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  • Annual Reviews
  • 2015-2019
  • 2000-2004  (2,241)
  • 1980-1984
  • 1975-1979
  • 1970-1974
  • 2001  (1,104)
  • 2000  (1,137)
Collection
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Years
  • 2015-2019
  • 2000-2004  (2,241)
  • 1980-1984
  • 1975-1979
  • 1970-1974
Year
  • 1
    Electronic Resource
    Electronic Resource
    STRUCTURE AND FUNCTION OF LIPID-DNA COMPLEXES FOR GENE DELIVERY (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 27-47 
    Details
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Owing to the rapid development of in vivo applications for non-viral gene delivery vectors, it is necessary to have a better understanding of how the structure-activity relationships of these lipid-DNA complexes are affected by their environment. Indeed, research in gene therapy first focused on in vitro cell culture studies to determine the mechanisms involved in the delivery of DNA into the cell. New biophysical techniques such as electron microscopy and X-ray diffraction have been developed to discern the structure of the lipid-DNA complex. However, further studies have revealed discrepancies between optimal lipid-DNA formulations for in vitro transfection and for in vivo administration of these vectors. Furthermore, some immune stimulatory effects have been associated with in vivo lipid-DNA administration. This review summarizes the current state of knowledge on in vitro and in vivo lipid-DNA complex transfections. New prospects of vectors for in vivo gene transfer are also discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.29.1.27
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  • 2
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    GCN5-RELATED N-ACETYLTRANSFERASES: A Structural Overview (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 81-103 
    Details
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Hundreds of acetyltransferases exist. All use a common acetyl donor-acetyl coenzyme A-and each exhibits remarkable specificity for acetyl acceptors, which include small molecules and proteins. Analysis of the primary sequences of these enzymes indicates that they can be sorted into several superfamilies. This review covers the three-dimensional structures of members of one of these superfamilies, now referred to in the literature as the GCN5-related N-acetyltransferases (GNAT), reflecting the importance of one functional category, the histone acetyltransferases. Despite the diversity of substrate specificities, members of the GNAT superfamily demonstrate remarkable similarity in protein topology and mode of acetyl coenzyme A binding, likely reflecting a conserved catalytic mechanism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.29.1.81
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  • 3
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    SIGNALING AND SUBCELLULAR TARGETING BY MEMBRANE-BINDING DOMAINS1 (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 49-79 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Protein kinase C homology-1 and -2, FYVE, and pleckstrin homology domains are ubiquitous in eukaryotic signal transduction and membrane-trafficking proteins. These domains regulate subcellular localization and protein function by binding to lipid ligands embedded in cell membranes. Structural and biochemical analysis of these domains has shown that their molecular mechanisms of membrane binding depend on a combination of specific and nonspecific interactions with membrane lipids. In vivo studies of green fluorescent protein fusions have highlighted the key roles of these domains in regulating protein localization to plasma and internal membranes in cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.29.1.49
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  • 4
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    MEASURING THE FORCES THAT CONTROL PROTEIN INTERACTIONS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 1-26 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Although the force fields and interaction energies that control protein behavior can be inferred indirectly from equilibrium and kinetic measurements, recent developments have made it possible to quantify directly (a) the ranges, magnitudes, and time dependence of the interaction energies and forces between biological materials; (b) the mechanical properties of isolated proteins; and (c) the strength of single receptor-ligand bonds. This review describes recent results obtained by using the atomic force microscope, optical tweezers, the surface force apparatus, and micropipette aspiration to quantify short-range protein-ligand interactions and the long-range, nonspecific forces that together control protein behavior. The examples presented illustrate the power of force measurements to quantify directly the force fields and energies that control protein behavior.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.29.1.1
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  • 5
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    DNA RECOGNITION BY Cys2His2 ZINC FINGER PROTEINS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 183-212 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Cys2His2 zinc fingers are one of the most common DNA-binding motifs found in eukaryotic transcription factors. These proteins typically contain several fingers that make tandem contacts along the DNA. Each finger has a conserved betabetaalpha structure, and amino acids on the surface of the alpha-helix contact bases in the major groove. This simple, modular structure of zinc finger proteins, and the wide variety of DNA sequences they can recognize, make them an attractive framework for attempts to design novel DNA-binding proteins. Several studies have selected fingers with new specificities, and there clearly are recurring patterns in the observed side chain-base interactions. However, the structural details of recognition are intricate enough that there are no general rules (a "recognition code") that would allow the design of an optimal protein for any desired target site. Construction of multifinger proteins is also complicated by interactions between neighboring fingers and the effect of the intervening linker. This review analyzes DNA recognition by Cys2His2 zinc fingers and summarizes progress in generating proteins with novel specificities from fingers selected by phage display.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.29.1.183
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  • 6
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    FAST KINETICS AND MECHANISMS IN PROTEIN FOLDING1 (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 327-359 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract This review describes how kinetic experiments using techniques with dramatically improved time resolution have contributed to understanding mechanisms in protein folding. Optical triggering with nanosecond laser pulses has made it possible to study the fastest-folding proteins as well as fundamental processes in folding for the first time. These include formation of alpha-helices, beta-sheets, and contacts between residues distant in sequence, as well as overall collapse of the polypeptide chain. Improvements in the time resolution of mixing experiments and the use of dynamic nuclear magnetic resonance methods have also allowed kinetic studies of proteins that fold too fast (〉 103 s-1) to be observed by conventional methods. Simple statistical mechanical models have been extremely useful in interpreting the experimental results. One of the surprises is that models originally developed for explaining the fast kinetics of secondary structure formation in isolated peptides are also successful in calculating folding rates of single domain proteins from their native three-dimensional structure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.29.1.327
