal components into a characteristic pedestal structure underneath adherent bacteria. In contrast to other intracellular pathogens that affect the actin cytoskeleton from inside the host cytoplasm, EPEC remains extracellular and transmits signals through the host cell plasma membrane via direct injection of virulence factors by a "molecular syringe," the bacterial type III secretion system. One injected factor is Tir, which functions as the plasma membrane receptor for EPEC adherence. Tir directly links extracellular EPEC through the epithelial membrane and firmly anchors it to the host cell actin cytoskeleton, thereby initiating pedestal formation. In addition to stimulating actin nucleation and polymerization in the host cell, EPEC activates several other signaling pathways that lead to tight junction disruption, inhibition of phagocytosis, altered ion secretion, and immune responses. This review summarizes recent developments in our understanding of EPEC pathogenesis and discusses similarities and differences between EPEC pedestals, focal contacts, and Listeria monocytogenes actin tails.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.16.1.173
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    BONE DEVELOPMENT (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 191-220 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Early development of the vertebrate skeleton depends on genes that pattern the distribution and proliferation of cells from cranial neural crest, sclerotomes, and lateral plate mesoderm into mesenchymal condensations at sites of future skeletal elements. Within these condensations, cells differentiate to chondrocytes or osteoblasts and form cartilages and bones under the control of various transcription factors. In most of the skeleton, organogenesis results in cartilage models of future bones; in these models cartilage is replaced by bone by the process of endochondral ossification. Lastly, through a controlled process of bone growth and remodeling the final skeleton is shaped and molded. Significant and exciting insights into all aspects of vertebrate skeletal development have been obtained through molecular and genetic studies of animal models and humans with inherited disorders of skeletal morphogenesis, organogenesis, and growth.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.16.1.191
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    CELLULAR SIGNALING AND VOLUME CONTROL IN STOMATAL MOVEMENTS IN PLANTS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 221-241 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Stomatal guard cells are unique as a plant cell model and, because of the depth of present knowledge on ion transport and its regulation, offer a first look at signal integration in higher plants. A large body of data indicates that Ca2+ and H+ act independently, integrating with protein kinases and phosphatases, to control the gating of the K+ and Cl- channels that mediate solute flux for stomatal movements. Oscillations in the cytosolic-free concentration of Ca2+ contribute to a signaling cassette, integrated within these events through an unusual coupling with membrane voltage for solute homeostasis. Similar cassettes are anticipated to include control pathways linked to cytosolic pH. Additional developments during the last two years point to events in membrane traffic that play equally important roles in stomatal control. Research in these areas is now adding entirely new dimensions to our understanding of guard cell signaling.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.16.1.221
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    THE DEVELOPMENTAL AND MOLECULAR BIOLOGY OF GENES THAT SUBDIVIDE THE BODY OF DROSOPHILA (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 243-271 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract During the past decade, much progress has been made in understanding how the adult fly is built. Some old concepts such as those of compartments and selector genes have been revitalized. In addition, recent work suggests the existence of genes involved in the regionalization of the adult that do not have all the features of selector genes. Nevertheless, they generate morphological distinctions within the body plan. Here we re-examine some of the defining criteria of selector genes and suggest that these newly characterized genes fulfill many, but not all, of these criteria. Further, we propose that these genes can be classified according to the domains in which they function. Finally, we discuss experiments that address the molecular mechanisms by which selector and selector-like gene products function in the fly.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.16.1.243
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    CAJAL BODIES: The First 100 Years (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 273-300 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Cajal bodies are small nuclear organelles first described nearly 100 years ago by Ramon y Cajal in vertebrate neural tissues. They have since been found in a variety of animal and plant nuclei, suggesting that they are involved in basic cellular processes. Cajal bodies contain a marker protein of unknown function, p80-coilin, and many components involved in transcription and processing of nuclear RNAs. Among these are the three eukaryotic RNA polymerases and factors required for transcribing and processing their respective nuclear transcripts: mRNA, rRNA, and pol III transcripts. A model is discussed in which Cajal bodies are the sites for preassembly of transcriptosomes, unitary particles involved in transcription and processing of RNA. A parallel is drawn to the nucleolus and the preassembly of ribosomes, which are unitary particles involved in translation of proteins.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.16.1.273
