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  • International Union of Crystallography  (6,604)
  • American Geophysical Union (AGU)
  • Annual Reviews
  • 2000-2004  (8,783)
  • 1980-1984
  • 1935-1939
  • 2002  (4,886)
  • 2000  (3,897)
Collection
Publisher
Years
  • 2000-2004  (8,783)
  • 1980-1984
  • 1935-1939
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 
    Details
    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 
    Details
    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 
    Details
    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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    MY ROAD TO BIOPHYSICS: Picking Flowers on the Way to Photosynthesis (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 1-44 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.31.082901.134147
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  • 10
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    NMR STUDIES OF LIPOPROTEIN STRUCTURE (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 177-206 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Early NMR structural studies of serum lipoproteins were based on 1H, 13C, 31P, and 2H studies of lipid components. From the early studies information on composition, lipid chain dynamics and order parameters, and monolayer organization resulted. More recently, selective or complete isotopic labeling techniques, combined with multidimensional NMR spectroscopy, have resulted in structural information of apoprotein fragments. Finally, use of heteronuclear three- and four-dimensional experiments have yielded solution structures and protein-lipid interactions of intact apolipoproteins C-I, C-II, and A-I.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.31.101101.140910
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  • 11
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    THE LINKAGE BETWEEN PROTEIN FOLDING AND FUNCTIONAL COOPERATIVITY: Two Sides of the Same Coin? (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 235-256 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract During the course of their biological function, proteins undergo different types of structural rearrangements ranging from local to large-scale conformational changes. These changes are usually triggered by their interactions with small-molecular-weight ligands or other macromolecules. Because binding interactions occur at specific sites and involve only a small number of residues, a chain of cooperative interactions is necessary for the propagation of binding signals to distal locations within the protein structure. This process requires an uneven structural distribution of protein stability and cooperativity as revealed by NMR-detected hydrogen/deuterium exchange experiments under native conditions. The distribution of stabilizing interactions does not only provide the architectural foundation to the three-dimensional structure of a protein, but it also provides the required framework for functional cooperativity. In this review, the statistical thermodynamic linkage between protein stability, functional cooperativity, and ligand binding is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.31.082901.134215
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  • 12
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    MAGNETIC RESONANCE STUDIES OF THE BACTERIORHODOPSIN PUMP CYCLE (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 73-95 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Active transport requires the alternation of substrate uptake and release with a switch in the access of the substrate binding site to the two sides of the membrane. Both the transfer and switch aspects of the photocycle have been subjects of magnetic resonance studies in bacteriorhodopsin. The results for ion transfer indicate that the Schiff base of the chromophore is hydrogen bonded before, during, and after its deprotonation. This suggests that the initial complex counterion of the Schiff base decomposes in such a way that the Schiff base carries its immediate hydrogen-bonding partner with it as it rotates during the first half of the photocycle. If so, bacteriorhodopsin acts as an inward-directed hydroxide pump rather than as an outward-directed proton pump. The studies of the access switch explore both protein-based and chromophore-based mechanisms. Combined with evidence from functional studies of mutants and other forms of spectroscopy, the results suggest that maintaining access to the extracellular side of the protein after photoisomerization involves twisting of the chromophore and that the decisive switch in access to the cytoplasmic side results from relaxation of the chromophore when the constraints on the Schiff base are released by decomposition of the complex counterion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.31.082901.134233
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  • 13
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    PIP2 AND PROTEINS: Interactions, Organization, and Information Flow (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 151-175 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract We review the physical properties of phosphatidylinositol 4,5-bisphosphate (PIP2) that determine both its specific interactions with protein domains of known structure and its nonspecific electrostatic sequestration by unstructured domains. Several investigators have postulated the existence of distinct pools of PIP2 within the cell to account for the myriad functions of this lipid. Recent experimental work indicates certain regions of the plasma membrane-membrane ruffles and nascent phagosomes-do indeed concentrate PIP2. We consider two mechanisms that could account for this phenomenon: local synthesis and electrostatic sequestration. We conclude by considering the hypothesis that proteins such as MARCKS bind a significant fraction of the PIP2 in a cell, helping to sequester it in lateral membrane domains, then release this lipid in response to local signals such as an increased concentration of Ca++/calmodulin or activation of protein kinase C.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.31.082901.134259
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  • 14
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    STRUCTURAL AND THERMODYNAMIC CORRELATES OF T CELL SIGNALING (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 121-149 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract The first crystal structures of intact T cell receptors (TCRs) bound to class I peptide-MHC (pMHCs) antigens were determined in 1996. Since then, further structures of class I TCR/pMHC complexes have explored the degree of structural variability in the TCR-pMHC system and the structural basis for positive and negative selection. The recent determination of class II and allogeneic class I TCR/pMHC structures, as well as those of accessory molecules (e.g., CD3), has pushed our knowledge of TCR/pMHC interactions into new realms, shedding light on clinical pathologies, such as graft rejection and graft-versus-host disease. Furthermore, the determination of coreceptor structures lays the foundation for a more comprehensive structural description of the supramolecular TCR signaling events and those assemblies that arise in the immunological synapse. While these telling photodocumentaries of the TCR/pMHC interaction are composed mainly from static crystal structures, a full description of the biological snapshots in T cell signaling requires additional analytical methods that record the dynamics of the process. To this end, surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), and ultracentrifugation (UC) have furnished both affinities and kinetics of the TCR/pMHC association. In the past year, structural, biochemical, and molecular biological data describing TCR/pMHC interactions have sublimely coalesced into a burgeoning well of understanding that promises to deliver further insights into T cell recognition. The coming years will, through a more intimate union of structural and kinetic data, allow many pressing questions to be addressed, such as how TCR/pMHC ligation is affected by coreceptor binding and what is the mechanism of TCR signaling in both early and late stages of T cell engagement with antigen-presenting cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.31.082901.134423
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  • 15
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    THE alpha-HELIX AND THE ORGANIZATION AND GATING OF CHANNELS (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 207-233 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract The structures of an increasing number of channels and other alpha-helical membrane proteins have been determined recently, including the KcsA potassium channel, the MscL mechanosensitive channel, and the AQP1 and GlpF members of the aquaporin family. In this chapter, the orientation and packing characteristics of bilayer-spanning helices are surveyed in integral membrane proteins. In the case of channels, alpha-helices create the sealed barrier that separates the hydrocarbon region of the bilayer from the permeation pathway for solutes. The helices surrounding the permeation pathway tend to be rather steeply tilted relative to the membrane normal and are consistently arranged in a right-handed bundle. The helical framework further provides a supporting scaffold for nonmembrane-spanning structures associated with channel selectivity. Although structural details remain scarce, the conformational changes associated with gating transitions between closed and open states of channels are reviewed, emphasizing the potential roles of helix-helix interactions in this process.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.31.082901.134329
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  • 16
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    PRINCIPLES AND BIOPHYSICAL APPLICATIONS OF LANTHANIDE-BASED PROBES (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 275-302 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Using luminescent lanthanides, instead of conventional fluorophores, as donor molecules in resonance energy transfer measurements offers many technical advantages and opens up a wide range of new applications. Advantages include farther measurable distances (~100 A) with greater accuracy, insensitivity to incomplete labeling, and the ability to use generic relatively large labels, when necessary. Applications highlighted include the study of ion channels in living cells, protein-protein interaction in cells, DNA-protein complexes, and high-throughput screening assays to measure peptide dimerization associated with DNA transcription factors and ligand-receptor interactions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.31.101101.140927
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  • 17
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    SINGLE-PARTICLE IMAGING OF MACROMOLECULES BY CRYO-ELECTRON MICROSCOPY (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 303-319 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Cryo-electron microscopy (cryo-EM) of biological molecules in single-particle (i.e., unordered, nonaggregated) form is a new approach to the study of molecular assemblies, which are often too large and flexible to be amenable to X-ray crystallography. New insights into biological function on the molecular level are expected from cryo-EM applied to the study of such complexes "trapped" at different stages of their conformational changes and dynamical interactions. Important molecular machines involved in the fundamental processes of transcription, mRNA splicing, and translation are examples for successful applications of the new technique, combined with structural knowledge gained by conventional techniques of structure determination, such as X-ray crystallography and NMR.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.31.082901.134202
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  • 18
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    RHODOPSIN: Insights from Recent Structural Studies (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 443-484 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract The recent report of the crystal structure of rhodopsin provides insights concerning structure-activity relationships in visual pigments and related G protein-coupled receptors (GPCRs). The seven transmembrane helices of rhodopsin are interrupted or kinked at multiple sites. An extensive network of interhelical interactions stabilizes the ground state of the receptor. The ligand-binding pocket of rhodopsin is remarkably compact, and several chromophore-protein interactions were not predicted from mutagenesis or spectroscopic studies. The helix movement model of receptor activation, which likely applies to all GPCRs of the rhodopsin family, is supported by several structural elements that suggest how light-induced conformational changes in the ligand-binding pocket are transmitted to the cytoplasmic surface. The cytoplasmic domain of the receptor includes a helical domain extending from the seventh transmembrane segment parallel to the bilayer surface. The cytoplasmic surface appears to be approximately large enough to bind to the transducin heterotrimer in a one-to-one complex. The structural basis for several unique biophysical properties of rhodopsin, including its extremely low dark noise level and high quantum efficiency, can now be addressed using a combination of structural biology and various spectroscopic methods. Future high-resolution structural studies of rhodopsin and other GPCRs will form the basis to elucidate the detailed molecular mechanism of GPCR-mediated signal transduction.