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  • 7
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    A DECADE OF CLC CHLORIDE CHANNELS: Structure, Mechanism, and Many Unsettled Questions (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 411-438 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract ClC-type chloride channels are ubiquitous throughout the biological world. Expressed in nearly every cell type, these proteins have a host of biological functions. With nine distinct homologues known in eukaryotes, the ClCs represent the only molecularly defined family of chloride channels. ClC channels exhibit features of molecular architecture and gating mechanisms unprecedented in other types of ion channels. They form two-pore homodimers, and their voltage-dependence arises not from charged residues in the protein, but rather via coupling of gating to the movement of chloride ions within the pore. Because the functional characteristics of only a few ClC channels have been studied in detail, we are still learning which properties are general to the whole family. New approaches, including structural analyses, will be crucial to an understanding of ClC architecture and function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.29.1.411
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  • 8
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    DESIGNED SEQUENCE-SPECIFIC MINOR GROOVE LIGANDS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 439-461 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract In the past decade, a general design for sequence-specific minor groove ligands has evolved, based on the natural products distamycin and netropsin. By utilizing a basic set of design rules for connecting pyrrole, imidazole, and hydroxypyrrole modules, new ligands can be prepared to target almost any sequence of interest with both high affinity and specificity. In this review we present the design rules with a brief history of how they evolved. The structural basis for sequence-specific recognition is explained, together with developments that allow linking of recognition modules that enable targeting of long DNA sequences. Examples of the affinity and specificity that can be achieved with a number of variations on the basic design are given. Recently these molecules have been used to compete with proteins both in vitro and in vivo, and a brief description of the experimental results are given.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.29.1.439
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  • 9
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    NMR PROBES OF MOLECULAR DYNAMICS: Overview and Comparison with Other Techniques (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 129-155 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract NMR spin relaxation spectroscopy is a powerful approach for characterizing intramolecular and overall rotational motions in proteins. This review describes experimental methods for measuring laboratory frame spin relaxation rate constants by high-resolution solution-state NMR spectroscopy, together with theoretical approaches for interpreting spin relaxation data in order to quantify protein conformational dynamics on picosecond-nanosecond time scales. Recent applications of these techniques to proteins are surveyed, and investigations of the contribution of conformational chain entropy to protein function are highlighted. Insights into the dynamical properties of proteins obtained from NMR spin relaxation spectroscopy are compared with results derived from other experimental and theoretical techniques.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.30.1.129
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  • 10
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    STRUCTURE OF PROTEINS INVOLVED IN SYNAPTIC VESICLE FUSION IN NEURONS (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 157-171 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract The fusion of vesicles with target membranes is controlled by a complex network of protein-protein and protein-lipid interactions. Structures of the SNARE complex, synaptotagmin III, nSec1, domains of the NSF chaperone and its adaptor SNAP, and Rab3 and some of its effectors provide the framework for developing molecular models of vesicle fusion and for designing experiments to test these models.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.30.1.157
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  • 11
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    AB INITIO PROTEIN STRUCTURE PREDICTION: Progress and Prospects (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 173-189 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Considerable recent progress has been made in the field of ab initio protein structure prediction, as witnessed by the third Critical Assessment of Structure Prediction (CASP3). In spite of this progress, much work remains, for the field has yet to produce consistently reliable ab initio structure prediction protocols. In this work, we review the features of current ab initio protocols in an attempt to highlight the foundations of recent progress in the field and suggest promising directions for future work.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.30.1.173
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  • 12
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    STRUCTURAL RELATIONSHIPS AMONG REGULATED AND UNREGULATED PHOSPHORYLASES (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 191-209 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Species and tissue-specific isozymes of phosphorylase display differences in regulatory properties consistent with their distinct roles in particular organisms and tissues. In this review, we compare crystallographic structures of regulated and unregulated phosphorylases, including maltodextrin phosphorylase (MalP) from Escherichia coli, glycogen phosphorylase from yeast, and mammalian isozymes from muscle and liver tissues. Mutagenesis and functional studies supplement the structural work and provide insights into the structural basis for allosteric control mechanisms. MalP, a simple, unregulated enzyme, is contrasted with the more complicated yeast and mammalian phosphorylases that have evolved regulatory sites onto the basic catalytic architecture. The human liver and muscle isozymes show differences structurally in their means of invoking allosteric activation. Phosphorylation, though common to both the yeast and mammalian enzymes, occurs at different sites and activates the enzymes by surprisingly different mechanisms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.30.1.191
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  • 13
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    BIOMOLECULAR SIMULATIONS: Recent Developments in Force Fields, Simulations of Enzyme Catalysis, Protein-Ligand, Protein-Protein, and Protein-Nucleic Acid Noncovalent Interactions (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 211-243 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Computer modeling has been developed and widely applied in studying molecules of biological interest. The force field is the cornerstone of computer simulations, and many force fields have been developed and successfully applied in these simulations. Two interesting areas are (a) studying enzyme catalytic mechanisms using a combination of quantum mechanics and molecular mechanics, and (b) studying macromolecular dynamics and interactions using molecular dynamics (MD) and free energy (FE) calculation methods. Enzyme catalysis involves forming and breaking of covalent bonds and requires the use of quantum mechanics. Noncovalent interactions appear ubiquitously in biology, but here we confine ourselves to review only noncovalent interactions between protein and protein, protein and ligand, and protein and nucleic acids.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.30.1.211