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    EPITHELIAL M CELLS: Differentiation and Function (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 301-332 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract M cells are distinctive epithelial cells that occur only in the follicle-associated epithelia that overlie organized mucosa-associated lymphoid tissues. They are structurally and functionally specialized for transepithelial transport, delivering foreign antigens and microorganisms to organized lymphoid tissues within the mucosae of the small and large intestines, tonsils and adenoids, and airways. M cell transport is a double-edged sword: Certain pathogens exploit the features of M cells that are intended to promote uptake for the purpose of immunological sampling. Eludication of the molecular architecture of M cell apical surfaces is important for understanding the strategies that pathogens use to exploit this pathway and for utilizing M cell transport for delivery of vaccines to the mucosal immune system. This article reviews the functional and biochemical features that distinguish M cells from other intestinal cell types. In addition it synthesizes the available information on development and differentiation of organized lymphoid tissues and the specialized epithelium associated with these immune inductive sites.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.16.1.301
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    DYNAMIN AND ITS ROLE IN MEMBRANE FISSION1 (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 483-519 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Dynamin, a 100-kDa GTPase, is an essential component of vesicle formation in receptor-mediated endocytosis, synaptic vesicle recycling, caveolae internalization, and possibly vesicle trafficking in and out of the Golgi. In addition to the GTPase domain, dynamin also contains a pleckstrin homology domain (PH) implicated in membrane binding, a GTPase effector domain (GED) shown to be essential for self-assembly and stimulated GTPase activity, and a C-terminal proline-rich domain (PRD), which contains several SH3-binding sites. Dynamin partners bind to the PRD and may either stimulate dynamin's GTPase activity or target dynamin to the plasma membrane. Purified dynamin readily self-assembles into rings or spirals. This striking structural property supports the hypothesis that dynamin wraps around the necks of budding vesicles where it plays a key role in membrane fission. The focus of this review is on the relationship between the GTPase and self-assembly properties of dynamin and its cellular function.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.16.1.483
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    THE ROLE OF ORPHAN NUCLEAR RECEPTORS IN THE REGULATION OF CHOLESTEROL HOMEOSTASIS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 459-481 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Cholesterol balance is maintained by a series of regulatory pathways that control the acquisition of cholesterol from endogenous and exogenous sources and the elimination of cholesterol, facilitated by its conversion to bile acids. Over the past decade, investigators have discovered that a family of membrane-bound transcription factors, sterol regulatory element-binding proteins (SREBPs), mediate the end-product repression of key enzymes of cholesterol biosynthesis. Recently orphan members of another family of transcription factors, the nuclear hormone receptors, have been found to regulate key pathways in bile acid metabolism, thereby controlling cholesterol elimination. The study of these orphan nuclear receptors suggests their potential as targets for new drug therapies.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.16.1.459
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    STRUCTURE AND REGULATION OF VOLTAGE-GATED Ca2+ CHANNELS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 521-555 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Voltage-gated Ca2+ channels mediate Ca2+ entry into cells in response to membrane depolarization. Electrophysiological studies reveal different Ca2+ currents designated L-, N-, P-, Q-, R-, and T-type. The high-voltage-activated Ca2+ channels that have been characterized biochemically are complexes of a pore-forming alpha1 subunit of ~190-250 kDa; a transmembrane, disulfide-linked complex of alpha2 and delta subunits; an intracellular beta subunit; and in some cases a transmembrane gamma subunit. Ten alpha1 subunits, four alpha2delta complexes, four beta subunits, and two gamma subunits are known. The Cav1 family of alpha1 subunits conduct L-type Ca2+ currents, which initiate muscle contraction, endocrine secretion, and gene transcription, and are regulated primarily by second messenger-activated protein phosphorylation pathways. The Cav2 family of alpha1 subunits conduct N-type, P/Q-type, and R-type Ca2+ currents, which initiate rapid synaptic transmission and are regulated primarily by direct interaction with G proteins and SNARE proteins and secondarily by protein phosphorylation. The Cav3 family of alpha1 subunits conduct T-type Ca2+ currents, which are activated and inactivated more rapidly and at more negative membrane potentials than other Ca2+ current types. The distinct structures and patterns of regulation of these three families of Ca2+ channels provide a flexible array of Ca2+ entry pathways in response to changes in membrane potential and a range of possibilities for regulation of Ca2+ entry by second messenger pathways and interacting proteins.