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    URL: http://dx.doi.org/10.1146/annurev.biophys.31.082901.134348
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  • 19
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    CONFORMATIONAL REGULATION OF INTEGRIN STRUCTURE AND FUNCTION (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 485-516 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Integrins are a structurally elaborate family of heterodimers that mediate divalent cation-dependent cell adhesion in a wide range of biological contexts. The inserted (I) domain binds ligand in the subset of integrins in which it is present. Its structure has been determined in two alternative conformations, termed open and closed. In striking similarity to signaling G proteins, rearrangement of a Mg2+-binding site is linked to large conformational movements in distant backbone regions. Mutations have been used to stabilize either the closed or open structures. These show that the snapshots of the open conformation seen only in the presence of a ligand or a ligand mimetic represent a high-affinity, ligand-binding conformation, whereas those of the closed conformation correspond to a low-affinity conformation. The C-terminal alpha-helix moves 10 A down the side of the domain in the open conformation. Locking in the conformation of the preceding loop is sufficient to increase affinity for ligand 9000-fold. This C-terminal "bell-rope" provides a mechanism for linkage to conformational movements in other domains. The transition from the closed to open conformation has been implicated in fast (〈1 s) regulation of integrin affinity in response to activation signals from inside the cell. Recent integrin structures and functional studies reveal interactions between beta-propeller, I, and I-like domains in the headpiece, and a critical role for integrin EGF domains in the stalk region. These studies suggest that the headpiece of the integrin faces down toward the membrane in the inactive conformation and extends upward in a "switchblade"-like opening motion upon activation. These long-range structural rearrangements of the entire integrin molecule involving multiple interdomain contacts appear closely linked to conformational changes in the I domain, which result in increased affinity and competence for ligand binding.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.31.101101.140922
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    A CELL BIOLOGICAL PERSPECTIVE ON ALZHEIMER'S DISEASE (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 18 (2002), S. 25-51 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The amyloid precursor protein and the proteases cleaving this protein are important players in the pathogenesis of Alzheimer's disease via the generation of the amyloid peptide. Physiologically, the amyloid precursor protein is implied in axonal vesicular trafficking and the proteases are implicated in developmentally important signaling pathways, most significantly those involving regulated intramembrane proteolysis or RIP. We discuss the cell biology behind the amyloid and tangle hypothesis for Alzheimer's disease, drawing on the many links to the fields of cell biology and developmental biology that have been established in the recent years.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.18.020402.142302
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  • 21
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    TYPE III PROTEIN SECRETION IN YERSINIA SPECIES (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 18 (2002), S. 107-133 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The type III mechanism of protein secretion is a pathogenic strategy shared by a number of gram-negative pathogens of plants and animals that has evolved in order to inject virulence proteins into the cytosol of target eukaryotic cells. The pathogens of the Yersinia genus represent a model system where much progress has been made in understanding this secretion pathway. Herein, we review what has been recently learned in yersiniae about the various environmental signals that induce type III secretion, how the synthesis of secretion substrates is regulated, and how such a diverse group of proteins is recognized as a substrate for secretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.18.012502.105912
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    BREAK INS AND BREAK OUTS: Viral Interactions with the Cytoskeleton of Mammalian Cells (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 18 (2002), S. 135-161 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The host cytoskeleton plays important roles in the entry, replication, and egress of viruses. An assortment of viruses hijack cellular motor proteins to move on microtubules toward the cell interior during the entry process; others reverse this transport during egress to move assembling virus particles toward the plasma membrane. Polymerization of actin filaments is sometimes used to propel viruses from cell to cell, while many viruses induce the destruction of select cytoskeletal filaments apparently to effect efficient egress. Indeed, the tactics used by any given virus to achieve its infectious life cycle are certain to involve multiple cytoskeletal interactions. Understanding these interactions, and their orchestration during viral infections, is providing unexpected insights into basic virology, viral pathogenesis, and the biology of the cytoskeleton.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.18.012502.105920
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    CHROMOSOME-MICROTUBULE INTERACTIONS DURING MITOSIS (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 18 (2002), S. 193-219 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Spindle microtubules interact with mitotic chromosomes, binding to their kinetochores to generate forces that are important for accurate chromosome segregation. Motor enzymes localized both at kinetochores and spindle poles help to form the biologically significant attachments between spindle fibers and their cargo, but microtubule-associated proteins without motor activity contribute to these junctions in important ways. This review examines the molecules necessary for chromosome-microtubule interaction in a range of well-studied organisms, using biological diversity to identify the factors that are essential for organized chromosome movement. We conclude that microtubule dynamics and the proteins that control them are likely to be more important for mitosis than the current enthusiasm for motor enzymes would suggest.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.18.032002.132412
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    THE CHLAMYDIAL INCLUSION: Escape from the Endocytic Pathway1 (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 18 (2002), S. 221-245 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Chlamydiae, bacterial obligate intracellular pathogens, are the etiologic agents of several human diseases. A large part of the chlamydial intracellular survival strategy involves the formation of a unique organelle called the inclusion that provides a protected site within which they replicate. The chlamydial inclusion is effectively isolated from endocytic pathways but is fusogenic with a subset of exocytic vesicles that deliver sphingomyelin from the Golgi apparatus to the plasma membrane. A combination of host and parasite functions contribute to the biogenesis of this compartment. Establishment of the mature inclusion is accompanied by the insertion of multiple chlamydial proteins, suggesting that chlamydiae actively modify the inclusion to define its interactions with the eukaryotic host cell. Despite being sequestered within a membrane-bound vacuole, chlamydiae clearly communicate with and manipulate the host cell from within this privileged intracellular niche.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.18.012502.105845
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    MOLECULAR MECHANISMS OF EPITHELIAL MORPHOGENESIS (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 18 (2002), S. 463-493 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Epithelial morphogenesis comprises the various processes by which epithelia contribute to organ formation and body shape. These complex and diverse events play a central role in animal development and regeneration. Recently, the characterization of some of the molecular mechanisms involved in epithelial morphogenesis has provided an abundance of new information on the role and regulation of the cytoskeleton, cell-cell adhesion, and cell-matrix adhesion in these processes. In this review, we discuss our current understanding of the molecular mechanisms driving cell shape changes, cell intercalation, fusion of epithelia, ingression, egression, and cell migration. Our discussion is mostly focused on results from Drosophila and mammalian tissue culture but also draws on the insights gained from other organisms.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.18.022602.131838