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  • 14
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    CHAPERONIN-MEDIATED PROTEIN FOLDING (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 245-269 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Molecular chaperones are required to assist folding of a subset of proteins in Escherichia coli. We describe a conceptual framework for understanding how the GroEL-GroES system assists misfolded proteins to reach their native states. The architecture of GroEL consists of double toroids stacked back-to-back. However, most of the fundamentals of the GroEL action can be described in terms of the single ring. A key idea in our framework is that, with coordinated ATP hydrolysis and GroES binding, GroEL participates actively by repeatedly unfolding the substrate protein (SP), provided that it is trapped in one of the misfolded states. We conjecture that the unfolding of SP becomes possible because a stretching force is transmitted to the SP when the GroEL particle undergoes allosteric transitions. Force-induced unfolding of the SP puts it on a higher free-energy point in the multidimensional energy landscape from which the SP can either reach the native conformation with some probability or be trapped in one of the competing basins of attraction (i.e., the SP undergoes kinetic partitioning). The model shows, in a natural way, that the time scales in the dynamics of the allosteric transitions are intimately coupled to folding rates of the SP. Several scenarios for chaperonin-assisted folding emerge depending on the interplay of the time scales governing the cycle. Further refinement of this framework may be necessary because single molecule experiments indicate that there is a great dispersion in the time scales governing the dynamics of the chaperonin cycle.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.30.1.245
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  • 15
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    PROPERTIES AND BIOLOGICAL ACTIVITIES OF THIOREDOXINS (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 421-455 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract The mammalian thioredoxins are a family of small (approximately 12 kDa) redox proteins that undergo NADPH-dependent reduction by thioredoxin reductase and in turn reduce oxidized cysteine groups on proteins. The two main thioredoxins are thioredoxin-1, a cytosolic and nuclear form, and thioredoxin-2, a mitochondrial form. Thioredoxin-1 has been studied more. It performs many biological actions including the supply of reducing equivalents to thioredoxin peroxidases and ribonucleotide reductase, the regulation of transcription factor activity, and the regulation of enzyme activity by heterodimer formation. Thioredoxin-1 stimulates cell growth and is an inhibitor of apoptosis. Thioredoxins may play a role in a variety of human diseases including cancer. An increased level of thioredoxin-1 is found in many human tumors, where it is associated with aggressive tumor growth. Drugs are being developed that inhibit thioredoxin and that have antitumor activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.30.1.421
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  • 16
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    INTERPRETING THE EFFECTS OF SMALL UNCHARGED SOLUTES ON PROTEIN-FOLDING EQUILIBRIA (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 271-306 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Proteins are designed to function in environments crowded by cosolutes, but most studies of protein equilibria are conducted in dilute solution. While there is no doubt that crowding changes protein equilibria, interpretations of the changes remain controversial. This review combines experimental observations on the effect of small uncharged cosolutes (mostly sugars) on protein stability with a discussion of the thermodynamics of cosolute-induced nonideality and critical assessments of the most commonly applied interpretations. Despite the controversy surrounding the most appropriate manner for interpreting these effects of thermodynamic nonideality arising from the presence of small cosolutes, experimental advantage may still be taken of the ability of the cosolute effect to promote not only protein stabilization but also protein self-association and complex formation between dissimilar reactants. This phenomenon clearly has potential ramifications in the cell, where the crowded environment could well induce the same effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.30.1.271
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  • 17
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    BINDING OF LIGANDS AND ACTIVATION OF TRANSCRIPTION BY NUCLEAR RECEPTORS (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 329-359 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Nuclear receptors (NRs) form a superfamily of ligand-inducible transcription factors composed of several domains. Recent structural studies focused on domain E, which harbors the ligand-binding site and the ligand-dependent transcription activation function AF-2. Structures of single representatives in an increasing number of various complexes as well as new structures of further NRs addressed issues such as discrimination of ligands, superagonism, isotype specificity, and partial agonism. Until today, one unique transcriptionally active form of domain E was determined; however, divergent tertiary structures of apo-forms and transcriptionally inactive forms are known. Thus, recent results link the transformation of NRs upon ligand binding to principles of protein folding. Furthermore, the ensemble of NR structures, including those of DNA-binding domains, provides one of the foundations for the understanding of interactions with transcription intermediary factors up to the characterization of the link between NR complexes and the basal transcriptional machinery at the structural level.
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    URL: http://dx.doi.org/10.1146/annurev.biophys.30.1.329
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  • 18
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    STRUCTURAL INSIGHTS INTO MICROTUBULE FUNCTION (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 397-420 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Microtubules are polymers that are essential for, among other functions, cell transport and cell division in all eukaryotes. The regulation of the microtubule system includes transcription of different tubulin isotypes, folding of alpha/beta-tubulin heterodimers, post-translation modification of tubulin, and nucleotide-based microtubule dynamics, as well as interaction with numerous microtubule-associated proteins that are themselves regulated. The result is the precise temporal and spatial pattern of microtubules that is observed throughout the cell cycle. The recent high-resolution analysis of the structure of tubulin and the microtubule has brought new insight to the study of microtubule function and regulation, as well as the mode of action of antimitotic drugs that disrupt normal microtubule behavior. The combination of structural, genetic, biochemical, and biophysical data should soon give us a fuller understanding of the exquisite details in the regulation of the microtubule cytoskeleton.