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    SECRETORY PROTEIN TRAFFICKING AND ORGANELLE DYNAMICS IN LIVING CELLS1 (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 557-589 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Green fluorescent protein chimerae acting as reporters for protein localization and trafficking within the secretory membrane system of living cells have been used in a wide variety of applications, including time-lapse imaging, double-labeling, energy transfer, quantitation, and photobleaching experiments. Results from this work are clarifying the steps involved in the formation, translocation, and fusion of transport intermediates; the organization and biogenesis of organelles; and the mechanisms of protein retention, sorting, and recycling in the secretory pathway. In so doing, they are broadening our thinking about the temporal and spatial relationships among secretory organelles and the membrane trafficking pathways that operate between them.
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    SUMO-NONCLASSICAL UBIQUITIN (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 591-626 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract SUMO (small ubiquitin-related modifier) is the best-characterized member of a growing family of ubiquitin-related proteins. It resembles ubiquitin in its structure, its ability to be ligated to other proteins, as well as in the mechanism of ligation. However, in contrast to ubiquitination-often the first step on a one-way road to protein degradation-SUMOlation does not seem to mark proteins for degradation. In fact, SUMO may even function as an antagonist of ubiquitin in the degradation of selected proteins. While most SUMO targets are still at large, available data provide compelling evidence for a role of SUMO in the regulation of protein-protein interactions and/or subcellular localization.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.16.1.591
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    VIRAL ENTRY INTO THE NUCLEUS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 627-651 
    Details
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Because many viruses replicate in the nucleus of their host cells, they must have ways of transporting their genome and other components into and out of this compartment. For the incoming virus particle, nuclear entry is often one of the final steps in a complex transport and uncoating program. Typically, it involves recognition by importins (karyopherins), transport to the nucleus, and binding to nuclear pore complexes. Although all viruses take advantage of cellular signals and factors, viruses and viral capsids vary considerably in size, structure, and in how they interact with the nuclear import machinery. Influenza and adenoviruses undergo extensive disassembly prior to genome import; herpesviruses release their genome into the nucleus without immediate capsid disassembly. Polyoma viruses, parvoviruses, and lentivirus preintegration complexes are thought to enter in intact form, whereas the corresponding complexes of onco-retroviruses have to wait for mitosis because they cannot infect interphase nuclei.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.16.1.627
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    CHEMICAL AND BIOLOGICAL STRATEGIES FOR ENGINEERING CELL SURFACE GLYCOSYLATION (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 17 (2001), S. 1-23 
    Details
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Oligosaccharides play a crucial role in many of the recognition, signaling, and adhesion events that take place at the surface of cells. Abnormalities in the synthesis or presentation of these carbohydrates can lead to misfolded and inactive proteins, as well as to several debilitating disease states. However, their diverse structures, which are the key to their function, have hampered studies by biologists and chemists alike. This review presents an overview of techniques for examining and manipulating cell surface oligosaccharides through genetic, enzymatic, and chemical strategies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.17.1.1
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    THE MYC/MAX/MAD NETWORK AND THE TRANSCRIPTIONAL CONTROL OF CELL BEHAVIOR (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 653-699 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The Myc/Max/Mad network comprises a group of transcription factors whose distinct interactions result in gene-specific transcriptional activation or repression. A great deal of research indicates that the functions of the network play roles in cell proliferation, differentiation, and death. In this review we focus on the Myc and Mad protein families and attempt to relate their biological functions to their transcriptional activities and gene targets. Both Myc and Mad, as well as the more recently described Mnt and Mga proteins, form heterodimers with Max, permitting binding to specific DNA sequences. These DNA-bound heterodimers recruit coactivator or corepressor complexes that generate alterations in chromatin structure, which in turn modulate transcription. Initial identification of target genes suggests that the network regulates genes involved in the cell cycle, growth, life span, and morphology. Because Myc and Mad proteins are expressed in response to diverse signaling pathways, the network can be viewed as a functional module which acts to convert environmental signals into specific gene-regulatory programs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.16.1.653