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    GOLGI ARCHITECTURE AND INHERITANCE (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 18 (2002), S. 379-420 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Golgi inheritance proceeds via sequential biogenesis and partitioning phases. Although little is known about Golgi growth and replication (biogenesis), ultrastructural and fluorescence analyses have provided a detailed, though still controversial, perspective of Golgi partitioning during mitosis in mammalian cells. Partitioning requires the fragmentation of the juxtanuclear ribbon of interconnected Golgi stacks into a multitude of tubulovesicular clusters. This process is choreographed by a cohort of mitotic kinases and an inhibition of heterotypic and homotypic Golgi membrane-fusion events. Our model posits that accurate partitioning occurs early in mitosis by the equilibration of Golgi components on either side of the metaphase plate. Disseminated Golgi components then coalesce to regenerate Golgi stacks during telophase. Semi-intact cell and cell-free assays have accurately recreated these processes and allowed their molecular dissection. This review attempts to integrate recent findings to depict a more coherent, synthetic molecular picture of mitotic Golgi fragmentation and reassembly. Of particular importance is the emerging concept of a highly regulated and dynamic Golgi structural matrix or template that interfaces with cargo receptors, Golgi enzymes, Rab-GTPases, and SNAREs to tightly couple biosynthetic transport to Golgi architecture. This structural framework may be instructive for Golgi biogenesis and may encode sufficient information to ensure accurate Golgi inheritance, thereby helping to resolve some of the current discrepancies between different workers.
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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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    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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    URL: http://dx.doi.org/10.1146/annurev.astro.38.1.613
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    KUIPER BELT OBJECTS: Relics from the Accretion Disk of the Sun (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Astronomy and Astrophysics 40 (2002), S. 63-101 
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    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract The Kuiper Belt consists of a large number of small, solid bodies in heliocentric orbit beyond Neptune. Discovered as recently as 1992, the Kuiper Belt objects (KBOs) are thought to hold the keys to understanding the early solar system, as well as the origin of outer solar system objects, such as the short-period comets and the Pluto-Charon binary. The KBOs are probably best viewed as aged relics of the Sun's accretion disk. Dynamical structures in the Kuiper Belt provide evidence for processes operative in the earliest days of the solar system, including a phase of planetary migration and a clearing phase, in which substantial mass was lost from the disk. Dust is produced to this day by collisions between KBOs. In its youth, the Kuiper Belt may have compared to the dust rings observed now around such stars as GG Tau and HR 4796A. This review presents the basic physical parameters of the KBOs and makes connections with the disks observed around nearby stars.
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    URL: http://dx.doi.org/10.1146/annurev.astro.40.060401.093818
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    COSMIC MICROWAVE BACKGROUND ANISOTROPIES (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Astronomy and Astrophysics 40 (2002), S. 171-216 
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    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract Cosmic microwave background (CMB) temperature anisotropies have and will continue to revolutionize our understanding of cosmology. The recent discovery of the previously predicted acoustic peaks in the power spectrum has established a working cosmological model: a critical density universe consisting of mainly dark matter and dark energy, which formed its structure through gravitational instability from quantum fluctuations during an inflationary epoch. Future observations should test this model and measure its key cosmological parameters with unprecedented precision. The phenomenology and cosmological implications of the acoustic peaks are developed in detail. Beyond the peaks, the yet to be detected secondary anisotropies and polarization present opportunities to study the physics of inflation and the dark energy. The analysis techniques devised to extract cosmological information from voluminous CMB data sets are outlined, given their increasing importance in experimental cosmology as a whole.
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    THE EVOLUTION OF X-RAY CLUSTERS OF GALAXIES (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Astronomy and Astrophysics 40 (2002), S. 539-577 
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    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract Considerable progress has been made over the past decade in the study of the evolutionary trends of the population of galaxy clusters in the Universe. In this review we focus on observations in the X-ray band. X-ray surveys with the ROSAT satellite, supplemented by follow-up studies with ASCA and Beppo-SAX, have allowed an assessment of the evolution of the space density of clusters out to z= 1 and the evolution of the physical properties of the intracluster medium out to z= 0.5. With the advent of Chandra and Newton-XMM and their unprecedented sensitivity and angular resolution, these studies have been extended beyond redshift unity and have revealed the complexity of the thermodynamical structure of clusters. The properties of the intracluster gas are significantly affected by nongravitational processes including star formation and Active Galactic Nuclei (AGN) activity. Convincing evidence has emerged for modest evolution of both the bulk of the X-ray cluster population and their thermodynamical properties since redshift unity. Such an observational scenario is consistent with hierarchical models of structure formation in a flat low-density universe with Omegam= 0.3 and sigma8= 0.7-0.8 for the normalization of the power spectrum. Basic methodologies for construction of X-ray-selected cluster samples are reviewed, and implications of cluster evolution for cosmological models are discussed.
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    THEORY OF GIANT PLANETS (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Astronomy and Astrophysics 40 (2002), S. 103-136 
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    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract Giant planet research has moved from the study of a handful of solar system objects to that of a class of bodies with dozens of known members. Since the original 1995 discovery of the first extrasolar giant planets (EGPs), the total number of known examples has increased to ~80 (circa November 2001). Current theoretical studies of giant planets emphasize predicted observable properties, such as luminosity, effective temperature, radius, external gravity field, atmospheric composition, and emergent spectra as a function of mass and age. This review focuses on the general theory of hydrogen-rich giant planets; smaller giant planets with the mass and composition of Uranus and Neptune are not covered. We discuss the status of the theory of the nonideal thermodynamics of hydrogen and hydrogen-helium mixtures under the conditions found in giant-planet interiors, and the experimental constraints on it. We provide an overview of observations of extrasolar giant planets and our own giant planets by which the theory can be validated.
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    CLUSTER MAGNETIC FIELDS (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Astronomy and Astrophysics 40 (2002), S. 319-348 
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    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract Magnetic fields in the intercluster medium have been measured using a variety of techniques, including studies of synchrotron relic and halo radio sources within clusters, studies of inverse Compton X-ray emission from clusters, surveys of Faraday rotation measures of polarized radio sources both within and behind clusters, and studies of cluster cold fronts in X-ray images. These measurements imply that most cluster atmospheres are substantially magnetized, with typical field strengths of order 1 muGauss with high areal filling factors out to Mpc radii. There is likely to be considerable variation in field strengths and topologies both within and between clusters, especially when comparing dynamically relaxed clusters to those that have recently undergone a merger. In some locations, such as the cores of cooling flow clusters, the magnetic fields reach levels of 10-40 muG and may be dynamically important. In all clusters the magnetic fields have a significant effect on energy transport in the intracluster medium. We also review current theories on the origin of cluster magnetic fields.