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    URL: http://dx.doi.org/10.1146/annurev.biophys.30.1.397
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  • 19
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    RIBOZYME STRUCTURES AND MECHANISMS (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 457-475 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract The past few years have seen exciting advances in understanding the structure and function of catalytic RNA. Crystal structures of several ribozymes have provided detailed insight into the folds of RNA molecules. Models of other biologically important RNAs have been constructed based on structural, phylogenetic, and biochemical data. However, many questions regarding the catalytic mechanisms of ribozymes remain. This review compares the structures and possible catalytic mechanisms of four small self-cleaving RNAs: the hammerhead, hairpin, hepatitis delta virus, and in vitro-selected lead-dependent ribozymes. The organization of these small catalysts is contrasted to that of larger ribozymes, such as the group I intron.
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    URL: http://dx.doi.org/10.1146/annurev.biophys.30.1.457
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  • 20
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    SALMONELLA INTERACTIONS WITH HOST CELLS: Type III Secretion at Work (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 17 (2001), S. 53-86 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The bacterial pathogen Salmonella enterica has evolved a very sophisticated functional interface with its vertebrate hosts. At the center of this interface is a specialized organelle, the type III secretion system, that directs the translocation of bacterial proteins into the host cell. Salmonella spp. encode two such systems that deliver a remarkable array of bacterial proteins capable of modulating a variety of cellular functions, including actin cytoskeleton dynamics, nuclear responses, and endocytic trafficking. Many of these bacterial proteins operate by faithful mimicry of host proteins, in some cases representing the result of extensive molecular tinkering and convergent evolution. The coordinated action of these type III secreted proteins secures the replication and survival of the bacteria avoiding overt damage to the host. The study of this remarkable pathogen is not only illuminating general paradigms in microbial pathogenesis but is also providing valuable insight into host cell functions.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.17.1.53
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    PATTERNING MECHANISMS CONTROLLING VERTEBRATE LIMB DEVELOPMENT (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 17 (2001), S. 87-132 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Vertebrate limb buds are embryonic structures for which much molecular and cellular data are known regarding the mechanisms that control pattern formation during development. Specialized regions of the developing limb bud, such as the zone of polarizing activity (ZPA), the apical ectodermal ridge (AER), and the non-ridge ectoderm, direct and coordinate the development of the limb bud along the anterior-posterior (AP), dorsal-ventral (DV), and proximal-distal (PD) axes, giving rise to a stereotyped pattern of elements well conserved among tetrapods. In recent years, specific gene functions have been shown to mediate the organizing and patterning activities of the ZPA, the AER, and the non-ridge ectoderm. The analysis of these gene functions has revealed the existence of complex interactions between signaling pathways operated by secreted factors of the HH, TGF-beta/BMP, WNT, and FGF superfamilies, which interact with many other genetic networks to control limb positioning, outgrowth, and patterning. The study of limb development has helped to establish paradigms for the analysis of pattern formation in many other embryonic structures and organs.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.17.1.87
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  • 22
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    IDENTIFICATION OF SELF THROUGH TWO-DIMENSIONAL CHEMISTRY AND SYNAPSES (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 17 (2001), S. 133-157 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Cells in the immune and nervous systems communicate through informational synapses. The two-dimensional chemistry underlying the process of synapse formation is beginning to be explored using fluorescence imaging and mechanical techniques. Early analysis of two-dimensional kinetic rates (kon and koff) and equilibrium constants (Kd) provides a number of biological insights. First, there are two regimes for adhesion-one disordered with slow kon and the other self-ordered with 104-fold faster kon. Despite huge variation in two-dimensional kon, the two-dimensional koff is like koff in solution, and two-dimensional koff is more closely related to intrinsic properties of the interaction than the two-dimensional kon. Thus difference in koff can be used to set signaling thresholds. Early signaling complexes are compartmentalized to generate synergistic signaling domains. Immune antigen receptor components have a role in neural synapse editing. This suggests significant parallels in informational synapse formation based on common two-dimensional chemistry and signaling strategies.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.17.1.133
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    POLARIZED CELL GROWTH IN HIGHER PLANTS (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 17 (2001), S. 159-187 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Pollen tubes and root hairs are highly elongated, cylindrically shaped cells whose polarized growth permits them to explore the environment for the benefit of the entire plant. Root hairs create an enormous surface area for the uptake of water and nutrients, whereas pollen tubes deliver the sperm cells to the ovule for fertilization. These cells grow exclusively at the apex and at prodigious rates (in excess of 200 nm/s for pollen tubes). Underlying this rapid growth are polarized ion gradients and fluxes, turnover of cytoskeletal elements (actin microfilaments), and exocytosis and endocytosis of membrane vesicles. Intracellular gradients of calcium and protons are spatially localized at the growing apex; inward fluxes of these ions are apically directed. These gradients and fluxes oscillate with the same frequency as the oscillations in growth rate but not with the same phase. Actin microfilaments, which together with myosin generate reverse fountain streaming, undergo rapid turnover in the apical domain, possibly being regulated by key actin-binding proteins, e.g., profilin, villin, and ADF/cofilin, in concert with the ion gradients. Exocytosis of vesicles at the apex, also dependent on the ion gradients, provides precursor material for the continuously expanding cell wall of the growing cell. Elucidation of the interactions and of the dynamics of these different components is providing unique insight into the mechanisms of polarized growth.