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    THROMBOSPONDINS: Multifunctional Regulators of Cell Interactions (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 17 (2001), S. 25-51 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Thrombospondins are secreted, multidomain macromolecules that act as regulators of cell interactions in vertebrates. Gene knockout mice constructed for two members of this family demonstrate roles in the organization and homeostasis of multiple tissues, with particularly significant activities in the regulation of angiogenesis. This review discusses the functions of thrombospondins with regard to their cellular mechanisms of action and highlights recent advances in understanding how multifactorial molecular interactions, at the cell surface and within extracellular matrix, produce cell-type-specific effects on cell behavior and the organization of matrix and tissues.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.17.1.25
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    STEM AND PROGENITOR CELLS: Origins, Phenotypes, Lineage Commitments, and Transdifferentiations (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 17 (2001), S. 387-403 
    Details
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Multipotent stem cells are clonal cells that self-renew as well as differentiate to regenerate adult tissues. Whereas stem cells and their fates are known by unique genetic marker studies, the fate and function of these cells are best studied by their prospective isolation. This review is about the properties of various highly purified tissue-specific multipotent stem cells and purified oligolineage progenitors. We contend that unless the stem or progenitor cells in question have been purified to near homogeneity, one cannot know whether their generation of expected (or unexpected) progeny is a property of a known cell type. It is interesting that in the hematopoietic system the only long-term self-renewing cells in the stem and progenitors pool are the hematopoietic stem cells. This fact is discussed in the context of normal and leukemic hematopoiesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.17.1.387
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    EMBRYO-DERIVED STEM CELLS: Of Mice and Men (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 17 (2001), S. 435-462 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Mouse embryonic stem cells are continuous cell lines derived directly from the fetal founder tissue of the preimplantation embryo. They can be expanded in culture while retaining the functional attributes of pluripotent early embryo cells. In particular, they can participate fully in fetal development when reintroduced into the embryo. The capacity for multilineage differentiation is reproduced in culture where embryonic stem cells can produce a wide range of well-defined cell types. This has stimulated interest in the isolation of analogous cells of human origin. Such human pluripotent stem cells could constitute a renewable source of more differentiated cells that could be employed to replace diseased or damaged tissue by cellular transplantation. In this review, the relationships between mouse embryonic stem cells, resident pluripotent cells in the embryo, and human embryo-derived cell lines are evaluated, and the prospects and challenges of embryo stem cell research are considered. This review is dedicated to Rosa Beddington FRS, a great developmental biologist, a wonderful colleague, and an inspirational advocate of human stem cell research.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.17.1.435
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    HOW MATRIX METALLOPROTEINASES REGULATE CELL BEHAVIOR (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 17 (2001), S. 463-516 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The matrix metalloproteinases (MMPs) constitute a multigene family of over 25 secreted and cell surface enzymes that process or degrade numerous pericellular substrates. Their targets include other proteinases, proteinase inhibitors, clotting factors, chemotactic molecules, latent growth factors, growth factor-binding proteins, cell surface receptors, cell-cell adhesion molecules, and virtually all structural extracellular matrix proteins. Thus MMPs are able to regulate many biologic processes and are closely regulated themselves. We review recent advances that help to explain how MMPs work, how they are controlled, and how they influence biologic behavior. These advances shed light on how the structure and function of the MMPs are related and on how their transcription, secretion, activation, inhibition, localization, and clearance are controlled. MMPs participate in numerous normal and abnormal processes, and there are new insights into the key substrates and mechanisms responsible for regulating some of these processes in vivo. Our knowledge in the field of MMP biology is rapidly expanding, yet we still do not fully understand how these enzymes regulate most processes of development, homeostasis, and disease.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.17.1.463