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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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    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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    DAVID CRIGHTON, 1942-2000: A Commentary on His Career and His Influence on Aeroacoustic Theory (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Fluid Mechanics 34 (2002), S. 37-49 
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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 David Crighton, a greatly admired figure in fluid mechanics, Head of the Department of Applied Mathematics and Theoretical Physics at Cambridge, and Master of Jesus College, Cambridge, died at the peak of his career. He had made important contributions to the theory of waves generated by unsteady flow. Crighton's work was always characterized by the application of rigorous mathematical approximations to fluid mechanical idealizations of practically relevant problems. At the time of his death, he was certainly the most influential British applied mathematical figure, and his former collaborators and students form a strong school that continues his special style of mathematical application. Rigorous analysis of well-posed aeroacoustical problems was transformed by David Crighton.
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    CAVITATION IN VORTICAL FLOWS (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Fluid Mechanics 34 (2002), S. 143-175 
    Details
    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 Cavitation in vortical structures is a common, albeit complex, problem in engineering applications. Cavitating vortical structures can be found on the blade surfaces, in the clearance passages, and at the hubs of various types of turbomachinery. Cavitating microvortices at the trailing edge of attached sheet cavitation can be highly erosive. Cavitating hub vortices in the draft tubes of hydroturbines can cause major surges and power swings. There is also mounting evidence that vortex cavitation is a dominant factor in the inception process in a broad range of turbulent flows. Most research has focused on the inception process, with limited attention paid to developed vortex cavitation. Wave-like disturbances on the surfaces of vapor cores are an important feature. Vortex core instabilities in microvortices are found to be important factors in the erosion mechanisms associated with sheet/cloud cavitation. Under certain circumstances, intense sound at discrete frequencies can result from a coupling between tip vortex disturbances and oscillating sheet cavitation. Vortex breakdown phenomena that have some commonalities are also noted, as are some differences with vortex breakdown in fully wetted flow. Simple vortex models can sometimes be used to describe the cavitation process in complex turbulent flows such as bluff body wakes and in plug valves. Although a vortex model for cavitation in jets does not exist, the mechanism of inception appears to be related to the process of vortex pairing. The pairing process can produce negative peaks in pressure that can exceed the rms value by a factor of ten, sometimes exceeding the dynamic pressure by a factor of two. A new and important issue is that cavitation is not only induced in vortical structures but is also a mechanism for vorticity generation.
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    URL: http://dx.doi.org/10.1146/annurev.fluid.34.082301.114957
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    MICROSTRUCTURAL EVOLUTION IN POLYMER BLENDS (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Fluid Mechanics 34 (2002), S. 177-210 
    Details
    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 Microstructure in an immiscible polymer blend consists of the size, shape, and orientation of the phases. Blends exhibit many interesting behaviors, including enhanced elasticity at small strains, drop-size hysteresis, enhanced shear thinning, and stress relaxation curves whose shapes are sensitive to deformation history. These behaviors are directly related to changes in the microstructure, which result from phase deformation, coalescence, retraction, and different types of breakup. These phenomena are reviewed, together with models that describe them. Rheological measurements can probe the microstructure because microstructure contributes directly to stress through interfacial tension. Rheo-optical experiments also provide important insights. Droplet theories explain most of the phenomena for Newtonian phases at low concentrations. Behaviors at high volume fractions or with strongly non-Newtonian phases are less well understood.
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    URL: http://dx.doi.org/10.1146/annurev.fluid.34.082301.144051
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    MOLECULAR ORIENTATION EFFECTS IN VISCOELASTICITY (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Fluid Mechanics 34 (2002), S. 417-444 
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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 Recent advances in the computational modeling of molecular conformational and orientational effects in the flow of viscoelastic fluids are described. These advances involve the coupling of molecular models for the underlying microstructure of macromolecules with the macroscopic equations of change. The kinetic theory for polymeric liquids is described along with the most useful micromechanical models for computing the fluid flow of polymeric liquids. Three levels of description are covered for the computation of molecular orientation effects: methods for molecular models for which closed-form, continuum-like evolution equations for average quantities describing molecular conformations can be obtained, hybrid methods that involve coupling direct solution of the Fokker-Planck equation describing the distribution function for molecular orientations with the equations of change, and hybrid methods that couple stochastic simulations of individual molecule trajectories with the macroscopic equations of change. Illustrative results for rheometric flows (flows with homogeneous, fixed kinematics) and complex flows are given.
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    URL: http://dx.doi.org/10.1146/annurev.fluid.34.083101.134818
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    FLUID DYNAMICS OF El NINO VARIABILITY (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Fluid Mechanics 34 (2002), S. 531-558 
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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 El Nino variability in the equatorial Tropical Pacific is characterized by sea-surface temperature anomalies and associated changes in the atmospheric circulation. Through an enormous monitoring effort over the last decades, the relevant time scales and spatial patterns are fairly well documented. In the meantime, a hierarchy of models has been developed to understand the physics of this phenomenon and to make predictions of future variability. In this review, the robust and relevant details of the observations, the fluid mechanical "building blocks," the theory of the deterministic part of the variability, and the impact of small-scale ("noise") and remote ("external") processes are evaluated.
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    URL: http://dx.doi.org/10.1146/annurev.fluid.34.090501.144936
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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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    URL: http://dx.doi.org/10.1146/annurev.genet.34.1.21
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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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    URL: http://dx.doi.org/10.1146/annurev.genet.34.1.563
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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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    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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    URL: http://dx.doi.org/10.1146/annurev.genet.34.1.479
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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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    URL: http://dx.doi.org/10.1146/annurev.genet.34.1.457
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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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    URL: http://dx.doi.org/10.1146/annurev.genet.34.1.499
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    GENETICS OF CRYPTOCOCCUS NEOFORMANS (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 36 (2002), S. 557-615 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Cryptococcus neoformans is a pathogenic fungus that primarily afflicts immunocompromised patients, infecting the central nervous system to cause meningoencephalitis that is uniformly fatal if untreated. C. neoformans is a basidiomycetous fungus with a defined sexual cycle that has been linked to differentiation and virulence. Recent advances in classical and molecular genetic approaches have allowed molecular descriptions of the pathways that control cell type and virulence. An ongoing genome sequencing project promises to reveal much about the evolution of this human fungal pathogen into three distinct varieties or species. C. neoformans shares features with both model ascomycetous yeasts (Saccharomyces cerevisiae, Schizosaccharomyces pombe) and basidiomycetous pathogens and mushrooms (Ustilago maydis, Coprinus cinereus, Schizophyllum commune), yet ongoing studies reveal unique features associated with virulence and the arrangement of the mating type locus. These advances have catapulted C. neoformans to center stage as a model of both fungal pathogenesis and the interesting approaches to life that the kingdom of fungi has adopted.
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    URL: http://dx.doi.org/10.1146/annurev.genet.36.052402.152652
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    TRANSVECTION EFFECTS IN DROSOPHILA (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 36 (2002), S. 521-556 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract An unusual feature of the Diptera is that homologous chromosomes are intimately synapsed in somatic cells. At a number of loci in Drosophila, this pairing can significantly influence gene expression. Such influences were first detected within the bithorax complex (BX-C) by E.B. Lewis, who coined the term transvection to describe them. Most cases of transvection involve the action of enhancers in trans. At several loci deletion of the promoter greatly increases this action in trans, suggesting that enhancers are normally tethered in cis by the promoter region. Transvection can also occur by the action of silencers in trans or by the spreading of position effect variegation from rearrangements having heterochromatic breakpoints to paired unrearranged chromosomes. Although not demonstrated, other cases of transvection may involve the production of joint RNAs by trans-splicing. Several cases of transvection require Zeste, a DNA-binding protein that is thought to facilitate homolog interactions by self-aggregation. Genes showing transvection can differ greatly in their response to pairing disruption. In several cases, transvection appears to require intimate synapsis of homologs. However, in at least one case (transvection of the iab-5,6,7 region of the BX-C), transvection is independent of synapsis within and surrounding the interacting gene. The latter example suggests that transvection could well occur in organisms that lack somatic pairing. In support of this, transvection-like phenomena have been described in a number of different organisms, including plants, fungi, and mammals.