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    BOUNDARIES IN DEVELOPMENT: Formation and Function (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 17 (2001), S. 189-214 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Developing organisms may contain billions of cells destined to differentiate in numerous different ways. One strategy organisms use to simplify the orchestration of development is the separation of cell populations into distinct functional units. Our expanding knowledge of boundary formation and function in different systems is beginning to reveal general principles of this process. Fields of cells are subdivided by the interpretation of morphogen gradients, and these subdivisions are then maintained and refined by local cell-cell interactions. Sharp and stable separation between cell populations requires special mechanisms to keep cells segregated, which in many cases appear to involve the regulation of cell affinity. Once cell populations become distinct, specialized cells are often induced along the borders between them. These boundary cells can then influence the patterning of surrounding cells, which can result in progressively finer subdivisions of a tissue. Much has been learned about the signaling pathways that establish boundaries, but a key challenge for the future remains to elucidate the cellular and molecular mechanisms that actually keep cell populations separated.
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    A FORTUNATE LIFE IN ASTRONOMY (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Astronomy and Astrophysics 38 (2000), S. 1-33 
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    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract I have had a very fortunate career in astronomy, benefiting greatly from numerous accidents of fate. I grew up in Cincinnati, Ohio, served in the US Army Air Force in World War II, and had all my further education at the University of Chicago, from PhB in the College to PhD in astronomy and astrophysics. There, as a postdoc at Princeton University, and as a young faculty member at Caltech and Mount Wilson and Palomar Observatories, I had excellent teachers and mentors. I have done research primarily on gaseous nebulae and active galactic nuclei, but also made a few early contributions on stellar interiors and the heating in the outer layers of the Sun. The major part of my scientific career was at the University of Wisconsin and Lick Observatory, but I also had three productive years at the Institute for Advanced Study.
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    X-RAY PROPERTIES OF GROUPS OF GALAXIES (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Astronomy and Astrophysics 38 (2000), S. 289-335 
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    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract ROSAT observations indicate that approximately half of all nearby groups of galaxies contain spatially extended X-ray emission. The radial extent of the X-ray emission is typically 50-500 h-1100 kpc or approximately 10-50% of the virial radius of the group. Diffuse X-ray emission is generally restricted to groups that contain at least one early-type galaxy. X-ray spectroscopy suggests the emission mechanism is most likely a combination of thermal bremsstrahlung and line emission. This interpretation requires that the entire volume of groups be filled with a hot, low-density gas known as the intragroup medium. ROSAT and ASCA observations indicate that the temperature of the diffuse gas in groups ranges from approximately 0.3 keV to 2 keV. Higher temperature groups tend to follow the correlations found for rich clusters between X-ray luminosity, temperature, and velocity dispersion. However, groups with temperatures below approximately 1 keV appear to fall off the cluster LX-T relationship (and possibly the LX-sigma and sigma-T cluster relationships, although evidence for these latter departures is at the present time not very strong). Deviations from the cluster LX-T relationship are consistent with preheating of the intragroup medium by an early generation of stars and supernovae. There is now considerable evidence that most X-ray groups are real, physical systems and not chance superpositions or large-scale filaments viewed edge-on. Assuming the intragroup gas is in hydrostatic equilibrium, X-ray observations can be used to estimate the masses of individual systems. ROSAT observations indicate that the typical mass of an X-ray group is ~1013 h-1100 M out to the radius to which X-ray emission is currently detected. The observed baryonic masses of groups are a small fraction of the X-ray determined masses, which implies that groups are dominated by dark matter. On scales of the virial radius, the dominant baryonic component in groups is likely the intragroup medium.
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    URL: http://dx.doi.org/10.1146/annurev.astro.38.1.289
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    OBSERVATIONS OF BROWN DWARFS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Astronomy and Astrophysics 38 (2000), S. 485-519 
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    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract The brown dwarfs occupy the gap between the least massive star and the most massive planet. They begin as dimly stellar in appearance and experience fusion (of at least deuterium) in their interiors. But they are never able to stabilize their luminosity or temperature and grow ever fainter and cooler with time. For that reason, they can be viewed as a constituent of baryonic "dark matter." Indeed, we currently have a hard time directly seeing an old brown dwarf beyond 100 pc. After 20 years of searching and false starts, the first confirmed brown dwarfs were announced in 1995. This was due to a combination of increased sensitivity, better search strategies, and new means of distinguishing substellar from stellar objects. Since then, a great deal of progress has been made on the observational front. We are now in a position to say a substantial amount about actual brown dwarfs. We have a rough idea of how many of them occur as solitary objects and how many are found in binary systems. We have obtained the first glimpse of atmospheres intermediate in temperature between stars and planets, in which dust formation is a crucial process. This has led to the proposal of the first new spectral classes in several decades and the need for new diagnostics for classification and setting the temperature scale. The first hints on the substellar mass function are in hand, although all current masses depend on models. It appears that numerically, brown dwarfs may well be almost as common as stars (though they appear not to contain a dynamically interesting amount of mass).