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    BIOLOGICAL BASKET WEAVING: Formation and Function of Clathrin-Coated Vesicles (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 17 (2001), S. 517-568 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract There has recently been considerable progress in understanding the regulation of clathrin-coated vesicle (CCV) formation and function. These advances are due to the determination of the structure of a number of CCV coat components at molecular resolution and the identification of novel regulatory proteins that control CCV formation in the cell. In addition, pathways of (a) phosphorylation, (b) receptor signaling, and (c) lipid modification that influence CCV formation, as well as the interaction between the cytoskeleton and CCV transport pathways are becoming better defined. It is evident that although clathrin coat assembly drives CCV formation, this fundamental reaction is modified by different regulatory proteins, depending on where CCVs are forming in the cell. This regulatory difference likely reflects the distinct biological roles of CCVs at the plasma membrane and trans-Golgi network, as well as the distinct properties of these membranes themselves. Tissue-specific functions of CCVs require even more-specialized regulation and defects in these pathways can now be correlated with human diseases.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.17.1.517
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    LEFT-RIGHT ASYMMETRY DETERMINATION IN VERTEBRATES (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 17 (2001), S. 779-805 
    Details
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract A distinctive and essential feature of the vertebrate body is a pronounced left-right asymmetry of internal organs and the central nervous system. Remarkably, the direction of left-right asymmetry is consistent among all normal individuals in a species and, for many organs, is also conserved across species, despite the normal health of individuals with mirror-image anatomy. The mechanisms that determine stereotypic left-right asymmetry have fascinated biologists for over a century. Only recently, however, has our understanding of the left-right patterning been pushed forward by links to specific genes and proteins. Here we examine the molecular biology of the three principal steps in left-right determination: breaking bilateral symmetry, propagation and reinforcement of pattern, and the translation of pattern into asymmetric organ morphogenesis.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.17.1.779
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    MOLECULAR BASES OF CIRCADIAN RHYTHMS (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 17 (2001), S. 215-253 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Circadian rhythms are found in most eukaryotes and some prokaryotes. The mechanism by which organisms maintain these roughly 24-h rhythms in the absence of environmental stimuli has long been a mystery and has recently been the subject of intense research. In the past few years, we have seen explosive progress in the understanding of the molecular basis of circadian rhythms in model systems ranging from cyanobacteria to mammals. This review attempts to outline these primarily genetic and biochemical findings and encompasses work done in cyanobacteria, Neurospora, higher plants, Drosophila, and rodents. Although actual clock components do not seem to be conserved between kingdoms, central clock mechanisms are conserved. Somewhat paradoxically, clock components that are conserved between species can be used in diverse ways. The different uses of common components may reflect the important role that the circadian clock plays in adaptation of species to particular environmental niches.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.17.1.215
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    GENE CO-OPTION IN PHYSIOLOGICAL AND MORPHOLOGICAL EVOLUTION (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 18 (2002), S. 53-80 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Co-option occurs when natural selection finds new uses for existing traits, including genes, organs, and other body structures. Genes can be co-opted to generate developmental and physiological novelties by changing their patterns of regulation, by changing the functions of the proteins they encode, or both. This often involves gene duplication followed by specialization of the resulting paralogous genes into particular functions. A major role for gene co-option in the evolution of development has long been assumed, and many recent comparative developmental and genomic studies have lent support to this idea. Although there