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    TOWARD MAINTAINING THE GENOME: DNA Damage and Replication Checkpoints (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 36 (2002), S. 617-656 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract DNA checkpoints play a significant role in cancer pathology, perhaps most notably in maintaining genome stability. This review summarizes the genetic and molecular mechanisms of checkpoint activation in response to DNA damage. The major checkpoint proteins common to all eukaryotes are identified and discussed, together with how the checkpoint proteins interact to induce arrest within each cell cycle phase. Also discussed are the molecular signals that activate checkpoint responses, including single-strand DNA, double-strand breaks, and aberrant replication forks. We address the connection between checkpoint proteins and damage repair mechanisms, how cells recover from an arrest response, and additional roles that checkpoint proteins play in DNA metabolism. Finally, the connection between checkpoint gene mutation and genomic instability is considered.
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    GENETIC APPROACHES TO MOLECULAR AND CELLULAR COGNITION: A Focus on LTP and Learning and Memory (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 36 (2002), S. 687-720 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Long-term potentiation (LTP) is the predominant experimental model for the synaptic plasticity mechanisms thought to underlie learning and memory. This review is focused on the contributions of genetics to the understanding of the role of LTP in learning and memory. These studies have used a combination of genetics, molecular biology, neurophysiology, and psychology to demonstrate that molecular mechanisms of synaptic plasticity are critical for learning and memory. Because of the large scope of this literature, we focus primarily on genetic studies of hippocampal-dependent learning. Altogether, these findings not only demonstrate a role for plasticity in learning, they also lay down the foundations for the new field of molecular and cellular cognition.
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    URL: http://dx.doi.org/10.1146/annurev.genet.36.062802.091007
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    THE FELINE GENOME PROJECT1 (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 36 (2002), S. 657-686 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract The compilation of a dense gene map and eventually a whole genome sequence (WGS) of the domestic cat holds considerable value for human genome annotation, for veterinary medicine, and for insight into the evolution of genome organization among mammals. Human association and veterinary studies of the cat, its domestic breeds, and its charismatic wild relatives of the family Felidae have rendered the species a powerful model for human hereditary diseases, for infectious disease agents, for adaptive evolutionary divergence, for conservation genetics, and for forensic applications. Here we review the advantages, rationale, and present strategy of a feline genome project, and we describe the disease models, comparative genomics, and biological applications posed by the full resolution of the cat's genome.
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    ESTIMATING F-STATISTICS (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genetics 36 (2002), S. 721-750 
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    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract A moment estimator of theta, the coancestry coefficient for alleles within a population, was described by Weir & Cockerham in 1984 (100) and is still widely cited. The estimate is used by population geneticists to characterize population structure, by ecologists to estimate migration rates, by animal breeders to describe genetic variation, and by forensic scientists to quantify the strength of matching DNA profiles. This review extends the work of Weir & Cockerham by allowing different levels of coancestry for different populations, and by allowing non-zero coancestries between pairs of populations. All estimates are relative to the average value of theta between pairs of populations. Moment estimates for within- and between-population theta values are likely to have large sampling variances, although these may be reduced by combining information over loci. Variances also decrease with the numbers of alleles at a locus, and with the numbers of populations sampled. This review also extends the work of Weir & Cockerham by employing maximum likelihood methods under the assumption that allele frequencies follow the normal distribution over populations. For the case of equal theta values within populations and zero theta values between populations, the maximum likelihood estimate is the same as that given by Robertson & Hill in 1984 (70). The review concludes by relating functions of theta values to times of population divergence under a pure drift model.
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    ELECTROKINETICALLY CONTROLLED MICROFLUIDIC ANALYSIS SYSTEMS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 155-181 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Electrokinetic forces are emerging as a powerful means to drive microfluidic systems with flow channel cross-sectional dimensions in the tens of micrometers and flow rates in the nanoliter per second range. These systems provide many advantages such as improved analysis speed, improved reproducibility, greatly reduced reagent consumption, and the ability to perform multiple operations in an integrated fashion. Planar microfabrication methods are used to make these analysis chips in materials such as glass or polymers. Many applications of this technology have been demonstrated, such as DNA separations, enzyme assays, immunoassays, and PCR amplification integrated with microfluidic assays. Further development of this technology is expected to yield higher levels of functionality of sample throughput on a single microfluidic analysis chip.
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    STRUCTURAL SYMMETRY AND PROTEIN FUNCTION (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 105-153 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract The majority of soluble and membrane-bound proteins in modern cells are symmetrical oligomeric complexes with two or more subunits. The evolutionary selection of symmetrical oligomeric complexes is driven by functional, genetic, and physicochemical needs. Large proteins are selected for specific morphological functions, such as formation of rings, containers, and filaments, and for cooperative functions, such as allosteric regulation and multivalent binding. Large proteins are also more stable against denaturation and have a reduced surface area exposed to solvent when compared with many individual, smaller proteins. Large proteins are constructed as oligomers for reasons of error control in synthesis, coding efficiency, and regulation of assembly. Symmetrical oligomers are favored because of stability and finite control of assembly. Several functions limit symmetry, such as interaction with DNA or membranes, and directional motion. Symmetry is broken or modified in many forms: quasisymmetry, in which identical subunits adopt similar but different conformations; pleomorphism, in which identical subunits form different complexes; pseudosymmetry, in which different molecules form approximately symmetrical complexes; and symmetry mismatch, in which oligomers of different symmetries interact along their respective symmetry axes. Asymmetry is also observed at several levels. Nearly all complexes show local asymmetry at the level of side chain conformation. Several complexes have reciprocating mechanisms in which the complex is asymmetric, but, over time, all subunits cycle through the same set of conformations. Global asymmetry is only rarely observed. Evolution of oligomeric complexes may favor the formation of dimers over complexes with higher cyclic symmetry, through a mechanism of prepositioned pairs of interacting residues. However, examples have been found for all of the crystallographic point groups, demonstrating that functional need can drive the evolution of any symmetry.
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    QUANTITATIVE CHEMICAL ANALYSIS OF SINGLE CELLS1 (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 239-263 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract A fundamental perspective can be achieved by targeting single cells for analysis with the goal of deconvoluting complex biological functions. However, single-cell studies have their own difficulties, such as minute volumes and sample amounts. Quantitative chemical analysis of single cells has emerged as a powerful new area in recent years due to several technological advancements. The development of microelectrodes has allowed the measurement of redox-active species as a function of cellular dynamics. This miniaturization trend is also evident in the separation sciences with the application of small column separations to single cells. Desorption ionization methods with mass spectrometric detection have shown single-cell capability owing to numerous technological developments. Finally, fluorescence imaging has also progressed to the point where single-cell dynamics can be probed by native fluorescence utilizing either single or multiple photon excitation. The results of these studies are reviewed with an emphasis on the quantitation of single-cell dynamics.