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    WINDS FROM HOT STARS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Astronomy and Astrophysics 38 (2000), S. 613-666 
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    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract This review deals with the winds from "normal" hot stars such as O-stars, B- and A-supergiants, and Central Stars of Planetary Nebulae with O-type spectra. The advanced diagnostic methods of stellar winds, including an assessment of the accuracy of the determinations of global stellar wind parameters (terminal velocities, mass-loss rates, wind momenta, and energies), are introduced and scaling relations as a function of stellar parameters are provided. Observational results are interpreted in the framework of the stationary, one-dimensional (1-D) theory of line-driven winds. Systematic effects caused by nonhomogeneous structures, time dependence, and deviations from spherical symmetry are discussed. The review finishes with a brief description of the role of stellar winds as extragalactic distance indicators and as tracers of the chemical composition of galaxies at high redshift.
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    TELESCOPES, RED STARS, AND CHILEAN SKIES (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Astronomy and Astrophysics 39 (2001), S. 1-18 
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    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
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    URL: http://dx.doi.org/10.1146/annurev.astro.39.1.1
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    THE NEW SOLAR CORONA1 (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Astronomy and Astrophysics 39 (2001), S. 175-210 
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    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract We focus on new observational capabilities (Yohkoh, SoHO, TRACE), observations, modeling approaches, and insights into physical processes of the solar corona. The most impressive new results and problems discussed in this article can be appreciated from the movies available on the Annual Reviews website and at http://www.lmsal.com/pub/araa/araa.html . "The Sun is new each day." Heraclites (ca 530-475 BC) "Everything flows." Heraclites (ca 530-475 BC)
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    STANDARD COSMOLOGY AND ALTERNATIVES: A Critical Appraisal (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Astronomy and Astrophysics 39 (2001), S. 211-248 
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    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract This review takes a critical look at the cosmological scenario at the turn of the century by examining the available cosmological models in the light of the present observational evidence. The center stage is held by the big bang models, which are collectively referred to here as standard cosmology (SC) and its extensions. SC itself is characterized by a seven parameter set of models based on Einstein's general theory of relativity. The seven parameters are H0, OmegaB, OmegaDM, OmegaLambda, OmegaR (describing the background universe, and A, n (specifying the amplitude and power law index of initial fluctuation spectrum). The extended SC includes extrapolations of the SC to earlier epochs when the mean energies of the particles were greater than about 100 GeV. The strength of the SC is seen to lie in its successful prediction of the expansion of the universe, the abundance of light nuclei, and the spectrum and anisotropies of the cosmic microwave background (CMBR). The SC has led to a whole class of theories of structure formation, which are, in principle, testable observationally. The subject of twentieth century cosmology gained considerably from occasional ideas different from the SC; some of these are briefly outlined and placed in historical perspective. Currently there is only one alternative cosmology, the quasi steady state cosmology (QSSC), that has been developed to a stage where it can be compared with observations and also with the SC. Although the SC does appear quite successful, there are still many unresolved issues that keep the cosmological scene fairly open.
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    Active Control of Sound (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Fluid Mechanics 32 (2000), S. 137-164 
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    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract The active control of sound waves has become an extraordinarily large and vigorous area of academic research and technological development. In this paper we describe the physical principles underlying the control of sound and review their application in a wide range of contexts. One scenario involves the control of noise from a primary source by the introduction of secondary sources, and this technique is described for fields in ducts, in free space, in enclosures (with particular reference to aircraft cabins), and for turbomachinery. A second scenario involves the use of the active control of sound to eliminate large-scale oscillations in more complicated flows, in which part of an unstable feedback cycle is mediated via acoustic waves. Successful applications of this idea include the control of combustion instabilities and compressor surge.
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    URL: http://dx.doi.org/10.1146/annurev.fluid.32.1.137
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    Laboratory Studies of Orographic Effects in Rotating and Stratified Flows (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Fluid Mechanics 32 (2000), S. 165-202 
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    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract This article reviews some aspects of the roles that laboratory experiments have played in the study of orographic effects in the Earth's atmosphere and oceans. The review focuses on, but is not restricted to, physical systems for which the effects of both background stratification and rotation are important. In the past, such laboratory studies have been largely decoupled from attempts to make quantitative comparisons with the results of numerical-model studies or observations from field programs. Rather, they have been used mostly in the important task of better understanding the physics of rotating and stratified flows. Furthermore, most laboratory experiments concerned with the effects of orography on either homogeneous or stratified rotating fluids have considered laminar flows, whereas their counterpart flows in the atmosphere and ocean are turbulent. We argue that laboratory investigations are likely to be more useful in addressing critical environmental problems if the studies are more closely allied with numerical-modeling efforts. The latter, in turn, should be tied to field projects, with the overall objective of improving our ability to predict the behavior of natural systems. In this same spirit, we conclude that far more attention should be given to the laboratory simulation of the turbulent characteristics of natural flows. The availability of rapidly developing technology to acquire and analyze laboratory data provides the capability necessary to support the increasingly important roles that laboratory experiments can play in understanding and predicting the behavior of our natural environment.
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    Capillary Effects on Surface Waves (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Fluid Mechanics 32 (2000), S. 241-274 
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    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract We concentrate on the rich effects that surface tension has on free and forced surface waves for linear, nonlinear, and especially strongly nonlinear waves close to or at breaking or their limiting form. These effects are discussed in the context of standing gravity and gravity-capillary waves, Faraday waves, and parasitic capillary waves. Focus is primarily on post-1989 research. Regarding standing waves, new waveforms and the large effect that small capillarity can have are considered. Faraday waves are discussed principally with regard to viscous effects, hysteresis, and limit cycles; nonlinear waveforms of low mode numbers; contact-line effects and surfactants; breaking and subharmonics; and drop ejection. Pattern formation and chaotic and nonlinear dynamics of Faraday waves are mentioned only briefly. Gravity and gravity-capillary wave generation of parasitic capillaries and dissipation are considered at length. We conclude with our view on the direction of future research in these areas.