is relatively less known about the molecular basis of co-option events involving developmental pathways, much can be drawn from well-studied examples of the co-option of structural proteins. Here, we summarize several case studies of both structural gene and developmental genetic circuit co-option and discuss how co-option may underlie major episodes of adaptive change in multicellular organisms. We also examine the phenomenon of intraspecific variability in gene expression patterns, which we propose to be one form of material for the co-option process. We integrate this information with recent models of gene family evolution to provide a framework for understanding the origin of co-optive evolution and the mechanisms by which natural selection promotes evolutionary novelty by inventing new uses for the genetic toolkit.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.18.020402.140619
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    THE MECHANISMS OF POLLINATION AND FERTILIZATION IN PLANTS (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 18 (2002), S. 81-105 
    Details
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract In flowering plants, pollen grains germinate to form pollen tubes that transport male gametes (sperm cells) to the egg cell in the embryo sac during sexual reproduction. Pollen tube biology is complex, presenting parallels with axon guidance and moving cell systems in animals. Pollen tube cells elongate on an active extracellular matrix in the style, ultimately guided by stylar and embryo sac signals. A well-documented recognition system occurs between pollen grains and the stigma in sporophytic self-incompatibility, where both receptor kinases in the stigma and their peptide ligands from pollen are now known. Complex mechanisms act to precisely target the sperm cells into the embryo sac. These events initiate double fertilization in which the two sperm cells from one pollen tube fuse to produce distinctly different products: one with the egg to produce the zygote and embryo and the other with the central cell to produce the endosperm.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.18.012502.083438
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    RECEPTOR KINASE SIGNALING IN PLANT DEVELOPMENT (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 18 (2002), S. 163-192 
    Details
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The Arabidopsis genome sequence has revealed that plants contain a much larger complement of receptor kinase genes than other organisms. Early analysis of these genes revealed involvement in a diverse array of developmental and defense functions that included gametophyte development, pollen-pistil interactions, shoot apical meristem equilibrium, hormone perception, and cell morphogenesis. Amino acid sequence motifs and binding studies indicate that the ectodomains are capable of binding, either directly or indirectly, various classes of molecules including proteins, carbohydrates, and steroids. Genetic and biochemical approaches have begun to identify other components of several signal transduction pathways. Some receptor-like kinases (RLKs) appear to function with coreceptors lacking kinase domains, and genome analysis suggests this might be true for many RLKs. The KAPP protein phosphatase functions as a negative regulator of at least two RLK systems, and in vitro studies suggest it could be a common component of more. Whether plant signaling systems display a modularity similar to animal systems remains to be determined. Future efforts will reveal unknown functions of other RLKs and elucidate the relationships among their signaling networks.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.18.012502.083431
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    CELLULAR CONTROL OF ACTIN NUCLEATION (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 18 (2002), S. 247-288 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Eukaryotic cells use actin polymerization to change shape, move, and internalize extracellular materials by phagocytosis and endocytosis, and to form contractile structures. In addition, several pathogens have evolved to use host cell actin assembly for attachment, internalization, and cell-to-cell spread. Although cells possess multiple mechanisms for initiating actin polymerization, attention in the past five years has focused on the regulation of actin nucleation-the formation of new actin filaments from actin monomers. The Arp2/3 complex and the multiple nucleation-promoting factors (NPFs) that regulate its activity comprise the only known cellular actin-nucleating factors and may represent a universal machine, conserved across eukaryotic phyla, that nucleates new actin filaments for various cellular structures with numerous functions. This review focuses on our current understanding of the mechanism of actin nucleation by the Arp2/3 complex and NPFs and how these factors work with other cytoskeletal proteins to generate structurally and functionally diverse actin arrays in cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.18.040202.112133
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