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    THE STRUCTURAL BIOLOGY OF MOLECULAR RECOGNITION BY VANCOMYCIN (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 265-289 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Vancomycin is the archetype among naturally occurring compounds known as glycopeptide antibiotics. Because it is a vital therapeutic agent used worldwide for the treatment of infections with gram-positive bacteria, emerging bacterial resistance to vancomycin is a major public health threat. Recent investigations into the mechanisms of action of glycopeptide antibiotics are driven by a need to understand their detailed mechanism of action so that new agents can be developed to overcome resistance. These investigations have revealed that glycopeptide antibiotics exhibit a rich array of complex cooperative phenomena when they bind target ligands, making them valuable model systems for the study of molecular recognition.
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    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 
    Details
    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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    URL: http://dx.doi.org/10.1146/annurev.biophys.29.1.213
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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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    URL: http://dx.doi.org/10.1146/annurev.biophys.29.1.463
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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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    URL: http://dx.doi.org/10.1146/annurev.biophys.29.1.361
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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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    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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    THE SEARCH AND ITS OUTCOME: High-Resolution Structures of Ribosomal Particles from Mesophilic, Thermophilic, and Halophilic Bacteria at Various Functional States (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 257-273 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract We determined the high-resolution structures of large and small ribosomal subunits from mesophilic and thermophilic bacteria and compared them with those of the thermophilic ribosome and the halophilic large subunit. We confirmed that the elements involved in intersubunit contacts and in substrate binding are inherently flexible and that a common ribosomal strategy is to utilize this conformational variability for optimizing its functional efficiency and minimizing nonproductive interactions. Under close-to-physiological conditions, these elements maintain well-ordered characteristic conformations. In unbound subunits, the features creating intersubunit bridges within associated ribosomes lie on the interface surface, and the features that bind factors and substrates reach toward the binding site only when conditions are ripe.
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    URL: http://dx.doi.org/10.1146/annurev.biophys.31.082901.134439
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    CONFORMATIONAL DYNAMICS OF THE CHROMATIN FIBER IN SOLUTION: Determinants, Mechanisms, and Functions (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 361-392 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Chromatin fibers are dynamic macromolecular assemblages that are intimately involved in nuclear function. This review focuses on recent advances centered on the molecular mechanisms and determinants of chromatin fiber dynamics in solution. Major points of emphasis are the functions of the core histone tail domains, linker histones, and a new class of proteins that assemble supramolecular chromatin structures. The discussion of important structural issues is set against a background of possible functional significance.
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    URL: http://dx.doi.org/10.1146/annurev.biophys.31.101101.140858
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    PARAMAGNETIC RESONANCE OF BIOLOGICAL METAL CENTERS (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 393-422 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract The review deals with recent advances in magnetic resonance spectroscopy (hf EPR and NMR) of paramagnetic metal centers in biological macromolecules. In the first half of our chapter, we present an overview of recent technical developments in the NMR of paramagnetic bio-macromolecules. These are illustrated by a variety of examples deriving mainly from the spectroscopy of metalloproteins and their complexes. The second half focuses on recent developments in high-frequency EPR spectroscopy and the application of the technique to copper, iron, and manganese proteins. Special attention is given to the work on single crystals of copper proteins.
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    URL: http://dx.doi.org/10.1146/annurev.biophys.31.091701.171000
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    FORCE EXERTION IN FUNGAL INFECTION (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 321-341 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Fungal pathogens of plants or animals invade their hosts either by secretion of lytic enzymes, exerting force, or by a combination of both. Although many fungi are thought to rely mostly on lysis of the host tissue, some plant pathogenic fungi differentiate complex infection cells that develop enormous turgor pressure, which in turn is translated into force used for invasion. In order to understand mechanisms of fungal infection in detail, methods have been developed that indirectly or directly measure turgor pressure and force. In this article, these methods are described and critically discussed, and their importance in analysis of fungal infection are outlined.
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    COMPUTATIONAL CELL BIOLOGY: Spatiotemporal Simulation of Cellular Events (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 423-441 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract The field of computational cell biology has emerged within the past 5 years because of the need to apply disciplined computational approaches to build and test complex hypotheses on the interacting structural, physical, and chemical features that underlie intracellular processes. To meet this need, newly developed software tools allow cell biologists and biophysicists to build models and generate simulations from them. The construction of general-purpose computational approaches is especially challenging if the spatial complexity of cellular systems is to be explicitly treated. This review surveys some of the existing efforts in this field with special emphasis on a system being developed in the authors' laboratory, Virtual Cell. The theories behind both stochastic and deterministic simulations are discussed. Examples of respective applications to cell biological problems in RNA trafficking and neuronal calcium dynamics are provided to illustrate these ideas.
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    URL: http://dx.doi.org/10.1146/annurev.biophys.31.101101.140930
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    ETHYLENE: A Gaseous Signal Molecule in Plants (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 1-18 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Ethylene regulates a multitude of plant processes, ranging from seed germination to organ senescence. Of particular economic importance is the role of ethylene as an inducer of fruit ripening. Ethylene is synthesized from S-adenosyl-L-methionine via 1-aminocyclopropane-1-carboxylic acid (ACC). The enzymes catalyzing the two reactions in this pathway are ACC synthase and ACC oxidase. Environmental and endogenous signals regulate ethylene biosynthesis primarily through differential expression of ACC synthase genes. Components of the ethylene signal transduction pathway have been identified by characterization of ethylene-response mutants in Arabidopsis thaliana. One class of mutations, exemplified by etr1, led to the identification of the ethylene receptors, which turned out to be related to bacterial two-component signaling systems. Mutations that eliminate ethylene binding to the receptor yield a dominant, ethylene-insensitive phenotype. CTR1 encodes a Raf-like Ser/Thr protein kinase that acts downstream from the ethylene receptor and may be part of a MAP kinase cascade. Mutants in CTR1 exhibit a constitutive ethylene-response phenotype. Both the ethylene receptors and CTR1 are negative regulators of ethylene responses. EIN2 and EIN3 are epistatic to CTR1, and mutations in either gene lead to ethylene insensitivity. Whereas the function of EIN2 in ethylene transduction is not known, EIN3 is a putative transcription factor involved in regulating expression of ethylene-responsive genes. Biotechnological modifications of ethylene synthesis and of sensitivity to ethylene are promising methods to prevent spoilage of agricultural products such as fruits, whose ripening is induced by ethylene.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.16.1.1
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    MECHANISMS OF SYNAPTIC VESICLE EXOCYTOSIS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 19-49 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Chemical synaptic transmission serves as the main form of cell to cell communication in the nervous system. Neurotransmitter release occurs through the process of regulated exocytosis, in which a synaptic vesicle releases its contents in response to an increase in calcium. The use of genetic, biochemical, structural, and functional studies has led to the identification of factors important in the synaptic vesicle life cycle. Here we focus on the prominent role of SNARE (soluble NSF attachment protein receptor) proteins during membrane fusion and the regulation of SNARE function by Rab3a, nSec1, and NSF. Many of the proteins important for transmitter release have homologs involved in intracellular vesicle transport, and all forms of vesicle trafficking share common basic principles. Finally, modifications to the synaptic exocytosis pathway are very likely to underlie certain forms of synaptic plasticity and therefore contribute to learning and memory.