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    Passive Scalars in Turbulent Flows (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Fluid Mechanics 32 (2000), S. 203-240 
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    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract Passive scalar behavior is important in turbulent mixing, combustion, and pollution and provides impetus for the study of turbulence itself. The conceptual framework of the subject, strongly influenced by the Kolmogorov cascade phenomenology, is undergoing a drastic reinterpretation as empirical evidence shows that local isotropy, both at the inertial and dissipation scales, is violated. New results of the complex morphology of the scalar field are reviewed, and they are related to the intermittency problem. Recent work on other aspects of passive scalar behavior-its spectrum, probability density function, flux, and variance-is also addressed.
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    Vapor Explosions (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Fluid Mechanics 32 (2000), S. 573-611 
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    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract A vapor explosion results from the rapid and intense heat transfer that may follow contact between a hot liquid and a cold, more volatile one. Because it can happen during severe-accident sequences of a nuclear power plan, that is, when a large part of the core is molten, vapor explosions have been widely studied. The different sequences of a vapor explosion are presented, including premixing, triggering, propagation, and expansion. Typical experimental results are also analyzed to understand the involved physics. Then the different physics involved in the sequences are addressed, as well as the present experimental program.
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    Flows Induced by Temperature Fields in a Rarefied Gas and their Ghost Effect on the Behavior of a Gas in the Continuum Limit (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Fluid Mechanics 32 (2000), S. 779-811 
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    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract In the framework of the classical gas dynamics, no steady flow is induced in a gas without an external force, such as gravity, by the effect of a temperature field. In a rarefied gas, on the other hand, the temperature field of a gas (often in combination with a solid boundary) plays an important role in inducing a steady flow. In the present article, we introduce various kinds of flows induced by the temperature effect and discuss their physical mechanisms. These flows vanish in the continuum limit (the limit where the mean free path of the gas molecules tends to zero), but it has been found recently that they, strangely, affect the behavior of a gas in this limit. This interesting effect, called a ghost effect, is also discussed.
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    ON THE FLUID MECHANICS OF FIRES1 (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Fluid Mechanics 33 (2001), S. 67-92 
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    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract Fluid mechanics research related to fire is reviewed with a focus on canonical flows, multiphysics coupling aspects, and experimental and numerical techniques. Fire is a low-speed, chemically reacting flow in which buoyancy plays an important role. Fire research has focused on two canonical flows, the reacting boundary layer and the reacting free plume. There is rich, multilateral, bidirectional coupling among fluid mechanics and scalar transport, combustion, and radiation. There is only a limited experimental fluid mechanics database for fire owing to measurement difficulties in the harsh environment and to the focus within the fire community on thermal/chemical consequences. Increasingly, computational fluid dynamics techniques are being used to provide engineering guidance on thermal/chemical consequences and to study fire phenomenology.
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    ROSSBY WAVE HYDRAULICS (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Fluid Mechanics 33 (2001), S. 207-230 
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    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract Models are considered for rotating flows over sills, through straits, and along coasts where the variation in geometry in the flow direction is slow but otherwise unrestricted. In addition to the (rotation-modified) free surface waves of nonrotating open channel hydraulics, with their predominantly vertical signature, slow Rossby or vorticity waves are possible when the background potential vorticity varies. In all but the simplest cases the conservation of energy and momentum fluxes is no longer sufficient to determine the flow behavior. Various additional modeling assumptions are reviewed, and time-dependent finite-amplitude and weakly nonlinear theories that include long Rossby wave dynamics are summarized.
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    TURBULENT RELATIVE DISPERSION (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Fluid Mechanics 33 (2001), S. 289-317 
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    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract This review begins with the classical foundations of relative dispersion in Kolmogorov's similarity scaling. Analysis of the special cases of isotropic and homogeneous scalar fields is then used to establish most simply the connection with turbulent mixing. The importance of the two-particle acceleration covariance in relative dispersion is demonstrated from the kinematics of the motion of particle-pairs. A summary of the development of two-particle Lagrangian stochastic models is given, with emphasis on the assumptions and constraints involved, and on predictions of the scalar variance field for inhomogeneous sources. Two-point closures and kinematic simulation are also reviewed in the context of their prediction of the Richardson constant and other fundamental constants. In the absence of reliable field data, direct numerical simulations and laboratory measurements seem most likely to provide suitable data with which to test the assumptions and predictions of these theories.
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    DYNAMIC LOCALIZATION OF BACTERIAL AND PLASMID CHROMOSOMES (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 34 (2000), S. 21-59 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Plasmid-encoded partition genes determine the dynamic localization of plasmid molecules from the mid-cell position to the 1/4 and 3/4 positions. Similarly, bacterial homologs of the plasmid genes participate in controlling the bidirectional migration of the replication origin (oriC) regions during sporulation and vegetative growth in Bacillus subtilis, but not in Escherichia coli. In E. coli, but not B. subtilis, the chromosomal DNA is fully methylated by DNA adenine methyltransferase. The E. coli SeqA protein, which binds preferentially to hemimethylated nascent DNA strands, exists as discrete foci in vivo. A single SeqA focus, which is a SeqA-hemimethylated DNA cluster, splits into two foci that then abruptly migrate bidirectionally to the 1/4 and 3/4 positions during replication. Replicated oriC copies are linked to each other for a substantial period of generation time, before separating from each other and migrating in opposite directions. The MukFEB complex of E. coli and Smc of B. subtilis appear to participate in the reorganization of bacterial sister chromosomes.