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    ERM-MERLIN AND EBP50 PROTEIN FAMILIES IN PLASMA MEMBRANE ORGANIZATION AND FUNCTION (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 113-143 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The ezrin-radixin-moesin (ERM) family of proteins have emerged as key regulatory molecules in linking F-actin to specific membrane proteins, especially in cell surface structures. Merlin, the product of the NF2 tumor suppressor gene, has sequence similarity to ERM proteins and binds to some of the same membrane proteins, but lacks a C-terminal F-actin binding site. In this review we discuss how ERM proteins and merlin are negatively regulated by an intramolecular association between their N- and C-terminal domains. Activation of at least ERM proteins can be accomplished by C-terminal phosphorylation in the presence of PIP2. We also discuss membrane proteins to which ERM and merlin bind, including those making an indirect linkage through the PDZ-containing adaptor molecules EBP50 and E3KARP. Finally, the function of these proteins in cortical structure, endocytic traffic, signal transduction, and growth control is discussed.
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    MOLECULAR REGULATION OF ADIPOGENESIS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 145-171 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Adipogenesis, or the development of fat cells from preadipocytes, has been one of the most intensely studied models of cellular differentiation. In part this has been because of the availability of in vitro models that faithfully recapitulate most of the critical aspects of fat cell formation in vivo. More recently, studies of adipogenesis have proceeded with the hope that manipulation of this process in humans might one day lead to a reduction in the burden of obesity and diabetes. This review explores some of the highlights of a large and burgeoning literature devoted to understanding adipogenesis at the molecular level. The hormonal and transcriptional control of adipogenesis is reviewed, as well as studies on a less well known type of fat cell, the brown adipocyte. Emphasis is placed, where possible, on in vivo studies with the hope that the results discussed may one day shed light on basic questions of cellular growth and differentiation in addition to possible benefits in human health.
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    GUT FEELINGS: Enteropathogenic E. coli (EPEC) Interactions with the Host (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 173-189 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Enteropathogenic Escherichia coli (EPEC) is a gram-negative bacterial pathogen that adheres to human intestinal epithelial cells, resulting in watery, persistent diarrhea. It subverts the host cell cytoskeleton, causing a rearrangement of cytoskeletal components into a characteristic pedestal structure underneath adherent bacteria. In contrast to other intracellular pathogens that affect the actin cytoskeleton from inside the host cytoplasm, EPEC remains extracellular and transmits signals through the host cell plasma membrane via direct injection of virulence factors by a "molecular syringe," the bacterial type III secretion system. One injected factor is Tir, which functions as the plasma membrane receptor for EPEC adherence. Tir directly links extracellular EPEC through the epithelial membrane and firmly anchors it to the host cell actin cytoskeleton, thereby initiating pedestal formation. In addition to stimulating actin nucleation and polymerization in the host cell, EPEC activates several other signaling pathways that lead to tight junction disruption, inhibition of phagocytosis, altered ion secretion, and immune responses. This review summarizes recent developments in our understanding of EPEC pathogenesis and discusses similarities and differences between EPEC pedestals, focal contacts, and Listeria monocytogenes actin tails.
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    BONE DEVELOPMENT (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 191-220 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Early development of the vertebrate skeleton depends on genes that pattern the distribution and proliferation of cells from cranial neural crest, sclerotomes, and lateral plate mesoderm into mesenchymal condensations at sites of future skeletal elements. Within these condensations, cells differentiate to chondrocytes or osteoblasts and form cartilages and bones under the control of various transcription factors. In most of the skeleton, organogenesis results in cartilage models of future bones; in these models cartilage is replaced by bone by the process of endochondral ossification. Lastly, through a controlled process of bone growth and remodeling the final skeleton is shaped and molded. Significant and exciting insights into all aspects of vertebrate skeletal development have been obtained through molecular and genetic studies of animal models and humans with inherited disorders of skeletal morphogenesis, organogenesis, and growth.
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    CELLULAR SIGNALING AND VOLUME CONTROL IN STOMATAL MOVEMENTS IN PLANTS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 221-241 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Stomatal guard cells are unique as a plant cell model and, because of the depth of present knowledge on ion transport and its regulation, offer a first look at signal integration in higher plants. A large body of data indicates that Ca2+ and H+ act independently, integrating with protein kinases and phosphatases, to control the gating of the K+ and Cl- channels that mediate solute flux for stomatal movements. Oscillations in the cytosolic-free concentration of Ca2+ contribute to a signaling cassette, integrated within these events through an unusual coupling with membrane voltage for solute homeostasis. Similar cassettes are anticipated to include control pathways linked to cytosolic pH. Additional developments during the last two years point to events in membrane traffic that play equally important roles in stomatal control. Research in these areas is now adding entirely new dimensions to our understanding of guard cell signaling.
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    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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    CAJAL BODIES: The First 100 Years (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 273-300 
    Details
    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.
    Type of Medium: Electronic Resource
    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 
    Details
    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.
    Type of Medium: Electronic Resource
    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 
    Details
    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.
    Type of Medium: Electronic Resource
    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 
    Details
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Green fluorescent protein chimerae acting as reporters for protein localization and trafficking within the secretory membrane system of living cells have been used in a wide variety of applications, including time-lapse imaging, double-labeling, energy transfer, quantitation, and photobleaching experiments. Results from this work are clarifying the steps involved in the formation, translocation, and fusion of transport intermediates; the organization and biogenesis of organelles; and the mechanisms of protein retention, sorting, and recycling in the secretory pathway. In so doing, they are broadening our thinking about the temporal and spatial relationships among secretory organelles and the membrane trafficking pathways that operate between them.
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    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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    VIRAL ENTRY INTO THE NUCLEUS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 627-651 
    Details
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Because many viruses replicate in the nucleus of their host cells, they must have ways of transporting their genome and other components into and out of this compartment. For the incoming virus particle, nuclear entry is often one of the final steps in a complex transport and uncoating program. Typically, it involves recognition by importins (karyopherins), transport to the nucleus, and binding to nuclear pore complexes. Although all viruses take advantage of cellular signals and factors, viruses and viral capsids vary considerably in size, structure, and in how they interact with the nuclear import machinery. Influenza and adenoviruses undergo extensive disassembly prior to genome import; herpesviruses release their genome into the nucleus without immediate capsid disassembly. Polyoma viruses, parvoviruses, and lentivirus preintegration complexes are thought to enter in intact form, whereas the corresponding complexes of onco-retroviruses have to wait for mitosis because they cannot infect interphase nuclei.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.16.1.627
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    THE MYC/MAX/MAD NETWORK AND THE TRANSCRIPTIONAL CONTROL OF CELL BEHAVIOR (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 653-699 
    Details
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The Myc/Max/Mad network comprises a group of transcription factors whose distinct interactions result in gene-specific transcriptional activation or repression. A great deal of research indicates that the functions of the network play roles in cell proliferation, differentiation, and death. In this review we focus on the Myc and Mad protein families and attempt to relate their biological functions to their transcriptional activities and gene targets. Both Myc and Mad, as well as the more recently described Mnt and Mga proteins, form heterodimers with Max, permitting binding to specific DNA sequences. These DNA-bound heterodimers recruit coactivator or corepressor complexes that generate alterations in chromatin structure, which in turn modulate transcription. Initial identification of target genes suggests that the network regulates genes involved in the cell cycle, growth, life span, and morphology. Because Myc and Mad proteins are expressed in response to diverse signaling pathways, the network can be viewed as a functional module which acts to convert environmental signals into specific gene-regulatory programs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.16.1.653
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    GENE CO-OPTION IN PHYSIOLOGICAL AND MORPHOLOGICAL EVOLUTION (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 18 (2002), S. 53-80 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Co-option occurs when natural selection finds new uses for existing traits, including genes, organs, and other body structures. Genes can be co-opted to generate developmental and physiological novelties by changing their patterns of regulation, by changing the functions of the proteins they encode, or both. This often involves gene duplication followed by specialization of the resulting paralogous genes into particular functions. A major role for gene co-option in the evolution of development has long been assumed, and many recent comparative developmental and genomic studies have lent support to this idea. Although there is relatively less known about the molecular basis of co-option events involving developmental pathways, much can be drawn from well-studied examples of the co-option of structural proteins. Here, we summarize several case studies of both structural gene and developmental genetic circuit co-option and discuss how co-option may underlie major episodes of adaptive change in multicellular organisms. We also examine the phenomenon of intraspecific variability in gene expression patterns, which we propose to be one form of material for the co-option process. We integrate this information with recent models of gene family evolution to provide a framework for understanding the origin of co-optive evolution and the mechanisms by which natural selection promotes evolutionary novelty by inventing new uses for the genetic toolkit.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.18.020402.140619
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    THE MECHANISMS OF POLLINATION AND FERTILIZATION IN PLANTS (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 18 (2002), S. 81-105 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract In flowering plants, pollen grains germinate to form pollen tubes that transport male gametes (sperm cells) to the egg cell in the embryo sac during sexual reproduction. Pollen tube biology is complex, presenting parallels with axon guidance and moving cell systems in animals. Pollen tube cells elongate on an active extracellular matrix in the style, ultimately guided by stylar and embryo sac signals. A well-documented recognition system occurs between pollen grains and the stigma in sporophytic self-incompatibility, where both receptor kinases in the stigma and their peptide ligands from pollen are now known. Complex mechanisms act to precisely target the sperm cells into the embryo sac. These events initiate double fertilization in which the two sperm cells from one pollen tube fuse to produce distinctly different products: one with the egg to produce the zygote and embryo and the other with the central cell to produce the endosperm.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.18.012502.083438
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    RECEPTOR KINASE SIGNALING IN PLANT DEVELOPMENT (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 18 (2002), S. 163-192 
    Details
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The Arabidopsis genome sequence has revealed that plants contain a much larger complement of receptor kinase genes than other organisms. Early analysis of these genes revealed involvement in a diverse array of developmental and defense functions that included gametophyte development, pollen-pistil interactions, shoot apical meristem equilibrium, hormone perception, and cell morphogenesis. Amino acid sequence motifs and binding studies indicate that the ectodomains are capable of binding, either directly or indirectly, various classes of molecules including proteins, carbohydrates, and steroids. Genetic and biochemical approaches have begun to identify other components of several signal transduction pathways. Some receptor-like kinases (RLKs) appear to function with coreceptors lacking kinase domains, and genome analysis suggests this might be true for many RLKs. The KAPP protein phosphatase functions as a negative regulator of at least two RLK systems, and in vitro studies suggest it could be a common component of more. Whether plant signaling systems display a modularity similar to animal systems remains to be determined. Future efforts will reveal unknown functions of other RLKs and elucidate the relationships among their signaling networks.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.18.012502.083431
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    CELLULAR CONTROL OF ACTIN NUCLEATION (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 18 (2002), S. 247-288 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Eukaryotic cells use actin polymerization to change shape, move, and internalize extracellular materials by phagocytosis and endocytosis, and to form contractile structures. In addition, several pathogens have evolved to use host cell actin assembly for attachment, internalization, and cell-to-cell spread. Although cells possess multiple mechanisms for initiating actin polymerization, attention in the past five years has focused on the regulation of actin nucleation-the formation of new actin filaments from actin monomers. The Arp2/3 complex and the multiple nucleation-promoting factors (NPFs) that regulate its activity comprise the only known cellular actin-nucleating factors and may represent a universal machine, conserved across eukaryotic phyla, that nucleates new actin filaments for various cellular structures with numerous functions. This review focuses on our current understanding of the mechanism of actin nucleation by the Arp2/3 complex and NPFs and how these factors work with other cytoskeletal proteins to generate structurally and functionally diverse actin arrays in cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.18.040202.112133
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    MEMBRANE FUSION IN EUKARYOTIC CELLS (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 18 (2002), S. 289-314 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Membrane fusion is a fundamental biochemical reaction and the final step in all vesicular trafficking events. It is crucial for the transfer of proteins and lipids between different compartments and for exo- and endocytic traffic of signaling molecules and receptors. It leads to the reconstruction of organelles such as the Golgi or the nuclear envelope, which decay into fragments during mitosis. Hence, controlled membrane fusion reactions are indispensible for the compartmental organization of eukaryotic cells; for their communication with the environment via hormones, neurotransmitters, growth factors, and receptors; and for the integration of cells into multicellular organisms. Intracellular pathogenic bacteria, such as Mycobacteria or Salmonellae, have developed means to control fusion reactions in their host cells. They persist in phagosomes whose fusion with lysosomes they actively suppress-a means to ensure survival inside host cells. The past decade has witnessed rapid progress in the elucidation of parts of the molecular machinery involved in these membrane fusion reactions. Whereas some elements of the fusion apparatus are remarkably similar in several compartments, there is an equally striking divergence of others. The purpose of this review is to highlight common features of different fusion reactions and the concepts that emerged from them but also to stress the differences and challenge parts of the current hypotheses. This review covers only the endoplasmic fusion reactions mentioned above, i.e., reactions initiated by contacts of membranes with their cytoplasmic faces. Ectoplasmic fusion events, which depend on an initial contact of the fusion partners via the membrane surfaces exposed to the surrounding medium are not discussed, nor are topics such as the entry of enveloped viruses, formation of syncytia, gamete fusion, or vesicle scission (a fusion reaction that leads to the fission of, e.g., transport vesicles).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.18.032202.114809
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    BACTERIAL TOXINS THAT MODIFY THE ACTIN CYTOSKELETON (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 18 (2002), S. 315-344 
    Details
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Bacterial pathogens utilize several strategies to modulate the organization of the actin cytoskeleton. Some bacterial toxins catalyze the covalent modification of actin or the Rho GTPases, which are involved in the control of the actin cytoskeleton. Other bacteria produce toxins that act as guanine nucleotide exchange factors or GTPase-activating proteins to modulate the nucleotide state of the Rho GTPases. This latter group of toxins provides a temporal modulation of the actin cytoskeleton. A third group of bacterial toxins act as adenylate cyclases, which directly elevate intracellular cAMP to supra-physiological levels. Each class of toxins gives the bacterial pathogen a selective advantage in modulating host cell resistance to infection.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.18.012502.134748
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    PROTEOLYSIS AND STEROL REGULATION (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 18 (2002), S. 345-378 
    Details
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The mammalian cell continuously adjusts its sterol content by regulating levels of key sterol synthetic enzymes and levels of LDL receptors that mediate uptake of cholesterol-laden particles. Control is brought about by sterol-regulated transcription of relevant genes and by regulated degradation of the committed step enzyme HMG-CoA reductase (HMGR). Current work has revealed that proteolysis is at the heart of each of these mechanistically distinct axes. Transcriptional control is effected by regulated cleavage of the membrane-bound transcription factor sterol regulatory element binding protein (SREBP), and HMGR degradation is brought about by ubiquitin-mediated degradation. In each case, ongoing cell biological processes are being harnessed to bring about regulation. The secretory pathway plays a central role in allowing sterol-mediated control of transcription. The constitutively active endoplasmic reticulum (ER) quality control apparatus is employed to bring about regulated destruction of HMGR. This review describes the methods and results of various studies to understand the mechanisms and molecules involved in these distinct but interrelated aspects of sterol regulation and the intriguing similarities that appear to exist at the levels of protein sequence and cell biology.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.18.032002.131219
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