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    POLYGENIC AND MULTIFACTORIAL DISEASE GENE ASSOCIATION IN MAN: Lessons from AIDS1 (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 34 (2000), S. 563-591 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract In an age when the majority of monogenic human disease genes have been identified, a particular challenge for the coming generation of human geneticists will be resolving complex polygenic and multifactorial diseases. The tools of molecular and population genetic association have much potential as well as peril in uncovering small cryptic genetic effects in disease. We have used a candidate gene approach to identify eight distinct human loci with alleles that in different ways influence the outcome of exposure to HIV-1, the AIDS virus. The successes in these gene hunts have validated the approach and illustrate the strengths and limitations of association analysis in an actual case history. The integration of genetic associations, well-described clinical cohorts, extensive basic research on AIDS pathogenesis, and functional interpretation of gene connections to disease offers a formula for detecting such genes in complex human genetic phenotypes.
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    COMPLEX TRAIT ANALYSIS IN THE MOUSE: The Strengths, The Limitations and The Promise Yet To Come (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 34 (2000), S. 653-686 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract In 1990, David Baltimore predicted that the 1990s would be the decade of the mouse (1). This certainly proved to be true: The mouse has contributed immensely to biological research through transgenic, embryonic stem cell (ES) knockout, and classical genetic technologies. But its usefulness as a model organism is by no means over; indeed it is still rising to its peak: The mouse as a model mammalian organism still has much to offer. This article reviews use of the mouse to dissect complex genetic traits using quantitative trait analysis, with a particular emphasis on medically important diseases.
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    ANIMAL MODELS OF TUMOR-SUPPRESSOR GENES (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 35 (2001), S. 209-241 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract The development of cancer requires multiple genetic alterations perturbing distinct cellular pathways. In human cancers, these alterations often arise owing to mutations in tumor-suppressor genes whose normal function is to either inhibit the proliferation, apoptosis, or differentiation of cells, or maintain their genomic integrity. Mouse models for tumor suppressors frequently provide definitive evidence for the antitumorigenic functions of these genes. In addition, animal models permit the identification of previously unsuspected roles of these genes in development and differentiation. The availability of null and tissue-specific mouse mutants for tumor-suppressor genes has greatly facilitated our understanding of the mechanisms leading to cancer. In this review, we describe mouse models for tumor-suppressor genes.
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    CHROMATIN INSULATORS AND BOUNDARIES: Effects on Transcription and Nuclear Organization (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 35 (2001), S. 193-208 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Chromatin boundaries and insulators are transcriptional regulatory elements that modulate interactions between enhancers and promoters and protect genes from silencing effects by the adjacent chromatin. Originally discovered in Drosophila, insulators have now been found in a variety of organisms, ranging from yeast to humans. They have been found interspersed with regulatory sequences in complex genes and at the boundaries between active and inactive chromatin. Insulators might modulate transcription by organizing the chromatin fiber within the nucleus through the establishment of higher-order domains of chromatin structure.
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    URL: http://dx.doi.org/10.1146/annurev.genet.35.102401.090349
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    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 
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    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.
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    MECHANISMS OF RETROVIRAL RECOMBINATION (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 35 (2001), S. 275-302 
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    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.
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    URL: http://dx.doi.org/10.1146/annurev.genet.35.102401.090551
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    NEW PERSPECTIVES ON NUCLEAR TRANSPORT (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 35 (2001), S. 341-364 
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    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.
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    URL: http://dx.doi.org/10.1146/annurev.genet.35.102401.090720
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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 
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    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.
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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 
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    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.
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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 
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    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.
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    URL: http://dx.doi.org/10.1146/annurev.genet.35.102401.090954
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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 
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    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.
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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 
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    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.
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    MOLECULAR GENETICS OF HEARING LOSS (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 35 (2001), S. 589-645 
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    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.
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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.
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    URL: http://dx.doi.org/10.1146/annurev.genet.35.102401.091334
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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 
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    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.
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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.
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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.
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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.
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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 
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    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.
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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.
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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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    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.
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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.
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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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    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 
    Details
    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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    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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    URL: http://dx.doi.org/10.1146/annurev.biophys.29.1.155
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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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    URL: http://dx.doi.org/10.1146/annurev.biophys.29.1.265
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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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    URL: http://dx.doi.org/10.1146/annurev.biophys.29.1.497
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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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    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.
    Type of Medium: Electronic Resource
    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 
    Details
    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.
    Type of Medium: Electronic Resource
    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 
    Details
    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.
    Type of Medium: Electronic Resource
    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 
    Details
    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.
    Type of Medium: Electronic Resource
    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.
    Type of Medium: Electronic Resource
    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 
    Details
    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.
    Type of Medium: Electronic Resource
    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.
    Type of Medium: Electronic Resource
    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.
    Type of Medium: Electronic Resource
    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 
    Details
    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.
    Type of Medium: Electronic Resource
    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 
    Details
    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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    URL: http://dx.doi.org/10.1146/annurev.cellbio.16.1.521
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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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.16.1.557
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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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.16.1.591
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